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@jax.org
Gene | ALK |
Variant | F1174I |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | ALK F1174I lies within the protein kinase domain of the Alk protein (UniProt.org). F1174I results in ligand-independent phosphorylation of the Alk protein, activation of Erk, Stat3 pathways, and is transforming in cell culture (PMID: 23104988). |
Associated Drug Resistance | |
Category Variants Paths |
ALK mutant ALK act mut ALK F1174I ALK mutant ALK F1174X ALK F1174I |
Transcript | NM_004304.5 |
gDNA | chr2:g.29220831A>T |
cDNA | c.3520T>A |
Protein | p.F1174I |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_004304 | chr2:g.29220831A>T | c.3520T>A | p.F1174I | RefSeq | GRCh38/hg38 |
NM_004304.5 | chr2:g.29220831A>T | c.3520T>A | p.F1174I | RefSeq | GRCh38/hg38 |
NM_004304.4 | chr2:g.29220831A>T | c.3520T>A | p.F1174I | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
EML4 - ALK ALK C1156Y ALK F1174I | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, ALK F1174I was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). | 29650534 |
EML4 - ALK ALK I1171N ALK F1174I | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and F1174I were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK F1174I | Advanced Solid Tumor | resistant | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and F1174I were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK F1174I | Advanced Solid Tumor | resistant | Ceritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and F1174I were resistant to treatment with Zykadia (ceritinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK F1174I | Advanced Solid Tumor | resistant | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and F1174I were resistant to treatment with Alunbrig (brigatinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK F1174I | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and F1174I were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK F1174I | Advanced Solid Tumor | resistant | Entrectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and F1174I were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK F1174I | 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 I1171N and F1174I in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK F1174I | lung non-small cell carcinoma | predicted - resistant | Lorlatinib | Preclinical - Pdx | Actionable | In a preclinical study, Lorbrena (lorlatinib) failed to inhibit tumor growth in a patient-derived xenograft (PDX) model of non-small cell lung cancer harboring EML4-ALK and expressing ALK I1171N and F1174I (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK F1174I | lung non-small cell carcinoma | predicted - resistant | Alectinib | Preclinical - Pdx | Actionable | In a preclinical study, Alecensa (alectinib) failed to inhibit tumor growth in a patient-derived xenograft (PDX) model of non-small cell lung cancer harboring EML4-ALK and expressing ALK I1171N and F1174I (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK F1174I | lung non-small cell carcinoma | sensitive | Gilteritinib | Preclinical - Pdx | Actionable | In a preclinical study, Xospata (gilteritinib) induced complete tumor regression in a patient-derived xenograft (PDX) model of non-small cell lung cancer harboring EML4-ALK and expressing ALK I1171N and F1174I, and also induced tumor regression when administered to separate PDX tumors which had demonstrated resistance to Alecensa (alectinib) or Lorbrena (lorlatinib) treatment (PMID: 33627640). | 33627640 |
EML4 - ALK ALK F1174I | Advanced Solid Tumor | predicted - resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174I demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK F1174I | 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 F1174I in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK F1174I | 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 F1174I in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK F1174I | 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 F1174I in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK F1174I | 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 F1174I in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK F1174I | 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 F1174I in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK F1174I | Advanced Solid Tumor | resistant | Entrectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174I were resistant to Rozlytrek (entrectinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK F1174I ALK G1202R | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and F1174I were resistant to Lorbrena (lorlatinib) in culture (PMID: 36201110). | 36201110 |
EML4 - ALK ALK F1174I ALK G1202R | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and F1174I were resistant to Xalkori (crizotinib) in culture (PMID: 36201110). | 36201110 |
EML4 - ALK ALK F1174I ALK G1202R | Advanced Solid Tumor | resistant | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and F1174I were resistant to Alecensa (alectinib) in culture (PMID: 36201110). | 36201110 |
EML4 - ALK ALK F1174I ALK G1202R | Advanced Solid Tumor | resistant | TPX-0131 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and F1174I were resistant to TPX-0131 in culture (PMID: 36201110). | 36201110 |
EML4 - ALK ALK F1174I ALK G1202R | Advanced Solid Tumor | resistant | Gilteritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and F1174I were resistant to Xospata (gilteritinib) in culture (PMID: 36201110). | 36201110 |