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Gene | ALK |
Variant | F1245C |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | ALK F1245C lies within the protein kinase domain of the Alk protein (UniProt.org). F1245C results in increased downstream signaling and is transforming in cell culture (PMID: 21838707, PMID: 25517749). |
Associated Drug Resistance | Y |
Category Variants Paths |
ALK mutant ALK act mut ALK F1245C ALK mutant ALK F1245X ALK F1245C |
Transcript | NM_004304.5 |
gDNA | chr2:g.29213993A>C |
cDNA | c.3734T>G |
Protein | p.F1245C |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_004304.4 | chr2:g.29213993A>C | c.3734T>G | p.F1245C | RefSeq | GRCh38/hg38 |
NM_004304 | chr2:g.29213993A>C | c.3734T>G | p.F1245C | RefSeq | GRCh38/hg38 |
NM_004304.5 | chr2:g.29213993A>C | c.3734T>G | p.F1245C | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
ALK F1245C | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, a transformed cell line expressing ALK F1245C was sensitive to Alunbrig (brigatinib) in culture, resulting in cell growth inhibition (PMID: 27049722). | 27049722 |
ALK F1245C | neuroblastoma | resistant | Crizotinib | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, Xalkori (crizotinib) did not inhibit growth of neuroblastoma cells over expressing ALK F1245C in culture, and only delayed tumor growth in patient-derived xenograft models harboring ALK F1245C (PMID: 26554404). | 26554404 |
ALK F1245C | neuroblastoma | sensitive | Lorlatinib | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited growth of neuroblastoma cells over expressing ALK F1245C in culture, and induced rapid and sustained complete tumor regression in patient-derived xenograft models harboring ALK F1245C (PMID: 26554404). | 26554404 |
ALK F1245C | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited foci formation more efficiently than Xalkori (crizotinib) in transformed cells overexpressing ALK F1245C in culture (PMID: 26554404). | 26554404 |
ALK F1245C | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) treatment inhibited Alk phosphorylation and viability in transformed cells expressing ALK F1245C in culture (PMID: 27483357). | 27483357 |
ALK F1245C | neuroblastoma | sensitive | Ceritinib + Ribociclib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of Zykadia (ceritinib) and Kisqali (ribociclib) inhibited proliferation in a neuroblastoma cell line harboring ALK F1245C in culture, and resulted in enhanced tumor growth inhibition compared to either Zykadia (ceritinib) or Kisqali (ribociclib) alone (P=0.04 and P<0.0001, respectively) and induced complete and sustained tumor regression in a patient-derived xenograft (PDX) model (PMID: 27986745). | 27986745 |
ALK F1245C | Advanced Solid Tumor | sensitive | Repotrectinib | Preclinical - Cell culture | Actionable | In a preclinical study, Augtyro (repotrectinib) decreased Alk phosphorylation and neurite outgrowth in cells expressing ALK F1245C in culture (PMID: 31852910). | 31852910 |
ALK F1245C | Advanced Solid Tumor | predicted - sensitive | TPX-0131 | Preclinical - Biochemical | Actionable | In a preclinical study, TPX-0131 inhibited kinase activity of ALK F1245C in an in vitro assay (PMID: 34158340). | 34158340 |