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Gene | FBXW7 |
Variant | R479H |
Impact List | missense |
Protein Effect | loss of function |
Gene Variant Descriptions | FBXW7 R479H lies within the WD repeat domain of the Fbxw7 protein (UniProt.org). R479H confers a loss of FBXW7-substrate interaction and impairs substrate degradation by FBXW7, resulting in activation of a Notch-driven reporter (PMID: 17575125). |
Associated Drug Resistance | |
Category Variants Paths |
FBXW7 mutant FBXW7 inact mut FBXW7 R479H |
Transcript | NM_033632.3 |
gDNA | chr4:g.152326213_152326214delGAinsAT |
cDNA | c.1436_1437delGAinsAT |
Protein | p.R479H |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
XM_011532083 | chr4:g.152326213_152326214delTCinsAT | c.1436_1437delGAinsAT | p.R479H | RefSeq | GRCh38/hg38 |
XM_024454123.1 | chr4:g.152326213_152326214delGAinsAT | c.1436_1437delGAinsAT | p.R479H | RefSeq | GRCh38/hg38 |
XM_047415900.1 | chr4:g.152326213_152326214delGAinsAT | c.1436_1437delGAinsAT | p.R479H | RefSeq | GRCh38/hg38 |
XM_047415897.1 | chr4:g.152326213_152326214delGAinsAT | c.1436_1437delGAinsAT | p.R479H | RefSeq | GRCh38/hg38 |
XM_017008362 | chr4:g.152326213_152326214delTCinsAT | c.1436_1437delGAinsAT | p.R479H | RefSeq | GRCh38/hg38 |
XM_047415898.1 | chr4:g.152326213_152326214delGAinsAT | c.1436_1437delGAinsAT | p.R479H | RefSeq | GRCh38/hg38 |
XM_011532085.2 | chr4:g.152326213_152326214delGAinsAT | c.1436_1437delGAinsAT | p.R479H | RefSeq | GRCh38/hg38 |
XM_047415901.1 | chr4:g.152326213_152326214delGAinsAT | c.1436_1437delGAinsAT | p.R479H | RefSeq | GRCh38/hg38 |
NM_001349798.1 | chr4:g.152326213_152326214delGAinsAT | c.1436_1437delGAinsAT | p.R479H | RefSeq | GRCh38/hg38 |
NM_033632.3 | chr4:g.152326213_152326214delGAinsAT | c.1436_1437delGAinsAT | p.R479H | RefSeq | GRCh38/hg38 |
XM_011532085.3 | chr4:g.152326213_152326214delGAinsAT | c.1436_1437delGAinsAT | p.R479H | RefSeq | GRCh38/hg38 |
XM_011532085 | chr4:g.152326213_152326214delTCinsAT | c.1436_1437delGAinsAT | p.R479H | RefSeq | GRCh38/hg38 |
XM_024454123.2 | chr4:g.152326213_152326214delGAinsAT | c.1436_1437delGAinsAT | p.R479H | RefSeq | GRCh38/hg38 |
XM_047415899.1 | chr4:g.152326213_152326214delGAinsAT | c.1436_1437delGAinsAT | p.R479H | RefSeq | GRCh38/hg38 |
XM_011532084.2 | chr4:g.152326213_152326214delGAinsAT | c.1436_1437delGAinsAT | p.R479H | RefSeq | GRCh38/hg38 |
NM_033632.3 | chr4:g.152326213_152326214delGAinsAT | c.1436_1437delGAinsAT | p.R479H | RefSeq | GRCh38/hg38 |
XM_024454122.1 | chr4:g.152326213_152326214delGAinsAT | c.1436_1437delGAinsAT | p.R479H | RefSeq | GRCh38/hg38 |
XM_011532084 | chr4:g.152326213_152326214delTCinsAT | c.1436_1437delGAinsAT | p.R479H | RefSeq | GRCh38/hg38 |
XM_024454124.1 | chr4:g.152326213_152326214delGAinsAT | c.1436_1437delGAinsAT | p.R479H | RefSeq | GRCh38/hg38 |
XM_024454121.1 | chr4:g.152326213_152326214delGAinsAT | c.1436_1437delGAinsAT | p.R479H | RefSeq | GRCh38/hg38 |
NM_033632 | chr4:g.152326213_152326214delTCinsAT | c.1436_1437delGAinsAT | p.R479H | RefSeq | GRCh38/hg38 |
XM_011532084.3 | chr4:g.152326213_152326214delGAinsAT | c.1436_1437delGAinsAT | p.R479H | RefSeq | GRCh38/hg38 |
NM_001349798.2 | chr4:g.152326213_152326214delGAinsAT | c.1436_1437delGAinsAT | p.R479H | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
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 | 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 | 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 | 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 | 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 | 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 | 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 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 |