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Gene | ALK |
Variant | C1237Y |
Impact List | missense |
Protein Effect | gain of function - predicted |
Gene Variant Descriptions | ALK C1237Y lies within the protein kinase domain of the Alk protein (UniProt.org). C1237Y results in both increased phosphorylation of Alk and proliferation, and has been demonstrated to confer resistance to Alk inhibitors in the context of EML4-ALK in culture (PMID: 38448512), 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 C1237Y |
Transcript | NM_004304.5 |
gDNA | chr2:g.29214017C>T |
cDNA | c.3710G>A |
Protein | p.C1237Y |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_004304.5 | chr2:g.29214017C>T | c.3710G>A | p.C1237Y | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
EML4 - ALK ALK C1237Y | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing EML4-ALK and ALK C1237Y were resistant to Xalcori (crizotinib) in culture (PMID: 38448512). | 38448512 |
EML4 - ALK ALK C1237Y | Advanced Solid Tumor | resistant | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing EML4-ALK and ALK C1237Y were resistant to Alunbrig (brigatinib) in culture (PMID: 38448512). | 38448512 |
EML4 - ALK ALK C1237Y | Advanced Solid Tumor | resistant | Ceritinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing EML4-ALK and ALK C1237Y were resistant to Zykadia (ceritinib) in culture (PMID: 38448512). | 38448512 |
EML4 - ALK ALK C1237Y | Advanced Solid Tumor | resistant | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing EML4-ALK and ALK C1237Y were resistant to Alecensa (alectinib) in culture (PMID: 38448512). | 38448512 |
EML4 - ALK ALK C1237Y | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing EML4-ALK and ALK C1237Y were resistant to Lorbrena (lorlatinib) in culture (PMID: 38448512). | 38448512 |
EML4 - ALK ALK C1237Y | Advanced Solid Tumor | resistant | TPX-0131 | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing EML4-ALK and ALK C1237Y were resistant to TPX-0131 in culture (PMID: 38448512). | 38448512 |
EML4 - ALK ALK C1237Y | Advanced Solid Tumor | resistant | Repotrectinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing EML4-ALK and ALK C1237Y were resistant to Augtyro (repotrectinib) in culture (PMID: 38448512). | 38448512 |
EML4 - ALK ALK C1235R ALK C1237Y | lung non-small cell carcinoma | predicted - resistant | Brigatinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with relapsed non-small cell lung cancer harboring EML4-ALK developed progressive disease while on treatment with Alunbrig (brigatinib), and was found to have acquired ALK C1235R and ALK C1237Y in trans by liquid biopsy (PMID: 38448512). | 38448512 |