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ALK G1123S - Gene Variant Detail

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Gene ALK
Variant G1123S
Impact List missense
Protein Effect unknown
Gene Variant Descriptions ALK G1123S lies within the protein kinase domain of the Alk protein (UniProt.org). G1123S has been demonstrated to confer drug resistance in culture (PMID: 26134233, PMID: 21948233), 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 G1123S

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Transcript NM_004304.5
gDNA chr2:g.29222600C>T
cDNA c.3367G>A
Protein p.G1123S
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_004304 chr2:g.29222600C>T c.3367G>A p.G1123S RefSeq GRCh38/hg38
NM_004304.5 chr2:g.29222600C>T c.3367G>A p.G1123S RefSeq GRCh38/hg38
NM_004304.4 chr2:g.29222600C>T c.3367G>A p.G1123S RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
ALK rearrange ALK G1123S lung adenocarcinoma predicted - resistant Ceritinib Case Reports/Case Series Actionable In a clinical case study, ALK G1123S was identified as an acquired mutation in a patient with ALK-rearranged lung adenocarcinoma whose disease relapsed 2 years after initial response to Zykadia (ceritinib) (PMID: 26134233). 26134233
ALK rearrange ALK G1123S lung adenocarcinoma predicted - sensitive Alectinib Case Reports/Case Series Actionable In a clinical case study, Alecensa (alectinib) treatment resulted in rapid response in a patient with ALK-rearranged lung adenocarcinoma with an acquired ALK G1123S mutation, whose disease had relapsed 2 years after initial response to Zykadia (ceritinib) (PMID: 26134233). 26134233
ALK G1123S ALK F1174L neuroblastoma resistant TAE684 Preclinical - Cell culture Actionable In a preclinical study, expression of ALK G1123S in neuroblastoma cells harboring an ALK F1174L mutation resulted in resistance to TAE684 in culture (PMID: 21948233). 21948233
EML4 - ALK ALK G1123S Advanced Solid Tumor sensitive Ensartinib Preclinical - Cell culture Actionable In a preclinical study, Ensacove (ensartinib) inhibited viability of a cell line expressing EML4-ALK with ALK G1123S in culture (PMID: 31446141). 31446141
EML4 - ALK ALK G1123S Advanced Solid Tumor sensitive Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) inhibited viability of a cell line expressing EML4-ALK with ALK G1123S in culture (PMID: 31446141). 31446141
EML4 - ALK ALK G1123S Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, a cell line expressing EML4-ALK with ALK G1123S was resistant to Zykadia (ceritinib) in culture (PMID: 31446141). 31446141
EML4 - ALK ALK G1123S Advanced Solid Tumor sensitive Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) inhibited viability of a cell line expressing EML4-ALK with ALK G1123S in culture (PMID: 31446141). 31446141
EML4 - ALK ALK G1123S Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited viability of a cell line expressing EML4-ALK with ALK G1123S in culture (PMID: 31446141). 31446141
EML4 - ALK ALK G1123S Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorbrena (lorlatinib) inhibited viability of a cell line expressing EML4-ALK with ALK G1123S in culture (PMID: 31446141). 31446141