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Gene | ALK |
Variant | F1174C |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | ALK F1174C lies within the protein kinase domain of the Alk protein (UniProt.org). F1174C confers a gain of function to Alk, as indicated by constitutive Alk phosphorylation in cell culture (PMID: 24509625, PMID: 22072639). |
Associated Drug Resistance | |
Category Variants Paths |
ALK mutant ALK act mut ALK F1174C ALK mutant ALK F1174X ALK F1174C |
Transcript | NM_004304.5 |
gDNA | chr2:g.29220830A>C |
cDNA | c.3521T>G |
Protein | p.F1174C |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_004304 | chr2:g.29220830A>C | c.3521T>G | p.F1174C | RefSeq | GRCh38/hg38 |
NM_004304.4 | chr2:g.29220830A>C | c.3521T>G | p.F1174C | RefSeq | GRCh38/hg38 |
NM_004304.5 | chr2:g.29220830A>C | c.3521T>G | p.F1174C | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
ALK F1174C | neuroblastoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a Phase I trial, Lorbrena (lorlatinib) treatment resulted in a partial response in a neuroblastoma patient harboring ALK F1174C, along with CDKN2A A102V (PMID: 37147298; NCT03107988). | 37147298 |
ALK F1174C | Advanced Solid Tumor | predicted - sensitive | TPX-0131 | Preclinical - Biochemical | Actionable | In a preclinical study, TPX-0131 inhibited kinase activity of ALK F1174C in an in vitro assay (PMID: 34158340). | 34158340 |
ALK F1174C | neuroblastoma | predicted - sensitive | Cyclophosphamide + Doxorubicin + Lorlatinib + Vincristine Sulfate | Preclinical - Pdx | Actionable | In a preclinical study, the combination of Lorbrena (lorlatinib), Cytoxan (cyclophosphamide), Adriamycin (doxorubicin), and Oncovin (vincristine) resulted in modest inhibition of tumor growth in a patient-derived xenograft (PDX) model of neuroblastoma harboring ALK F1174C (PMID: 36602782). | 36602782 |