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| Gene | FBXW7 |
| Variant | K444fs |
| Impact List | frameshift |
| Protein Effect | loss of function - predicted |
| Gene Variant Descriptions | FBXW7 K444fs results in a change in the amino acid sequence of the Fbxw7 protein beginning at aa 444 of 707, likely resulting in premature truncation of the functional protein (UniProt.org). K444fs has not been characterized however, due to the effects of other truncation mutations downstream of K444 (PMID: 24838835), is predicted to lead to a loss of Fbxw7 protein function. |
| Associated Drug Resistance | |
| Category Variants Paths |
FBXW7 mutant FBXW7 inact mut FBXW7 K444fs |
| Transcript | NM_001349798.2 |
| gDNA | chr4:g.(152328296_152328297) |
| cDNA | c.(1330_1329) |
| Protein | p.K444fs |
| Source Database | RefSeq |
| Genome Build | GRCh38/hg38 |
| Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
|---|---|---|---|---|---|
| XM_011532085 | chr4:g.152328298_152328299insCCGGGGGGGGGGA | c.1329_1330insCCCCCCCCCGGTC | p.K444fs*32 | RefSeq | GRCh38/hg38 |
| XM_047415899.1 | chr4:g.(152328296_152328297) | c.(1330_1329) | p.K444fs | RefSeq | GRCh38/hg38 |
| XM_017008362 | chr4:g.152328298_152328299insCCGGGGGGGGGGA | c.1329_1330insCCCCCCCCCGGTC | p.K444fs*32 | RefSeq | GRCh38/hg38 |
| NM_018315 | chr4:g.152326081delT | c.1331delA | p.K444fs*32 | RefSeq | GRCh38/hg38 |
| XM_011532084 | chr4:g.152328298_152328299insCCGGGGGGGGGGA | c.1329_1330insCCCCCCCCCGGTC | p.K444fs*32 | RefSeq | GRCh38/hg38 |
| XM_024454125.1 | chr4:g.(152328212_152328213) | c.(1330_1329) | p.K444fs | RefSeq | GRCh38/hg38 |
| XM_011532085.2 | chr4:g.(152328296_152328297) | c.(1330_1329) | p.K444fs | RefSeq | GRCh38/hg38 |
| XM_011532084.3 | chr4:g.(152328296_152328297) | c.(1330_1329) | p.K444fs | RefSeq | GRCh38/hg38 |
| XM_024454123.2 | chr4:g.(152328296_152328297) | c.(1330_1329) | p.K444fs | RefSeq | GRCh38/hg38 |
| XM_047415901.1 | chr4:g.(152328296_152328297) | c.(1330_1329) | p.K444fs | RefSeq | GRCh38/hg38 |
| XM_011532087.2 | chr4:g.(152328212_152328213) | c.(1330_1329) | p.K444fs | RefSeq | GRCh38/hg38 |
| XM_011532085.3 | chr4:g.(152328296_152328297) | c.(1330_1329) | p.K444fs | RefSeq | GRCh38/hg38 |
| NM_001349798.1 | chr4:g.(152328296_152328297) | c.(1330_1329) | p.K444fs | RefSeq | GRCh38/hg38 |
| XM_024454122.1 | chr4:g.(152328296_152328297) | c.(1330_1329) | p.K444fs | RefSeq | GRCh38/hg38 |
| XM_011532086.2 | chr4:g.(152328212_152328213) | c.(1330_1329) | p.K444fs | RefSeq | GRCh38/hg38 |
| XM_047415897.1 | chr4:g.(152328296_152328297) | c.(1330_1329) | p.K444fs | RefSeq | GRCh38/hg38 |
| XM_011532084.2 | chr4:g.(152328296_152328297) | c.(1330_1329) | p.K444fs | RefSeq | GRCh38/hg38 |
| XM_011532086 | chr4:g.152328213_152328214insCGGGGGGGGGGGGGCAC | c.1328_1329insGTGCCCCCCCCCCCCCG | p.K444fs*32 | RefSeq | GRCh38/hg38 |
| XM_024454121.1 | chr4:g.(152328296_152328297) | c.(1330_1329) | p.K444fs | RefSeq | GRCh38/hg38 |
| XM_047415900.1 | chr4:g.(152328296_152328297) | c.(1330_1329) | p.K444fs | RefSeq | GRCh38/hg38 |
| XM_047415898.1 | chr4:g.(152328296_152328297) | c.(1330_1329) | p.K444fs | RefSeq | GRCh38/hg38 |
| XM_047415902.1 | chr4:g.(152328212_152328213) | c.(1330_1329) | p.K444fs | RefSeq | GRCh38/hg38 |
| NM_033632.3 | chr4:g.(152328296_152328297) | c.(1330_1329) | p.K444fs | RefSeq | GRCh38/hg38 |
| NM_001349798.2 | chr4:g.(152328296_152328297) | c.(1330_1329) | p.K444fs | RefSeq | GRCh38/hg38 |
| XM_011532083 | chr4:g.152328298_152328299insCCGGGGGGGGGGA | c.1329_1330insCCCCCCCCCGGTC | p.K444fs*32 | RefSeq | GRCh38/hg38 |
| XM_024454123.1 | chr4:g.(152328296_152328297) | c.(1330_1329) | p.K444fs | RefSeq | GRCh38/hg38 |
| XM_011532087 | chr4:g.152328213_152328214insCGGGGGGGGGGGGGCAC | c.1328_1329insGTGCCCCCCCCCCCCCG | p.K444fs*32 | RefSeq | GRCh38/hg38 |
| NM_018315.5 | chr4:g.(152326080_152326081) | c.(1330_1329) | p.K444fs | RefSeq | GRCh38/hg38 |
| XM_011532087.3 | chr4:g.(152328212_152328213) | c.(1330_1329) | p.K444fs | RefSeq | GRCh38/hg38 |
| NM_033632 | chr4:g.152328298_152328299insCCGGGGGGGGGGA | c.1329_1330insCCCCCCCCCGGTC | p.K444fs*32 | RefSeq | GRCh38/hg38 |
| XM_011532086.3 | chr4:g.(152328212_152328213) | c.(1330_1329) | p.K444fs | RefSeq | GRCh38/hg38 |
| NM_033632.3 | chr4:g.(152328296_152328297) | c.(1330_1329) | p.K444fs | RefSeq | GRCh38/hg38 |
| XM_024454124.1 | chr4:g.(152328296_152328297) | c.(1330_1329) | p.K444fs | RefSeq | GRCh38/hg38 |
| NM_018315.4 | chr4:g.(152326080_152326081) | c.(1330_1329) | p.K444fs | RefSeq | GRCh38/hg38 |
| 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 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 | 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 |