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Gene | ALK |
Variant | I1171N |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | ALK I1171N lies within the protein kinase domain of the Alk protein (UniProt.org). I1171N results in increased ligand-independent Alk phosphorylation and activation of the Stat pathway in culture (PMID: 23239810, PMID: 21838707), activation in in vitro assays (PMID: 33674381, PMID: 25517749), is transforming in cell culture (PMID: 23239810, (PMID: 33674381, PMID: 25517749), and has been demonstrated to occur as a secondary resistance mutation in the context of ALK fusions (PMID: 27565911). |
Associated Drug Resistance | Y |
Category Variants Paths |
ALK mutant ALK act mut ALK I1171N ALK mutant ALK I1171X ALK I1171N |
Transcript | NM_004304.5 |
gDNA | chr2:g.29222347A>T |
cDNA | c.3512T>A |
Protein | p.I1171N |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_004304.4 | chr2:g.29222347A>T | c.3512T>A | p.I1171N | RefSeq | GRCh38/hg38 |
NM_004304.5 | chr2:g.29222347A>T | c.3512T>A | p.I1171N | RefSeq | GRCh38/hg38 |
NM_004304 | chr2:g.29222347A>T | c.3512T>A | p.I1171N | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
ALK I1171N | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, a transformed cell line expressing ALK I1171N was sensitive to Alunbrig (brigatinib) in culture, resulting in cell growth inhibition (PMID: 27049722). | 27049722 |
ALK I1171N | 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 I1171N in culture (PMID: 31852910). | 31852910 |
ALK I1171N | Advanced Solid Tumor | decreased response | TPX-0131 | Preclinical - Biochemical | Actionable | In a preclinical study, ALK I1171N demonstrated reduced sensitivity to TPX-0131 in an in vitro kinase assay (PMID: 34158340). | 34158340 |