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Gene | FBXW7 |
Variant | S396fs |
Impact List | frameshift |
Protein Effect | loss of function - predicted |
Gene Variant Descriptions | FBXW7 S396fs results in a change in the amino acid sequence of the Fbxw7 protein beginning at aa 396 of 707, likely resulting in premature truncation of the functional protein (UniProt.org). S396fs results in increased expression and activity of Myc, Hif1a, and Notch1 compared to wild-type Fbxw7 in cell culture (PMID: 30510140), and therefore, is predicted to lead to a loss of Fbxw7 protein function. |
Associated Drug Resistance | |
Category Variants Paths |
FBXW7 mutant FBXW7 inact mut FBXW7 S396fs |
Transcript | NM_033632.3 |
gDNA | chr4:g.(152329722_152329723) |
cDNA | c.(1186_1185) |
Protein | p.S396fs |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_018315 | chr4:g.(152326224_152326225) | c.(1186_1185) | p.S396fs | RefSeq | GRCh38/hg38 |
XM_024454121.1 | chr4:g.(152329722_152329723) | c.(1186_1185) | p.S396fs | RefSeq | GRCh38/hg38 |
XM_024454123.2 | chr4:g.(152329722_152329723) | c.(1186_1185) | p.S396fs | RefSeq | GRCh38/hg38 |
NM_033632.3 | chr4:g.(152329722_152329723) | c.(1186_1185) | p.S396fs | RefSeq | GRCh38/hg38 |
NM_033632 | chr4:g.(152329722_152329723) | c.(1186_1185) | p.S396fs | RefSeq | GRCh38/hg38 |
XM_011532084.2 | chr4:g.(152329722_152329723) | c.(1186_1185) | p.S396fs | RefSeq | GRCh38/hg38 |
XM_047415900.1 | chr4:g.(152329722_152329723) | c.(1186_1185) | p.S396fs | RefSeq | GRCh38/hg38 |
XM_047415901.1 | chr4:g.(152329722_152329723) | c.(1186_1185) | p.S396fs | RefSeq | GRCh38/hg38 |
NM_018315.5 | chr4:g.(152326224_152326225) | c.(1186_1185) | p.S396fs | RefSeq | GRCh38/hg38 |
NM_001349798.2 | chr4:g.(152329722_152329723) | c.(1186_1185) | p.S396fs | RefSeq | GRCh38/hg38 |
XM_047415899.1 | chr4:g.(152329722_152329723) | c.(1186_1185) | p.S396fs | RefSeq | GRCh38/hg38 |
NM_033632.3 | chr4:g.(152329722_152329723) | c.(1186_1185) | p.S396fs | RefSeq | GRCh38/hg38 |
XM_011532084.3 | chr4:g.(152329722_152329723) | c.(1186_1185) | p.S396fs | RefSeq | GRCh38/hg38 |
XM_024454122.1 | chr4:g.(152329722_152329723) | c.(1186_1185) | p.S396fs | RefSeq | GRCh38/hg38 |
XM_011532084 | chr4:g.(152329722_152329723) | c.(1186_1185) | p.S396fs | RefSeq | GRCh38/hg38 |
NM_018315.4 | chr4:g.(152326224_152326225) | c.(1186_1185) | p.S396fs | RefSeq | GRCh38/hg38 |
XM_047415897.1 | chr4:g.(152329722_152329723) | c.(1186_1185) | p.S396fs | RefSeq | GRCh38/hg38 |
XM_011532085.3 | chr4:g.(152329722_152329723) | c.(1186_1185) | p.S396fs | RefSeq | GRCh38/hg38 |
NM_001349798.1 | chr4:g.(152329722_152329723) | c.(1186_1185) | p.S396fs | RefSeq | GRCh38/hg38 |
XM_011532083 | chr4:g.(152329722_152329723) | c.(1186_1185) | p.S396fs | RefSeq | GRCh38/hg38 |
XM_047415898.1 | chr4:g.(152329722_152329723) | c.(1186_1185) | p.S396fs | RefSeq | GRCh38/hg38 |
XM_024454123.1 | chr4:g.(152329722_152329723) | c.(1186_1185) | p.S396fs | RefSeq | GRCh38/hg38 |
XM_017008362 | chr4:g.(152329722_152329723) | c.(1186_1185) | p.S396fs | RefSeq | GRCh38/hg38 |
XM_011532085.2 | chr4:g.(152329722_152329723) | c.(1186_1185) | p.S396fs | RefSeq | GRCh38/hg38 |
XM_011532085 | chr4:g.(152329722_152329723) | c.(1186_1185) | p.S396fs | RefSeq | GRCh38/hg38 |
XM_024454124.1 | chr4:g.(152329722_152329723) | c.(1186_1185) | p.S396fs | 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 | 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 | 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 | 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 | 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 | 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 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 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 |