Gene Variant Detail

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Gene ALK
Variant F1174V
Impact List missense
Protein Effect gain of function - predicted
Gene Variant Descriptions ALK F1174V lies within the protein kinase domain of the Alk protein (UniProt.org). F1174V results in constitutive activation of the Alk protein in cell culture (PMID: 21242967) and has been demonstrated to occur as a secondary resistance mutation in the context of ALK fusions (PMID: 24675041), and therefore, is predicted to lead to a gain of Alk protein function.
Associated Drug Resistance Y
Category Variants Paths

ALK mutant ALK act mut ALK F1174V

ALK mutant ALK F1174X ALK F1174V

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Transcript NM_004304.5
gDNA chr2:g.29220831A>C
cDNA c.3520T>G
Protein p.F1174V
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_004304 chr2:g.29220831A>C c.3520T>G p.F1174V RefSeq GRCh38/hg38
NM_004304.4 chr2:g.29220831A>C c.3520T>G p.F1174V RefSeq GRCh38/hg38
NM_004304.5 chr2:g.29220831A>C c.3520T>G p.F1174V RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
ALK F1174V neuroblastoma sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, neuroblastoma cells harboring ALK F1174V were sensitive to Alunbrig (brigatinib) in culture and in vivo, resulting in inhibition of both Alk activity and cell proliferation (PMID: 27049722). 27049722
ALK F1174V neuroblastoma predicted - sensitive Crizotinib Case Reports/Case Series Actionable In a Phase I/II trial (ADVL0912), Xalkori (crizotinib) treatment resulted in an objective response of 15% (3/20) in pediatric patients with relapsed/refractory neuroblastoma harboring ALK activating mutations or amplifications, a patient harboring ALK F1174V stayed on treatment for 3 cycles until disease progression (PMID: 33568345; NCT00939770). 33568345
ALK F1174V neuroblastoma predicted - resistant Repotrectinib Preclinical - Pdx Actionable In a preclinical study, a neuroblastoma patient-derived xenograft (PDX) model harboring ALK F1174V was resistant to treatment with Augtyro (repotrectinib) (PMID: 34482287). 34482287
ALK F1174V neuroblastoma predicted - sensitive Irinotecan + Repotrectinib + Temozolomide Preclinical - Pdx Actionable In a preclinical study, combination treatment with Augtyro (repotrectinib), Camptosar (irinotecan), and Temodar (temozolomide) resulted in inhibition of tumor growth in a patient-derived xenograft (PDX) model of neuroblastoma harboring ALK F1174V (PMID: 34482287). 34482287
ALK F1174V neuroblastoma sensitive Lorlatinib Case Reports/Case Series Actionable In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a complete response lasting greater than 20 months in a patient with neuroblastoma harboring ALK F1174V (PMID: 37561984). 37561984
ALK F1174V neuroblastoma sensitive Lorlatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Lorbrena (lorlatinib) treatment inhibited proliferation of a neuroblastoma cell line harboring ALK F1174V in culture and inhibited tumor growth in a cell line xenograft model (PMID: 27483357). 27483357
ALK F1174V neuroblastoma sensitive Entrectinib Preclinical - Cell culture Actionable In a preclinical study, Rozlytrek (entrectinib) treatment inhibited ALK phosphorylation, downstream signaling, and viability of a neuroblastoma cell line harboring ALK F1174V in culture (PMID: 35085006). 35085006