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Gene FBXW7
Variant R479Q
Impact List missense
Protein Effect loss of function
Gene Variant Descriptions FBXW7 R479Q lies within WD repeat 3 of the Fbxw7 protein (UniProt.org). R479Q confers a loss of FBXW7-substrate interation and impairs substrate degradation by FBXW7, resulting in sustained Notch1 intracellular domain and Myc expression (PMID: 17646409, PMID: 25450649), and aberrant subcellular nuclear localization and loss of Notch1 intracellular domain binding in culture (PMID: 30510140).
Associated Drug Resistance

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Transcript NM_033632
gDNA chr4:g.152326214C>T
cDNA c.1436G>A
Protein p.R479Q
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
XM_011532084 chr4:g.152326214C>T c.1436G>A p.R479Q RefSeq GRCh38/hg38
XM_011532085 chr4:g.152326214C>T c.1436G>A p.R479Q RefSeq GRCh38/hg38
NM_033632 chr4:g.152326214C>T c.1436G>A p.R479Q RefSeq GRCh38/hg38
XM_011532083 chr4:g.152326214C>T c.1436G>A p.R479Q RefSeq GRCh38/hg38
XM_017008362 chr4:g.152326214C>T c.1436G>A p.R479Q RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
FBXW7 R479Q T-cell adult acute lymphocytic leukemia resistant MRK-003 Preclinical Actionable In a preclinical study, FBXW7 R479Q conferred resistance to gamma secretase inhibitor, MRK-003, by activation of the NOTCH pathway and stablization of MYC as demonstrated in T cell acute lymphoblastic leukemia (T-ALL) cell lines (PMID: 17646409). 17646409
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
FBXW7 inact mut Advanced Solid Tumor sensitive Entinostat Preclinical Actionable In a preclinical study, entinostat (MS-275) inhibited cancer cells from advanced solid tumors and hematological cells harboring FBXW7 inactivating mutations in culture (PMID: 23274910). 23274910
FBXW7 inact mut hematologic cancer sensitive AR-42 Preclinical Actionable In a preclinical study, AR-42 inhibited human hematologic cancer cell lines harboring FBXW7 inactivating mutations in culture (PMID: 23274910). 23274910
FBXW7 inact mut hematologic cancer sensitive Entinostat Preclinical Actionable In a preclinical study, entinostat (MS-275) inhibited cancer cells from advanced solid tumors and hematological cells harboring FBXW7 inactivating mutations in culture (PMID: 23274910). 23274910
FBXW7 inact mut Advanced Solid Tumor resistant Docetaxel Preclinical Actionable In a preclinical study, human cancer cell lines harboring FBXW7 inactivating mutations were resistant to docetaxel in culture (PMID: 23274910). 23274910
FBXW7 inact mut Advanced Solid Tumor sensitive AR-42 Preclinical Actionable In a preclinical study, AR-42 inhibited human cancer cell lines harboring FBXW7 inactivating mutations in culture (PMID: 23274910). 23274910
FBXW7 inact mut hematologic cancer sensitive Belinostat Preclinical Actionable In a preclinical study, Beleodaq (belinostat) inhibited human hematologic cancer cell lines harboring FBXW7 inactivating mutations in culture (PMID: 23274910). 23274910
FBXW7 inact mut breast cancer sensitive Sirolimus Preclinical - Cell line xenograft Actionable In a preclinical study, breast cancer cells harboring a FBXW7 mutation demonstrated sensitivity to Rapamune (sirolimus) in culture and in cell line xenograft models (PMID: 18787170). 18787170
FBXW7 inact mut Advanced Solid Tumor sensitive Belinostat Preclinical Actionable In a preclinical study, Beleodaq (belinostat) inhibited human cancer cell lines harboring FBXW7 inactivating mutations in culture (PMID: 23274910). 23274910
FBXW7 mutant Her2-receptor negative breast cancer predicted - sensitive LY3039478 Phase I Actionable In a Phase I trial, LY3039478 treatment resulted in partial response lasted 9.5 months in a patient with hormone receptor-positive, Erbb2 (Her2)-negative breast cancer harboring FBXW7 mutation (PMID: 30060061; NCT01695005). 30060061
Molecular Profile Protein Effect Treatment Approaches
FBXW7 R479Q loss of function mTORC1 Inhibitor