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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 |
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 |
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 | Protein Effect | Treatment Approaches |
---|---|---|
ALK F1245V | gain of function | ALK Inhibitor |
EML4 - ALK ALK F1245V | ||
EML4 - ALK ALK D1203N ALK F1245V |