Gene Variant Detail

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Gene FBXW7
Variant W425R
Impact List missense
Protein Effect loss of function
Gene Variant Descriptions FBXW7 W425R lies within WD repeat 2 of the Fbxw7 protein (UniProt.org). W425R results in degradation of Mcl1, but confers a loss of function to the Fbxw7 protein as demonstrated by impaired degradation of cyclin E, c-Myc, and Braf in cultured cells (PMID: 32907612) and leads to dimerization with wild-type Fbxw7 in cultured cells, thereby preventing degradation of NICD and potentially resulting in increased Notch signaling (PMID: 27247421), and confers resistance to some BET inhibitors in cultured cells (PMID: 32907612).
Associated Drug Resistance Y

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Transcript NM_033632.3
gDNA chr4:g.152328353A>T
cDNA c.1273T>A
Protein p.W425R
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
XM_024454121.1 chr4:g.152328353A>T c.1273T>A p.W425R RefSeq GRCh38/hg38
XM_024454124.1 chr4:g.152328353A>T c.1273T>A p.W425R RefSeq GRCh38/hg38
XM_011532085.2 chr4:g.152328353A>T c.1273T>A p.W425R RefSeq GRCh38/hg38
NM_033632.3 chr4:g.152328353A>T c.1273T>A p.W425R RefSeq GRCh38/hg38
XM_024454123.1 chr4:g.152328353A>T c.1273T>A p.W425R RefSeq GRCh38/hg38
NM_001349798.1 chr4:g.152328353A>T c.1273T>A p.W425R RefSeq GRCh38/hg38
XM_024454122.1 chr4:g.152328353A>T c.1273T>A p.W425R RefSeq GRCh38/hg38
XM_011532084.2 chr4:g.152328353A>T c.1273T>A p.W425R RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
FBXW7 W425R adult T-cell leukemia resistant Birabresib Preclinical - Cell culture Actionable In a preclinical study, adult T cell leukemia cells expressing FBXW7 W425R demonstrated resistance to treatment with Birabresib (OTX015) in culture (PMID: 32907612). 32907612
FBXW7 W425R adult T-cell leukemia resistant JQ1 Preclinical - Cell culture Actionable In a preclinical study, adult T cell leukemia cells expressing FBXW7 W425R demonstrated resistance to treatment with JQ1 in culture (PMID: 32907612). 32907612
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
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 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 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 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 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 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 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 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 W425R loss of function mTORC1 Inhibitor