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Gene | ALK |
Variant | V1180L |
Impact List | missense |
Protein Effect | unknown |
Gene Variant Descriptions | ALK V1180L lies within the protein kinase domain of the Alk protein (UniProt.org). V1180L has been demonstrated to occur as a secondary resistance mutation in the context of EML4-ALK (PMID: 25228534, PMID: 27432227, PMID: 35324529), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Aug 2024). |
Associated Drug Resistance | Y |
Category Variants Paths |
ALK mutant ALK V1180X ALK V1180L |
Transcript | NM_004304.5 |
gDNA | chr2:g.29220813C>G |
cDNA | c.3538G>C |
Protein | p.V1180L |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_004304 | chr2:g.29220813C>G | c.3538G>C | p.V1180L | RefSeq | GRCh38/hg38 |
NM_004304.4 | chr2:g.29220813C>G | c.3538G>C | p.V1180L | RefSeq | GRCh38/hg38 |
NM_004304.5 | chr2:g.29220813C>G | c.3538G>C | p.V1180L | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
ALK V1180L | lung non-small cell carcinoma | predicted - sensitive | Brigatinib | Case Reports/Case Series | Actionable | In a Phase II trial (ALTA-2), Alunbrig (brigatinib) therapy resulted in a partial response, with a progression-free survival of 11 months, in a patient with advanced non-small cell lung cancer harboring ALK V1180L who previously progressed on Alecensa (alectinib) therapy (PMID: 36096442; NCT05421936). | 36096442 |
ALK V1180L | Advanced Solid Tumor | predicted - sensitive | TPX-0131 | Preclinical - Biochemical | Actionable | In a preclinical study, TPX-0131 inhibited kinase activity of ALK V1180L in an in vitro assay (PMID: 34158340). | 34158340 |