Missing content? – Request curation!
Request curation for specific Genes, Variants, or PubMed publications.
Have questions, comments, or suggestions? - Let us know!
Email us at : ckbsupport@genomenon.com
Gene | ALK |
Variant | R1275Q |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | ALK R1275Q lies within the protein kinase domain of the Alk protein (UniProt.org). R1275Q confers a gain of function to the Alk protein as demonstrated by transformation activity in cell culture and increased downstream signalling in in vitro assays (PMID: 21838707, PMID: 29533785). |
Associated Drug Resistance | |
Category Variants Paths |
ALK mutant ALK act mut ALK R1275Q ALK mutant ALK R1275X ALK R1275Q |
Transcript | NM_004304.5 |
gDNA | chr2:g.29209798C>T |
cDNA | c.3824G>A |
Protein | p.R1275Q |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_004304.5 | chr2:g.29209798C>T | c.3824G>A | p.R1275Q | RefSeq | GRCh38/hg38 |
NM_004304.4 | chr2:g.29209798C>T | c.3824G>A | p.R1275Q | RefSeq | GRCh38/hg38 |
NM_004304 | chr2:g.29209798C>T | c.3824G>A | p.R1275Q | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
ALK R1275Q TP53 wild-type | neuroblastoma | sensitive | Idasanutlin + TAE684 | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of TAE684 and Idasanutlin (RG7388) inhibited growth of a TP53 wild-type neuroblastoma cell line harboring ALK R1275Q in culture (PMID: 36602782). | 36602782 |
ALK R1275Q TP53 wild-type | neuroblastoma | sensitive | Alectinib + Idasanutlin | Preclinical - Cell culture | Actionable | In a preclinical study, Alecensa (alectinib) and Idasanutlin (RG7388) synergistically inhibited growth of a TP53 wild-type neuroblastoma cell line harboring ALK R1275Q in culture (PMID: 36602782). | 36602782 |
ALK R1275Q TP53 wild-type | neuroblastoma | sensitive | Ceritinib + CGM097 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of Zykadia (ceritinib) and CGM097 inhibited Alk signaling and resulted in synergistic inhibition of proliferation in a TP53 wild-type neuroblastoma cell line harboring ALK R1275Q in culture and induced tumor regression in a cell line xenograft model (PMID: 28425916). | 28425916 |
ALK F1174L ALK R1275Q | 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, and a patient harboring both ALK F1174L and ALK R1275Q stayed on treatment for 3 cycles until disease progression (PMID: 33568345; NCT00939770). | 33568345 |
EML4 - ALK ALK R1275Q | Advanced Solid Tumor | sensitive | TQ-B3139 | Preclinical - Cell culture | Actionable | In a preclinical study, TQ-B3139 (CT-711) inhibited proliferation of cells expressing EML4-ALK with ALK R1275Q in culture (PMID: 30210922). | 30210922 |
EML4 - ALK ALK R1275Q | Advanced Solid Tumor | sensitive | APG-2449 | Preclinical - Cell culture | Actionable | In a preclinical study, APG-2449 inhibited proliferation of cells expressing EML4-ALK with ALK R1275Q in culture (PMID: 35820889). | 35820889 |
ALK G1202R ALK R1275Q | neuroblastoma | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, a neuroblastoma cell line harboring ALK R1275Q and expressing G1202R was resistant to Lorbrena (lorlatinib) in culture (PMID: 37147298). | 37147298 |
ALK L1196M ALK R1275Q | neuroblastoma | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, a neuroblastoma cell line harboring ALK R1275Q and expressing L1196M was resistant to Lorbrena (lorlatinib) in culture (PMID: 37147298). | 37147298 |
ALK G1202R ALK R1275Q BRAF V600E | neuroblastoma | predicted - resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a Phase I trial, a neuroblastoma patient harboring ALK R1275Q developed progressive disease on treatment with Lorbrena (lorlatinib) and was found to have acquired ALK G1202R and BRAF V600E via circulating tumor DNA (PMID: 37147298; NCT03107988). | 37147298 |