id string | task_type string | pipeline string | difficulty string | num_hops int64 | question string | context string | reasoning_chain dict | answer string | choices list | modalities list | modality_data list | evidence list | metadata unknown | path_confidence_score float64 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
co_mech_00001 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_000179.3(MSH6):c.1350_1351del (p.Phe451fs) affects the TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain pathway, citing each molecular step. | NM_000179.3(MSH6):c.1350_1351del (p.Phe451fs) VARIANT_IN_GENE MSH6 -> MSH6 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BRCA1 -> BRCA1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH TP53 -> TP53 GENE_PARTICIPATES_IN_PATHWAY TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000179.3(MSH6):c.1350_1351del (p.Phe451fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000179.3(MSH6):c.1350_1351del (p.Phe451fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_conf... | NM_000179.3(MSH6):c.1350_1351del (p.Phe451fs) VARIANT_IN_GENE MSH6 -> MSH6 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BRCA1 -> BRCA1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH TP53 -> TP53 GENE_PARTICIPATES_IN_PATHWAY TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain | null | [
"expression",
"intercell_role",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "MSH6",
"source_db": "UniProt",
"payload": {
"accession": "P52701",
"sequence": "MSRQSTLYSFFPKSPALSDANKASARASREGGRAAAAPGASPSPGGDAAWSEAGPGPRPLARSASPPKAKNLNGGLRRSVAPAAPTSCDFSPGDLVWAKMEGYPWWPCLVYNHPFDGTFIREKGKSVRVHVQFF... | [
{
"source_db": "ClinVar",
"source_id": "MSH6",
"text": "NM_000179.3(MSH6):c.1350_1351del (p.Phe451fs) VARIANT_IN_GENE MSH6",
"confidence": 1
},
{
"source_db": "STRING",
"source_id": "BRCA1",
"text": "MSH6 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BRCA1",
"confidence": 0.996
},
{
... | {
"variant": "NM_000179.3(MSH6):c.1350_1351del (p.Phe451fs)",
"pathway": "TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain"
} | 0.998749 |
co_mech_00002 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which GRCh38/hg38 5q15-22.2(chr5:93193104-113287795)x1 affects the Assembly and cell surface presentation of NMDA receptors pathway, citing each molecular step. | GRCh38/hg38 5q15-22.2(chr5:93193104-113287795)x1 VARIANT_IN_GENE APC -> APC GENE_ANNOTATED_WITH_GO_TERM protein kinase binding -> TUBA4A GENE_ANNOTATED_WITH_GO_TERM protein kinase binding -> TUBA4A GENE_PARTICIPATES_IN_PATHWAY Assembly and cell surface presentation of NMDA receptors | {
"steps": [
{
"hop": 1,
"source_node_id": "GRCh38/hg38 5q15-22.2(chr5:93193104-113287795)x1",
"source_node_type": "VARIANT",
"source_node_label": "GRCh38/hg38 5q15-22.2(chr5:93193104-113287795)x1",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edg... | GRCh38/hg38 5q15-22.2(chr5:93193104-113287795)x1 VARIANT_IN_GENE APC -> APC GENE_ANNOTATED_WITH_GO_TERM protein kinase binding -> TUBA4A GENE_ANNOTATED_WITH_GO_TERM protein kinase binding -> TUBA4A GENE_PARTICIPATES_IN_PATHWAY Assembly and cell surface presentation of NMDA receptors | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "APC",
"source_db": "UniProt",
"payload": {
"accession": "P25054",
"sequence": "MAAASYDQLLKQVEALKMENSNLRQELEDNSNHLTKLETEASNMKEVLKQLQGSIEDEAMASSGQIDLLERLKELNLDSSNFPGVKLRSKMSLRSYGSREGSVSSRSGECSPVPMGSFPRRGFVNGSRESTGYLE... | [
{
"source_db": "ClinVar",
"source_id": "APC",
"text": "GRCh38/hg38 5q15-22.2(chr5:93193104-113287795)x1 VARIANT_IN_GENE APC",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0019901",
"text": "APC GENE_ANNOTATED_WITH_GO_TERM protein kinase binding",
"confidence": 0.6
}... | {
"variant": "GRCh38/hg38 5q15-22.2(chr5:93193104-113287795)x1",
"pathway": "Assembly and cell surface presentation of NMDA receptors"
} | 0.774597 |
co_mech_00003 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_022552.5(DNMT3A):c.1092dup (p.Tyr365fs) affects the Negative regulation of FGFR1 signaling pathway, citing each molecular step. | NM_022552.5(DNMT3A):c.1092dup (p.Tyr365fs) VARIANT_IN_GENE DNMT3A -> DNMT3A GENE_ANNOTATED_WITH_GO_TERM zinc ion binding -> CBL GENE_ANNOTATED_WITH_GO_TERM zinc ion binding -> CBL GENE_PARTICIPATES_IN_PATHWAY Negative regulation of FGFR1 signaling | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_022552.5(DNMT3A):c.1092dup (p.Tyr365fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_022552.5(DNMT3A):c.1092dup (p.Tyr365fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence... | NM_022552.5(DNMT3A):c.1092dup (p.Tyr365fs) VARIANT_IN_GENE DNMT3A -> DNMT3A GENE_ANNOTATED_WITH_GO_TERM zinc ion binding -> CBL GENE_ANNOTATED_WITH_GO_TERM zinc ion binding -> CBL GENE_PARTICIPATES_IN_PATHWAY Negative regulation of FGFR1 signaling | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "DNMT3A",
"source_db": "UniProt",
"payload": {
"accession": "Q9Y6K1",
"sequence": "MPAMPSSGPGDTSSSAAEREEDRKDGEEQEEPRGKEERQEPSTTARKVGRPGRKRKHPPVESGDTPKDPAVISKSPSMAQDSGASELLPNGDLEKRSEPQPEEGSPAGGQKGGAPAEGEGAAETLPEASRAV... | [
{
"source_db": "ClinVar",
"source_id": "DNMT3A",
"text": "NM_022552.5(DNMT3A):c.1092dup (p.Tyr365fs) VARIANT_IN_GENE DNMT3A",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0008270",
"text": "DNMT3A GENE_ANNOTATED_WITH_GO_TERM zinc ion binding",
"confidence": 0.6
},
... | {
"variant": "NM_022552.5(DNMT3A):c.1092dup (p.Tyr365fs)",
"pathway": "Negative regulation of FGFR1 signaling"
} | 0.774597 |
co_mech_00004 | mechanistic_explanation | coding_variant | hard | 5 | Explain the molecular mechanism by which NM_004960.4(FUS):c.1574C>T (p.Pro525Leu) affects the PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases pathway, citing each molecular step. | NM_004960.4(FUS):c.1574C>T (p.Pro525Leu) VARIANT_IN_GENE FUS -> FUS GENE_ANNOTATED_WITH_GO_TERM zinc ion binding -> BRAF GENE_ANNOTATED_WITH_GO_TERM zinc ion binding -> BRAF PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH NRAS -> NRAS GENE_PARTICIPATES_IN_PATHWAY PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_004960.4(FUS):c.1574C>T (p.Pro525Leu)",
"source_node_type": "VARIANT",
"source_node_label": "NM_004960.4(FUS):c.1574C>T (p.Pro525Leu)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1... | NM_004960.4(FUS):c.1574C>T (p.Pro525Leu) VARIANT_IN_GENE FUS -> FUS GENE_ANNOTATED_WITH_GO_TERM zinc ion binding -> BRAF GENE_ANNOTATED_WITH_GO_TERM zinc ion binding -> BRAF PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH NRAS -> NRAS GENE_PARTICIPATES_IN_PATHWAY PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases | null | [
"conservation",
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "evolutionary",
"tag": "conservation",
"anchor_node_id": "NM_004960.4(FUS):c.1574C>T (p.Pro525Leu)",
"source_db": "UCSC_phyloP",
"payload": {
"chrom": "chr16",
"pos": 31191431,
"track": "phyloP100way",
"window": 20,
"scores": [
2.37301,
2... | [
{
"source_db": "ClinVar",
"source_id": "FUS",
"text": "NM_004960.4(FUS):c.1574C>T (p.Pro525Leu) VARIANT_IN_GENE FUS",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0008270",
"text": "FUS GENE_ANNOTATED_WITH_GO_TERM zinc ion binding",
"confidence": 0.6
},
{
"sou... | {
"variant": "NM_004960.4(FUS):c.1574C>T (p.Pro525Leu)",
"pathway": "PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases"
} | 0.81503 |
co_mech_00005 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_001042492.3(NF1):c.5857C>G (p.Leu1953Val) affects the Late endosomal microautophagy pathway, citing each molecular step. | NM_001042492.3(NF1):c.5857C>G (p.Leu1953Val) VARIANT_IN_GENE NF1 -> NF1 GENE_ANNOTATED_WITH_GO_TERM Ras protein signal transduction -> PARK7 GENE_ANNOTATED_WITH_GO_TERM Ras protein signal transduction -> PARK7 GENE_PARTICIPATES_IN_PATHWAY Late endosomal microautophagy | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_001042492.3(NF1):c.5857C>G (p.Leu1953Val)",
"source_node_type": "VARIANT",
"source_node_label": "NM_001042492.3(NF1):c.5857C>G (p.Leu1953Val)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confid... | NM_001042492.3(NF1):c.5857C>G (p.Leu1953Val) VARIANT_IN_GENE NF1 -> NF1 GENE_ANNOTATED_WITH_GO_TERM Ras protein signal transduction -> PARK7 GENE_ANNOTATED_WITH_GO_TERM Ras protein signal transduction -> PARK7 GENE_PARTICIPATES_IN_PATHWAY Late endosomal microautophagy | null | [
"conservation",
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "evolutionary",
"tag": "conservation",
"anchor_node_id": "NM_001042492.3(NF1):c.5857C>G (p.Leu1953Val)",
"source_db": "UCSC_phyloP",
"payload": {
"chrom": "chr17",
"pos": 31334882,
"track": "phyloP100way",
"window": 20,
"scores": [
7.41041,
... | [
{
"source_db": "ClinVar",
"source_id": "NF1",
"text": "NM_001042492.3(NF1):c.5857C>G (p.Leu1953Val) VARIANT_IN_GENE NF1",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0007265",
"text": "NF1 GENE_ANNOTATED_WITH_GO_TERM Ras protein signal transduction",
"confidence": 0.... | {
"variant": "NM_001042492.3(NF1):c.5857C>G (p.Leu1953Val)",
"pathway": "Late endosomal microautophagy"
} | 0.774597 |
co_mech_00006 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_000051.4(ATM):c.7629_7629+1delinsA affects the Apoptotic cleavage of cellular proteins pathway, citing each molecular step. | NM_000051.4(ATM):c.7629_7629+1delinsA VARIANT_IN_GENE ATM -> ATM GENE_ANNOTATED_WITH_GO_TERM DNA damage response -> APC GENE_ANNOTATED_WITH_GO_TERM DNA damage response -> APC GENE_PARTICIPATES_IN_PATHWAY Apoptotic cleavage of cellular proteins | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000051.4(ATM):c.7629_7629+1delinsA",
"source_node_type": "VARIANT",
"source_node_label": "NM_000051.4(ATM):c.7629_7629+1delinsA",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1,
... | NM_000051.4(ATM):c.7629_7629+1delinsA VARIANT_IN_GENE ATM -> ATM GENE_ANNOTATED_WITH_GO_TERM DNA damage response -> APC GENE_ANNOTATED_WITH_GO_TERM DNA damage response -> APC GENE_PARTICIPATES_IN_PATHWAY Apoptotic cleavage of cellular proteins | null | [
"expression",
"protein_sequence"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "ATM",
"source_db": "UniProt",
"payload": {
"accession": "Q13315",
"sequence": "MSLVLNDLLICCRQLEHDRATERKKEVEKFKRLIRDPETIKHLDRHSDSKQGKYLNWDAVFRFLQKYIQKETECLRIAKPNVSASTQASRQKKMQEISSLVKYFIKCANRRAPRLKCQELLNYIMDTVKDSSNGA... | [
{
"source_db": "ClinVar",
"source_id": "ATM",
"text": "NM_000051.4(ATM):c.7629_7629+1delinsA VARIANT_IN_GENE ATM",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0006974",
"text": "ATM GENE_ANNOTATED_WITH_GO_TERM DNA damage response",
"confidence": 0.6
},
{
"sou... | {
"variant": "NM_000051.4(ATM):c.7629_7629+1delinsA",
"pathway": "Apoptotic cleavage of cellular proteins"
} | 0.774597 |
co_mech_00007 | mechanistic_explanation | coding_variant | hard | 5 | Explain the molecular mechanism by which NM_007294.4(BRCA1):c.192T>G (p.Cys64Trp) affects the crenolanib-resistant FLT3 mutants pathway, citing each molecular step. | NM_007294.4(BRCA1):c.192T>G (p.Cys64Trp) VARIANT_IN_GENE BRCA1 -> BRCA1 GENE_ANNOTATED_WITH_GO_TERM transcription cis-regulatory region binding -> CEBPA GENE_ANNOTATED_WITH_GO_TERM transcription cis-regulatory region binding -> CEBPA PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH FLT3 -> FLT3 GENE_PARTICIPATES_IN_PATHWAY crenola... | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_007294.4(BRCA1):c.192T>G (p.Cys64Trp)",
"source_node_type": "VARIANT",
"source_node_label": "NM_007294.4(BRCA1):c.192T>G (p.Cys64Trp)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1... | NM_007294.4(BRCA1):c.192T>G (p.Cys64Trp) VARIANT_IN_GENE BRCA1 -> BRCA1 GENE_ANNOTATED_WITH_GO_TERM transcription cis-regulatory region binding -> CEBPA GENE_ANNOTATED_WITH_GO_TERM transcription cis-regulatory region binding -> CEBPA PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH FLT3 -> FLT3 GENE_PARTICIPATES_IN_PATHWAY crenola... | null | [
"expression",
"intercell_role",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "BRCA1",
"source_db": "UniProt",
"payload": {
"accession": "P38398",
"sequence": "MDLSALRVEEVQNVINAMQKILECPICLELIKEPVSTKCDHIFCKFCMLKLLNQKKGPSQCPLCKNDITKRSLQESTRFSQLVEELLKIICAFQLDTGLEYANSYNFAKKENNSPEHLKDEVSIIQSMGYRNR... | [
{
"source_db": "ClinVar",
"source_id": "BRCA1",
"text": "NM_007294.4(BRCA1):c.192T>G (p.Cys64Trp) VARIANT_IN_GENE BRCA1",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0000976",
"text": "BRCA1 GENE_ANNOTATED_WITH_GO_TERM transcription cis-regulatory region binding",
"c... | {
"variant": "NM_007294.4(BRCA1):c.192T>G (p.Cys64Trp)",
"pathway": "crenolanib-resistant FLT3 mutants"
} | 0.812072 |
co_mech_00008 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_002303.6(LEPR):c.1846del (p.Arg615_Leu616insTer) affects the Signaling by LTK in cancer pathway, citing each molecular step. | NM_002303.6(LEPR):c.1846del (p.Arg615_Leu616insTer) VARIANT_IN_GENE LEPR -> LEPR GENE_ANNOTATED_WITH_GO_TERM phagocytosis -> PIK3CA GENE_ANNOTATED_WITH_GO_TERM phagocytosis -> PIK3CA GENE_PARTICIPATES_IN_PATHWAY Signaling by LTK in cancer | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_002303.6(LEPR):c.1846del (p.Arg615_Leu616insTer)",
"source_node_type": "VARIANT",
"source_node_label": "NM_002303.6(LEPR):c.1846del (p.Arg615_Leu616insTer)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
... | NM_002303.6(LEPR):c.1846del (p.Arg615_Leu616insTer) VARIANT_IN_GENE LEPR -> LEPR GENE_ANNOTATED_WITH_GO_TERM phagocytosis -> PIK3CA GENE_ANNOTATED_WITH_GO_TERM phagocytosis -> PIK3CA GENE_PARTICIPATES_IN_PATHWAY Signaling by LTK in cancer | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "LEPR",
"source_db": "UniProt",
"payload": {
"accession": "P48357",
"sequence": "MICQKFCVVLLHWEFIYVITAFNLSYPITPWRFKLSCMPPNSTYDYFLLPAGLSKNTSNSNGHYETAVEPKFNSSGTHFSNLSKTTFHCCFRSEQDRNCSLCADNIEGKTFVSTVNSLVFQQIDANWNIQCWLK... | [
{
"source_db": "ClinVar",
"source_id": "LEPR",
"text": "NM_002303.6(LEPR):c.1846del (p.Arg615_Leu616insTer) VARIANT_IN_GENE LEPR",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0006909",
"text": "LEPR GENE_ANNOTATED_WITH_GO_TERM phagocytosis",
"confidence": 0.6
},
... | {
"variant": "NM_002303.6(LEPR):c.1846del (p.Arg615_Leu616insTer)",
"pathway": "Signaling by LTK in cancer"
} | 0.774597 |
co_mech_00009 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_000038.6(APC):c.1626+2T>C affects the B-WICH complex positively regulates rRNA expression pathway, citing each molecular step. | NM_000038.6(APC):c.1626+2T>C VARIANT_IN_GENE APC -> APC GENE_ANNOTATED_WITH_GO_TERM protein kinase binding -> ACTB GENE_ANNOTATED_WITH_GO_TERM protein kinase binding -> ACTB GENE_PARTICIPATES_IN_PATHWAY B-WICH complex positively regulates rRNA expression | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000038.6(APC):c.1626+2T>C",
"source_node_type": "VARIANT",
"source_node_label": "NM_000038.6(APC):c.1626+2T>C",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1,
"edge_source_db"... | NM_000038.6(APC):c.1626+2T>C VARIANT_IN_GENE APC -> APC GENE_ANNOTATED_WITH_GO_TERM protein kinase binding -> ACTB GENE_ANNOTATED_WITH_GO_TERM protein kinase binding -> ACTB GENE_PARTICIPATES_IN_PATHWAY B-WICH complex positively regulates rRNA expression | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "APC",
"source_db": "UniProt",
"payload": {
"accession": "P25054",
"sequence": "MAAASYDQLLKQVEALKMENSNLRQELEDNSNHLTKLETEASNMKEVLKQLQGSIEDEAMASSGQIDLLERLKELNLDSSNFPGVKLRSKMSLRSYGSREGSVSSRSGECSPVPMGSFPRRGFVNGSRESTGYLE... | [
{
"source_db": "ClinVar",
"source_id": "APC",
"text": "NM_000038.6(APC):c.1626+2T>C VARIANT_IN_GENE APC",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0019901",
"text": "APC GENE_ANNOTATED_WITH_GO_TERM protein kinase binding",
"confidence": 0.6
},
{
"source_db... | {
"variant": "NM_000038.6(APC):c.1626+2T>C",
"pathway": "B-WICH complex positively regulates rRNA expression"
} | 0.774597 |
co_mech_00010 | mechanistic_explanation | coding_variant | medium | 4 | Explain the molecular mechanism by which NM_000057.4(BLM):c.2809C>T (p.Gln937Ter) affects the Transcriptional Regulation by E2F6 pathway, citing each molecular step. | NM_000057.4(BLM):c.2809C>T (p.Gln937Ter) VARIANT_IN_GENE BLM -> BLM GENE_PARTICIPATES_IN_PATHWAY SUMOylation of DNA damage response and repair proteins -> BRCA1 GENE_PARTICIPATES_IN_PATHWAY SUMOylation of DNA damage response and repair proteins -> BRCA1 GENE_PARTICIPATES_IN_PATHWAY Transcriptional Regulation by E2F6 | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000057.4(BLM):c.2809C>T (p.Gln937Ter)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000057.4(BLM):c.2809C>T (p.Gln937Ter)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1... | NM_000057.4(BLM):c.2809C>T (p.Gln937Ter) VARIANT_IN_GENE BLM -> BLM GENE_PARTICIPATES_IN_PATHWAY SUMOylation of DNA damage response and repair proteins -> BRCA1 GENE_PARTICIPATES_IN_PATHWAY SUMOylation of DNA damage response and repair proteins -> BRCA1 GENE_PARTICIPATES_IN_PATHWAY Transcriptional Regulation by E2F6 | null | [
"expression",
"intercell_role",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "BLM",
"source_db": "UniProt",
"payload": {
"accession": "P54132",
"sequence": "MAAVPQNNLQEQLERHSARTLNNKLSLSKPKFSGFTFKKKTSSDNNVSVTNVSVAKTPVLRNKDVNVTEDFSFSEPLPNTTNQQRVKDFFKNAPAGQETQRGGSKSLLPDFLQTPKEVVCTTQNTPTVKKSRDTA... | [
{
"source_db": "ClinVar",
"source_id": "BLM",
"text": "NM_000057.4(BLM):c.2809C>T (p.Gln937Ter) VARIANT_IN_GENE BLM",
"confidence": 1
},
{
"source_db": "Reactome",
"source_id": "R-HSA-3108214",
"text": "BLM GENE_PARTICIPATES_IN_PATHWAY SUMOylation of DNA damage response and repair pr... | {
"variant": "NM_000057.4(BLM):c.2809C>T (p.Gln937Ter)",
"pathway": "Transcriptional Regulation by E2F6"
} | 1 |
co_mech_00011 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_000455.5(STK11):c.923G>T (p.Trp308Leu) affects the Defective CFTR causes cystic fibrosis pathway, citing each molecular step. | NM_000455.5(STK11):c.923G>T (p.Trp308Leu) VARIANT_IN_GENE STK11 -> STK11 GENE_ANNOTATED_WITH_GO_TERM DNA damage response -> PSMA6 GENE_ANNOTATED_WITH_GO_TERM DNA damage response -> PSMA6 GENE_PARTICIPATES_IN_PATHWAY Defective CFTR causes cystic fibrosis | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000455.5(STK11):c.923G>T (p.Trp308Leu)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000455.5(STK11):c.923G>T (p.Trp308Leu)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence":... | NM_000455.5(STK11):c.923G>T (p.Trp308Leu) VARIANT_IN_GENE STK11 -> STK11 GENE_ANNOTATED_WITH_GO_TERM DNA damage response -> PSMA6 GENE_ANNOTATED_WITH_GO_TERM DNA damage response -> PSMA6 GENE_PARTICIPATES_IN_PATHWAY Defective CFTR causes cystic fibrosis | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "STK11",
"source_db": "UniProt",
"payload": {
"accession": "Q15831",
"sequence": "MEVVDPQQLGMFTEGELMSVGMDTFIHRIDSTEVIYQPRRKRAKLIGKYLMGDLLGEGSYGKVKEVLDSETLCRRAVKILKKKKLRRIPNGEANVKKEIQLLRRLRHKNVIQLVDVLYNEEKQKMYMVMEYCV... | [
{
"source_db": "ClinVar",
"source_id": "STK11",
"text": "NM_000455.5(STK11):c.923G>T (p.Trp308Leu) VARIANT_IN_GENE STK11",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0006974",
"text": "STK11 GENE_ANNOTATED_WITH_GO_TERM DNA damage response",
"confidence": 0.6
},
... | {
"variant": "NM_000455.5(STK11):c.923G>T (p.Trp308Leu)",
"pathway": "Defective CFTR causes cystic fibrosis"
} | 0.774597 |
co_mech_00012 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_000251.3(MSH2):c.2588dup (p.Tyr863Ter) affects the Post-translational protein phosphorylation pathway, citing each molecular step. | NM_000251.3(MSH2):c.2588dup (p.Tyr863Ter) VARIANT_IN_GENE MSH2 -> MSH2 GENE_ANNOTATED_WITH_GO_TERM protein homodimerization activity -> APOE GENE_ANNOTATED_WITH_GO_TERM protein homodimerization activity -> APOE GENE_PARTICIPATES_IN_PATHWAY Post-translational protein phosphorylation | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000251.3(MSH2):c.2588dup (p.Tyr863Ter)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000251.3(MSH2):c.2588dup (p.Tyr863Ter)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence":... | NM_000251.3(MSH2):c.2588dup (p.Tyr863Ter) VARIANT_IN_GENE MSH2 -> MSH2 GENE_ANNOTATED_WITH_GO_TERM protein homodimerization activity -> APOE GENE_ANNOTATED_WITH_GO_TERM protein homodimerization activity -> APOE GENE_PARTICIPATES_IN_PATHWAY Post-translational protein phosphorylation | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "MSH2",
"source_db": "UniProt",
"payload": {
"accession": "P43246",
"sequence": "MAVQPKETLQLESAAEVGFVRFFQGMPEKPTTTVRLFDRGDFYTAHGEDALLAAREVFKTQGVIKYMGPAGAKNLQSVVLSKMNFESFVKDLLLVRQYRVEVYKNRAGNKASKENDWYLAYKASPGNLSQFEDI... | [
{
"source_db": "ClinVar",
"source_id": "MSH2",
"text": "NM_000251.3(MSH2):c.2588dup (p.Tyr863Ter) VARIANT_IN_GENE MSH2",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0042803",
"text": "MSH2 GENE_ANNOTATED_WITH_GO_TERM protein homodimerization activity",
"confidence": ... | {
"variant": "NM_000251.3(MSH2):c.2588dup (p.Tyr863Ter)",
"pathway": "Post-translational protein phosphorylation"
} | 0.774597 |
co_mech_00013 | mechanistic_explanation | coding_variant | medium | 4 | Explain the molecular mechanism by which NC_000005.9:g.(?_112090582)_(112137086_?)dup affects the Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells pathway, citing each molecular step. | NC_000005.9:g.(?_112090582)_(112137086_?)dup VARIANT_IN_GENE APC -> APC GENE_PARTICIPATES_IN_PATHWAY Disassembly of the destruction complex and recruitment of AXIN to the membrane -> PPP2R1B GENE_PARTICIPATES_IN_PATHWAY Disassembly of the destruction complex and recruitment of AXIN to the membrane -> PPP2R1B GENE_PARTI... | {
"steps": [
{
"hop": 1,
"source_node_id": "NC_000005.9:g.(?_112090582)_(112137086_?)dup",
"source_node_type": "VARIANT",
"source_node_label": "NC_000005.9:g.(?_112090582)_(112137086_?)dup",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confid... | NC_000005.9:g.(?_112090582)_(112137086_?)dup VARIANT_IN_GENE APC -> APC GENE_PARTICIPATES_IN_PATHWAY Disassembly of the destruction complex and recruitment of AXIN to the membrane -> PPP2R1B GENE_PARTICIPATES_IN_PATHWAY Disassembly of the destruction complex and recruitment of AXIN to the membrane -> PPP2R1B GENE_PARTI... | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "APC",
"source_db": "UniProt",
"payload": {
"accession": "P25054",
"sequence": "MAAASYDQLLKQVEALKMENSNLRQELEDNSNHLTKLETEASNMKEVLKQLQGSIEDEAMASSGQIDLLERLKELNLDSSNFPGVKLRSKMSLRSYGSREGSVSSRSGECSPVPMGSFPRRGFVNGSRESTGYLE... | [
{
"source_db": "ClinVar",
"source_id": "APC",
"text": "NC_000005.9:g.(?_112090582)_(112137086_?)dup VARIANT_IN_GENE APC",
"confidence": 1
},
{
"source_db": "Reactome",
"source_id": "R-HSA-4641262",
"text": "APC GENE_PARTICIPATES_IN_PATHWAY Disassembly of the destruction complex and r... | {
"variant": "NC_000005.9:g.(?_112090582)_(112137086_?)dup",
"pathway": "Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells"
} | 1 |
co_mech_00014 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_000251.3(MSH2):c.2613_2614delinsAT (p.Lys872Ter) affects the Negative regulation of NOTCH4 signaling pathway, citing each molecular step. | NM_000251.3(MSH2):c.2613_2614delinsAT (p.Lys872Ter) VARIANT_IN_GENE MSH2 -> MSH2 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> AKT1 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> AKT1 GENE_PARTICIPATES_IN_PATHWAY Negative regulation of NOTCH4 signaling | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000251.3(MSH2):c.2613_2614delinsAT (p.Lys872Ter)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000251.3(MSH2):c.2613_2614delinsAT (p.Lys872Ter)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
... | NM_000251.3(MSH2):c.2613_2614delinsAT (p.Lys872Ter) VARIANT_IN_GENE MSH2 -> MSH2 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> AKT1 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> AKT1 GENE_PARTICIPATES_IN_PATHWAY Negative regulation of NOTCH4 signaling | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "MSH2",
"source_db": "UniProt",
"payload": {
"accession": "P43246",
"sequence": "MAVQPKETLQLESAAEVGFVRFFQGMPEKPTTTVRLFDRGDFYTAHGEDALLAAREVFKTQGVIKYMGPAGAKNLQSVVLSKMNFESFVKDLLLVRQYRVEVYKNRAGNKASKENDWYLAYKASPGNLSQFEDI... | [
{
"source_db": "ClinVar",
"source_id": "MSH2",
"text": "NM_000251.3(MSH2):c.2613_2614delinsAT (p.Lys872Ter) VARIANT_IN_GENE MSH2",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0005524",
"text": "MSH2 GENE_ANNOTATED_WITH_GO_TERM ATP binding",
"confidence": 0.6
},
{... | {
"variant": "NM_000251.3(MSH2):c.2613_2614delinsAT (p.Lys872Ter)",
"pathway": "Negative regulation of NOTCH4 signaling"
} | 0.774597 |
co_mech_00015 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NC_000002.11:g.(?_47707825)_(47710120_?)del affects the Regulation of activated PAK-2p34 by proteasome mediated degradation pathway, citing each molecular step. | NC_000002.11:g.(?_47707825)_(47710120_?)del VARIANT_IN_GENE MSH2 -> MSH2 GENE_ANNOTATED_WITH_GO_TERM DNA repair -> PSMA6 GENE_ANNOTATED_WITH_GO_TERM DNA repair -> PSMA6 GENE_PARTICIPATES_IN_PATHWAY Regulation of activated PAK-2p34 by proteasome mediated degradation | {
"steps": [
{
"hop": 1,
"source_node_id": "NC_000002.11:g.(?_47707825)_(47710120_?)del",
"source_node_type": "VARIANT",
"source_node_label": "NC_000002.11:g.(?_47707825)_(47710120_?)del",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confiden... | NC_000002.11:g.(?_47707825)_(47710120_?)del VARIANT_IN_GENE MSH2 -> MSH2 GENE_ANNOTATED_WITH_GO_TERM DNA repair -> PSMA6 GENE_ANNOTATED_WITH_GO_TERM DNA repair -> PSMA6 GENE_PARTICIPATES_IN_PATHWAY Regulation of activated PAK-2p34 by proteasome mediated degradation | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "MSH2",
"source_db": "UniProt",
"payload": {
"accession": "P43246",
"sequence": "MAVQPKETLQLESAAEVGFVRFFQGMPEKPTTTVRLFDRGDFYTAHGEDALLAAREVFKTQGVIKYMGPAGAKNLQSVVLSKMNFESFVKDLLLVRQYRVEVYKNRAGNKASKENDWYLAYKASPGNLSQFEDI... | [
{
"source_db": "ClinVar",
"source_id": "MSH2",
"text": "NC_000002.11:g.(?_47707825)_(47710120_?)del VARIANT_IN_GENE MSH2",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0006281",
"text": "MSH2 GENE_ANNOTATED_WITH_GO_TERM DNA repair",
"confidence": 0.6
},
{
"sou... | {
"variant": "NC_000002.11:g.(?_47707825)_(47710120_?)del",
"pathway": "Regulation of activated PAK-2p34 by proteasome mediated degradation"
} | 0.774597 |
co_mech_00016 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_000546.6(TP53):c.370T>C (p.Cys124Arg) affects the Insertion of tail-anchored proteins into the endoplasmic reticulum membrane pathway, citing each molecular step. | NM_000546.6(TP53):c.370T>C (p.Cys124Arg) VARIANT_IN_GENE TP53 -> TP53 GENE_ANNOTATED_WITH_GO_TERM negative regulation of cell population proliferation -> APP GENE_ANNOTATED_WITH_GO_TERM negative regulation of cell population proliferation -> APP GENE_PARTICIPATES_IN_PATHWAY Insertion of tail-anchored proteins into the ... | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000546.6(TP53):c.370T>C (p.Cys124Arg)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000546.6(TP53):c.370T>C (p.Cys124Arg)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1... | NM_000546.6(TP53):c.370T>C (p.Cys124Arg) VARIANT_IN_GENE TP53 -> TP53 GENE_ANNOTATED_WITH_GO_TERM negative regulation of cell population proliferation -> APP GENE_ANNOTATED_WITH_GO_TERM negative regulation of cell population proliferation -> APP GENE_PARTICIPATES_IN_PATHWAY Insertion of tail-anchored proteins into the ... | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "TP53",
"source_db": "UniProt",
"payload": {
"accession": "P04637",
"sequence": "MEEPQSDPSVEPPLSQETFSDLWKLLPENNVLSPLPSQAMDDLMLSPDDIEQWFTEDPGPDEAPRMPEAAPPVAPAPAAPTPAAPAPAPSWPLSSSVPSQKTYQGSYGFRLGFLHSGTAKSVTCTYSPALNKMF... | [
{
"source_db": "ClinVar",
"source_id": "TP53",
"text": "NM_000546.6(TP53):c.370T>C (p.Cys124Arg) VARIANT_IN_GENE TP53",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0008285",
"text": "TP53 GENE_ANNOTATED_WITH_GO_TERM negative regulation of cell population proliferation",
... | {
"variant": "NM_000546.6(TP53):c.370T>C (p.Cys124Arg)",
"pathway": "Insertion of tail-anchored proteins into the endoplasmic reticulum membrane"
} | 0.774597 |
co_mech_00017 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_000535.7(PMS2):c.1756del (p.Ser586fs) affects the MAPK pathway, citing each molecular step. | NM_000535.7(PMS2):c.1756del (p.Ser586fs) VARIANT_IN_GENE PMS2 -> PMS2 GENE_PARTICIPATES_IN_PATHWAY TP53 Regulates Transcription of DNA Repair Genes -> BRCA1 GENE_PARTICIPATES_IN_PATHWAY TP53 Regulates Transcription of DNA Repair Genes -> BRCA1 GENE_PARTICIPATES_IN_PATHWAY MAPK | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000535.7(PMS2):c.1756del (p.Ser586fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000535.7(PMS2):c.1756del (p.Ser586fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1... | NM_000535.7(PMS2):c.1756del (p.Ser586fs) VARIANT_IN_GENE PMS2 -> PMS2 GENE_PARTICIPATES_IN_PATHWAY TP53 Regulates Transcription of DNA Repair Genes -> BRCA1 GENE_PARTICIPATES_IN_PATHWAY TP53 Regulates Transcription of DNA Repair Genes -> BRCA1 GENE_PARTICIPATES_IN_PATHWAY MAPK | null | [
"expression",
"intercell_role",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "PMS2",
"source_db": "UniProt",
"payload": {
"accession": "P54278",
"sequence": "MERAESSSTEPAKAIKPIDRKSVHQICSGQVVLSLSTAVKELVENSLDAGATNIDLKLKDYGVDLIEVSDNGCGVEEENFEGLTLKHHTSKIQEFADLTQVETFGFRGEALSSLCALSDVTISTCHASAKVGTR... | [
{
"source_db": "ClinVar",
"source_id": "PMS2",
"text": "NM_000535.7(PMS2):c.1756del (p.Ser586fs) VARIANT_IN_GENE PMS2",
"confidence": 1
},
{
"source_db": "Reactome",
"source_id": "R-HSA-6796648",
"text": "PMS2 GENE_PARTICIPATES_IN_PATHWAY TP53 Regulates Transcription of DNA Repair Ge... | {
"variant": "NM_000535.7(PMS2):c.1756del (p.Ser586fs)",
"pathway": "MAPK"
} | 0.960185 |
co_mech_00018 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_000059.4(BRCA2):c.7806-1G>C affects the Formation of definitive endoderm pathway, citing each molecular step. | NM_000059.4(BRCA2):c.7806-1G>C VARIANT_IN_GENE BRCA2 -> BRCA2 GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription -> CDH1 GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription -> CDH1 GENE_PARTICIPATES_IN_PATHWAY Formation of definitive endoderm | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000059.4(BRCA2):c.7806-1G>C",
"source_node_type": "VARIANT",
"source_node_label": "NM_000059.4(BRCA2):c.7806-1G>C",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1,
"edge_source... | NM_000059.4(BRCA2):c.7806-1G>C VARIANT_IN_GENE BRCA2 -> BRCA2 GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription -> CDH1 GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription -> CDH1 GENE_PARTICIPATES_IN_PATHWAY Formation of definitive endoderm | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "BRCA2",
"source_db": "UniProt",
"payload": {
"accession": "P51587",
"sequence": "MPIGSKERPTFFEIFKTRCNKADLGPISLNWFEELSSEAPPYNSEPAEESEHKNNNYEPNLFKTPQRKPSYNQLASTPIIFKEQGLTLPLYQSPVKELDKFKLDLGRNVPNSRHKSLRTVKTKMDQADDVSCP... | [
{
"source_db": "ClinVar",
"source_id": "BRCA2",
"text": "NM_000059.4(BRCA2):c.7806-1G>C VARIANT_IN_GENE BRCA2",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0045893",
"text": "BRCA2 GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription",
"conf... | {
"variant": "NM_000059.4(BRCA2):c.7806-1G>C",
"pathway": "Formation of definitive endoderm"
} | 0.774597 |
co_mech_00019 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_004360.5(CDH1):c.617_623dup (p.Glu208delinsAspTyrTer) affects the Signaling by BRAF and RAF1 fusions pathway, citing each molecular step. | NM_004360.5(CDH1):c.617_623dup (p.Glu208delinsAspTyrTer) VARIANT_IN_GENE CDH1 -> CDH1 GENE_ANNOTATED_WITH_GO_TERM calcium ion binding -> BRAF GENE_ANNOTATED_WITH_GO_TERM calcium ion binding -> BRAF GENE_PARTICIPATES_IN_PATHWAY Signaling by BRAF and RAF1 fusions | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_004360.5(CDH1):c.617_623dup (p.Glu208delinsAspTyrTer)",
"source_node_type": "VARIANT",
"source_node_label": "NM_004360.5(CDH1):c.617_623dup (p.Glu208delinsAspTyrTer)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "cura... | NM_004360.5(CDH1):c.617_623dup (p.Glu208delinsAspTyrTer) VARIANT_IN_GENE CDH1 -> CDH1 GENE_ANNOTATED_WITH_GO_TERM calcium ion binding -> BRAF GENE_ANNOTATED_WITH_GO_TERM calcium ion binding -> BRAF GENE_PARTICIPATES_IN_PATHWAY Signaling by BRAF and RAF1 fusions | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "CDH1",
"source_db": "UniProt",
"payload": {
"accession": "P12830",
"sequence": "MGPWSRSLSALLLLLQVSSWLCQEPEPCHPGFDAESYTFTVPRRHLERGRVLGRVNFEDCTGRQRTAYFSLDTRFKVGTDGVITVKRPLRFHNPQIHFLVYAWDSTYRKFSTKVTLNTVGHHHRPPPHQASVSG... | [
{
"source_db": "ClinVar",
"source_id": "CDH1",
"text": "NM_004360.5(CDH1):c.617_623dup (p.Glu208delinsAspTyrTer) VARIANT_IN_GENE CDH1",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0005509",
"text": "CDH1 GENE_ANNOTATED_WITH_GO_TERM calcium ion binding",
"confidence":... | {
"variant": "NM_004360.5(CDH1):c.617_623dup (p.Glu208delinsAspTyrTer)",
"pathway": "Signaling by BRAF and RAF1 fusions"
} | 0.774597 |
co_mech_00020 | mechanistic_explanation | coding_variant | hard | 5 | Explain the molecular mechanism by which NM_007194.4(CHEK2):c.1111_1127dup (p.Glu377fs) affects the Synthesis of PIPs at the late endosome membrane pathway, citing each molecular step. | NM_007194.4(CHEK2):c.1111_1127dup (p.Glu377fs) VARIANT_IN_GENE CHEK2 -> CHEK2 GENE_ANNOTATED_WITH_GO_TERM protein homodimerization activity -> ALS2 GENE_ANNOTATED_WITH_GO_TERM protein homodimerization activity -> ALS2 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH FIG4 -> FIG4 GENE_PARTICIPATES_IN_PATHWAY Synthesis of PIPs at th... | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_007194.4(CHEK2):c.1111_1127dup (p.Glu377fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_007194.4(CHEK2):c.1111_1127dup (p.Glu377fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_co... | NM_007194.4(CHEK2):c.1111_1127dup (p.Glu377fs) VARIANT_IN_GENE CHEK2 -> CHEK2 GENE_ANNOTATED_WITH_GO_TERM protein homodimerization activity -> ALS2 GENE_ANNOTATED_WITH_GO_TERM protein homodimerization activity -> ALS2 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH FIG4 -> FIG4 GENE_PARTICIPATES_IN_PATHWAY Synthesis of PIPs at th... | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "CHEK2",
"source_db": "UniProt",
"payload": {
"accession": "O96017",
"sequence": "MSRESDVEAQQSHGSSACSQPHGSVTQSQGSSSQSQGISSSSTSTMPNSSQSSHSSSGTLSSLETVSTQELYSIPEDQEPEDQEPEEPTPAPWARLWALQDGFANLECVNDNYWFGRDKSCEYCFDEPLLKRT... | [
{
"source_db": "ClinVar",
"source_id": "CHEK2",
"text": "NM_007194.4(CHEK2):c.1111_1127dup (p.Glu377fs) VARIANT_IN_GENE CHEK2",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0042803",
"text": "CHEK2 GENE_ANNOTATED_WITH_GO_TERM protein homodimerization activity",
"confi... | {
"variant": "NM_007194.4(CHEK2):c.1111_1127dup (p.Glu377fs)",
"pathway": "Synthesis of PIPs at the late endosome membrane"
} | 0.789864 |
co_mech_00021 | mechanistic_explanation | coding_variant | hard | 3 | Explain the molecular mechanism by which NM_000251.3(MSH2):c.2639del (p.Gly880fs) affects the TP53 Regulates Transcription of Caspase Activators and Caspases pathway, citing each molecular step. | NM_000251.3(MSH2):c.2639del (p.Gly880fs) VARIANT_IN_GENE MSH2 -> MSH2 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH ATM -> ATM GENE_PARTICIPATES_IN_PATHWAY TP53 Regulates Transcription of Caspase Activators and Caspases | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000251.3(MSH2):c.2639del (p.Gly880fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000251.3(MSH2):c.2639del (p.Gly880fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1... | NM_000251.3(MSH2):c.2639del (p.Gly880fs) VARIANT_IN_GENE MSH2 -> MSH2 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH ATM -> ATM GENE_PARTICIPATES_IN_PATHWAY TP53 Regulates Transcription of Caspase Activators and Caspases | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "MSH2",
"source_db": "UniProt",
"payload": {
"accession": "P43246",
"sequence": "MAVQPKETLQLESAAEVGFVRFFQGMPEKPTTTVRLFDRGDFYTAHGEDALLAAREVFKTQGVIKYMGPAGAKNLQSVVLSKMNFESFVKDLLLVRQYRVEVYKNRAGNKASKENDWYLAYKASPGNLSQFEDI... | [
{
"source_db": "ClinVar",
"source_id": "MSH2",
"text": "NM_000251.3(MSH2):c.2639del (p.Gly880fs) VARIANT_IN_GENE MSH2",
"confidence": 1
},
{
"source_db": "STRING",
"source_id": "ATM",
"text": "MSH2 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH ATM",
"confidence": 0.999
},
{
"sourc... | {
"variant": "NM_000251.3(MSH2):c.2639del (p.Gly880fs)",
"pathway": "TP53 Regulates Transcription of Caspase Activators and Caspases"
} | 0.999667 |
co_mech_00022 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_004960.4(FUS):c.1449_1488del (p.Tyr484fs) affects the UCH proteinases pathway, citing each molecular step. | NM_004960.4(FUS):c.1449_1488del (p.Tyr484fs) VARIANT_IN_GENE FUS -> FUS GENE_ANNOTATED_WITH_GO_TERM positive regulation of double-strand break repair via homologous recombination -> ACTB GENE_ANNOTATED_WITH_GO_TERM positive regulation of double-strand break repair via homologous recombination -> ACTB GENE_PARTICIPATES_... | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_004960.4(FUS):c.1449_1488del (p.Tyr484fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_004960.4(FUS):c.1449_1488del (p.Tyr484fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confid... | NM_004960.4(FUS):c.1449_1488del (p.Tyr484fs) VARIANT_IN_GENE FUS -> FUS GENE_ANNOTATED_WITH_GO_TERM positive regulation of double-strand break repair via homologous recombination -> ACTB GENE_ANNOTATED_WITH_GO_TERM positive regulation of double-strand break repair via homologous recombination -> ACTB GENE_PARTICIPATES_... | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "FUS",
"source_db": "UniProt",
"payload": {
"accession": "P35637",
"sequence": "MASNDYTQQATQSYGAYPTQPGQGYSQQSSQPYGQQSYSGYSQSTDTSGYGQSSYSSYGQSQNTGYGTQSTPQGYGSTGGYGSSQSSQSSYGQQSSYPGYGQQPAPSSTSGSYGSSSQSSSYGQPQSGSYSQQPS... | [
{
"source_db": "ClinVar",
"source_id": "FUS",
"text": "NM_004960.4(FUS):c.1449_1488del (p.Tyr484fs) VARIANT_IN_GENE FUS",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:1905168",
"text": "FUS GENE_ANNOTATED_WITH_GO_TERM positive regulation of double-strand break repair via ... | {
"variant": "NM_004960.4(FUS):c.1449_1488del (p.Tyr484fs)",
"pathway": "UCH proteinases"
} | 0.774597 |
co_mech_00023 | mechanistic_explanation | coding_variant | hard | 3 | Explain the molecular mechanism by which NM_000546.6(TP53):c.1000G>T (p.Gly334Trp) affects the Meiotic recombination pathway, citing each molecular step. | NM_000546.6(TP53):c.1000G>T (p.Gly334Trp) VARIANT_IN_GENE TP53 -> BRCA1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH TP53 -> BRCA1 GENE_PARTICIPATES_IN_PATHWAY Meiotic recombination | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000546.6(TP53):c.1000G>T (p.Gly334Trp)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000546.6(TP53):c.1000G>T (p.Gly334Trp)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence":... | NM_000546.6(TP53):c.1000G>T (p.Gly334Trp) VARIANT_IN_GENE TP53 -> BRCA1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH TP53 -> BRCA1 GENE_PARTICIPATES_IN_PATHWAY Meiotic recombination | null | [
"conservation",
"expression",
"intercell_role",
"protein_sequence",
"protein_structure"
] | [
{
"family": "evolutionary",
"tag": "conservation",
"anchor_node_id": "NM_000546.6(TP53):c.1000G>T (p.Gly334Trp)",
"source_db": "UCSC_phyloP",
"payload": {
"chrom": "chr17",
"pos": 7670709,
"track": "phyloP100way",
"window": 20,
"scores": [
0.558512,
... | [
{
"source_db": "ClinVar",
"source_id": "TP53",
"text": "NM_000546.6(TP53):c.1000G>T (p.Gly334Trp) VARIANT_IN_GENE TP53",
"confidence": 1
},
{
"source_db": "STRING",
"source_id": "BRCA1",
"text": "BRCA1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH TP53",
"confidence": 0.999
},
{
"... | {
"variant": "NM_000546.6(TP53):c.1000G>T (p.Gly334Trp)",
"pathway": "Meiotic recombination"
} | 0.999667 |
co_mech_00024 | mechanistic_explanation | coding_variant | medium | 4 | Explain the molecular mechanism by which NM_004360.5(CDH1):c.467G>A (p.Trp156Ter) affects the SMAC (DIABLO) binds to IAPs pathway, citing each molecular step. | NM_004360.5(CDH1):c.467G>A (p.Trp156Ter) VARIANT_IN_GENE CDH1 -> CDH1 GENE_PARTICIPATES_IN_PATHWAY Apoptotic cleavage of cell adhesion proteins -> CASP3 GENE_PARTICIPATES_IN_PATHWAY Apoptotic cleavage of cell adhesion proteins -> CASP3 GENE_PARTICIPATES_IN_PATHWAY SMAC (DIABLO) binds to IAPs | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_004360.5(CDH1):c.467G>A (p.Trp156Ter)",
"source_node_type": "VARIANT",
"source_node_label": "NM_004360.5(CDH1):c.467G>A (p.Trp156Ter)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1... | NM_004360.5(CDH1):c.467G>A (p.Trp156Ter) VARIANT_IN_GENE CDH1 -> CDH1 GENE_PARTICIPATES_IN_PATHWAY Apoptotic cleavage of cell adhesion proteins -> CASP3 GENE_PARTICIPATES_IN_PATHWAY Apoptotic cleavage of cell adhesion proteins -> CASP3 GENE_PARTICIPATES_IN_PATHWAY SMAC (DIABLO) binds to IAPs | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "CDH1",
"source_db": "UniProt",
"payload": {
"accession": "P12830",
"sequence": "MGPWSRSLSALLLLLQVSSWLCQEPEPCHPGFDAESYTFTVPRRHLERGRVLGRVNFEDCTGRQRTAYFSLDTRFKVGTDGVITVKRPLRFHNPQIHFLVYAWDSTYRKFSTKVTLNTVGHHHRPPPHQASVSG... | [
{
"source_db": "ClinVar",
"source_id": "CDH1",
"text": "NM_004360.5(CDH1):c.467G>A (p.Trp156Ter) VARIANT_IN_GENE CDH1",
"confidence": 1
},
{
"source_db": "Reactome",
"source_id": "R-HSA-351906",
"text": "CDH1 GENE_PARTICIPATES_IN_PATHWAY Apoptotic cleavage of cell adhesion proteins"... | {
"variant": "NM_004360.5(CDH1):c.467G>A (p.Trp156Ter)",
"pathway": "SMAC (DIABLO) binds to IAPs "
} | 1 |
co_mech_00025 | mechanistic_explanation | coding_variant | hard | 3 | Explain the molecular mechanism by which NM_000038.6(APC):c.916_917insTA (p.Ser306fs) affects the Formation of axial mesoderm pathway, citing each molecular step. | NM_000038.6(APC):c.916_917insTA (p.Ser306fs) VARIANT_IN_GENE APC -> APC PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH CTNNB1 -> CTNNB1 GENE_PARTICIPATES_IN_PATHWAY Formation of axial mesoderm | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000038.6(APC):c.916_917insTA (p.Ser306fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000038.6(APC):c.916_917insTA (p.Ser306fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confid... | NM_000038.6(APC):c.916_917insTA (p.Ser306fs) VARIANT_IN_GENE APC -> APC PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH CTNNB1 -> CTNNB1 GENE_PARTICIPATES_IN_PATHWAY Formation of axial mesoderm | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "APC",
"source_db": "UniProt",
"payload": {
"accession": "P25054",
"sequence": "MAAASYDQLLKQVEALKMENSNLRQELEDNSNHLTKLETEASNMKEVLKQLQGSIEDEAMASSGQIDLLERLKELNLDSSNFPGVKLRSKMSLRSYGSREGSVSSRSGECSPVPMGSFPRRGFVNGSRESTGYLE... | [
{
"source_db": "ClinVar",
"source_id": "APC",
"text": "NM_000038.6(APC):c.916_917insTA (p.Ser306fs) VARIANT_IN_GENE APC",
"confidence": 1
},
{
"source_db": "STRING",
"source_id": "CTNNB1",
"text": "APC PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH CTNNB1",
"confidence": 0.999
},
{
... | {
"variant": "NM_000038.6(APC):c.916_917insTA (p.Ser306fs)",
"pathway": "Formation of axial mesoderm"
} | 0.999667 |
co_mech_00026 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_001243133.2(NLRP3):c.926T>C (p.Phe309Ser) affects the Chylomicron assembly pathway, citing each molecular step. | NM_001243133.2(NLRP3):c.926T>C (p.Phe309Ser) VARIANT_IN_GENE NLRP3 -> NLRP3 GENE_ANNOTATED_WITH_GO_TERM negative regulation of inflammatory response -> APOE GENE_ANNOTATED_WITH_GO_TERM negative regulation of inflammatory response -> APOE GENE_PARTICIPATES_IN_PATHWAY Chylomicron assembly | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_001243133.2(NLRP3):c.926T>C (p.Phe309Ser)",
"source_node_type": "VARIANT",
"source_node_label": "NM_001243133.2(NLRP3):c.926T>C (p.Phe309Ser)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confid... | NM_001243133.2(NLRP3):c.926T>C (p.Phe309Ser) VARIANT_IN_GENE NLRP3 -> NLRP3 GENE_ANNOTATED_WITH_GO_TERM negative regulation of inflammatory response -> APOE GENE_ANNOTATED_WITH_GO_TERM negative regulation of inflammatory response -> APOE GENE_PARTICIPATES_IN_PATHWAY Chylomicron assembly | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "NLRP3",
"source_db": "UniProt",
"payload": {
"accession": "Q96P20",
"sequence": "MKMASTRCKLARYLEDLEDVDLKKFKMHLEDYPPQKGCIPLPRGQTEKADHVDLATLMIDFNGEEKAWAMAVWIFAAINRRDLYEKAKRDEPKWGSDNARVSNPTVICQEDSIEEEWMGLLEYLSRISICKMK... | [
{
"source_db": "ClinVar",
"source_id": "NLRP3",
"text": "NM_001243133.2(NLRP3):c.926T>C (p.Phe309Ser) VARIANT_IN_GENE NLRP3",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0050728",
"text": "NLRP3 GENE_ANNOTATED_WITH_GO_TERM negative regulation of inflammatory response",
... | {
"variant": "NM_001243133.2(NLRP3):c.926T>C (p.Phe309Ser)",
"pathway": "Chylomicron assembly"
} | 0.774597 |
co_mech_00027 | mechanistic_explanation | coding_variant | hard | 5 | Explain the molecular mechanism by which NM_203446.3(SYNJ1):c.3457del (p.Gly1152_Val1153insTer) affects the POU5F1 (OCT4), SOX2, NANOG repress genes related to differentiation pathway, citing each molecular step. | NM_203446.3(SYNJ1):c.3457del (p.Gly1152_Val1153insTer) VARIANT_IN_GENE SYNJ1 -> SYNJ1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BIN1 -> BIN1 GENE_ANNOTATED_WITH_GO_TERM negative regulation of transcription by RNA polymerase II -> SOX2 GENE_ANNOTATED_WITH_GO_TERM negative regulation of transcription by RNA polymerase II -> S... | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_203446.3(SYNJ1):c.3457del (p.Gly1152_Val1153insTer)",
"source_node_type": "VARIANT",
"source_node_label": "NM_203446.3(SYNJ1):c.3457del (p.Gly1152_Val1153insTer)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated"... | NM_203446.3(SYNJ1):c.3457del (p.Gly1152_Val1153insTer) VARIANT_IN_GENE SYNJ1 -> SYNJ1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BIN1 -> BIN1 GENE_ANNOTATED_WITH_GO_TERM negative regulation of transcription by RNA polymerase II -> SOX2 GENE_ANNOTATED_WITH_GO_TERM negative regulation of transcription by RNA polymerase II -> S... | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "SYNJ1",
"source_db": "UniProt",
"payload": {
"accession": "O43426",
"sequence": "MAFSKGFRIYHKLDPPPFSLIVETRHKEECLMFESGAVAVLSSAEKEAIKGTYSKVLDAYGLLGVLRLNLGDTMLHYLVLVTGCMSVGKIQESEVFRVTSTEFISLRIDSSDEDRISEVRKVLNSGNFYFAWS... | [
{
"source_db": "ClinVar",
"source_id": "SYNJ1",
"text": "NM_203446.3(SYNJ1):c.3457del (p.Gly1152_Val1153insTer) VARIANT_IN_GENE SYNJ1",
"confidence": 1
},
{
"source_db": "STRING",
"source_id": "BIN1",
"text": "SYNJ1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BIN1",
"confidence": 0.994
... | {
"variant": "NM_203446.3(SYNJ1):c.3457del (p.Gly1152_Val1153insTer)",
"pathway": "POU5F1 (OCT4), SOX2, NANOG repress genes related to differentiation"
} | 0.814213 |
co_mech_00028 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_007294.4(BRCA1):c.4698_4699del (p.Gly1567fs) affects the E2F-enabled inhibition of pre-replication complex formation pathway, citing each molecular step. | NM_007294.4(BRCA1):c.4698_4699del (p.Gly1567fs) VARIANT_IN_GENE BRCA1 -> BRCA1 GENE_ANNOTATED_WITH_GO_TERM DNA damage response -> CDK1 GENE_ANNOTATED_WITH_GO_TERM DNA damage response -> CDK1 GENE_PARTICIPATES_IN_PATHWAY E2F-enabled inhibition of pre-replication complex formation | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_007294.4(BRCA1):c.4698_4699del (p.Gly1567fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_007294.4(BRCA1):c.4698_4699del (p.Gly1567fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_... | NM_007294.4(BRCA1):c.4698_4699del (p.Gly1567fs) VARIANT_IN_GENE BRCA1 -> BRCA1 GENE_ANNOTATED_WITH_GO_TERM DNA damage response -> CDK1 GENE_ANNOTATED_WITH_GO_TERM DNA damage response -> CDK1 GENE_PARTICIPATES_IN_PATHWAY E2F-enabled inhibition of pre-replication complex formation | null | [
"expression",
"intercell_role",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "BRCA1",
"source_db": "UniProt",
"payload": {
"accession": "P38398",
"sequence": "MDLSALRVEEVQNVINAMQKILECPICLELIKEPVSTKCDHIFCKFCMLKLLNQKKGPSQCPLCKNDITKRSLQESTRFSQLVEELLKIICAFQLDTGLEYANSYNFAKKENNSPEHLKDEVSIIQSMGYRNR... | [
{
"source_db": "ClinVar",
"source_id": "BRCA1",
"text": "NM_007294.4(BRCA1):c.4698_4699del (p.Gly1567fs) VARIANT_IN_GENE BRCA1",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0006974",
"text": "BRCA1 GENE_ANNOTATED_WITH_GO_TERM DNA damage response",
"confidence": 0.6
... | {
"variant": "NM_007294.4(BRCA1):c.4698_4699del (p.Gly1567fs)",
"pathway": "E2F-enabled inhibition of pre-replication complex formation"
} | 0.774597 |
co_mech_00029 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_000038.6(APC):c.1336_1342del(p.Ile446fs) affects the Downregulation of SMAD2/3:SMAD4 transcriptional activity pathway, citing each molecular step. | NM_000038.6(APC):c.1336_1342del(p.Ile446fs) VARIANT_HAS_VEP_CONSEQUENCE APC -> APC GENE_ANNOTATED_WITH_GO_TERM insulin receptor signaling pathway -> MAPK1 GENE_ANNOTATED_WITH_GO_TERM insulin receptor signaling pathway -> MAPK1 GENE_PARTICIPATES_IN_PATHWAY Downregulation of SMAD2/3:SMAD4 transcriptional activity | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000038.6(APC):c.1336_1342del(p.Ile446fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000038.6(APC):c.1336_1342del(p.Ile446fs)",
"edge_relation": "VARIANT_HAS_VEP_CONSEQUENCE",
"edge_evidence_type": "computational_pred... | NM_000038.6(APC):c.1336_1342del(p.Ile446fs) VARIANT_HAS_VEP_CONSEQUENCE APC -> APC GENE_ANNOTATED_WITH_GO_TERM insulin receptor signaling pathway -> MAPK1 GENE_ANNOTATED_WITH_GO_TERM insulin receptor signaling pathway -> MAPK1 GENE_PARTICIPATES_IN_PATHWAY Downregulation of SMAD2/3:SMAD4 transcriptional activity | null | [
"expression",
"protein_sequence",
"protein_structure",
"snp_sequence"
] | [
{
"family": "sequence",
"tag": "snp_sequence",
"anchor_node_id": "NM_000038.6(APC):c.1336_1342del(p.Ile446fs)",
"source_db": "Ensembl",
"payload": {
"chrom": "5",
"pos": 112821919,
"ref_allele": "ATCTGTC",
"alt_allele": "-",
"ref_context": "ATGGTTTATGTTGATTTTATTTTTC... | [
{
"source_db": "Ensembl_VEP",
"source_id": "APC",
"text": "NM_000038.6(APC):c.1336_1342del(p.Ile446fs) VARIANT_HAS_VEP_CONSEQUENCE APC",
"confidence": 0.95
},
{
"source_db": "GO",
"source_id": "GO:0008286",
"text": "APC GENE_ANNOTATED_WITH_GO_TERM insulin receptor signaling pathway",... | {
"variant": "NM_000038.6(APC):c.1336_1342del(p.Ile446fs)",
"pathway": "Downregulation of SMAD2/3:SMAD4 transcriptional activity"
} | 0.764727 |
co_mech_00030 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_000314.8(PTEN):c.338_391del (p.Ser113_Arg130del) affects the Neutrophil degranulation pathway, citing each molecular step. | NM_000314.8(PTEN):c.338_391del (p.Ser113_Arg130del) VARIANT_IN_GENE PTEN -> PTEN GENE_ANNOTATED_WITH_GO_TERM PDZ domain binding -> PSEN1 GENE_ANNOTATED_WITH_GO_TERM PDZ domain binding -> PSEN1 GENE_PARTICIPATES_IN_PATHWAY Neutrophil degranulation | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000314.8(PTEN):c.338_391del (p.Ser113_Arg130del)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000314.8(PTEN):c.338_391del (p.Ser113_Arg130del)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
... | NM_000314.8(PTEN):c.338_391del (p.Ser113_Arg130del) VARIANT_IN_GENE PTEN -> PTEN GENE_ANNOTATED_WITH_GO_TERM PDZ domain binding -> PSEN1 GENE_ANNOTATED_WITH_GO_TERM PDZ domain binding -> PSEN1 GENE_PARTICIPATES_IN_PATHWAY Neutrophil degranulation | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "PTEN",
"source_db": "UniProt",
"payload": {
"accession": "P60484",
"sequence": "MTAIIKEIVSRNKRRYQEDGFDLDLTYIYPNIIAMGFPAERLEGVYRNNIDDVVRFLDSKHKNHYKIYNLCAERHYDTAKFNCRVAQYPFEDHNPPQLELIKPFCEDLDQWLSEDDNHVAAIHCKAGKGRTGVM... | [
{
"source_db": "ClinVar",
"source_id": "PTEN",
"text": "NM_000314.8(PTEN):c.338_391del (p.Ser113_Arg130del) VARIANT_IN_GENE PTEN",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0030165",
"text": "PTEN GENE_ANNOTATED_WITH_GO_TERM PDZ domain binding",
"confidence": 0.6
... | {
"variant": "NM_000314.8(PTEN):c.338_391del (p.Ser113_Arg130del)",
"pathway": "Neutrophil degranulation"
} | 0.774597 |
co_mech_00031 | mechanistic_explanation | coding_variant | hard | 3 | Explain the molecular mechanism by which NM_001042492.3(NF1):c.2113del (p.Val705fs) affects the FRS-mediated FGFR4 signaling pathway, citing each molecular step. | NM_001042492.3(NF1):c.2113del (p.Val705fs) VARIANT_IN_GENE NF1 -> NF1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH NRAS -> NRAS GENE_PARTICIPATES_IN_PATHWAY FRS-mediated FGFR4 signaling | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_001042492.3(NF1):c.2113del (p.Val705fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_001042492.3(NF1):c.2113del (p.Val705fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence... | NM_001042492.3(NF1):c.2113del (p.Val705fs) VARIANT_IN_GENE NF1 -> NF1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH NRAS -> NRAS GENE_PARTICIPATES_IN_PATHWAY FRS-mediated FGFR4 signaling | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "NF1",
"source_db": "UniProt",
"payload": {
"accession": "P21359",
"sequence": "MAAHRPVEWVQAVVSRFDEQLPIKTGQQNTHTKVSTEHNKECLINISKYKFSLVISGLTTILKNVNNMRIFGEAAEKNLYLSQLIILDTLEKCLAGQPKDTMRLDETMLVKQLLPEICHFLHTCREGNQHAAELR... | [
{
"source_db": "ClinVar",
"source_id": "NF1",
"text": "NM_001042492.3(NF1):c.2113del (p.Val705fs) VARIANT_IN_GENE NF1",
"confidence": 1
},
{
"source_db": "STRING",
"source_id": "NRAS",
"text": "NF1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH NRAS",
"confidence": 0.994
},
{
"sour... | {
"variant": "NM_001042492.3(NF1):c.2113del (p.Val705fs)",
"pathway": "FRS-mediated FGFR4 signaling"
} | 0.997996 |
co_mech_00032 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_000021.4(PSEN1):c.854C>T (p.Ala285Val) affects the Defective binding of RB1 mutants to E2F1,(E2F2, E2F3) pathway, citing each molecular step. | NM_000021.4(PSEN1):c.854C>T (p.Ala285Val) VARIANT_IN_GENE PSEN1 -> PSEN1 GENE_ANNOTATED_WITH_GO_TERM DNA damage response -> CCND1 GENE_ANNOTATED_WITH_GO_TERM DNA damage response -> CCND1 GENE_PARTICIPATES_IN_PATHWAY Defective binding of RB1 mutants to E2F1,(E2F2, E2F3) | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000021.4(PSEN1):c.854C>T (p.Ala285Val)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000021.4(PSEN1):c.854C>T (p.Ala285Val)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence":... | NM_000021.4(PSEN1):c.854C>T (p.Ala285Val) VARIANT_IN_GENE PSEN1 -> PSEN1 GENE_ANNOTATED_WITH_GO_TERM DNA damage response -> CCND1 GENE_ANNOTATED_WITH_GO_TERM DNA damage response -> CCND1 GENE_PARTICIPATES_IN_PATHWAY Defective binding of RB1 mutants to E2F1,(E2F2, E2F3) | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "PSEN1",
"source_db": "UniProt",
"payload": {
"accession": "P49768",
"sequence": "MTELPAPLSYFQNAQMSEDNHLSNTVRSQNDNRERQEHNDRRSLGHPEPLSNGRPQGNSRQVVEQDEEEDEELTLKYGAKHVIMLFVPVTLCMVVVVATIKSVSFYTRKDGQLIYTPFTEDTETVGQRALHSI... | [
{
"source_db": "ClinVar",
"source_id": "PSEN1",
"text": "NM_000021.4(PSEN1):c.854C>T (p.Ala285Val) VARIANT_IN_GENE PSEN1",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0006974",
"text": "PSEN1 GENE_ANNOTATED_WITH_GO_TERM DNA damage response",
"confidence": 0.6
},
... | {
"variant": "NM_000021.4(PSEN1):c.854C>T (p.Ala285Val)",
"pathway": "Defective binding of RB1 mutants to E2F1,(E2F2, E2F3)"
} | 0.774597 |
co_mech_00033 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_000789.4(ACE):c.973del (p.Val325fs) affects the Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs) pathway, citing each molecular step. | NM_000789.4(ACE):c.973del (p.Val325fs) VARIANT_IN_GENE ACE -> ACE GENE_ANNOTATED_WITH_GO_TERM zinc ion binding -> DNMT3A GENE_ANNOTATED_WITH_GO_TERM zinc ion binding -> DNMT3A GENE_PARTICIPATES_IN_PATHWAY Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs) | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000789.4(ACE):c.973del (p.Val325fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000789.4(ACE):c.973del (p.Val325fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1,
... | NM_000789.4(ACE):c.973del (p.Val325fs) VARIANT_IN_GENE ACE -> ACE GENE_ANNOTATED_WITH_GO_TERM zinc ion binding -> DNMT3A GENE_ANNOTATED_WITH_GO_TERM zinc ion binding -> DNMT3A GENE_PARTICIPATES_IN_PATHWAY Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs) | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "ACE",
"source_db": "UniProt",
"payload": {
"accession": "P12821",
"sequence": "MGAASGRRGPGLLLPLPLLLLLPPQPALALDPGLQPGNFSADEAGAQLFAQSYNSSAEQVLFQSVAASWAHDTNITAENARRQEEAALLSQEFAEAWGQKAKELYEPIWQNFTDPQLRRIIGAVRTLGSANLPLA... | [
{
"source_db": "ClinVar",
"source_id": "ACE",
"text": "NM_000789.4(ACE):c.973del (p.Val325fs) VARIANT_IN_GENE ACE",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0008270",
"text": "ACE GENE_ANNOTATED_WITH_GO_TERM zinc ion binding",
"confidence": 0.6
},
{
"sourc... | {
"variant": "NM_000789.4(ACE):c.973del (p.Val325fs)",
"pathway": "Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)"
} | 0.774597 |
co_mech_00034 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_000455.5(STK11):c.735-10C>A affects the Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant pathway, citing each molecular step. | NM_000455.5(STK11):c.735-10C>A VARIANT_IN_GENE STK11 -> STK11 GENE_ANNOTATED_WITH_GO_TERM negative regulation of cell population proliferation -> NOTCH1 GENE_ANNOTATED_WITH_GO_TERM negative regulation of cell population proliferation -> NOTCH1 GENE_PARTICIPATES_IN_PATHWAY Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:... | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000455.5(STK11):c.735-10C>A",
"source_node_type": "VARIANT",
"source_node_label": "NM_000455.5(STK11):c.735-10C>A",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1,
"edge_source... | NM_000455.5(STK11):c.735-10C>A VARIANT_IN_GENE STK11 -> STK11 GENE_ANNOTATED_WITH_GO_TERM negative regulation of cell population proliferation -> NOTCH1 GENE_ANNOTATED_WITH_GO_TERM negative regulation of cell population proliferation -> NOTCH1 GENE_PARTICIPATES_IN_PATHWAY Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:... | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "STK11",
"source_db": "UniProt",
"payload": {
"accession": "Q15831",
"sequence": "MEVVDPQQLGMFTEGELMSVGMDTFIHRIDSTEVIYQPRRKRAKLIGKYLMGDLLGEGSYGKVKEVLDSETLCRRAVKILKKKKLRRIPNGEANVKKEIQLLRRLRHKNVIQLVDVLYNEEKQKMYMVMEYCV... | [
{
"source_db": "ClinVar",
"source_id": "STK11",
"text": "NM_000455.5(STK11):c.735-10C>A VARIANT_IN_GENE STK11",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0008285",
"text": "STK11 GENE_ANNOTATED_WITH_GO_TERM negative regulation of cell population proliferation",
"co... | {
"variant": "NM_000455.5(STK11):c.735-10C>A",
"pathway": "Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant"
} | 0.774597 |
co_mech_00035 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_005157.6(ABL1):c.706G>A (p.Glu236Lys) affects the Binding of TCF/LEF:CTNNB1 to target gene promoters pathway, citing each molecular step. | NM_005157.6(ABL1):c.706G>A (p.Glu236Lys) VARIANT_IN_GENE ABL1 -> ABL1 GENE_ANNOTATED_WITH_GO_TERM DNA damage response -> MYC GENE_ANNOTATED_WITH_GO_TERM DNA damage response -> MYC GENE_PARTICIPATES_IN_PATHWAY Binding of TCF/LEF:CTNNB1 to target gene promoters | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_005157.6(ABL1):c.706G>A (p.Glu236Lys)",
"source_node_type": "VARIANT",
"source_node_label": "NM_005157.6(ABL1):c.706G>A (p.Glu236Lys)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1... | NM_005157.6(ABL1):c.706G>A (p.Glu236Lys) VARIANT_IN_GENE ABL1 -> ABL1 GENE_ANNOTATED_WITH_GO_TERM DNA damage response -> MYC GENE_ANNOTATED_WITH_GO_TERM DNA damage response -> MYC GENE_PARTICIPATES_IN_PATHWAY Binding of TCF/LEF:CTNNB1 to target gene promoters | null | [
"conservation",
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "evolutionary",
"tag": "conservation",
"anchor_node_id": "NM_005157.6(ABL1):c.706G>A (p.Glu236Lys)",
"source_db": "UCSC_phyloP",
"payload": {
"chrom": "chr9",
"pos": 130862919,
"track": "phyloP100way",
"window": 20,
"scores": [
7.8164,
-0... | [
{
"source_db": "ClinVar",
"source_id": "ABL1",
"text": "NM_005157.6(ABL1):c.706G>A (p.Glu236Lys) VARIANT_IN_GENE ABL1",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0006974",
"text": "ABL1 GENE_ANNOTATED_WITH_GO_TERM DNA damage response",
"confidence": 0.6
},
{
... | {
"variant": "NM_005157.6(ABL1):c.706G>A (p.Glu236Lys)",
"pathway": "Binding of TCF/LEF:CTNNB1 to target gene promoters"
} | 0.774597 |
co_mech_00036 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_000059.4(BRCA2):c.2184del (p.Asp728fs) affects the Regulation of MITF-M-dependent genes involved in cell cycle and proliferation pathway, citing each molecular step. | NM_000059.4(BRCA2):c.2184del (p.Asp728fs) VARIANT_IN_GENE BRCA2 -> BRCA2 GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription -> CTNNB1 GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription -> CTNNB1 GENE_PARTICIPATES_IN_PATHWAY Regulation of MITF-M-dependent genes inv... | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000059.4(BRCA2):c.2184del (p.Asp728fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000059.4(BRCA2):c.2184del (p.Asp728fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence":... | NM_000059.4(BRCA2):c.2184del (p.Asp728fs) VARIANT_IN_GENE BRCA2 -> BRCA2 GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription -> CTNNB1 GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription -> CTNNB1 GENE_PARTICIPATES_IN_PATHWAY Regulation of MITF-M-dependent genes inv... | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "BRCA2",
"source_db": "UniProt",
"payload": {
"accession": "P51587",
"sequence": "MPIGSKERPTFFEIFKTRCNKADLGPISLNWFEELSSEAPPYNSEPAEESEHKNNNYEPNLFKTPQRKPSYNQLASTPIIFKEQGLTLPLYQSPVKELDKFKLDLGRNVPNSRHKSLRTVKTKMDQADDVSCP... | [
{
"source_db": "ClinVar",
"source_id": "BRCA2",
"text": "NM_000059.4(BRCA2):c.2184del (p.Asp728fs) VARIANT_IN_GENE BRCA2",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0045893",
"text": "BRCA2 GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription"... | {
"variant": "NM_000059.4(BRCA2):c.2184del (p.Asp728fs)",
"pathway": "Regulation of MITF-M-dependent genes involved in cell cycle and proliferation"
} | 0.774597 |
co_mech_00037 | mechanistic_explanation | coding_variant | hard | 3 | Explain the molecular mechanism by which NM_004364.5(CEBPA):c.918_919insGCGCTGCTTGGCCTTGTCGCAGAC (p.Arg306_Asn307insAlaLeuLeuGlyLeuValAlaAsp) affects the Inactivation of CSF3 (G-CSF) signaling pathway, citing each molecular step. | NM_004364.5(CEBPA):c.918_919insGCGCTGCTTGGCCTTGTCGCAGAC (p.Arg306_Asn307insAlaLeuLeuGlyLeuValAlaAsp) VARIANT_IN_GENE CEBPA -> CSF3R PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH CEBPA -> CSF3R GENE_PARTICIPATES_IN_PATHWAY Inactivation of CSF3 (G-CSF) signaling | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_004364.5(CEBPA):c.918_919insGCGCTGCTTGGCCTTGTCGCAGAC (p.Arg306_Asn307insAlaLeuLeuGlyLeuValAlaAsp)",
"source_node_type": "VARIANT",
"source_node_label": "NM_004364.5(CEBPA):c.918_919insGCGCTGCTTGGCCTTGTCGCAGAC (p.Arg306_Asn307insAlaLeuLeuGlyLeu... | NM_004364.5(CEBPA):c.918_919insGCGCTGCTTGGCCTTGTCGCAGAC (p.Arg306_Asn307insAlaLeuLeuGlyLeuValAlaAsp) VARIANT_IN_GENE CEBPA -> CSF3R PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH CEBPA -> CSF3R GENE_PARTICIPATES_IN_PATHWAY Inactivation of CSF3 (G-CSF) signaling | null | [
"conservation",
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "evolutionary",
"tag": "conservation",
"anchor_node_id": "NM_004364.5(CEBPA):c.918_919insGCGCTGCTTGGCCTTGTCGCAGAC (p.Arg306_Asn307insAlaLeuLeuGlyLeuValAlaAsp)",
"source_db": "UCSC_phyloP",
"payload": {
"chrom": "chr19",
"pos": 33301496,
"track": "phyloP100way",
... | [
{
"source_db": "ClinVar",
"source_id": "CEBPA",
"text": "NM_004364.5(CEBPA):c.918_919insGCGCTGCTTGGCCTTGTCGCAGAC (p.Arg306_Asn307insAlaLeuLeuGlyLeuValAlaAsp) VARIANT_IN_GENE CEBPA",
"confidence": 1
},
{
"source_db": "STRING",
"source_id": "CSF3R",
"text": "CSF3R PROTEIN_FUNCTIONALLY_... | {
"variant": "NM_004364.5(CEBPA):c.918_919insGCGCTGCTTGGCCTTGTCGCAGAC (p.Arg306_Asn307insAlaLeuLeuGlyLeuValAlaAsp)",
"pathway": "Inactivation of CSF3 (G-CSF) signaling"
} | 0.978195 |
co_mech_00038 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_000535.7(PMS2):c.713del (p.Ser238fs) affects the Senescence-Associated Secretory Phenotype (SASP) pathway, citing each molecular step. | NM_000535.7(PMS2):c.713del (p.Ser238fs) VARIANT_IN_GENE PMS2 -> PMS2 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> CDK4 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> CDK4 GENE_PARTICIPATES_IN_PATHWAY Senescence-Associated Secretory Phenotype (SASP) | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000535.7(PMS2):c.713del (p.Ser238fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000535.7(PMS2):c.713del (p.Ser238fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1,
... | NM_000535.7(PMS2):c.713del (p.Ser238fs) VARIANT_IN_GENE PMS2 -> PMS2 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> CDK4 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> CDK4 GENE_PARTICIPATES_IN_PATHWAY Senescence-Associated Secretory Phenotype (SASP) | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "PMS2",
"source_db": "UniProt",
"payload": {
"accession": "P54278",
"sequence": "MERAESSSTEPAKAIKPIDRKSVHQICSGQVVLSLSTAVKELVENSLDAGATNIDLKLKDYGVDLIEVSDNGCGVEEENFEGLTLKHHTSKIQEFADLTQVETFGFRGEALSSLCALSDVTISTCHASAKVGTR... | [
{
"source_db": "ClinVar",
"source_id": "PMS2",
"text": "NM_000535.7(PMS2):c.713del (p.Ser238fs) VARIANT_IN_GENE PMS2",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0005524",
"text": "PMS2 GENE_ANNOTATED_WITH_GO_TERM ATP binding",
"confidence": 0.6
},
{
"source... | {
"variant": "NM_000535.7(PMS2):c.713del (p.Ser238fs)",
"pathway": "Senescence-Associated Secretory Phenotype (SASP)"
} | 0.774597 |
co_mech_00039 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_004380.3(CREBBP):c.5790dup (p.Thr1931fs) affects the EGFR interacts with phospholipase C-gamma pathway, citing each molecular step. | NM_004380.3(CREBBP):c.5790dup (p.Thr1931fs) VARIANT_IN_GENE CREBBP -> CREBBP GENE_ANNOTATED_WITH_GO_TERM positive regulation of transcription by RNA polymerase II -> EGFR GENE_ANNOTATED_WITH_GO_TERM positive regulation of transcription by RNA polymerase II -> EGFR GENE_PARTICIPATES_IN_PATHWAY EGFR interacts with phosph... | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_004380.3(CREBBP):c.5790dup (p.Thr1931fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_004380.3(CREBBP):c.5790dup (p.Thr1931fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confiden... | NM_004380.3(CREBBP):c.5790dup (p.Thr1931fs) VARIANT_IN_GENE CREBBP -> CREBBP GENE_ANNOTATED_WITH_GO_TERM positive regulation of transcription by RNA polymerase II -> EGFR GENE_ANNOTATED_WITH_GO_TERM positive regulation of transcription by RNA polymerase II -> EGFR GENE_PARTICIPATES_IN_PATHWAY EGFR interacts with phosph... | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "CREBBP",
"source_db": "UniProt",
"payload": {
"accession": "Q92793",
"sequence": "MAENLLDGPPNPKRAKLSSPGFSANDSTDFGSLFDLENDLPDELIPNGGELGLLNSGNLVPDAASKHKQLSELLRGGSGSSINPGIGNVSASSPVQQGLGGQAQGQPNSANMASLSAMGKSPLSQGDSSAPS... | [
{
"source_db": "ClinVar",
"source_id": "CREBBP",
"text": "NM_004380.3(CREBBP):c.5790dup (p.Thr1931fs) VARIANT_IN_GENE CREBBP",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0045944",
"text": "CREBBP GENE_ANNOTATED_WITH_GO_TERM positive regulation of transcription by RNA po... | {
"variant": "NM_004380.3(CREBBP):c.5790dup (p.Thr1931fs)",
"pathway": "EGFR interacts with phospholipase C-gamma"
} | 0.774597 |
co_mech_00040 | mechanistic_explanation | coding_variant | hard | 5 | Explain the molecular mechanism by which NM_004333.6(BRAF):c.1082A>T (p.Asp361Val) affects the SLC-mediated transport of neurotransmitters pathway, citing each molecular step. | NM_004333.6(BRAF):c.1082A>T (p.Asp361Val) VARIANT_IN_GENE BRAF -> BRAF GENE_ANNOTATED_WITH_GO_TERM epidermal growth factor receptor signaling pathway -> ADRA2A GENE_ANNOTATED_WITH_GO_TERM epidermal growth factor receptor signaling pathway -> ADRA2A PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH SLC6A2 -> SLC6A2 GENE_PARTICIPATES... | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_004333.6(BRAF):c.1082A>T (p.Asp361Val)",
"source_node_type": "VARIANT",
"source_node_label": "NM_004333.6(BRAF):c.1082A>T (p.Asp361Val)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence":... | NM_004333.6(BRAF):c.1082A>T (p.Asp361Val) VARIANT_IN_GENE BRAF -> BRAF GENE_ANNOTATED_WITH_GO_TERM epidermal growth factor receptor signaling pathway -> ADRA2A GENE_ANNOTATED_WITH_GO_TERM epidermal growth factor receptor signaling pathway -> ADRA2A PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH SLC6A2 -> SLC6A2 GENE_PARTICIPATES... | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "BRAF",
"source_db": "UniProt",
"payload": {
"accession": "P15056",
"sequence": "MAALSGGGGGGAEPGQALFNGDMEPEAGAGAGAAASSAADPAIPEEVWNIKQMIKLTQEHIEALLDKFGGEHNPPSIYLEAYEEYTSKLDALQQREQQLLESLGNGTDFSVSSSASMDTVTSSSSSSLSVLPSS... | [
{
"source_db": "ClinVar",
"source_id": "BRAF",
"text": "NM_004333.6(BRAF):c.1082A>T (p.Asp361Val) VARIANT_IN_GENE BRAF",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0007173",
"text": "BRAF GENE_ANNOTATED_WITH_GO_TERM epidermal growth factor receptor signaling pathway",
... | {
"variant": "NM_004333.6(BRAF):c.1082A>T (p.Asp361Val)",
"pathway": "SLC-mediated transport of neurotransmitters"
} | 0.780001 |
co_mech_00041 | mechanistic_explanation | coding_variant | hard | 5 | Explain the molecular mechanism by which NM_032043.3(BRIP1):c.1066C>T (p.Arg356Ter) affects the Signaling downstream of RAS mutants pathway, citing each molecular step. | NM_032043.3(BRIP1):c.1066C>T (p.Arg356Ter) VARIANT_IN_GENE BRIP1 -> BRIP1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BRCA2 -> BRCA2 GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription -> ACTB GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription -> ACTB GENE_PARTICIPATES_IN... | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_032043.3(BRIP1):c.1066C>T (p.Arg356Ter)",
"source_node_type": "VARIANT",
"source_node_label": "NM_032043.3(BRIP1):c.1066C>T (p.Arg356Ter)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence... | NM_032043.3(BRIP1):c.1066C>T (p.Arg356Ter) VARIANT_IN_GENE BRIP1 -> BRIP1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BRCA2 -> BRCA2 GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription -> ACTB GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription -> ACTB GENE_PARTICIPATES_IN... | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "BRIP1",
"source_db": "UniProt",
"payload": {
"accession": "Q9BX63",
"sequence": "MSSMWSEYTIGGVKIYFPYKAYPSQLAMMNSILRGLNSKQHCLLESPTGSGKSLALLCSALAWQQSLSGKPADEGVSEKAEVQLSCCCACHSKDFTNNDMNQGTSRHFNYPSTPPSERNGTSSTCQDSPEKTT... | [
{
"source_db": "ClinVar",
"source_id": "BRIP1",
"text": "NM_032043.3(BRIP1):c.1066C>T (p.Arg356Ter) VARIANT_IN_GENE BRIP1",
"confidence": 1
},
{
"source_db": "STRING",
"source_id": "BRCA2",
"text": "BRIP1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BRCA2",
"confidence": 0.998
},
{
... | {
"variant": "NM_032043.3(BRIP1):c.1066C>T (p.Arg356Ter)",
"pathway": "Signaling downstream of RAS mutants"
} | 0.814867 |
co_mech_00042 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_003106.4(SOX2):c.621C>A (p.Tyr207Ter) affects the ERBB2 Activates PTK6 Signaling pathway, citing each molecular step. | NM_003106.4(SOX2):c.621C>A (p.Tyr207Ter) VARIANT_IN_GENE SOX2 -> SOX2 GENE_ANNOTATED_WITH_GO_TERM neuron differentiation -> EGFR GENE_ANNOTATED_WITH_GO_TERM neuron differentiation -> EGFR GENE_PARTICIPATES_IN_PATHWAY ERBB2 Activates PTK6 Signaling | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_003106.4(SOX2):c.621C>A (p.Tyr207Ter)",
"source_node_type": "VARIANT",
"source_node_label": "NM_003106.4(SOX2):c.621C>A (p.Tyr207Ter)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1... | NM_003106.4(SOX2):c.621C>A (p.Tyr207Ter) VARIANT_IN_GENE SOX2 -> SOX2 GENE_ANNOTATED_WITH_GO_TERM neuron differentiation -> EGFR GENE_ANNOTATED_WITH_GO_TERM neuron differentiation -> EGFR GENE_PARTICIPATES_IN_PATHWAY ERBB2 Activates PTK6 Signaling | null | [
"conservation",
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "evolutionary",
"tag": "conservation",
"anchor_node_id": "NM_003106.4(SOX2):c.621C>A (p.Tyr207Ter)",
"source_db": "UCSC_phyloP",
"payload": {
"chrom": "chr3",
"pos": 181712981,
"track": "phyloP100way",
"window": 20,
"scores": [
10.003,
7.... | [
{
"source_db": "ClinVar",
"source_id": "SOX2",
"text": "NM_003106.4(SOX2):c.621C>A (p.Tyr207Ter) VARIANT_IN_GENE SOX2",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0030182",
"text": "SOX2 GENE_ANNOTATED_WITH_GO_TERM neuron differentiation",
"confidence": 0.6
},
{... | {
"variant": "NM_003106.4(SOX2):c.621C>A (p.Tyr207Ter)",
"pathway": "ERBB2 Activates PTK6 Signaling"
} | 0.774597 |
co_mech_00043 | mechanistic_explanation | coding_variant | hard | 5 | Explain the molecular mechanism by which NM_000251.3(MSH2):c.331del (p.Ala111fs) affects the Formation of the posterior neural plate pathway, citing each molecular step. | NM_000251.3(MSH2):c.331del (p.Ala111fs) VARIANT_IN_GENE MSH2 -> MSH2 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BRCA1 -> BRCA1 GENE_ANNOTATED_WITH_GO_TERM transcription cis-regulatory region binding -> SOX2 GENE_ANNOTATED_WITH_GO_TERM transcription cis-regulatory region binding -> SOX2 GENE_PARTICIPATES_IN_PATHWAY Formation ... | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000251.3(MSH2):c.331del (p.Ala111fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000251.3(MSH2):c.331del (p.Ala111fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1,
... | NM_000251.3(MSH2):c.331del (p.Ala111fs) VARIANT_IN_GENE MSH2 -> MSH2 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BRCA1 -> BRCA1 GENE_ANNOTATED_WITH_GO_TERM transcription cis-regulatory region binding -> SOX2 GENE_ANNOTATED_WITH_GO_TERM transcription cis-regulatory region binding -> SOX2 GENE_PARTICIPATES_IN_PATHWAY Formation ... | null | [
"expression",
"intercell_role",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "MSH2",
"source_db": "UniProt",
"payload": {
"accession": "P43246",
"sequence": "MAVQPKETLQLESAAEVGFVRFFQGMPEKPTTTVRLFDRGDFYTAHGEDALLAAREVFKTQGVIKYMGPAGAKNLQSVVLSKMNFESFVKDLLLVRQYRVEVYKNRAGNKASKENDWYLAYKASPGNLSQFEDI... | [
{
"source_db": "ClinVar",
"source_id": "MSH2",
"text": "NM_000251.3(MSH2):c.331del (p.Ala111fs) VARIANT_IN_GENE MSH2",
"confidence": 1
},
{
"source_db": "STRING",
"source_id": "BRCA1",
"text": "MSH2 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BRCA1",
"confidence": 0.994
},
{
"so... | {
"variant": "NM_000251.3(MSH2):c.331del (p.Ala111fs)",
"pathway": "Formation of the posterior neural plate"
} | 0.814213 |
co_mech_00044 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_003900.5(SQSTM1):c.686C>A (p.Ser229Ter) affects the NOTCH1 Intracellular Domain Regulates Transcription pathway, citing each molecular step. | NM_003900.5(SQSTM1):c.686C>A (p.Ser229Ter) VARIANT_IN_GENE SQSTM1 -> SQSTM1 GENE_ANNOTATED_WITH_GO_TERM ubiquitin protein ligase binding -> MYC GENE_ANNOTATED_WITH_GO_TERM ubiquitin protein ligase binding -> MYC GENE_PARTICIPATES_IN_PATHWAY NOTCH1 Intracellular Domain Regulates Transcription | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_003900.5(SQSTM1):c.686C>A (p.Ser229Ter)",
"source_node_type": "VARIANT",
"source_node_label": "NM_003900.5(SQSTM1):c.686C>A (p.Ser229Ter)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence... | NM_003900.5(SQSTM1):c.686C>A (p.Ser229Ter) VARIANT_IN_GENE SQSTM1 -> SQSTM1 GENE_ANNOTATED_WITH_GO_TERM ubiquitin protein ligase binding -> MYC GENE_ANNOTATED_WITH_GO_TERM ubiquitin protein ligase binding -> MYC GENE_PARTICIPATES_IN_PATHWAY NOTCH1 Intracellular Domain Regulates Transcription | null | [
"conservation",
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "evolutionary",
"tag": "conservation",
"anchor_node_id": "NM_003900.5(SQSTM1):c.686C>A (p.Ser229Ter)",
"source_db": "UCSC_phyloP",
"payload": {
"chrom": "chr5",
"pos": 179825158,
"track": "phyloP100way",
"window": 20,
"scores": [
0.05123619999999... | [
{
"source_db": "ClinVar",
"source_id": "SQSTM1",
"text": "NM_003900.5(SQSTM1):c.686C>A (p.Ser229Ter) VARIANT_IN_GENE SQSTM1",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0031625",
"text": "SQSTM1 GENE_ANNOTATED_WITH_GO_TERM ubiquitin protein ligase binding",
"confide... | {
"variant": "NM_003900.5(SQSTM1):c.686C>A (p.Ser229Ter)",
"pathway": "NOTCH1 Intracellular Domain Regulates Transcription"
} | 0.774597 |
co_mech_00045 | mechanistic_explanation | coding_variant | hard | 3 | Explain the molecular mechanism by which NM_007294.4(BRCA1):c.5467+1_5467+16del affects the Zygotic genome activation (ZGA) pathway, citing each molecular step. | NM_007294.4(BRCA1):c.5467+1_5467+16del VARIANT_IN_GENE BRCA1 -> BRCA1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH TP53 -> TP53 GENE_PARTICIPATES_IN_PATHWAY Zygotic genome activation (ZGA) | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_007294.4(BRCA1):c.5467+1_5467+16del",
"source_node_type": "VARIANT",
"source_node_label": "NM_007294.4(BRCA1):c.5467+1_5467+16del",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1,
... | NM_007294.4(BRCA1):c.5467+1_5467+16del VARIANT_IN_GENE BRCA1 -> BRCA1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH TP53 -> TP53 GENE_PARTICIPATES_IN_PATHWAY Zygotic genome activation (ZGA) | null | [
"expression",
"intercell_role",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "BRCA1",
"source_db": "UniProt",
"payload": {
"accession": "P38398",
"sequence": "MDLSALRVEEVQNVINAMQKILECPICLELIKEPVSTKCDHIFCKFCMLKLLNQKKGPSQCPLCKNDITKRSLQESTRFSQLVEELLKIICAFQLDTGLEYANSYNFAKKENNSPEHLKDEVSIIQSMGYRNR... | [
{
"source_db": "ClinVar",
"source_id": "BRCA1",
"text": "NM_007294.4(BRCA1):c.5467+1_5467+16del VARIANT_IN_GENE BRCA1",
"confidence": 1
},
{
"source_db": "STRING",
"source_id": "TP53",
"text": "BRCA1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH TP53",
"confidence": 0.999
},
{
"so... | {
"variant": "NM_007294.4(BRCA1):c.5467+1_5467+16del",
"pathway": "Zygotic genome activation (ZGA)"
} | 0.999667 |
co_mech_00046 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_032043.3(BRIP1):c.204_205+1delinsAGT affects the PI5P Regulates TP53 Acetylation pathway, citing each molecular step. | NM_032043.3(BRIP1):c.204_205+1delinsAGT VARIANT_IN_GENE BRIP1 -> BRIP1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BRCA1 -> BRCA1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH TP53 -> TP53 GENE_PARTICIPATES_IN_PATHWAY PI5P Regulates TP53 Acetylation | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_032043.3(BRIP1):c.204_205+1delinsAGT",
"source_node_type": "VARIANT",
"source_node_label": "NM_032043.3(BRIP1):c.204_205+1delinsAGT",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1,
... | NM_032043.3(BRIP1):c.204_205+1delinsAGT VARIANT_IN_GENE BRIP1 -> BRIP1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BRCA1 -> BRCA1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH TP53 -> TP53 GENE_PARTICIPATES_IN_PATHWAY PI5P Regulates TP53 Acetylation | null | [
"expression",
"intercell_role",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "BRIP1",
"source_db": "UniProt",
"payload": {
"accession": "Q9BX63",
"sequence": "MSSMWSEYTIGGVKIYFPYKAYPSQLAMMNSILRGLNSKQHCLLESPTGSGKSLALLCSALAWQQSLSGKPADEGVSEKAEVQLSCCCACHSKDFTNNDMNQGTSRHFNYPSTPPSERNGTSSTCQDSPEKTT... | [
{
"source_db": "ClinVar",
"source_id": "BRIP1",
"text": "NM_032043.3(BRIP1):c.204_205+1delinsAGT VARIANT_IN_GENE BRIP1",
"confidence": 1
},
{
"source_db": "STRING",
"source_id": "BRCA1",
"text": "BRIP1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BRCA1",
"confidence": 0.999
},
{
... | {
"variant": "NM_032043.3(BRIP1):c.204_205+1delinsAGT",
"pathway": "PI5P Regulates TP53 Acetylation"
} | 0.9995 |
co_mech_00047 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_000535.7(PMS2):c.613C>T (p.Gln205Ter) affects the Formation of the ureteric bud pathway, citing each molecular step. | NM_000535.7(PMS2):c.613C>T (p.Gln205Ter) VARIANT_IN_GENE PMS2 -> PMS2 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> RET GENE_ANNOTATED_WITH_GO_TERM ATP binding -> RET GENE_PARTICIPATES_IN_PATHWAY Formation of the ureteric bud | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000535.7(PMS2):c.613C>T (p.Gln205Ter)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000535.7(PMS2):c.613C>T (p.Gln205Ter)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1... | NM_000535.7(PMS2):c.613C>T (p.Gln205Ter) VARIANT_IN_GENE PMS2 -> PMS2 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> RET GENE_ANNOTATED_WITH_GO_TERM ATP binding -> RET GENE_PARTICIPATES_IN_PATHWAY Formation of the ureteric bud | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "PMS2",
"source_db": "UniProt",
"payload": {
"accession": "P54278",
"sequence": "MERAESSSTEPAKAIKPIDRKSVHQICSGQVVLSLSTAVKELVENSLDAGATNIDLKLKDYGVDLIEVSDNGCGVEEENFEGLTLKHHTSKIQEFADLTQVETFGFRGEALSSLCALSDVTISTCHASAKVGTR... | [
{
"source_db": "ClinVar",
"source_id": "PMS2",
"text": "NM_000535.7(PMS2):c.613C>T (p.Gln205Ter) VARIANT_IN_GENE PMS2",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0005524",
"text": "PMS2 GENE_ANNOTATED_WITH_GO_TERM ATP binding",
"confidence": 0.6
},
{
"sourc... | {
"variant": "NM_000535.7(PMS2):c.613C>T (p.Gln205Ter)",
"pathway": "Formation of the ureteric bud"
} | 0.774597 |
co_mech_00048 | mechanistic_explanation | coding_variant | hard | 5 | Explain the molecular mechanism by which NM_001291415.2(KDM6A):c.620-2A>G affects the PD-L1(CD274) glycosylation and translocation to plasma membrane pathway, citing each molecular step. | NM_001291415.2(KDM6A):c.620-2A>G VARIANT_IN_GENE KDM6A -> KDM6A PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH KMT2C -> Single allele VARIANT_IN_GENE KMT2C -> Single allele VARIANT_IN_GENE CD274 -> CD274 GENE_PARTICIPATES_IN_PATHWAY PD-L1(CD274) glycosylation and translocation to plasma membrane | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_001291415.2(KDM6A):c.620-2A>G",
"source_node_type": "VARIANT",
"source_node_label": "NM_001291415.2(KDM6A):c.620-2A>G",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1,
"edge_so... | NM_001291415.2(KDM6A):c.620-2A>G VARIANT_IN_GENE KDM6A -> KDM6A PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH KMT2C -> Single allele VARIANT_IN_GENE KMT2C -> Single allele VARIANT_IN_GENE CD274 -> CD274 GENE_PARTICIPATES_IN_PATHWAY PD-L1(CD274) glycosylation and translocation to plasma membrane | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "KDM6A",
"source_db": "UniProt",
"payload": {
"accession": "O15550",
"sequence": "MKSCGVSLATAAAAAAAFGDEEKKMAAGKASGESEEASPSLTAEEREALGGLDSRLFGFVRFHEDGARTKALLGKAVRCYESLILKAEGKVESDFFCQLGHFNLLLEDYPKALSAYQRYYSLQSDYWKNAAFL... | [
{
"source_db": "ClinVar",
"source_id": "KDM6A",
"text": "NM_001291415.2(KDM6A):c.620-2A>G VARIANT_IN_GENE KDM6A",
"confidence": 1
},
{
"source_db": "STRING",
"source_id": "KMT2C",
"text": "KDM6A PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH KMT2C",
"confidence": 0.999
},
{
"source... | {
"variant": "NM_001291415.2(KDM6A):c.620-2A>G",
"pathway": "PD-L1(CD274) glycosylation and translocation to plasma membrane"
} | 0.9998 |
co_mech_00049 | mechanistic_explanation | coding_variant | medium | 4 | Explain the molecular mechanism by which NM_004360.5(CDH1):c.1020_1051del (p.Tyr341fs) affects the HATs acetylate histones pathway, citing each molecular step. | NM_004360.5(CDH1):c.1020_1051del (p.Tyr341fs) VARIANT_IN_GENE CDH1 -> CDH1 GENE_PARTICIPATES_IN_PATHWAY Adherens junctions interactions -> ACTB GENE_PARTICIPATES_IN_PATHWAY Adherens junctions interactions -> ACTB GENE_PARTICIPATES_IN_PATHWAY HATs acetylate histones | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_004360.5(CDH1):c.1020_1051del (p.Tyr341fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_004360.5(CDH1):c.1020_1051del (p.Tyr341fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_conf... | NM_004360.5(CDH1):c.1020_1051del (p.Tyr341fs) VARIANT_IN_GENE CDH1 -> CDH1 GENE_PARTICIPATES_IN_PATHWAY Adherens junctions interactions -> ACTB GENE_PARTICIPATES_IN_PATHWAY Adherens junctions interactions -> ACTB GENE_PARTICIPATES_IN_PATHWAY HATs acetylate histones | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "CDH1",
"source_db": "UniProt",
"payload": {
"accession": "P12830",
"sequence": "MGPWSRSLSALLLLLQVSSWLCQEPEPCHPGFDAESYTFTVPRRHLERGRVLGRVNFEDCTGRQRTAYFSLDTRFKVGTDGVITVKRPLRFHNPQIHFLVYAWDSTYRKFSTKVTLNTVGHHHRPPPHQASVSG... | [
{
"source_db": "ClinVar",
"source_id": "CDH1",
"text": "NM_004360.5(CDH1):c.1020_1051del (p.Tyr341fs) VARIANT_IN_GENE CDH1",
"confidence": 1
},
{
"source_db": "Reactome",
"source_id": "R-HSA-418990",
"text": "CDH1 GENE_PARTICIPATES_IN_PATHWAY Adherens junctions interactions",
"co... | {
"variant": "NM_004360.5(CDH1):c.1020_1051del (p.Tyr341fs)",
"pathway": "HATs acetylate histones"
} | 1 |
co_mech_00050 | mechanistic_explanation | coding_variant | hard | 5 | Explain the molecular mechanism by which NM_000789.4(ACE):c.2165_2168del (p.Lys722fs) affects the Activated NTRK3 signals through RAS pathway, citing each molecular step. | NM_000789.4(ACE):c.2165_2168del (p.Lys722fs) VARIANT_IN_GENE ACE -> ACE GENE_ANNOTATED_WITH_GO_TERM zinc ion binding -> BRAF GENE_ANNOTATED_WITH_GO_TERM zinc ion binding -> BRAF PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH NRAS -> NRAS GENE_PARTICIPATES_IN_PATHWAY Activated NTRK3 signals through RAS | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000789.4(ACE):c.2165_2168del (p.Lys722fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000789.4(ACE):c.2165_2168del (p.Lys722fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confid... | NM_000789.4(ACE):c.2165_2168del (p.Lys722fs) VARIANT_IN_GENE ACE -> ACE GENE_ANNOTATED_WITH_GO_TERM zinc ion binding -> BRAF GENE_ANNOTATED_WITH_GO_TERM zinc ion binding -> BRAF PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH NRAS -> NRAS GENE_PARTICIPATES_IN_PATHWAY Activated NTRK3 signals through RAS | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "ACE",
"source_db": "UniProt",
"payload": {
"accession": "P12821",
"sequence": "MGAASGRRGPGLLLPLPLLLLLPPQPALALDPGLQPGNFSADEAGAQLFAQSYNSSAEQVLFQSVAASWAHDTNITAENARRQEEAALLSQEFAEAWGQKAKELYEPIWQNFTDPQLRRIIGAVRTLGSANLPLA... | [
{
"source_db": "ClinVar",
"source_id": "ACE",
"text": "NM_000789.4(ACE):c.2165_2168del (p.Lys722fs) VARIANT_IN_GENE ACE",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0008270",
"text": "ACE GENE_ANNOTATED_WITH_GO_TERM zinc ion binding",
"confidence": 0.6
},
{
... | {
"variant": "NM_000789.4(ACE):c.2165_2168del (p.Lys722fs)",
"pathway": "Activated NTRK3 signals through RAS"
} | 0.81503 |
co_mech_00051 | mechanistic_explanation | coding_variant | hard | 5 | Explain the molecular mechanism by which NM_013254.4(TBK1):c.68_70delinsCC (p.Val23fs) affects the Ras activation upon Ca2+ influx through NMDA receptor pathway, citing each molecular step. | NM_013254.4(TBK1):c.68_70delinsCC (p.Val23fs) VARIANT_IN_GENE TBK1 -> TBK1 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> KIF5A GENE_ANNOTATED_WITH_GO_TERM ATP binding -> KIF5A PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH NEFL -> NEFL GENE_PARTICIPATES_IN_PATHWAY Ras activation upon Ca2+ influx through NMDA receptor | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_013254.4(TBK1):c.68_70delinsCC (p.Val23fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_013254.4(TBK1):c.68_70delinsCC (p.Val23fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_conf... | NM_013254.4(TBK1):c.68_70delinsCC (p.Val23fs) VARIANT_IN_GENE TBK1 -> TBK1 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> KIF5A GENE_ANNOTATED_WITH_GO_TERM ATP binding -> KIF5A PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH NEFL -> NEFL GENE_PARTICIPATES_IN_PATHWAY Ras activation upon Ca2+ influx through NMDA receptor | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "TBK1",
"source_db": "UniProt",
"payload": {
"accession": "Q9UHD2",
"sequence": "MQSTSNHLWLLSDILGQGATANVFRGRHKKTGDLFAIKVFNNISFLRPVDVQMREFEVLKKLNHKNIVKLFAIEEETTTRHKVLIMEFCPCGSLYTVLEEPSNAYGLPESEFLIVLRDVVGGMNHLRENGIVHR... | [
{
"source_db": "ClinVar",
"source_id": "TBK1",
"text": "NM_013254.4(TBK1):c.68_70delinsCC (p.Val23fs) VARIANT_IN_GENE TBK1",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0005524",
"text": "TBK1 GENE_ANNOTATED_WITH_GO_TERM ATP binding",
"confidence": 0.6
},
{
"... | {
"variant": "NM_013254.4(TBK1):c.68_70delinsCC (p.Val23fs)",
"pathway": "Ras activation upon Ca2+ influx through NMDA receptor"
} | 0.806873 |
co_mech_00052 | mechanistic_explanation | coding_variant | medium | 4 | Explain the molecular mechanism by which NM_000465.4(BARD1):c.1336_1337del (p.Tyr446fs) affects the Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells pathway, citing each molecular step. | NM_000465.4(BARD1):c.1336_1337del (p.Tyr446fs) VARIANT_IN_GENE BARD1 -> BARD1 GENE_PARTICIPATES_IN_PATHWAY HDR through Single Strand Annealing (SSA) -> ABL1 GENE_PARTICIPATES_IN_PATHWAY HDR through Single Strand Annealing (SSA) -> ABL1 GENE_PARTICIPATES_IN_PATHWAY Turbulent (oscillatory, disturbed) flow shear stress ac... | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000465.4(BARD1):c.1336_1337del (p.Tyr446fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000465.4(BARD1):c.1336_1337del (p.Tyr446fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_co... | NM_000465.4(BARD1):c.1336_1337del (p.Tyr446fs) VARIANT_IN_GENE BARD1 -> BARD1 GENE_PARTICIPATES_IN_PATHWAY HDR through Single Strand Annealing (SSA) -> ABL1 GENE_PARTICIPATES_IN_PATHWAY HDR through Single Strand Annealing (SSA) -> ABL1 GENE_PARTICIPATES_IN_PATHWAY Turbulent (oscillatory, disturbed) flow shear stress ac... | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "BARD1",
"source_db": "UniProt",
"payload": {
"accession": "Q99728",
"sequence": "MPDNRQPRNRQPRIRSGNEPRSAPAMEPDGRGAWAHSRAALDRLEKLLRCSRCTNILREPVCLGGCEHIFCSNCVSDCIGTGCPVCYTPAWIQDLKINRQLDSMIQLCSKLRNLLHDNELSDLKEDKPRKSLF... | [
{
"source_db": "ClinVar",
"source_id": "BARD1",
"text": "NM_000465.4(BARD1):c.1336_1337del (p.Tyr446fs) VARIANT_IN_GENE BARD1",
"confidence": 1
},
{
"source_db": "Reactome",
"source_id": "R-HSA-5685938",
"text": "BARD1 GENE_PARTICIPATES_IN_PATHWAY HDR through Single Strand Annealing ... | {
"variant": "NM_000465.4(BARD1):c.1336_1337del (p.Tyr446fs)",
"pathway": "Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells"
} | 1 |
co_mech_00053 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_004380.3(CREBBP):c.2854_2863dup (p.Gln955fs) affects the Co-inhibition by PD-1 pathway, citing each molecular step. | NM_004380.3(CREBBP):c.2854_2863dup (p.Gln955fs) VARIANT_IN_GENE CREBBP -> CREBBP GENE_ANNOTATED_WITH_GO_TERM zinc ion binding -> CD4 GENE_ANNOTATED_WITH_GO_TERM zinc ion binding -> CD4 GENE_PARTICIPATES_IN_PATHWAY Co-inhibition by PD-1 | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_004380.3(CREBBP):c.2854_2863dup (p.Gln955fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_004380.3(CREBBP):c.2854_2863dup (p.Gln955fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_... | NM_004380.3(CREBBP):c.2854_2863dup (p.Gln955fs) VARIANT_IN_GENE CREBBP -> CREBBP GENE_ANNOTATED_WITH_GO_TERM zinc ion binding -> CD4 GENE_ANNOTATED_WITH_GO_TERM zinc ion binding -> CD4 GENE_PARTICIPATES_IN_PATHWAY Co-inhibition by PD-1 | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "CREBBP",
"source_db": "UniProt",
"payload": {
"accession": "Q92793",
"sequence": "MAENLLDGPPNPKRAKLSSPGFSANDSTDFGSLFDLENDLPDELIPNGGELGLLNSGNLVPDAASKHKQLSELLRGGSGSSINPGIGNVSASSPVQQGLGGQAQGQPNSANMASLSAMGKSPLSQGDSSAPS... | [
{
"source_db": "ClinVar",
"source_id": "CREBBP",
"text": "NM_004380.3(CREBBP):c.2854_2863dup (p.Gln955fs) VARIANT_IN_GENE CREBBP",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0008270",
"text": "CREBBP GENE_ANNOTATED_WITH_GO_TERM zinc ion binding",
"confidence": 0.6
... | {
"variant": "NM_004380.3(CREBBP):c.2854_2863dup (p.Gln955fs)",
"pathway": "Co-inhibition by PD-1"
} | 0.774597 |
co_mech_00054 | mechanistic_explanation | coding_variant | hard | 3 | Explain the molecular mechanism by which NM_000251.3(MSH2):c.2524G>T (p.Glu842Ter) affects the G2/M DNA damage checkpoint pathway, citing each molecular step. | NM_000251.3(MSH2):c.2524G>T (p.Glu842Ter) VARIANT_IN_GENE MSH2 -> MSH2 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BRCA1 -> BRCA1 GENE_PARTICIPATES_IN_PATHWAY G2/M DNA damage checkpoint | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000251.3(MSH2):c.2524G>T (p.Glu842Ter)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000251.3(MSH2):c.2524G>T (p.Glu842Ter)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence":... | NM_000251.3(MSH2):c.2524G>T (p.Glu842Ter) VARIANT_IN_GENE MSH2 -> MSH2 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BRCA1 -> BRCA1 GENE_PARTICIPATES_IN_PATHWAY G2/M DNA damage checkpoint | null | [
"expression",
"intercell_role",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "MSH2",
"source_db": "UniProt",
"payload": {
"accession": "P43246",
"sequence": "MAVQPKETLQLESAAEVGFVRFFQGMPEKPTTTVRLFDRGDFYTAHGEDALLAAREVFKTQGVIKYMGPAGAKNLQSVVLSKMNFESFVKDLLLVRQYRVEVYKNRAGNKASKENDWYLAYKASPGNLSQFEDI... | [
{
"source_db": "ClinVar",
"source_id": "MSH2",
"text": "NM_000251.3(MSH2):c.2524G>T (p.Glu842Ter) VARIANT_IN_GENE MSH2",
"confidence": 1
},
{
"source_db": "STRING",
"source_id": "BRCA1",
"text": "MSH2 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BRCA1",
"confidence": 0.994
},
{
"... | {
"variant": "NM_000251.3(MSH2):c.2524G>T (p.Glu842Ter)",
"pathway": "G2/M DNA damage checkpoint"
} | 0.997996 |
co_mech_00055 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_005022.4(PFN1):c.341T>G (p.Met114Arg) affects the Pexophagy pathway, citing each molecular step. | NM_005022.4(PFN1):c.341T>G (p.Met114Arg) VARIANT_IN_GENE PFN1 -> PFN1 GENE_ANNOTATED_WITH_GO_TERM protein stabilization -> ATM GENE_ANNOTATED_WITH_GO_TERM protein stabilization -> ATM GENE_PARTICIPATES_IN_PATHWAY Pexophagy | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_005022.4(PFN1):c.341T>G (p.Met114Arg)",
"source_node_type": "VARIANT",
"source_node_label": "NM_005022.4(PFN1):c.341T>G (p.Met114Arg)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1... | NM_005022.4(PFN1):c.341T>G (p.Met114Arg) VARIANT_IN_GENE PFN1 -> PFN1 GENE_ANNOTATED_WITH_GO_TERM protein stabilization -> ATM GENE_ANNOTATED_WITH_GO_TERM protein stabilization -> ATM GENE_PARTICIPATES_IN_PATHWAY Pexophagy | null | [
"conservation",
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "evolutionary",
"tag": "conservation",
"anchor_node_id": "NM_005022.4(PFN1):c.341T>G (p.Met114Arg)",
"source_db": "UCSC_phyloP",
"payload": {
"chrom": "chr17",
"pos": 4945982,
"track": "phyloP100way",
"window": 20,
"scores": [
6.4594000000000005,... | [
{
"source_db": "ClinVar",
"source_id": "PFN1",
"text": "NM_005022.4(PFN1):c.341T>G (p.Met114Arg) VARIANT_IN_GENE PFN1",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0050821",
"text": "PFN1 GENE_ANNOTATED_WITH_GO_TERM protein stabilization",
"confidence": 0.6
},
{
... | {
"variant": "NM_005022.4(PFN1):c.341T>G (p.Met114Arg)",
"pathway": "Pexophagy"
} | 0.774597 |
co_mech_00056 | mechanistic_explanation | coding_variant | hard | 5 | Explain the molecular mechanism by which NM_003482.4(KMT2D):c.2578_2579del (p.Leu860fs) affects the Activation of AKT2 pathway, citing each molecular step. | NM_003482.4(KMT2D):c.2578_2579del (p.Leu860fs) VARIANT_IN_GENE KMT2D -> KMT2D GENE_ANNOTATED_WITH_GO_TERM positive regulation of transcription by RNA polymerase II -> AKT1 GENE_ANNOTATED_WITH_GO_TERM positive regulation of transcription by RNA polymerase II -> AKT2 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH AKT1 -> AKT2 GENE... | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_003482.4(KMT2D):c.2578_2579del (p.Leu860fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_003482.4(KMT2D):c.2578_2579del (p.Leu860fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_co... | NM_003482.4(KMT2D):c.2578_2579del (p.Leu860fs) VARIANT_IN_GENE KMT2D -> KMT2D GENE_ANNOTATED_WITH_GO_TERM positive regulation of transcription by RNA polymerase II -> AKT1 GENE_ANNOTATED_WITH_GO_TERM positive regulation of transcription by RNA polymerase II -> AKT2 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH AKT1 -> AKT2 GENE... | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "KMT2D",
"source_db": "UniProt",
"payload": {
"accession": "O14686",
"sequence": "MDSQKLAGEDKDSEPAADGPAASEDPSATESDLPNPHVGEVSVLSSGSPRLQETPQDCSGGPVRRCALCNCGEPSLHGQRELRRFELPFDWPRCPVVSPGGSPGPNEAVLPSEDLSQIGFPEGLTPAHLGEPG... | [
{
"source_db": "ClinVar",
"source_id": "KMT2D",
"text": "NM_003482.4(KMT2D):c.2578_2579del (p.Leu860fs) VARIANT_IN_GENE KMT2D",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0045944",
"text": "KMT2D GENE_ANNOTATED_WITH_GO_TERM positive regulation of transcription by RNA po... | {
"variant": "NM_003482.4(KMT2D):c.2578_2579del (p.Leu860fs)",
"pathway": "Activation of AKT2"
} | 0.81372 |
co_mech_00057 | mechanistic_explanation | coding_variant | hard | 5 | Explain the molecular mechanism by which NM_000038.6(APC):c.4652_4653del (p.Lys1551fs) affects the Signaling by RAS GAP mutants pathway, citing each molecular step. | NM_000038.6(APC):c.4652_4653del (p.Lys1551fs) VARIANT_IN_GENE APC -> APC GENE_ANNOTATED_WITH_GO_TERM insulin receptor signaling pathway -> PIK3CA GENE_ANNOTATED_WITH_GO_TERM insulin receptor signaling pathway -> PIK3CA PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH KRAS -> KRAS GENE_PARTICIPATES_IN_PATHWAY Signaling by RAS GAP m... | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000038.6(APC):c.4652_4653del (p.Lys1551fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000038.6(APC):c.4652_4653del (p.Lys1551fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_conf... | NM_000038.6(APC):c.4652_4653del (p.Lys1551fs) VARIANT_IN_GENE APC -> APC GENE_ANNOTATED_WITH_GO_TERM insulin receptor signaling pathway -> PIK3CA GENE_ANNOTATED_WITH_GO_TERM insulin receptor signaling pathway -> PIK3CA PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH KRAS -> KRAS GENE_PARTICIPATES_IN_PATHWAY Signaling by RAS GAP m... | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "APC",
"source_db": "UniProt",
"payload": {
"accession": "P25054",
"sequence": "MAAASYDQLLKQVEALKMENSNLRQELEDNSNHLTKLETEASNMKEVLKQLQGSIEDEAMASSGQIDLLERLKELNLDSSNFPGVKLRSKMSLRSYGSREGSVSSRSGECSPVPMGSFPRRGFVNGSRESTGYLE... | [
{
"source_db": "ClinVar",
"source_id": "APC",
"text": "NM_000038.6(APC):c.4652_4653del (p.Lys1551fs) VARIANT_IN_GENE APC",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0008286",
"text": "APC GENE_ANNOTATED_WITH_GO_TERM insulin receptor signaling pathway",
"confidence"... | {
"variant": "NM_000038.6(APC):c.4652_4653del (p.Lys1551fs)",
"pathway": "Signaling by RAS GAP mutants"
} | 0.814867 |
co_mech_00058 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which GRCh37/hg19 6q26(chr6:162622150-162683772) affects the RET signaling pathway, citing each molecular step. | GRCh37/hg19 6q26(chr6:162622150-162683772) VARIANT_IN_GENE PRKN -> PRKN GENE_ANNOTATED_WITH_GO_TERM negative regulation of gene expression -> PIK3CA GENE_ANNOTATED_WITH_GO_TERM negative regulation of gene expression -> PIK3CA GENE_PARTICIPATES_IN_PATHWAY RET signaling | {
"steps": [
{
"hop": 1,
"source_node_id": "GRCh37/hg19 6q26(chr6:162622150-162683772)",
"source_node_type": "VARIANT",
"source_node_label": "GRCh37/hg19 6q26(chr6:162622150-162683772)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence... | GRCh37/hg19 6q26(chr6:162622150-162683772) VARIANT_IN_GENE PRKN -> PRKN GENE_ANNOTATED_WITH_GO_TERM negative regulation of gene expression -> PIK3CA GENE_ANNOTATED_WITH_GO_TERM negative regulation of gene expression -> PIK3CA GENE_PARTICIPATES_IN_PATHWAY RET signaling | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "PRKN",
"source_db": "UniProt",
"payload": {
"accession": "O60260",
"sequence": "MIVFVRFNSSHGFPVEVDSDTSIFQLKEVVAKRQGVPADQLRVIFAGKELRNDWTVQNCDLDQQSIVHIVQRPWRKGQEMNATGGDDPRNAAGGCEREPQSLTRVDLSSSVLPGDSVGLAVILHTDSRKDSPPA... | [
{
"source_db": "ClinVar",
"source_id": "PRKN",
"text": "GRCh37/hg19 6q26(chr6:162622150-162683772) VARIANT_IN_GENE PRKN",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0010629",
"text": "PRKN GENE_ANNOTATED_WITH_GO_TERM negative regulation of gene expression",
"confide... | {
"variant": "GRCh37/hg19 6q26(chr6:162622150-162683772)",
"pathway": "RET signaling"
} | 0.774597 |
co_mech_00059 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_004984.2:c.2993delG affects the HCMV Early Events pathway, citing each molecular step. | NM_004984.2:c.2993delG VARIANT_IN_GENE KIF5A -> KIF5A GENE_ANNOTATED_WITH_GO_TERM ATP binding -> EGFR GENE_ANNOTATED_WITH_GO_TERM ATP binding -> EGFR GENE_PARTICIPATES_IN_PATHWAY HCMV Early Events | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_004984.2:c.2993delG",
"source_node_type": "VARIANT",
"source_node_label": "NM_004984.2:c.2993delG",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1,
"edge_source_db": "ClinVar",... | NM_004984.2:c.2993delG VARIANT_IN_GENE KIF5A -> KIF5A GENE_ANNOTATED_WITH_GO_TERM ATP binding -> EGFR GENE_ANNOTATED_WITH_GO_TERM ATP binding -> EGFR GENE_PARTICIPATES_IN_PATHWAY HCMV Early Events | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "KIF5A",
"source_db": "UniProt",
"payload": {
"accession": "Q12840",
"sequence": "MAETNNECSIKVLCRFRPLNQAEILRGDKFIPIFQGDDSVVIGGKPYVFDRVFPPNTTQEQVYHACAMQIVKDVLAGYNGTIFAYGQTSSGKTHTMEGKLHDPQLMGIIPRIARDIFNHIYSMDENLEFHIKV... | [
{
"source_db": "ClinVar",
"source_id": "KIF5A",
"text": "NM_004984.2:c.2993delG VARIANT_IN_GENE KIF5A",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0005524",
"text": "KIF5A GENE_ANNOTATED_WITH_GO_TERM ATP binding",
"confidence": 0.6
},
{
"source_db": "GO",
... | {
"variant": "NM_004984.2:c.2993delG",
"pathway": "HCMV Early Events"
} | 0.774597 |
co_mech_00060 | mechanistic_explanation | coding_variant | hard | 5 | Explain the molecular mechanism by which NM_000059.4(BRCA2):c.2885dup (p.His962fs) affects the Advanced glycosylation endproduct receptor signaling pathway, citing each molecular step. | NM_000059.4(BRCA2):c.2885dup (p.His962fs) VARIANT_IN_GENE BRCA2 -> BRCA2 GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription -> APOE GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription -> APOE PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH APP -> APP GENE_PARTICIPATES_IN_PATH... | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000059.4(BRCA2):c.2885dup (p.His962fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000059.4(BRCA2):c.2885dup (p.His962fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence":... | NM_000059.4(BRCA2):c.2885dup (p.His962fs) VARIANT_IN_GENE BRCA2 -> BRCA2 GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription -> APOE GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription -> APOE PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH APP -> APP GENE_PARTICIPATES_IN_PATH... | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "BRCA2",
"source_db": "UniProt",
"payload": {
"accession": "P51587",
"sequence": "MPIGSKERPTFFEIFKTRCNKADLGPISLNWFEELSSEAPPYNSEPAEESEHKNNNYEPNLFKTPQRKPSYNQLASTPIIFKEQGLTLPLYQSPVKELDKFKLDLGRNVPNSRHKSLRTVKTKMDQADDVSCP... | [
{
"source_db": "ClinVar",
"source_id": "BRCA2",
"text": "NM_000059.4(BRCA2):c.2885dup (p.His962fs) VARIANT_IN_GENE BRCA2",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0045893",
"text": "BRCA2 GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription"... | {
"variant": "NM_000059.4(BRCA2):c.2885dup (p.His962fs)",
"pathway": "Advanced glycosylation endproduct receptor signaling"
} | 0.81503 |
co_mech_00061 | mechanistic_explanation | coding_variant | medium | 4 | Explain the molecular mechanism by which NM_023110.3(FGFR1):c.1460G>A (p.Gly487Asp) affects the Signaling by cytosolic FGFR1 fusion mutants pathway, citing each molecular step. | NM_023110.3(FGFR1):c.1460G>A (p.Gly487Asp) VARIANT_IN_GENE FGFR1 -> FGFR1 GENE_PARTICIPATES_IN_PATHWAY Signaling by FGFR1 in disease -> PIK3CA GENE_PARTICIPATES_IN_PATHWAY Signaling by FGFR1 in disease -> PIK3CA GENE_PARTICIPATES_IN_PATHWAY Signaling by cytosolic FGFR1 fusion mutants | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_023110.3(FGFR1):c.1460G>A (p.Gly487Asp)",
"source_node_type": "VARIANT",
"source_node_label": "NM_023110.3(FGFR1):c.1460G>A (p.Gly487Asp)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence... | NM_023110.3(FGFR1):c.1460G>A (p.Gly487Asp) VARIANT_IN_GENE FGFR1 -> FGFR1 GENE_PARTICIPATES_IN_PATHWAY Signaling by FGFR1 in disease -> PIK3CA GENE_PARTICIPATES_IN_PATHWAY Signaling by FGFR1 in disease -> PIK3CA GENE_PARTICIPATES_IN_PATHWAY Signaling by cytosolic FGFR1 fusion mutants | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "FGFR1",
"source_db": "UniProt",
"payload": {
"accession": "P11362",
"sequence": "MWSWKCLLFWAVLVTATLCTARPSPTLPEQAQPWGAPVEVESFLVHPGDLLQLRCRLRDDVQSINWLRDGVQLAESNRTRITGEEVEVQDSVPADSGLYACVTSSPSGSDTTYFSVNVSDALPSSEDDDDDDD... | [
{
"source_db": "ClinVar",
"source_id": "FGFR1",
"text": "NM_023110.3(FGFR1):c.1460G>A (p.Gly487Asp) VARIANT_IN_GENE FGFR1",
"confidence": 1
},
{
"source_db": "Reactome",
"source_id": "R-HSA-5655302",
"text": "FGFR1 GENE_PARTICIPATES_IN_PATHWAY Signaling by FGFR1 in disease",
"con... | {
"variant": "NM_023110.3(FGFR1):c.1460G>A (p.Gly487Asp)",
"pathway": "Signaling by cytosolic FGFR1 fusion mutants"
} | 1 |
co_mech_00062 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_000546.6(TP53):c.560-2A>C affects the TRAF3-dependent IRF activation pathway pathway, citing each molecular step. | NM_000546.6(TP53):c.560-2A>C VARIANT_IN_GENE TP53 -> TP53 GENE_ANNOTATED_WITH_GO_TERM RNA polymerase II-specific DNA-binding transcription factor binding -> TBK1 GENE_ANNOTATED_WITH_GO_TERM RNA polymerase II-specific DNA-binding transcription factor binding -> TBK1 GENE_PARTICIPATES_IN_PATHWAY TRAF3-dependent IRF activ... | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000546.6(TP53):c.560-2A>C",
"source_node_type": "VARIANT",
"source_node_label": "NM_000546.6(TP53):c.560-2A>C",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1,
"edge_source_db"... | NM_000546.6(TP53):c.560-2A>C VARIANT_IN_GENE TP53 -> TP53 GENE_ANNOTATED_WITH_GO_TERM RNA polymerase II-specific DNA-binding transcription factor binding -> TBK1 GENE_ANNOTATED_WITH_GO_TERM RNA polymerase II-specific DNA-binding transcription factor binding -> TBK1 GENE_PARTICIPATES_IN_PATHWAY TRAF3-dependent IRF activ... | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "TP53",
"source_db": "UniProt",
"payload": {
"accession": "P04637",
"sequence": "MEEPQSDPSVEPPLSQETFSDLWKLLPENNVLSPLPSQAMDDLMLSPDDIEQWFTEDPGPDEAPRMPEAAPPVAPAPAAPTPAAPAPAPSWPLSSSVPSQKTYQGSYGFRLGFLHSGTAKSVTCTYSPALNKMF... | [
{
"source_db": "ClinVar",
"source_id": "TP53",
"text": "NM_000546.6(TP53):c.560-2A>C VARIANT_IN_GENE TP53",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0061629",
"text": "TP53 GENE_ANNOTATED_WITH_GO_TERM RNA polymerase II-specific DNA-binding transcription factor binding... | {
"variant": "NM_000546.6(TP53):c.560-2A>C",
"pathway": "TRAF3-dependent IRF activation pathway"
} | 0.774597 |
co_mech_00063 | mechanistic_explanation | coding_variant | medium | 4 | Explain the molecular mechanism by which NM_000249.4(MLH1):c.380+2T>C affects the Regulation of MITF-M-dependent genes involved in DNA replication, damage repair and senescence pathway, citing each molecular step. | NM_000249.4(MLH1):c.380+2T>C VARIANT_IN_GENE MLH1 -> MLH1 GENE_PARTICIPATES_IN_PATHWAY TP53 Regulates Transcription of DNA Repair Genes -> BRCA1 GENE_PARTICIPATES_IN_PATHWAY TP53 Regulates Transcription of DNA Repair Genes -> BRCA1 GENE_PARTICIPATES_IN_PATHWAY Regulation of MITF-M-dependent genes involved in DNA replic... | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000249.4(MLH1):c.380+2T>C",
"source_node_type": "VARIANT",
"source_node_label": "NM_000249.4(MLH1):c.380+2T>C",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1,
"edge_source_db"... | NM_000249.4(MLH1):c.380+2T>C VARIANT_IN_GENE MLH1 -> MLH1 GENE_PARTICIPATES_IN_PATHWAY TP53 Regulates Transcription of DNA Repair Genes -> BRCA1 GENE_PARTICIPATES_IN_PATHWAY TP53 Regulates Transcription of DNA Repair Genes -> BRCA1 GENE_PARTICIPATES_IN_PATHWAY Regulation of MITF-M-dependent genes involved in DNA replic... | null | [
"expression",
"intercell_role",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "MLH1",
"source_db": "UniProt",
"payload": {
"accession": "P40692",
"sequence": "MSFVAGVIRRLDETVVNRIAAGEVIQRPANAIKEMIENCLDAKSTSIQVIVKEGGLKLIQIQDNGTGIRKEDLDIVCERFTTSKLQSFEDLASISTYGFRGEALASISHVAHVTITTKTADGKCAYRASYSDGK... | [
{
"source_db": "ClinVar",
"source_id": "MLH1",
"text": "NM_000249.4(MLH1):c.380+2T>C VARIANT_IN_GENE MLH1",
"confidence": 1
},
{
"source_db": "Reactome",
"source_id": "R-HSA-6796648",
"text": "MLH1 GENE_PARTICIPATES_IN_PATHWAY TP53 Regulates Transcription of DNA Repair Genes",
"c... | {
"variant": "NM_000249.4(MLH1):c.380+2T>C",
"pathway": "Regulation of MITF-M-dependent genes involved in DNA replication, damage repair and senescence"
} | 1 |
co_mech_00064 | mechanistic_explanation | coding_variant | hard | 5 | Explain the molecular mechanism by which NM_000136.3(FANCC):c.1060C>T (p.Gln354Ter) affects the Loss of Nlp from mitotic centrosomes pathway, citing each molecular step. | NM_000136.3(FANCC):c.1060C>T (p.Gln354Ter) VARIANT_IN_GENE AOPEP -> AOPEP GENE_ANNOTATED_WITH_GO_TERM zinc ion binding -> BIRC5 GENE_ANNOTATED_WITH_GO_TERM zinc ion binding -> BIRC5 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH CDK1 -> CDK1 GENE_PARTICIPATES_IN_PATHWAY Loss of Nlp from mitotic centrosomes | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000136.3(FANCC):c.1060C>T (p.Gln354Ter)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000136.3(FANCC):c.1060C>T (p.Gln354Ter)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence... | NM_000136.3(FANCC):c.1060C>T (p.Gln354Ter) VARIANT_IN_GENE AOPEP -> AOPEP GENE_ANNOTATED_WITH_GO_TERM zinc ion binding -> BIRC5 GENE_ANNOTATED_WITH_GO_TERM zinc ion binding -> BIRC5 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH CDK1 -> CDK1 GENE_PARTICIPATES_IN_PATHWAY Loss of Nlp from mitotic centrosomes | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "AOPEP",
"source_db": "UniProt",
"payload": {
"accession": "Q8N6M6",
"sequence": "MDIQLDPARDDLPLMANTSHILVKHYVLDLDVDFESQVIEGTIVLFLEDGNRFKKQNSSIEEACQSESNKACKFGMPEPCHIPVTNARTFSSEMEYNDFAICSKGEKDTSDKDGNHDNQEHASGISSSKYCCD... | [
{
"source_db": "ClinVar",
"source_id": "AOPEP",
"text": "NM_000136.3(FANCC):c.1060C>T (p.Gln354Ter) VARIANT_IN_GENE AOPEP",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0008270",
"text": "AOPEP GENE_ANNOTATED_WITH_GO_TERM zinc ion binding",
"confidence": 0.6
},
{
... | {
"variant": "NM_000136.3(FANCC):c.1060C>T (p.Gln354Ter)",
"pathway": "Loss of Nlp from mitotic centrosomes"
} | 0.814703 |
co_mech_00065 | mechanistic_explanation | coding_variant | hard | 5 | Explain the molecular mechanism by which NM_001903.5(CTNNA1):c.33dup (p.Lys12fs) affects the PI-3K cascade:FGFR2 pathway, citing each molecular step. | NM_001903.5(CTNNA1):c.33dup (p.Lys12fs) VARIANT_IN_GENE CTNNA1 -> CTNNA1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH CDH1 -> CDH1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH EGFR -> EGFR PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH PIK3CA -> PIK3CA GENE_PARTICIPATES_IN_PATHWAY PI-3K cascade:FGFR2 | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_001903.5(CTNNA1):c.33dup (p.Lys12fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_001903.5(CTNNA1):c.33dup (p.Lys12fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1,
... | NM_001903.5(CTNNA1):c.33dup (p.Lys12fs) VARIANT_IN_GENE CTNNA1 -> CTNNA1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH CDH1 -> CDH1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH EGFR -> EGFR PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH PIK3CA -> PIK3CA GENE_PARTICIPATES_IN_PATHWAY PI-3K cascade:FGFR2 | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "CTNNA1",
"source_db": "UniProt",
"payload": {
"accession": "P35221",
"sequence": "MTAVHAGNINFKWDPKSLEIRTLAVERLLEPLVTQVTTLVNTNSKGPSNKKRGRSKKAHVLAASVEQATENFLEKGDKIAKESQFLKEELVAAVEDVRKQGDLMKAAAGEFADDPCSSVKRGNMVRAARALL... | [
{
"source_db": "ClinVar",
"source_id": "CTNNA1",
"text": "NM_001903.5(CTNNA1):c.33dup (p.Lys12fs) VARIANT_IN_GENE CTNNA1",
"confidence": 1
},
{
"source_db": "STRING",
"source_id": "CDH1",
"text": "CTNNA1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH CDH1",
"confidence": 0.999
},
{
... | {
"variant": "NM_001903.5(CTNNA1):c.33dup (p.Lys12fs)",
"pathway": "PI-3K cascade:FGFR2"
} | 0.9994 |
co_mech_00066 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_007194.4(CHEK2):c.779del (p.Gly259_Ser260insTer) affects the Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs) pathway, citing each molecular step. | NM_007194.4(CHEK2):c.779del (p.Gly259_Ser260insTer) VARIANT_IN_GENE CHEK2 -> CHEK2 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> ACTB GENE_ANNOTATED_WITH_GO_TERM ATP binding -> ACTB GENE_PARTICIPATES_IN_PATHWAY Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs) | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_007194.4(CHEK2):c.779del (p.Gly259_Ser260insTer)",
"source_node_type": "VARIANT",
"source_node_label": "NM_007194.4(CHEK2):c.779del (p.Gly259_Ser260insTer)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
... | NM_007194.4(CHEK2):c.779del (p.Gly259_Ser260insTer) VARIANT_IN_GENE CHEK2 -> CHEK2 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> ACTB GENE_ANNOTATED_WITH_GO_TERM ATP binding -> ACTB GENE_PARTICIPATES_IN_PATHWAY Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs) | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "CHEK2",
"source_db": "UniProt",
"payload": {
"accession": "O96017",
"sequence": "MSRESDVEAQQSHGSSACSQPHGSVTQSQGSSSQSQGISSSSTSTMPNSSQSSHSSSGTLSSLETVSTQELYSIPEDQEPEDQEPEEPTPAPWARLWALQDGFANLECVNDNYWFGRDKSCEYCFDEPLLKRT... | [
{
"source_db": "ClinVar",
"source_id": "CHEK2",
"text": "NM_007194.4(CHEK2):c.779del (p.Gly259_Ser260insTer) VARIANT_IN_GENE CHEK2",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0005524",
"text": "CHEK2 GENE_ANNOTATED_WITH_GO_TERM ATP binding",
"confidence": 0.6
},
... | {
"variant": "NM_007194.4(CHEK2):c.779del (p.Gly259_Ser260insTer)",
"pathway": "Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)"
} | 0.774597 |
co_mech_00067 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_000314.8(PTEN):c.490_491dup (p.Gly165fs) affects the Developmental Lineage of Mammary Stem Cells pathway, citing each molecular step. | NM_000314.8(PTEN):c.490_491dup (p.Gly165fs) VARIANT_IN_GENE PTEN -> PTEN GENE_ANNOTATED_WITH_GO_TERM negative regulation of cell migration -> CDH1 GENE_ANNOTATED_WITH_GO_TERM negative regulation of cell migration -> CDH1 GENE_PARTICIPATES_IN_PATHWAY Developmental Lineage of Mammary Stem Cells | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000314.8(PTEN):c.490_491dup (p.Gly165fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000314.8(PTEN):c.490_491dup (p.Gly165fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confiden... | NM_000314.8(PTEN):c.490_491dup (p.Gly165fs) VARIANT_IN_GENE PTEN -> PTEN GENE_ANNOTATED_WITH_GO_TERM negative regulation of cell migration -> CDH1 GENE_ANNOTATED_WITH_GO_TERM negative regulation of cell migration -> CDH1 GENE_PARTICIPATES_IN_PATHWAY Developmental Lineage of Mammary Stem Cells | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "PTEN",
"source_db": "UniProt",
"payload": {
"accession": "P60484",
"sequence": "MTAIIKEIVSRNKRRYQEDGFDLDLTYIYPNIIAMGFPAERLEGVYRNNIDDVVRFLDSKHKNHYKIYNLCAERHYDTAKFNCRVAQYPFEDHNPPQLELIKPFCEDLDQWLSEDDNHVAAIHCKAGKGRTGVM... | [
{
"source_db": "ClinVar",
"source_id": "PTEN",
"text": "NM_000314.8(PTEN):c.490_491dup (p.Gly165fs) VARIANT_IN_GENE PTEN",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0030336",
"text": "PTEN GENE_ANNOTATED_WITH_GO_TERM negative regulation of cell migration",
"confide... | {
"variant": "NM_000314.8(PTEN):c.490_491dup (p.Gly165fs)",
"pathway": "Developmental Lineage of Mammary Stem Cells"
} | 0.774597 |
co_mech_00068 | mechanistic_explanation | coding_variant | hard | 5 | Explain the molecular mechanism by which NM_001199397.3(NEK1):c.464G>C (p.Ser155Thr) affects the AUF1 (hnRNP D0) binds and destabilizes mRNA pathway, citing each molecular step. | NM_001199397.3(NEK1):c.464G>C (p.Ser155Thr) VARIANT_IN_GENE NEK1 -> NEK1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH CFAP410 -> CFAP410 GENE_ANNOTATED_WITH_GO_TERM DNA damage response -> PSMA6 GENE_ANNOTATED_WITH_GO_TERM DNA damage response -> PSMA6 GENE_PARTICIPATES_IN_PATHWAY AUF1 (hnRNP D0) binds and destabilizes mRNA | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_001199397.3(NEK1):c.464G>C (p.Ser155Thr)",
"source_node_type": "VARIANT",
"source_node_label": "NM_001199397.3(NEK1):c.464G>C (p.Ser155Thr)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confiden... | NM_001199397.3(NEK1):c.464G>C (p.Ser155Thr) VARIANT_IN_GENE NEK1 -> NEK1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH CFAP410 -> CFAP410 GENE_ANNOTATED_WITH_GO_TERM DNA damage response -> PSMA6 GENE_ANNOTATED_WITH_GO_TERM DNA damage response -> PSMA6 GENE_PARTICIPATES_IN_PATHWAY AUF1 (hnRNP D0) binds and destabilizes mRNA | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "NEK1",
"source_db": "UniProt",
"payload": {
"accession": "Q96PY6",
"sequence": "MEKYVRLQKIGEGSFGKAILVKSTEDGRQYVIKEINISRMSSKEREESRREVAVLANMKHPNIVQYRESFEENGSLYIVMDYCEGGDLFKRINAQKGVLFQEDQILDWFVQICLALKHVHDRKILHRDIKSQNI... | [
{
"source_db": "ClinVar",
"source_id": "NEK1",
"text": "NM_001199397.3(NEK1):c.464G>C (p.Ser155Thr) VARIANT_IN_GENE NEK1",
"confidence": 1
},
{
"source_db": "STRING",
"source_id": "CFAP410",
"text": "NEK1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH CFAP410",
"confidence": 0.982
},
{... | {
"variant": "NM_001199397.3(NEK1):c.464G>C (p.Ser155Thr)",
"pathway": "AUF1 (hnRNP D0) binds and destabilizes mRNA"
} | 0.812237 |
co_mech_00069 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_000044.6(AR):c.2612C>T (p.Ala871Val) affects the ponatinib-resistant FLT3 mutants pathway, citing each molecular step. | NM_000044.6(AR):c.2612C>T (p.Ala871Val) VARIANT_IN_GENE AR -> AR GENE_ANNOTATED_WITH_GO_TERM positive regulation of cell population proliferation -> FLT3 GENE_ANNOTATED_WITH_GO_TERM positive regulation of cell population proliferation -> FLT3 GENE_PARTICIPATES_IN_PATHWAY ponatinib-resistant FLT3 mutants | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000044.6(AR):c.2612C>T (p.Ala871Val)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000044.6(AR):c.2612C>T (p.Ala871Val)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1,
... | NM_000044.6(AR):c.2612C>T (p.Ala871Val) VARIANT_IN_GENE AR -> AR GENE_ANNOTATED_WITH_GO_TERM positive regulation of cell population proliferation -> FLT3 GENE_ANNOTATED_WITH_GO_TERM positive regulation of cell population proliferation -> FLT3 GENE_PARTICIPATES_IN_PATHWAY ponatinib-resistant FLT3 mutants | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "AR",
"source_db": "UniProt",
"payload": {
"accession": "P10275",
"sequence": "MEVQLGLGRVYPRPPSKTYRGAFQNLFQSVREVIQNPGPRHPEAASAAPPGASLLLLQQQQQQQQQQQQQQQQQQQQQQQETSPRQQQQQQGEDGSPQAHRRGPTGYLVLDEEQQPSQPQSALECHPERGCVPEPG... | [
{
"source_db": "ClinVar",
"source_id": "AR",
"text": "NM_000044.6(AR):c.2612C>T (p.Ala871Val) VARIANT_IN_GENE AR",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0008284",
"text": "AR GENE_ANNOTATED_WITH_GO_TERM positive regulation of cell population proliferation",
"co... | {
"variant": "NM_000044.6(AR):c.2612C>T (p.Ala871Val)",
"pathway": "ponatinib-resistant FLT3 mutants"
} | 0.774597 |
co_mech_00070 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_007294.4(BRCA1):c.3729del (p.Arg1243fs) affects the CHD6, CHD7, CHD8, CHD9 subfamily pathway, citing each molecular step. | NM_007294.4(BRCA1):c.3729del (p.Arg1243fs) VARIANT_IN_GENE BRCA1 -> BRCA1 GENE_ANNOTATED_WITH_GO_TERM ubiquitin protein ligase binding -> CTNNB1 GENE_ANNOTATED_WITH_GO_TERM ubiquitin protein ligase binding -> CTNNB1 GENE_PARTICIPATES_IN_PATHWAY CHD6, CHD7, CHD8, CHD9 subfamily | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_007294.4(BRCA1):c.3729del (p.Arg1243fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_007294.4(BRCA1):c.3729del (p.Arg1243fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence... | NM_007294.4(BRCA1):c.3729del (p.Arg1243fs) VARIANT_IN_GENE BRCA1 -> BRCA1 GENE_ANNOTATED_WITH_GO_TERM ubiquitin protein ligase binding -> CTNNB1 GENE_ANNOTATED_WITH_GO_TERM ubiquitin protein ligase binding -> CTNNB1 GENE_PARTICIPATES_IN_PATHWAY CHD6, CHD7, CHD8, CHD9 subfamily | null | [
"expression",
"intercell_role",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "BRCA1",
"source_db": "UniProt",
"payload": {
"accession": "P38398",
"sequence": "MDLSALRVEEVQNVINAMQKILECPICLELIKEPVSTKCDHIFCKFCMLKLLNQKKGPSQCPLCKNDITKRSLQESTRFSQLVEELLKIICAFQLDTGLEYANSYNFAKKENNSPEHLKDEVSIIQSMGYRNR... | [
{
"source_db": "ClinVar",
"source_id": "BRCA1",
"text": "NM_007294.4(BRCA1):c.3729del (p.Arg1243fs) VARIANT_IN_GENE BRCA1",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0031625",
"text": "BRCA1 GENE_ANNOTATED_WITH_GO_TERM ubiquitin protein ligase binding",
"confidence... | {
"variant": "NM_007294.4(BRCA1):c.3729del (p.Arg1243fs)",
"pathway": "CHD6, CHD7, CHD8, CHD9 subfamily"
} | 0.774597 |
co_mech_00071 | mechanistic_explanation | coding_variant | hard | 5 | Explain the molecular mechanism by which NM_014845.6(FIG4):c.1207C>T (p.Gln403Ter) affects the RAS signaling downstream of NF1 loss-of-function variants pathway, citing each molecular step. | NM_014845.6(FIG4):c.1207C>T (p.Gln403Ter) VARIANT_IN_GENE FIG4 -> ALS2 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH FIG4 -> ALS2 GENE_ANNOTATED_WITH_GO_TERM GTPase activator activity -> NF1 GENE_ANNOTATED_WITH_GO_TERM GTPase activator activity -> NF1 GENE_PARTICIPATES_IN_PATHWAY RAS signaling downstream of NF1 loss-of-function... | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_014845.6(FIG4):c.1207C>T (p.Gln403Ter)",
"source_node_type": "VARIANT",
"source_node_label": "NM_014845.6(FIG4):c.1207C>T (p.Gln403Ter)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence":... | NM_014845.6(FIG4):c.1207C>T (p.Gln403Ter) VARIANT_IN_GENE FIG4 -> ALS2 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH FIG4 -> ALS2 GENE_ANNOTATED_WITH_GO_TERM GTPase activator activity -> NF1 GENE_ANNOTATED_WITH_GO_TERM GTPase activator activity -> NF1 GENE_PARTICIPATES_IN_PATHWAY RAS signaling downstream of NF1 loss-of-function... | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "FIG4",
"source_db": "UniProt",
"payload": {
"accession": "Q92562",
"sequence": "MPTAAAPIISSVQKLVLYETRARYFLVGSNNAETKYRVLKIDRTEPKDLVIIDDRHVYTQQEVRELLGRLDLGNRTKMGQKGSSGLFRAVSAFGVVGFVRFLEGYYIVLITKRRKMADIGGHAIYKVEDTNMIY... | [
{
"source_db": "ClinVar",
"source_id": "FIG4",
"text": "NM_014845.6(FIG4):c.1207C>T (p.Gln403Ter) VARIANT_IN_GENE FIG4",
"confidence": 1
},
{
"source_db": "STRING",
"source_id": "ALS2",
"text": "ALS2 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH FIG4",
"confidence": 0.854
},
{
"so... | {
"variant": "NM_014845.6(FIG4):c.1207C>T (p.Gln403Ter)",
"pathway": "RAS signaling downstream of NF1 loss-of-function variants"
} | 0.789864 |
co_mech_00072 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_000057.4(BLM):c.2548_2555+12del affects the Drug resistance in ERBB2 TMD/JMD mutants pathway, citing each molecular step. | NM_000057.4(BLM):c.2548_2555+12del VARIANT_IN_GENE BLM -> BLM GENE_ANNOTATED_WITH_GO_TERM ATP binding -> ERBB2 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> ERBB2 GENE_PARTICIPATES_IN_PATHWAY Drug resistance in ERBB2 TMD/JMD mutants | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000057.4(BLM):c.2548_2555+12del",
"source_node_type": "VARIANT",
"source_node_label": "NM_000057.4(BLM):c.2548_2555+12del",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1,
"edg... | NM_000057.4(BLM):c.2548_2555+12del VARIANT_IN_GENE BLM -> BLM GENE_ANNOTATED_WITH_GO_TERM ATP binding -> ERBB2 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> ERBB2 GENE_PARTICIPATES_IN_PATHWAY Drug resistance in ERBB2 TMD/JMD mutants | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "BLM",
"source_db": "UniProt",
"payload": {
"accession": "P54132",
"sequence": "MAAVPQNNLQEQLERHSARTLNNKLSLSKPKFSGFTFKKKTSSDNNVSVTNVSVAKTPVLRNKDVNVTEDFSFSEPLPNTTNQQRVKDFFKNAPAGQETQRGGSKSLLPDFLQTPKEVVCTTQNTPTVKKSRDTA... | [
{
"source_db": "ClinVar",
"source_id": "BLM",
"text": "NM_000057.4(BLM):c.2548_2555+12del VARIANT_IN_GENE BLM",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0005524",
"text": "BLM GENE_ANNOTATED_WITH_GO_TERM ATP binding",
"confidence": 0.6
},
{
"source_db": "G... | {
"variant": "NM_000057.4(BLM):c.2548_2555+12del",
"pathway": "Drug resistance in ERBB2 TMD/JMD mutants"
} | 0.774597 |
co_mech_00073 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_003482.4(KMT2D):c.7613dup (p.Gln2540fs) affects the Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7 pathway, citing each molecular step. | NM_003482.4(KMT2D):c.7613dup (p.Gln2540fs) VARIANT_IN_GENE KMT2D -> KMT2D GENE_ANNOTATED_WITH_GO_TERM positive regulation of transcription by RNA polymerase II -> TBK1 GENE_ANNOTATED_WITH_GO_TERM positive regulation of transcription by RNA polymerase II -> TBK1 GENE_PARTICIPATES_IN_PATHWAY Regulation of TBK1, IKKε (IKB... | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_003482.4(KMT2D):c.7613dup (p.Gln2540fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_003482.4(KMT2D):c.7613dup (p.Gln2540fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence... | NM_003482.4(KMT2D):c.7613dup (p.Gln2540fs) VARIANT_IN_GENE KMT2D -> KMT2D GENE_ANNOTATED_WITH_GO_TERM positive regulation of transcription by RNA polymerase II -> TBK1 GENE_ANNOTATED_WITH_GO_TERM positive regulation of transcription by RNA polymerase II -> TBK1 GENE_PARTICIPATES_IN_PATHWAY Regulation of TBK1, IKKε (IKB... | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "KMT2D",
"source_db": "UniProt",
"payload": {
"accession": "O14686",
"sequence": "MDSQKLAGEDKDSEPAADGPAASEDPSATESDLPNPHVGEVSVLSSGSPRLQETPQDCSGGPVRRCALCNCGEPSLHGQRELRRFELPFDWPRCPVVSPGGSPGPNEAVLPSEDLSQIGFPEGLTPAHLGEPG... | [
{
"source_db": "ClinVar",
"source_id": "KMT2D",
"text": "NM_003482.4(KMT2D):c.7613dup (p.Gln2540fs) VARIANT_IN_GENE KMT2D",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0045944",
"text": "KMT2D GENE_ANNOTATED_WITH_GO_TERM positive regulation of transcription by RNA polyme... | {
"variant": "NM_003482.4(KMT2D):c.7613dup (p.Gln2540fs)",
"pathway": "Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7 "
} | 0.774597 |
co_mech_00074 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_000535.7(PMS2):c.546del (p.Met184fs) affects the Sensory processing of sound by outer hair cells of the cochlea pathway, citing each molecular step. | NM_000535.7(PMS2):c.546del (p.Met184fs) VARIANT_IN_GENE PMS2 -> PMS2 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> ACTB GENE_ANNOTATED_WITH_GO_TERM ATP binding -> ACTB GENE_PARTICIPATES_IN_PATHWAY Sensory processing of sound by outer hair cells of the cochlea | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000535.7(PMS2):c.546del (p.Met184fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000535.7(PMS2):c.546del (p.Met184fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1,
... | NM_000535.7(PMS2):c.546del (p.Met184fs) VARIANT_IN_GENE PMS2 -> PMS2 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> ACTB GENE_ANNOTATED_WITH_GO_TERM ATP binding -> ACTB GENE_PARTICIPATES_IN_PATHWAY Sensory processing of sound by outer hair cells of the cochlea | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "PMS2",
"source_db": "UniProt",
"payload": {
"accession": "P54278",
"sequence": "MERAESSSTEPAKAIKPIDRKSVHQICSGQVVLSLSTAVKELVENSLDAGATNIDLKLKDYGVDLIEVSDNGCGVEEENFEGLTLKHHTSKIQEFADLTQVETFGFRGEALSSLCALSDVTISTCHASAKVGTR... | [
{
"source_db": "ClinVar",
"source_id": "PMS2",
"text": "NM_000535.7(PMS2):c.546del (p.Met184fs) VARIANT_IN_GENE PMS2",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0005524",
"text": "PMS2 GENE_ANNOTATED_WITH_GO_TERM ATP binding",
"confidence": 0.6
},
{
"source... | {
"variant": "NM_000535.7(PMS2):c.546del (p.Met184fs)",
"pathway": "Sensory processing of sound by outer hair cells of the cochlea"
} | 0.774597 |
co_mech_00075 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_000546.6(TP53):c.693del (p.Ile232fs) affects the PRC2 methylates histones and DNA pathway, citing each molecular step. | NM_000546.6(TP53):c.693del (p.Ile232fs) VARIANT_IN_GENE TP53 -> TP53 GENE_ANNOTATED_WITH_GO_TERM RNA polymerase II cis-regulatory region sequence-specific DNA binding -> DNMT3A GENE_ANNOTATED_WITH_GO_TERM RNA polymerase II cis-regulatory region sequence-specific DNA binding -> DNMT3A GENE_PARTICIPATES_IN_PATHWAY PRC2 m... | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000546.6(TP53):c.693del (p.Ile232fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000546.6(TP53):c.693del (p.Ile232fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1,
... | NM_000546.6(TP53):c.693del (p.Ile232fs) VARIANT_IN_GENE TP53 -> TP53 GENE_ANNOTATED_WITH_GO_TERM RNA polymerase II cis-regulatory region sequence-specific DNA binding -> DNMT3A GENE_ANNOTATED_WITH_GO_TERM RNA polymerase II cis-regulatory region sequence-specific DNA binding -> DNMT3A GENE_PARTICIPATES_IN_PATHWAY PRC2 m... | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "TP53",
"source_db": "UniProt",
"payload": {
"accession": "P04637",
"sequence": "MEEPQSDPSVEPPLSQETFSDLWKLLPENNVLSPLPSQAMDDLMLSPDDIEQWFTEDPGPDEAPRMPEAAPPVAPAPAAPTPAAPAPAPSWPLSSSVPSQKTYQGSYGFRLGFLHSGTAKSVTCTYSPALNKMF... | [
{
"source_db": "ClinVar",
"source_id": "TP53",
"text": "NM_000546.6(TP53):c.693del (p.Ile232fs) VARIANT_IN_GENE TP53",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0000978",
"text": "TP53 GENE_ANNOTATED_WITH_GO_TERM RNA polymerase II cis-regulatory region sequence-specifi... | {
"variant": "NM_000546.6(TP53):c.693del (p.Ile232fs)",
"pathway": "PRC2 methylates histones and DNA"
} | 0.774597 |
co_mech_00076 | mechanistic_explanation | coding_variant | hard | 5 | Explain the molecular mechanism by which NM_012179.4(FBXO7):c.316_317del (p.Leu106fs) affects the SMAC(DIABLO)-mediated dissociation of IAP:caspase complexes pathway, citing each molecular step. | NM_012179.4(FBXO7):c.316_317del (p.Leu106fs) VARIANT_IN_GENE FBXO7 -> FBXO7 GENE_PARTICIPATES_IN_PATHWAY Neddylation -> CDKN1A GENE_PARTICIPATES_IN_PATHWAY Neddylation -> CASP3 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH CDKN1A -> CASP3 GENE_PARTICIPATES_IN_PATHWAY SMAC(DIABLO)-mediated dissociation of IAP:caspase complexes | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_012179.4(FBXO7):c.316_317del (p.Leu106fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_012179.4(FBXO7):c.316_317del (p.Leu106fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confid... | NM_012179.4(FBXO7):c.316_317del (p.Leu106fs) VARIANT_IN_GENE FBXO7 -> FBXO7 GENE_PARTICIPATES_IN_PATHWAY Neddylation -> CDKN1A GENE_PARTICIPATES_IN_PATHWAY Neddylation -> CASP3 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH CDKN1A -> CASP3 GENE_PARTICIPATES_IN_PATHWAY SMAC(DIABLO)-mediated dissociation of IAP:caspase complexes | null | [
"conservation",
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "evolutionary",
"tag": "conservation",
"anchor_node_id": "NM_012179.4(FBXO7):c.316_317del (p.Leu106fs)",
"source_db": "UCSC_phyloP",
"payload": {
"chrom": "chr22",
"pos": 32479173,
"track": "phyloP100way",
"window": 20,
"scores": [
1.84637,
... | [
{
"source_db": "ClinVar",
"source_id": "FBXO7",
"text": "NM_012179.4(FBXO7):c.316_317del (p.Leu106fs) VARIANT_IN_GENE FBXO7",
"confidence": 1
},
{
"source_db": "Reactome",
"source_id": "R-HSA-8951664",
"text": "FBXO7 GENE_PARTICIPATES_IN_PATHWAY Neddylation",
"confidence": 1
},... | {
"variant": "NM_012179.4(FBXO7):c.316_317del (p.Leu106fs)",
"pathway": "SMAC(DIABLO)-mediated dissociation of IAP:caspase complexes "
} | 0.999199 |
co_mech_00077 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_032043.3(BRIP1):c.628-5_629del affects the Regulation of TP53 Activity through Methylation pathway, citing each molecular step. | NM_032043.3(BRIP1):c.628-5_629del VARIANT_IN_GENE BRIP1 -> BRIP1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BRCA1 -> BRCA1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH TP53 -> TP53 GENE_PARTICIPATES_IN_PATHWAY Regulation of TP53 Activity through Methylation | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_032043.3(BRIP1):c.628-5_629del",
"source_node_type": "VARIANT",
"source_node_label": "NM_032043.3(BRIP1):c.628-5_629del",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1,
"edge_... | NM_032043.3(BRIP1):c.628-5_629del VARIANT_IN_GENE BRIP1 -> BRIP1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BRCA1 -> BRCA1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH TP53 -> TP53 GENE_PARTICIPATES_IN_PATHWAY Regulation of TP53 Activity through Methylation | null | [
"expression",
"intercell_role",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "BRIP1",
"source_db": "UniProt",
"payload": {
"accession": "Q9BX63",
"sequence": "MSSMWSEYTIGGVKIYFPYKAYPSQLAMMNSILRGLNSKQHCLLESPTGSGKSLALLCSALAWQQSLSGKPADEGVSEKAEVQLSCCCACHSKDFTNNDMNQGTSRHFNYPSTPPSERNGTSSTCQDSPEKTT... | [
{
"source_db": "ClinVar",
"source_id": "BRIP1",
"text": "NM_032043.3(BRIP1):c.628-5_629del VARIANT_IN_GENE BRIP1",
"confidence": 1
},
{
"source_db": "STRING",
"source_id": "BRCA1",
"text": "BRIP1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BRCA1",
"confidence": 0.999
},
{
"sourc... | {
"variant": "NM_032043.3(BRIP1):c.628-5_629del",
"pathway": "Regulation of TP53 Activity through Methylation"
} | 0.9995 |
co_mech_00078 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_000251.3(MSH2):c.2524G>T (p.Glu842Ter) affects the SUMOylation of intracellular receptors pathway, citing each molecular step. | NM_000251.3(MSH2):c.2524G>T (p.Glu842Ter) VARIANT_IN_GENE MSH2 -> MSH2 GENE_ANNOTATED_WITH_GO_TERM male gonad development -> AR GENE_ANNOTATED_WITH_GO_TERM male gonad development -> AR GENE_PARTICIPATES_IN_PATHWAY SUMOylation of intracellular receptors | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000251.3(MSH2):c.2524G>T (p.Glu842Ter)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000251.3(MSH2):c.2524G>T (p.Glu842Ter)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence":... | NM_000251.3(MSH2):c.2524G>T (p.Glu842Ter) VARIANT_IN_GENE MSH2 -> MSH2 GENE_ANNOTATED_WITH_GO_TERM male gonad development -> AR GENE_ANNOTATED_WITH_GO_TERM male gonad development -> AR GENE_PARTICIPATES_IN_PATHWAY SUMOylation of intracellular receptors | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "MSH2",
"source_db": "UniProt",
"payload": {
"accession": "P43246",
"sequence": "MAVQPKETLQLESAAEVGFVRFFQGMPEKPTTTVRLFDRGDFYTAHGEDALLAAREVFKTQGVIKYMGPAGAKNLQSVVLSKMNFESFVKDLLLVRQYRVEVYKNRAGNKASKENDWYLAYKASPGNLSQFEDI... | [
{
"source_db": "ClinVar",
"source_id": "MSH2",
"text": "NM_000251.3(MSH2):c.2524G>T (p.Glu842Ter) VARIANT_IN_GENE MSH2",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0008584",
"text": "MSH2 GENE_ANNOTATED_WITH_GO_TERM male gonad development",
"confidence": 0.6
},
... | {
"variant": "NM_000251.3(MSH2):c.2524G>T (p.Glu842Ter)",
"pathway": "SUMOylation of intracellular receptors"
} | 0.774597 |
co_mech_00079 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_000535.7(PMS2):c.485T>A (p.Leu162Ter) affects the lestaurtinib-resistant FLT3 mutants pathway, citing each molecular step. | NM_000535.7(PMS2):c.485T>A (p.Leu162Ter) VARIANT_IN_GENE PMS2 -> PMS2 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> FLT3 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> FLT3 GENE_PARTICIPATES_IN_PATHWAY lestaurtinib-resistant FLT3 mutants | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000535.7(PMS2):c.485T>A (p.Leu162Ter)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000535.7(PMS2):c.485T>A (p.Leu162Ter)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1... | NM_000535.7(PMS2):c.485T>A (p.Leu162Ter) VARIANT_IN_GENE PMS2 -> PMS2 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> FLT3 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> FLT3 GENE_PARTICIPATES_IN_PATHWAY lestaurtinib-resistant FLT3 mutants | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "PMS2",
"source_db": "UniProt",
"payload": {
"accession": "P54278",
"sequence": "MERAESSSTEPAKAIKPIDRKSVHQICSGQVVLSLSTAVKELVENSLDAGATNIDLKLKDYGVDLIEVSDNGCGVEEENFEGLTLKHHTSKIQEFADLTQVETFGFRGEALSSLCALSDVTISTCHASAKVGTR... | [
{
"source_db": "ClinVar",
"source_id": "PMS2",
"text": "NM_000535.7(PMS2):c.485T>A (p.Leu162Ter) VARIANT_IN_GENE PMS2",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0005524",
"text": "PMS2 GENE_ANNOTATED_WITH_GO_TERM ATP binding",
"confidence": 0.6
},
{
"sourc... | {
"variant": "NM_000535.7(PMS2):c.485T>A (p.Leu162Ter)",
"pathway": "lestaurtinib-resistant FLT3 mutants"
} | 0.774597 |
co_mech_00080 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_003482.4(KMT2D):c.10090C>T (p.Gln3364Ter) affects the MET interacts with TNS proteins pathway, citing each molecular step. | NM_003482.4(KMT2D):c.10090C>T (p.Gln3364Ter) VARIANT_IN_GENE KMT2D -> KMT2D GENE_ANNOTATED_WITH_GO_TERM positive regulation of transcription by RNA polymerase II -> HGF GENE_ANNOTATED_WITH_GO_TERM positive regulation of transcription by RNA polymerase II -> HGF GENE_PARTICIPATES_IN_PATHWAY MET interacts with TNS protei... | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_003482.4(KMT2D):c.10090C>T (p.Gln3364Ter)",
"source_node_type": "VARIANT",
"source_node_label": "NM_003482.4(KMT2D):c.10090C>T (p.Gln3364Ter)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confid... | NM_003482.4(KMT2D):c.10090C>T (p.Gln3364Ter) VARIANT_IN_GENE KMT2D -> KMT2D GENE_ANNOTATED_WITH_GO_TERM positive regulation of transcription by RNA polymerase II -> HGF GENE_ANNOTATED_WITH_GO_TERM positive regulation of transcription by RNA polymerase II -> HGF GENE_PARTICIPATES_IN_PATHWAY MET interacts with TNS protei... | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "KMT2D",
"source_db": "UniProt",
"payload": {
"accession": "O14686",
"sequence": "MDSQKLAGEDKDSEPAADGPAASEDPSATESDLPNPHVGEVSVLSSGSPRLQETPQDCSGGPVRRCALCNCGEPSLHGQRELRRFELPFDWPRCPVVSPGGSPGPNEAVLPSEDLSQIGFPEGLTPAHLGEPG... | [
{
"source_db": "ClinVar",
"source_id": "KMT2D",
"text": "NM_003482.4(KMT2D):c.10090C>T (p.Gln3364Ter) VARIANT_IN_GENE KMT2D",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0045944",
"text": "KMT2D GENE_ANNOTATED_WITH_GO_TERM positive regulation of transcription by RNA poly... | {
"variant": "NM_003482.4(KMT2D):c.10090C>T (p.Gln3364Ter)",
"pathway": "MET interacts with TNS proteins"
} | 0.774597 |
co_mech_00081 | mechanistic_explanation | coding_variant | hard | 5 | Explain the molecular mechanism by which NM_000059.4(BRCA2):c.9859del (p.Cys3287fs) affects the Collagen degradation pathway, citing each molecular step. | NM_000059.4(BRCA2):c.9859del (p.Cys3287fs) VARIANT_IN_GENE BRCA2 -> BRCA2 GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription -> NOTCH1 GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription -> ADAM10 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH NOTCH1 -> ADAM10 GENE_PARTICIPA... | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000059.4(BRCA2):c.9859del (p.Cys3287fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000059.4(BRCA2):c.9859del (p.Cys3287fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence... | NM_000059.4(BRCA2):c.9859del (p.Cys3287fs) VARIANT_IN_GENE BRCA2 -> BRCA2 GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription -> NOTCH1 GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription -> ADAM10 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH NOTCH1 -> ADAM10 GENE_PARTICIPA... | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "BRCA2",
"source_db": "UniProt",
"payload": {
"accession": "P51587",
"sequence": "MPIGSKERPTFFEIFKTRCNKADLGPISLNWFEELSSEAPPYNSEPAEESEHKNNNYEPNLFKTPQRKPSYNQLASTPIIFKEQGLTLPLYQSPVKELDKFKLDLGRNVPNSRHKSLRTVKTKMDQADDVSCP... | [
{
"source_db": "ClinVar",
"source_id": "BRCA2",
"text": "NM_000059.4(BRCA2):c.9859del (p.Cys3287fs) VARIANT_IN_GENE BRCA2",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0045893",
"text": "BRCA2 GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription... | {
"variant": "NM_000059.4(BRCA2):c.9859del (p.Cys3287fs)",
"pathway": "Collagen degradation"
} | 0.802407 |
co_mech_00082 | mechanistic_explanation | coding_variant | hard | 5 | Explain the molecular mechanism by which NM_001904.4(CTNNB1):c.1097T>G (p.Leu366Ter) affects the Polymerase switching pathway, citing each molecular step. | NM_001904.4(CTNNB1):c.1097T>G (p.Leu366Ter) VARIANT_IN_GENE CTNNB1 -> CREBBP PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH CTNNB1 -> CREBBP GENE_ANNOTATED_WITH_GO_TERM damaged DNA binding -> POLD1 GENE_ANNOTATED_WITH_GO_TERM damaged DNA binding -> POLD1 GENE_PARTICIPATES_IN_PATHWAY Polymerase switching | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_001904.4(CTNNB1):c.1097T>G (p.Leu366Ter)",
"source_node_type": "VARIANT",
"source_node_label": "NM_001904.4(CTNNB1):c.1097T>G (p.Leu366Ter)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confiden... | NM_001904.4(CTNNB1):c.1097T>G (p.Leu366Ter) VARIANT_IN_GENE CTNNB1 -> CREBBP PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH CTNNB1 -> CREBBP GENE_ANNOTATED_WITH_GO_TERM damaged DNA binding -> POLD1 GENE_ANNOTATED_WITH_GO_TERM damaged DNA binding -> POLD1 GENE_PARTICIPATES_IN_PATHWAY Polymerase switching | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "CTNNB1",
"source_db": "UniProt",
"payload": {
"accession": "P35222",
"sequence": "MATQADLMELDMAMEPDRKAAVSHWQQQSYLDSGIHSGATTTAPSLSGKGNPEEEDVDTSQVLYEWEQGFSQSFTQEQVADIDGQYAMTRAQRVRAAMFPETLDEGMQIPSTQFDAAHPTNVQRLAEPSQML... | [
{
"source_db": "ClinVar",
"source_id": "CTNNB1",
"text": "NM_001904.4(CTNNB1):c.1097T>G (p.Leu366Ter) VARIANT_IN_GENE CTNNB1",
"confidence": 1
},
{
"source_db": "STRING",
"source_id": "CREBBP",
"text": "CREBBP PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH CTNNB1",
"confidence": 0.999
},... | {
"variant": "NM_001904.4(CTNNB1):c.1097T>G (p.Leu366Ter)",
"pathway": "Polymerase switching"
} | 0.81503 |
co_mech_00083 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_000249.4(MLH1):c.193G>C (p.Gly65Arg) affects the Mitotic Prophase pathway, citing each molecular step. | NM_000249.4(MLH1):c.193G>C (p.Gly65Arg) VARIANT_IN_GENE MLH1 -> MLH1 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> CDK1 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> CDK1 GENE_PARTICIPATES_IN_PATHWAY Mitotic Prophase | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000249.4(MLH1):c.193G>C (p.Gly65Arg)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000249.4(MLH1):c.193G>C (p.Gly65Arg)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1,
... | NM_000249.4(MLH1):c.193G>C (p.Gly65Arg) VARIANT_IN_GENE MLH1 -> MLH1 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> CDK1 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> CDK1 GENE_PARTICIPATES_IN_PATHWAY Mitotic Prophase | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "MLH1",
"source_db": "UniProt",
"payload": {
"accession": "P40692",
"sequence": "MSFVAGVIRRLDETVVNRIAAGEVIQRPANAIKEMIENCLDAKSTSIQVIVKEGGLKLIQIQDNGTGIRKEDLDIVCERFTTSKLQSFEDLASISTYGFRGEALASISHVAHVTITTKTADGKCAYRASYSDGK... | [
{
"source_db": "ClinVar",
"source_id": "MLH1",
"text": "NM_000249.4(MLH1):c.193G>C (p.Gly65Arg) VARIANT_IN_GENE MLH1",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0005524",
"text": "MLH1 GENE_ANNOTATED_WITH_GO_TERM ATP binding",
"confidence": 0.6
},
{
"source... | {
"variant": "NM_000249.4(MLH1):c.193G>C (p.Gly65Arg)",
"pathway": "Mitotic Prophase"
} | 0.774597 |
co_mech_00084 | mechanistic_explanation | coding_variant | hard | 5 | Explain the molecular mechanism by which NM_001101.5(ACTB):c.802G>C (p.Gly268Arg) affects the Heme biosynthesis pathway, citing each molecular step. | NM_001101.5(ACTB):c.802G>C (p.Gly268Arg) VARIANT_IN_GENE ACTB -> ACTB PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH PFN1 -> PFN1 GENE_PARTICIPATES_IN_PATHWAY Platelet degranulation -> ALB GENE_PARTICIPATES_IN_PATHWAY Platelet degranulation -> ALB GENE_PARTICIPATES_IN_PATHWAY Heme biosynthesis | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_001101.5(ACTB):c.802G>C (p.Gly268Arg)",
"source_node_type": "VARIANT",
"source_node_label": "NM_001101.5(ACTB):c.802G>C (p.Gly268Arg)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1... | NM_001101.5(ACTB):c.802G>C (p.Gly268Arg) VARIANT_IN_GENE ACTB -> ACTB PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH PFN1 -> PFN1 GENE_PARTICIPATES_IN_PATHWAY Platelet degranulation -> ALB GENE_PARTICIPATES_IN_PATHWAY Platelet degranulation -> ALB GENE_PARTICIPATES_IN_PATHWAY Heme biosynthesis | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "ACTB",
"source_db": "UniProt",
"payload": {
"accession": "P60709",
"sequence": "MDDDIAALVVDNGSGMCKAGFAGDDAPRAVFPSIVGRPRHQGVMVGMGQKDSYVGDEAQSKRGILTLKYPIEHGIVTNWDDMEKIWHHTFYNELRVAPEEHPVLLTEAPLNPKANREKMTQIMFETFNTPAMYV... | [
{
"source_db": "ClinVar",
"source_id": "ACTB",
"text": "NM_001101.5(ACTB):c.802G>C (p.Gly268Arg) VARIANT_IN_GENE ACTB",
"confidence": 1
},
{
"source_db": "STRING",
"source_id": "PFN1",
"text": "ACTB PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH PFN1",
"confidence": 0.999
},
{
"sou... | {
"variant": "NM_001101.5(ACTB):c.802G>C (p.Gly268Arg)",
"pathway": "Heme biosynthesis"
} | 0.9998 |
co_mech_00085 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_004364.5(CEBPA):c.946_947insGGA (p.Glu316delinsGlyLys) affects the PI3K events in ERBB4 signaling pathway, citing each molecular step. | NM_004364.5(CEBPA):c.946_947insGGA (p.Glu316delinsGlyLys) VARIANT_IN_GENE CEBPA -> CEBPA PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH FLT3 -> FLT3 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH PIK3CA -> PIK3CA GENE_PARTICIPATES_IN_PATHWAY PI3K events in ERBB4 signaling | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_004364.5(CEBPA):c.946_947insGGA (p.Glu316delinsGlyLys)",
"source_node_type": "VARIANT",
"source_node_label": "NM_004364.5(CEBPA):c.946_947insGGA (p.Glu316delinsGlyLys)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "cu... | NM_004364.5(CEBPA):c.946_947insGGA (p.Glu316delinsGlyLys) VARIANT_IN_GENE CEBPA -> CEBPA PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH FLT3 -> FLT3 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH PIK3CA -> PIK3CA GENE_PARTICIPATES_IN_PATHWAY PI3K events in ERBB4 signaling | null | [
"conservation",
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "evolutionary",
"tag": "conservation",
"anchor_node_id": "NM_004364.5(CEBPA):c.946_947insGGA (p.Glu316delinsGlyLys)",
"source_db": "UCSC_phyloP",
"payload": {
"chrom": "chr19",
"pos": 33301468,
"track": "phyloP100way",
"window": 20,
"scores": [
2... | [
{
"source_db": "ClinVar",
"source_id": "CEBPA",
"text": "NM_004364.5(CEBPA):c.946_947insGGA (p.Glu316delinsGlyLys) VARIANT_IN_GENE CEBPA",
"confidence": 1
},
{
"source_db": "STRING",
"source_id": "FLT3",
"text": "CEBPA PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH FLT3",
"confidence": 0.9... | {
"variant": "NM_004364.5(CEBPA):c.946_947insGGA (p.Glu316delinsGlyLys)",
"pathway": "PI3K events in ERBB4 signaling"
} | 0.984597 |
co_mech_00086 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_000179.3(MSH6):c.699_702dup (p.Thr235Ter) affects the Activation of the pre-replicative complex pathway, citing each molecular step. | NM_000179.3(MSH6):c.699_702dup (p.Thr235Ter) VARIANT_IN_GENE MSH6 -> POLD1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH MSH6 -> POLD1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH POLE -> POLE GENE_PARTICIPATES_IN_PATHWAY Activation of the pre-replicative complex | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000179.3(MSH6):c.699_702dup (p.Thr235Ter)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000179.3(MSH6):c.699_702dup (p.Thr235Ter)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confid... | NM_000179.3(MSH6):c.699_702dup (p.Thr235Ter) VARIANT_IN_GENE MSH6 -> POLD1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH MSH6 -> POLD1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH POLE -> POLE GENE_PARTICIPATES_IN_PATHWAY Activation of the pre-replicative complex | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "MSH6",
"source_db": "UniProt",
"payload": {
"accession": "P52701",
"sequence": "MSRQSTLYSFFPKSPALSDANKASARASREGGRAAAAPGASPSPGGDAAWSEAGPGPRPLARSASPPKAKNLNGGLRRSVAPAAPTSCDFSPGDLVWAKMEGYPWWPCLVYNHPFDGTFIREKGKSVRVHVQFF... | [
{
"source_db": "ClinVar",
"source_id": "MSH6",
"text": "NM_000179.3(MSH6):c.699_702dup (p.Thr235Ter) VARIANT_IN_GENE MSH6",
"confidence": 1
},
{
"source_db": "STRING",
"source_id": "POLD1",
"text": "POLD1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH MSH6",
"confidence": 0.995
},
{
... | {
"variant": "NM_000179.3(MSH6):c.699_702dup (p.Thr235Ter)",
"pathway": "Activation of the pre-replicative complex"
} | 0.998498 |
co_mech_00087 | mechanistic_explanation | coding_variant | hard | 5 | Explain the molecular mechanism by which NM_000059.4(BRCA2):c.6206dup (p.Leu2069fs) affects the Estrogen-stimulated signaling through PRKCZ pathway, citing each molecular step. | NM_000059.4(BRCA2):c.6206dup (p.Leu2069fs) VARIANT_IN_GENE BRCA2 -> BRCA2 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BRCA1 -> BRCA1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH TP53 -> MAPK1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH TP53 -> MAPK1 GENE_PARTICIPATES_IN_PATHWAY Estrogen-stimulated signaling through PRKCZ | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000059.4(BRCA2):c.6206dup (p.Leu2069fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000059.4(BRCA2):c.6206dup (p.Leu2069fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence... | NM_000059.4(BRCA2):c.6206dup (p.Leu2069fs) VARIANT_IN_GENE BRCA2 -> BRCA2 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BRCA1 -> BRCA1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH TP53 -> MAPK1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH TP53 -> MAPK1 GENE_PARTICIPATES_IN_PATHWAY Estrogen-stimulated signaling through PRKCZ | null | [
"expression",
"intercell_role",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "BRCA2",
"source_db": "UniProt",
"payload": {
"accession": "P51587",
"sequence": "MPIGSKERPTFFEIFKTRCNKADLGPISLNWFEELSSEAPPYNSEPAEESEHKNNNYEPNLFKTPQRKPSYNQLASTPIIFKEQGLTLPLYQSPVKELDKFKLDLGRNVPNSRHKSLRTVKTKMDQADDVSCP... | [
{
"source_db": "ClinVar",
"source_id": "BRCA2",
"text": "NM_000059.4(BRCA2):c.6206dup (p.Leu2069fs) VARIANT_IN_GENE BRCA2",
"confidence": 1
},
{
"source_db": "STRING",
"source_id": "BRCA1",
"text": "BRCA2 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BRCA1",
"confidence": 0.999
},
{
... | {
"variant": "NM_000059.4(BRCA2):c.6206dup (p.Leu2069fs)",
"pathway": "Estrogen-stimulated signaling through PRKCZ"
} | 0.9992 |
co_mech_00088 | mechanistic_explanation | coding_variant | hard | 3 | Explain the molecular mechanism by which NM_004380.3(CREBBP):c.4021C>T (p.Arg1341Ter) affects the Somitogenesis pathway, citing each molecular step. | NM_004380.3(CREBBP):c.4021C>T (p.Arg1341Ter) VARIANT_IN_GENE CREBBP -> CREBBP PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH CTNNB1 -> CTNNB1 GENE_PARTICIPATES_IN_PATHWAY Somitogenesis | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_004380.3(CREBBP):c.4021C>T (p.Arg1341Ter)",
"source_node_type": "VARIANT",
"source_node_label": "NM_004380.3(CREBBP):c.4021C>T (p.Arg1341Ter)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confid... | NM_004380.3(CREBBP):c.4021C>T (p.Arg1341Ter) VARIANT_IN_GENE CREBBP -> CREBBP PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH CTNNB1 -> CTNNB1 GENE_PARTICIPATES_IN_PATHWAY Somitogenesis | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "CREBBP",
"source_db": "UniProt",
"payload": {
"accession": "Q92793",
"sequence": "MAENLLDGPPNPKRAKLSSPGFSANDSTDFGSLFDLENDLPDELIPNGGELGLLNSGNLVPDAASKHKQLSELLRGGSGSSINPGIGNVSASSPVQQGLGGQAQGQPNSANMASLSAMGKSPLSQGDSSAPS... | [
{
"source_db": "ClinVar",
"source_id": "CREBBP",
"text": "NM_004380.3(CREBBP):c.4021C>T (p.Arg1341Ter) VARIANT_IN_GENE CREBBP",
"confidence": 1
},
{
"source_db": "STRING",
"source_id": "CTNNB1",
"text": "CREBBP PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH CTNNB1",
"confidence": 0.999
}... | {
"variant": "NM_004380.3(CREBBP):c.4021C>T (p.Arg1341Ter)",
"pathway": "Somitogenesis"
} | 0.999667 |
co_mech_00089 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which BCHE Cynthiana affects the NOTCH3 Intracellular Domain Regulates Transcription pathway, citing each molecular step. | BCHE Cynthiana VARIANT_IN_GENE BCHE -> BCHE GENE_ANNOTATED_WITH_GO_TERM negative regulation of cell population proliferation -> NOTCH1 GENE_ANNOTATED_WITH_GO_TERM negative regulation of cell population proliferation -> NOTCH1 GENE_PARTICIPATES_IN_PATHWAY NOTCH3 Intracellular Domain Regulates Transcription | {
"steps": [
{
"hop": 1,
"source_node_id": "BCHE Cynthiana",
"source_node_type": "VARIANT",
"source_node_label": "BCHE Cynthiana",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1,
"edge_source_db": "ClinVar",
"target_n... | BCHE Cynthiana VARIANT_IN_GENE BCHE -> BCHE GENE_ANNOTATED_WITH_GO_TERM negative regulation of cell population proliferation -> NOTCH1 GENE_ANNOTATED_WITH_GO_TERM negative regulation of cell population proliferation -> NOTCH1 GENE_PARTICIPATES_IN_PATHWAY NOTCH3 Intracellular Domain Regulates Transcription | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "BCHE",
"source_db": "UniProt",
"payload": {
"accession": "P06276",
"sequence": "MHSKVTIICIRFLFWFLLLCMLIGKSHTEDDIIIATKNGKVRGMNLTVFGGTVTAFLGIPYAQPPLGRLRFKKPQSLTKWSDIWNATKYANSCCQNIDQSFPGFHGSEMWNPNTDLSEDCLYLNVWIPAPKPKN... | [
{
"source_db": "ClinVar",
"source_id": "BCHE",
"text": "BCHE Cynthiana VARIANT_IN_GENE BCHE",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0008285",
"text": "BCHE GENE_ANNOTATED_WITH_GO_TERM negative regulation of cell population proliferation",
"confidence": 0.6
},... | {
"variant": "BCHE Cynthiana",
"pathway": "NOTCH3 Intracellular Domain Regulates Transcription"
} | 0.774597 |
co_mech_00090 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_014845.6(FIG4):c.294del (p.Phe98fs) affects the Dengue Virus-Host Interactions pathway, citing each molecular step. | NM_014845.6(FIG4):c.294del (p.Phe98fs) VARIANT_IN_GENE FIG4 -> ALS2 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH FIG4 -> ALS2 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH FUS -> FUS GENE_PARTICIPATES_IN_PATHWAY Dengue Virus-Host Interactions | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_014845.6(FIG4):c.294del (p.Phe98fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_014845.6(FIG4):c.294del (p.Phe98fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1,
... | NM_014845.6(FIG4):c.294del (p.Phe98fs) VARIANT_IN_GENE FIG4 -> ALS2 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH FIG4 -> ALS2 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH FUS -> FUS GENE_PARTICIPATES_IN_PATHWAY Dengue Virus-Host Interactions | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "FIG4",
"source_db": "UniProt",
"payload": {
"accession": "Q92562",
"sequence": "MPTAAAPIISSVQKLVLYETRARYFLVGSNNAETKYRVLKIDRTEPKDLVIIDDRHVYTQQEVRELLGRLDLGNRTKMGQKGSSGLFRAVSAFGVVGFVRFLEGYYIVLITKRRKMADIGGHAIYKVEDTNMIY... | [
{
"source_db": "ClinVar",
"source_id": "FIG4",
"text": "NM_014845.6(FIG4):c.294del (p.Phe98fs) VARIANT_IN_GENE FIG4",
"confidence": 1
},
{
"source_db": "STRING",
"source_id": "ALS2",
"text": "ALS2 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH FIG4",
"confidence": 0.854
},
{
"sourc... | {
"variant": "NM_014845.6(FIG4):c.294del (p.Phe98fs)",
"pathway": "Dengue Virus-Host Interactions"
} | 0.91534 |
co_mech_00091 | mechanistic_explanation | coding_variant | hard | 5 | Explain the molecular mechanism by which NM_032043.3(BRIP1):c.2429_2432dup (p.Pro812fs) affects the STAT5 Activation pathway, citing each molecular step. | NM_032043.3(BRIP1):c.2429_2432dup (p.Pro812fs) VARIANT_IN_GENE BRIP1 -> BRIP1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH MLH1 -> MLH1 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> FLT3 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> FLT3 GENE_PARTICIPATES_IN_PATHWAY STAT5 Activation | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_032043.3(BRIP1):c.2429_2432dup (p.Pro812fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_032043.3(BRIP1):c.2429_2432dup (p.Pro812fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_co... | NM_032043.3(BRIP1):c.2429_2432dup (p.Pro812fs) VARIANT_IN_GENE BRIP1 -> BRIP1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH MLH1 -> MLH1 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> FLT3 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> FLT3 GENE_PARTICIPATES_IN_PATHWAY STAT5 Activation | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "BRIP1",
"source_db": "UniProt",
"payload": {
"accession": "Q9BX63",
"sequence": "MSSMWSEYTIGGVKIYFPYKAYPSQLAMMNSILRGLNSKQHCLLESPTGSGKSLALLCSALAWQQSLSGKPADEGVSEKAEVQLSCCCACHSKDFTNNDMNQGTSRHFNYPSTPPSERNGTSSTCQDSPEKTT... | [
{
"source_db": "ClinVar",
"source_id": "BRIP1",
"text": "NM_032043.3(BRIP1):c.2429_2432dup (p.Pro812fs) VARIANT_IN_GENE BRIP1",
"confidence": 1
},
{
"source_db": "STRING",
"source_id": "MLH1",
"text": "BRIP1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH MLH1",
"confidence": 0.999
},
{... | {
"variant": "NM_032043.3(BRIP1):c.2429_2432dup (p.Pro812fs)",
"pathway": "STAT5 Activation"
} | 0.81503 |
co_mech_00092 | mechanistic_explanation | coding_variant | hard | 5 | Explain the molecular mechanism by which NM_023110.3(FGFR1):c.1916T>C (p.Ile639Thr) affects the Platelet sensitization by LDL pathway, citing each molecular step. | NM_023110.3(FGFR1):c.1916T>C (p.Ile639Thr) VARIANT_IN_GENE FGFR1 -> FGFR1 GENE_ENCODES_PROTEIN FGFR1 -> PPP2R1B PROTEIN_PHYSICALLY_INTERACTS_WITH FGFR1 -> PPP2R1B GENE_ENCODES_PROTEIN PPP2R1B -> PPP2R1B GENE_PARTICIPATES_IN_PATHWAY Platelet sensitization by LDL | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_023110.3(FGFR1):c.1916T>C (p.Ile639Thr)",
"source_node_type": "VARIANT",
"source_node_label": "NM_023110.3(FGFR1):c.1916T>C (p.Ile639Thr)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence... | NM_023110.3(FGFR1):c.1916T>C (p.Ile639Thr) VARIANT_IN_GENE FGFR1 -> FGFR1 GENE_ENCODES_PROTEIN FGFR1 -> PPP2R1B PROTEIN_PHYSICALLY_INTERACTS_WITH FGFR1 -> PPP2R1B GENE_ENCODES_PROTEIN PPP2R1B -> PPP2R1B GENE_PARTICIPATES_IN_PATHWAY Platelet sensitization by LDL | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "FGFR1",
"source_db": "UniProt",
"payload": {
"accession": "P11362",
"sequence": "MWSWKCLLFWAVLVTATLCTARPSPTLPEQAQPWGAPVEVESFLVHPGDLLQLRCRLRDDVQSINWLRDGVQLAESNRTRITGEEVEVQDSVPADSGLYACVTSSPSGSDTTYFSVNVSDALPSSEDDDDDDD... | [
{
"source_db": "ClinVar",
"source_id": "FGFR1",
"text": "NM_023110.3(FGFR1):c.1916T>C (p.Ile639Thr) VARIANT_IN_GENE FGFR1",
"confidence": 1
},
{
"source_db": "bridge",
"source_id": "2260",
"text": "FGFR1 GENE_ENCODES_PROTEIN FGFR1",
"confidence": 0.9
},
{
"source_db": "Bi... | {
"variant": "NM_023110.3(FGFR1):c.1916T>C (p.Ile639Thr)",
"pathway": "Platelet sensitization by LDL"
} | 0.93874 |
co_mech_00093 | mechanistic_explanation | coding_variant | hard | 5 | Explain the molecular mechanism by which NM_006000.3(TUBA4A):c.313C>T (p.Arg105Cys) affects the Androgen pathway, citing each molecular step. | NM_006000.3(TUBA4A):c.313C>T (p.Arg105Cys) VARIANT_IN_GENE TUBA4A -> TUBA4A PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH MAPT -> MAPT GENE_ANNOTATED_WITH_GO_TERM DNA damage response -> BRCA1 GENE_ANNOTATED_WITH_GO_TERM DNA damage response -> BRCA1 GENE_PARTICIPATES_IN_PATHWAY Androgen | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_006000.3(TUBA4A):c.313C>T (p.Arg105Cys)",
"source_node_type": "VARIANT",
"source_node_label": "NM_006000.3(TUBA4A):c.313C>T (p.Arg105Cys)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence... | NM_006000.3(TUBA4A):c.313C>T (p.Arg105Cys) VARIANT_IN_GENE TUBA4A -> TUBA4A PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH MAPT -> MAPT GENE_ANNOTATED_WITH_GO_TERM DNA damage response -> BRCA1 GENE_ANNOTATED_WITH_GO_TERM DNA damage response -> BRCA1 GENE_PARTICIPATES_IN_PATHWAY Androgen | null | [
"conservation",
"expression",
"intercell_role",
"protein_sequence",
"protein_structure"
] | [
{
"family": "evolutionary",
"tag": "conservation",
"anchor_node_id": "NM_006000.3(TUBA4A):c.313C>T (p.Arg105Cys)",
"source_db": "UCSC_phyloP",
"payload": {
"chrom": "chr2",
"pos": 219251627,
"track": "phyloP100way",
"window": 20,
"scores": [
3.67813,
... | [
{
"source_db": "ClinVar",
"source_id": "TUBA4A",
"text": "NM_006000.3(TUBA4A):c.313C>T (p.Arg105Cys) VARIANT_IN_GENE TUBA4A",
"confidence": 1
},
{
"source_db": "STRING",
"source_id": "MAPT",
"text": "TUBA4A PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH MAPT",
"confidence": 0.981
},
{
... | {
"variant": "NM_006000.3(TUBA4A):c.313C>T (p.Arg105Cys)",
"pathway": "Androgen"
} | 0.786101 |
co_mech_00094 | mechanistic_explanation | coding_variant | hard | 3 | Explain the molecular mechanism by which NM_000546.6(TP53):c.801_818del (p.Asn268_Arg273del) affects the MAP2K and MAPK activation pathway, citing each molecular step. | NM_000546.6(TP53):c.801_818del (p.Asn268_Arg273del) VARIANT_IN_GENE TP53 -> MAPK1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH TP53 -> MAPK1 GENE_PARTICIPATES_IN_PATHWAY MAP2K and MAPK activation | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000546.6(TP53):c.801_818del (p.Asn268_Arg273del)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000546.6(TP53):c.801_818del (p.Asn268_Arg273del)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
... | NM_000546.6(TP53):c.801_818del (p.Asn268_Arg273del) VARIANT_IN_GENE TP53 -> MAPK1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH TP53 -> MAPK1 GENE_PARTICIPATES_IN_PATHWAY MAP2K and MAPK activation | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "TP53",
"source_db": "UniProt",
"payload": {
"accession": "P04637",
"sequence": "MEEPQSDPSVEPPLSQETFSDLWKLLPENNVLSPLPSQAMDDLMLSPDDIEQWFTEDPGPDEAPRMPEAAPPVAPAPAAPTPAAPAPAPSWPLSSSVPSQKTYQGSYGFRLGFLHSGTAKSVTCTYSPALNKMF... | [
{
"source_db": "ClinVar",
"source_id": "TP53",
"text": "NM_000546.6(TP53):c.801_818del (p.Asn268_Arg273del) VARIANT_IN_GENE TP53",
"confidence": 1
},
{
"source_db": "STRING",
"source_id": "MAPK1",
"text": "MAPK1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH TP53",
"confidence": 0.998
},... | {
"variant": "NM_000546.6(TP53):c.801_818del (p.Asn268_Arg273del)",
"pathway": "MAP2K and MAPK activation"
} | 0.999333 |
co_mech_00095 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_003482.4(KMT2D):c.16438A>G (p.Asn5480Asp) affects the The NLRP1 inflammasome pathway, citing each molecular step. | NM_003482.4(KMT2D):c.16438A>G (p.Asn5480Asp) VARIANT_IN_GENE KMT2D -> KMT2D GENE_ANNOTATED_WITH_GO_TERM positive regulation of cell population proliferation -> BCL2 GENE_ANNOTATED_WITH_GO_TERM positive regulation of cell population proliferation -> BCL2 GENE_PARTICIPATES_IN_PATHWAY The NLRP1 inflammasome | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_003482.4(KMT2D):c.16438A>G (p.Asn5480Asp)",
"source_node_type": "VARIANT",
"source_node_label": "NM_003482.4(KMT2D):c.16438A>G (p.Asn5480Asp)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confid... | NM_003482.4(KMT2D):c.16438A>G (p.Asn5480Asp) VARIANT_IN_GENE KMT2D -> KMT2D GENE_ANNOTATED_WITH_GO_TERM positive regulation of cell population proliferation -> BCL2 GENE_ANNOTATED_WITH_GO_TERM positive regulation of cell population proliferation -> BCL2 GENE_PARTICIPATES_IN_PATHWAY The NLRP1 inflammasome | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "KMT2D",
"source_db": "UniProt",
"payload": {
"accession": "O14686",
"sequence": "MDSQKLAGEDKDSEPAADGPAASEDPSATESDLPNPHVGEVSVLSSGSPRLQETPQDCSGGPVRRCALCNCGEPSLHGQRELRRFELPFDWPRCPVVSPGGSPGPNEAVLPSEDLSQIGFPEGLTPAHLGEPG... | [
{
"source_db": "ClinVar",
"source_id": "KMT2D",
"text": "NM_003482.4(KMT2D):c.16438A>G (p.Asn5480Asp) VARIANT_IN_GENE KMT2D",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0008284",
"text": "KMT2D GENE_ANNOTATED_WITH_GO_TERM positive regulation of cell population prolifera... | {
"variant": "NM_003482.4(KMT2D):c.16438A>G (p.Asn5480Asp)",
"pathway": "The NLRP1 inflammasome"
} | 0.774597 |
co_mech_00096 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_003482.4(KMT2D):c.4290T>G (p.Cys1430Trp) affects the Signaling by ERBB4 pathway, citing each molecular step. | NM_003482.4(KMT2D):c.4290T>G (p.Cys1430Trp) VARIANT_IN_GENE KMT2D -> KMT2D GENE_ANNOTATED_WITH_GO_TERM positive regulation of cell population proliferation -> EGFR GENE_ANNOTATED_WITH_GO_TERM positive regulation of cell population proliferation -> EGFR GENE_PARTICIPATES_IN_PATHWAY Signaling by ERBB4 | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_003482.4(KMT2D):c.4290T>G (p.Cys1430Trp)",
"source_node_type": "VARIANT",
"source_node_label": "NM_003482.4(KMT2D):c.4290T>G (p.Cys1430Trp)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confiden... | NM_003482.4(KMT2D):c.4290T>G (p.Cys1430Trp) VARIANT_IN_GENE KMT2D -> KMT2D GENE_ANNOTATED_WITH_GO_TERM positive regulation of cell population proliferation -> EGFR GENE_ANNOTATED_WITH_GO_TERM positive regulation of cell population proliferation -> EGFR GENE_PARTICIPATES_IN_PATHWAY Signaling by ERBB4 | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "KMT2D",
"source_db": "UniProt",
"payload": {
"accession": "O14686",
"sequence": "MDSQKLAGEDKDSEPAADGPAASEDPSATESDLPNPHVGEVSVLSSGSPRLQETPQDCSGGPVRRCALCNCGEPSLHGQRELRRFELPFDWPRCPVVSPGGSPGPNEAVLPSEDLSQIGFPEGLTPAHLGEPG... | [
{
"source_db": "ClinVar",
"source_id": "KMT2D",
"text": "NM_003482.4(KMT2D):c.4290T>G (p.Cys1430Trp) VARIANT_IN_GENE KMT2D",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0008284",
"text": "KMT2D GENE_ANNOTATED_WITH_GO_TERM positive regulation of cell population proliferat... | {
"variant": "NM_003482.4(KMT2D):c.4290T>G (p.Cys1430Trp)",
"pathway": "Signaling by ERBB4"
} | 0.774597 |
co_mech_00097 | mechanistic_explanation | coding_variant | medium | 4 | Explain the molecular mechanism by which NM_001904.4(CTNNB1):c.1849dup (p.Val617fs) affects the SPOP-mediated proteasomal degradation of PD-L1(CD274) pathway, citing each molecular step. | NM_001904.4(CTNNB1):c.1849dup (p.Val617fs) VARIANT_IN_GENE CTNNB1 -> CTNNB1 GENE_PARTICIPATES_IN_PATHWAY Transcriptional Regulation by VENTX -> CCND1 GENE_PARTICIPATES_IN_PATHWAY Transcriptional Regulation by VENTX -> CCND1 GENE_PARTICIPATES_IN_PATHWAY SPOP-mediated proteasomal degradation of PD-L1(CD274) | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_001904.4(CTNNB1):c.1849dup (p.Val617fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_001904.4(CTNNB1):c.1849dup (p.Val617fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence... | NM_001904.4(CTNNB1):c.1849dup (p.Val617fs) VARIANT_IN_GENE CTNNB1 -> CTNNB1 GENE_PARTICIPATES_IN_PATHWAY Transcriptional Regulation by VENTX -> CCND1 GENE_PARTICIPATES_IN_PATHWAY Transcriptional Regulation by VENTX -> CCND1 GENE_PARTICIPATES_IN_PATHWAY SPOP-mediated proteasomal degradation of PD-L1(CD274) | null | [
"conservation",
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "evolutionary",
"tag": "conservation",
"anchor_node_id": "NM_001904.4(CTNNB1):c.1849dup (p.Val617fs)",
"source_db": "UCSC_phyloP",
"payload": {
"chrom": "chr3",
"pos": 41236390,
"track": "phyloP100way",
"window": 20,
"scores": [
9.24743,
... | [
{
"source_db": "ClinVar",
"source_id": "CTNNB1",
"text": "NM_001904.4(CTNNB1):c.1849dup (p.Val617fs) VARIANT_IN_GENE CTNNB1",
"confidence": 1
},
{
"source_db": "Reactome",
"source_id": "R-HSA-8853884",
"text": "CTNNB1 GENE_PARTICIPATES_IN_PATHWAY Transcriptional Regulation by VENTX",... | {
"variant": "NM_001904.4(CTNNB1):c.1849dup (p.Val617fs)",
"pathway": "SPOP-mediated proteasomal degradation of PD-L1(CD274)"
} | 1 |
co_mech_00098 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_001042492.3(NF1):c.1356del (p.Gly453fs) affects the Signaling by Hippo pathway, citing each molecular step. | NM_001042492.3(NF1):c.1356del (p.Gly453fs) VARIANT_IN_GENE NF1 -> NF1 GENE_ANNOTATED_WITH_GO_TERM positive regulation of neuron apoptotic process -> CASP3 GENE_ANNOTATED_WITH_GO_TERM positive regulation of neuron apoptotic process -> CASP3 GENE_PARTICIPATES_IN_PATHWAY Signaling by Hippo | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_001042492.3(NF1):c.1356del (p.Gly453fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_001042492.3(NF1):c.1356del (p.Gly453fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence... | NM_001042492.3(NF1):c.1356del (p.Gly453fs) VARIANT_IN_GENE NF1 -> NF1 GENE_ANNOTATED_WITH_GO_TERM positive regulation of neuron apoptotic process -> CASP3 GENE_ANNOTATED_WITH_GO_TERM positive regulation of neuron apoptotic process -> CASP3 GENE_PARTICIPATES_IN_PATHWAY Signaling by Hippo | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "NF1",
"source_db": "UniProt",
"payload": {
"accession": "P21359",
"sequence": "MAAHRPVEWVQAVVSRFDEQLPIKTGQQNTHTKVSTEHNKECLINISKYKFSLVISGLTTILKNVNNMRIFGEAAEKNLYLSQLIILDTLEKCLAGQPKDTMRLDETMLVKQLLPEICHFLHTCREGNQHAAELR... | [
{
"source_db": "ClinVar",
"source_id": "NF1",
"text": "NM_001042492.3(NF1):c.1356del (p.Gly453fs) VARIANT_IN_GENE NF1",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0043525",
"text": "NF1 GENE_ANNOTATED_WITH_GO_TERM positive regulation of neuron apoptotic process",
"c... | {
"variant": "NM_001042492.3(NF1):c.1356del (p.Gly453fs)",
"pathway": "Signaling by Hippo"
} | 0.774597 |
co_mech_00099 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_000038.6(APC):c.1365del (p.Lys455fs) affects the Carnitine shuttle pathway, citing each molecular step. | NM_000038.6(APC):c.1365del (p.Lys455fs) VARIANT_IN_GENE APC -> APC GENE_ANNOTATED_WITH_GO_TERM nervous system development -> RXRA GENE_ANNOTATED_WITH_GO_TERM nervous system development -> RXRA GENE_PARTICIPATES_IN_PATHWAY Carnitine shuttle | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000038.6(APC):c.1365del (p.Lys455fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000038.6(APC):c.1365del (p.Lys455fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1,
... | NM_000038.6(APC):c.1365del (p.Lys455fs) VARIANT_IN_GENE APC -> APC GENE_ANNOTATED_WITH_GO_TERM nervous system development -> RXRA GENE_ANNOTATED_WITH_GO_TERM nervous system development -> RXRA GENE_PARTICIPATES_IN_PATHWAY Carnitine shuttle | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "APC",
"source_db": "UniProt",
"payload": {
"accession": "P25054",
"sequence": "MAAASYDQLLKQVEALKMENSNLRQELEDNSNHLTKLETEASNMKEVLKQLQGSIEDEAMASSGQIDLLERLKELNLDSSNFPGVKLRSKMSLRSYGSREGSVSSRSGECSPVPMGSFPRRGFVNGSRESTGYLE... | [
{
"source_db": "ClinVar",
"source_id": "APC",
"text": "NM_000038.6(APC):c.1365del (p.Lys455fs) VARIANT_IN_GENE APC",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0007399",
"text": "APC GENE_ANNOTATED_WITH_GO_TERM nervous system development",
"confidence": 0.6
},
{... | {
"variant": "NM_000038.6(APC):c.1365del (p.Lys455fs)",
"pathway": "Carnitine shuttle"
} | 0.774597 |
co_mech_00100 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_000249.4(MLH1):c.1658_1661del (p.Thr553fs) affects the Prolactin receptor signaling pathway, citing each molecular step. | NM_000249.4(MLH1):c.1658_1661del (p.Thr553fs) VARIANT_IN_GENE MLH1 -> MLH1 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> JAK2 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> JAK2 GENE_PARTICIPATES_IN_PATHWAY Prolactin receptor signaling | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000249.4(MLH1):c.1658_1661del (p.Thr553fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000249.4(MLH1):c.1658_1661del (p.Thr553fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_conf... | NM_000249.4(MLH1):c.1658_1661del (p.Thr553fs) VARIANT_IN_GENE MLH1 -> MLH1 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> JAK2 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> JAK2 GENE_PARTICIPATES_IN_PATHWAY Prolactin receptor signaling | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "MLH1",
"source_db": "UniProt",
"payload": {
"accession": "P40692",
"sequence": "MSFVAGVIRRLDETVVNRIAAGEVIQRPANAIKEMIENCLDAKSTSIQVIVKEGGLKLIQIQDNGTGIRKEDLDIVCERFTTSKLQSFEDLASISTYGFRGEALASISHVAHVTITTKTADGKCAYRASYSDGK... | [
{
"source_db": "ClinVar",
"source_id": "MLH1",
"text": "NM_000249.4(MLH1):c.1658_1661del (p.Thr553fs) VARIANT_IN_GENE MLH1",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0005524",
"text": "MLH1 GENE_ANNOTATED_WITH_GO_TERM ATP binding",
"confidence": 0.6
},
{
"... | {
"variant": "NM_000249.4(MLH1):c.1658_1661del (p.Thr553fs)",
"pathway": "Prolactin receptor signaling"
} | 0.774597 |
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