Gene Variant Detail

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Gene ALK
Variant F1245V
Impact List missense
Protein Effect gain of function
Gene Variant Descriptions ALK F1245V lies within the protein kinase domain of the Alk protein (UniProt.org). F1245V confers a gain of function to the Alk protein, as it results in increased Alk kinase activity in vitro and leads to transformation activity in cell culture (PMID: 25517749, PMID: 33674381, PMID: 25517749).
Associated Drug Resistance

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Transcript NM_004304.4
gDNA chr2:g.29213994A>C
cDNA c.3733T>G
Protein p.F1245V
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_004304 chr2:g.29213994A>C c.3733T>G p.F1245V RefSeq GRCh38/hg38
NM_004304.4 chr2:g.29213994A>C c.3733T>G p.F1245V RefSeq GRCh38/hg38

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
ALK F1245V neuroblastoma predicted - sensitive Entrectinib Case Reports/Case Series Actionable In a clinical study, combined analysis of 2 Phase I trials showed Rozlytrek (entrectinib) treatment to result in a partial response that lasted 8.3 months in a patient with neuroblastoma harboring ALK F1245V, who remained on treatment for over 3.5 years due to clinical benefit (PMID: 28183697). 28183697
EML4 - ALK ALK F1245V Advanced Solid Tumor sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1245V in culture (PMID: 33627640). 33627640
EML4 - ALK ALK F1245V Advanced Solid Tumor resistant Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1245V were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK F1245V Advanced Solid Tumor sensitive Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1245V in culture (PMID: 33627640). 33627640
EML4 - ALK ALK F1245V Advanced Solid Tumor sensitive Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1245V in culture (PMID: 33627640). 33627640
EML4 - ALK ALK F1245V Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1245V in culture (PMID: 33627640). 33627640
EML4 - ALK ALK F1245V Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1245V in culture (PMID: 33627640). 33627640
EML4 - ALK ALK F1245V Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1245V in culture (PMID: 33627640). 33627640
EML4 - ALK ALK D1203N ALK F1245V Advanced Solid Tumor resistant Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK D1203N and F1245V were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK D1203N ALK F1245V Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK D1203N and F1245V in culture (PMID: 33627640). 33627640
EML4 - ALK ALK D1203N ALK F1245V Advanced Solid Tumor predicted - resistant Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK D1203N and F1245V demonstrated resistance to treatment with Xospata (gilteritinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK D1203N ALK F1245V Advanced Solid Tumor predicted - resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK D1203N and F1245V demonstrated resistance to treatment with Zykadia (ceritinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK D1203N ALK F1245V Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK D1203N and F1245V were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK D1203N ALK F1245V Advanced Solid Tumor sensitive Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) inhibited viability of transformed cells expressing EML4-ALK with ALK D1203N and F1245V in culture (PMID: 33627640). 33627640
EML4 - ALK ALK D1203N ALK F1245V Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK D1203N and F1245V in culture (PMID: 33627640). 33627640
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
ALK mutant lung non-small cell carcinoma no benefit Crizotinib + Onalespib Phase II Actionable In a Phase II trial, Onalespib (AT13387) and Xalkori (crizotinib) combination treatment did not significantly improve median progression free survival (269 vs 266 days) or objective response rate (55.4%, 38/68 vs 45.3%, 31/68) compared to Xalkori (crizotinib) single treatment in patients with non-small cell lung carcinoma harboring either an ALK mutation or ALK rearrangement (J Clin Oncol 34, 2016 (suppl; abstr 9059); NCT01712217). detail...
ALK mutant lung non-small cell carcinoma no benefit Belizatinib Phase I Actionable In a Phase I trial, treatment with Belizatinib (TSR-011) in ALK inhibitor-naive non-small cell lung cancer patients (n=14) harboring either an ALK mutation, ALK amplification, or an ALK rearrangement resulted in a partial response in 6 patients and stable disease in 8 patients, however, it was determined that the drug resulted in limited efficacy and development of the drug was discontinued (PMID: 31217479; NCT02048488). 31217479
Molecular Profile Protein Effect Treatment Approaches
ALK F1245V gain of function ALK Inhibitor
EML4 - ALK ALK F1245V
EML4 - ALK ALK D1203N ALK F1245V