FBXW7 W425R
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
Category Variants Paths

FBXW7 mutant FBXW7 inact mut FBXW7 W425R

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Transcript NM_001349798.2
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_047415900.1 chr4:g.152328353A>T c.1273T>A p.W425R RefSeq GRCh38/hg38
XM_024454121.1 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
XM_024454122.1 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_047415898.1 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
XM_047415899.1 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_047415901.1 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_011532085.3 chr4:g.152328353A>T c.1273T>A p.W425R RefSeq GRCh38/hg38
XM_024454123.2 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_011532084.3 chr4:g.152328353A>T c.1273T>A p.W425R RefSeq GRCh38/hg38
XM_047415897.1 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_001349798.2 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 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 endometrial cancer predicted - sensitive RP-3500 + RP-6306 Phase I Actionable In a Phase I trial (MYTHIC), treatment with the combination of RP-6306 and RP-3500 in ovarian or endometrial cancer patients harboring CCNE1 amplification, FBXW7 mutations, and/or PPP2R1A mutations resulted in a clinical benefit rate (CBR) of 79%, a median progression-free survival (mPFS) of 21 weeks, and a response rate of 38% in ovarian cancer (n=24), and a CBR of 48%, mPFS of 17 weeks, and a response rate of 26% in endometrial cancer (n=27) (Cancer Res (2025) 85 (8_Supplement_2): CT262; NCT04855656). detail...
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 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 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 REC-2282 Preclinical Actionable In a preclinical study, REC-2282 (AR-42) inhibited human hematologic 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 Advanced Solid Tumor sensitive REC-2282 Preclinical Actionable In a preclinical study, REC-2282 (AR-42) inhibited human cancer cell lines harboring FBXW7 inactivating mutations in culture (PMID: 23274910). 23274910
FBXW7 mutant Her2-receptor negative breast cancer predicted - sensitive LY3039478 Case Reports/Case Series 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