Starting April 21, you’ll be asked to log in or sign up for a free account after viewing 10 content pages each month.
Don’t worry—creating an account is quick and easy, and it comes with added benefits! Once logged in, you’ll not only continue accessing the content you already enjoy, but you’ll also unlock exclusive features like interactive donut plots for variant protein effects and variant impacts across the gene.
Stay tuned for these updates, and thank you for being part of our community!
Missing content? – Request curation!
Request curation for specific Genes, Variants, or PubMed publications.
Have questions, comments, or suggestions? - Let us know!
Email us at : ckbsupport@genomenon.com
Gene | FBXW7 |
Variant | R505C |
Impact List | missense |
Protein Effect | loss of function |
Gene Variant Descriptions | FBXW7 R505C lies within WD repeat 4 of the Fbxw7 protein (UniProt.org). R505C results in ubiquitination and degradation of Braf similar to wild-type Fbxw7 in cultured cells (PMID: 32907612), but confers a loss of function to Fbxw7 as indicated by a loss of binding to NICD in cell culture (PMID: 17646409), impaired degradation of NICD, resulting in increased activity in a luciferase assay (PMID: 27247421), failure to degrade cyclin E, c-Myc, and Mcl1 in cell culture (PMID: 32907612), aberrant subnuclear localization (PMID: 30510140), and impaired degradation of Klf5 in cell culture (PMID: 28963353). |
Associated Drug Resistance | |
Category Variants Paths |
FBXW7 mutant FBXW7 inact mut FBXW7 R505C |
Transcript | NM_033632.3 |
gDNA | chr4:g.152326137G>A |
cDNA | c.1513C>T |
Protein | p.R505C |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
XM_011532085.3 | chr4:g.152326137G>A | c.1513C>T | p.R505C | RefSeq | GRCh38/hg38 |
XM_011532085.2 | chr4:g.152326137G>A | c.1513C>T | p.R505C | RefSeq | GRCh38/hg38 |
NM_001349798.2 | chr4:g.152326137G>A | c.1513C>T | p.R505C | RefSeq | GRCh38/hg38 |
NM_033632 | chr4:g.152326137G>A | c.1513C>T | p.R505C | RefSeq | GRCh38/hg38 |
NM_001349798.1 | chr4:g.152326137G>A | c.1513C>T | p.R505C | RefSeq | GRCh38/hg38 |
XM_011532084.2 | chr4:g.152326137G>A | c.1513C>T | p.R505C | RefSeq | GRCh38/hg38 |
NM_033632.3 | chr4:g.152326137G>A | c.1513C>T | p.R505C | RefSeq | GRCh38/hg38 |
XM_047415899.1 | chr4:g.152326137G>A | c.1513C>T | p.R505C | RefSeq | GRCh38/hg38 |
XM_047415900.1 | chr4:g.152326137G>A | c.1513C>T | p.R505C | RefSeq | GRCh38/hg38 |
XM_047415897.1 | chr4:g.152326137G>A | c.1513C>T | p.R505C | RefSeq | GRCh38/hg38 |
XM_047415901.1 | chr4:g.152326137G>A | c.1513C>T | p.R505C | RefSeq | GRCh38/hg38 |
XM_011532084.3 | chr4:g.152326137G>A | c.1513C>T | p.R505C | RefSeq | GRCh38/hg38 |
XM_047415898.1 | chr4:g.152326137G>A | c.1513C>T | p.R505C | RefSeq | GRCh38/hg38 |
XM_024454123.2 | chr4:g.152326137G>A | c.1513C>T | p.R505C | RefSeq | GRCh38/hg38 |
XM_011532084 | chr4:g.152326137G>A | c.1513C>T | p.R505C | RefSeq | GRCh38/hg38 |
XM_024454124.1 | chr4:g.152326137G>A | c.1513C>T | p.R505C | RefSeq | GRCh38/hg38 |
XM_017008362 | chr4:g.152326137G>A | c.1513C>T | p.R505C | RefSeq | GRCh38/hg38 |
XM_024454123.1 | chr4:g.152326137G>A | c.1513C>T | p.R505C | RefSeq | GRCh38/hg38 |
XM_024454122.1 | chr4:g.152326137G>A | c.1513C>T | p.R505C | RefSeq | GRCh38/hg38 |
XM_011532083 | chr4:g.152326137G>A | c.1513C>T | p.R505C | RefSeq | GRCh38/hg38 |
NM_033632.3 | chr4:g.152326137G>A | c.1513C>T | p.R505C | RefSeq | GRCh38/hg38 |
XM_024454121.1 | chr4:g.152326137G>A | c.1513C>T | p.R505C | RefSeq | GRCh38/hg38 |
XM_011532085 | chr4:g.152326137G>A | c.1513C>T | p.R505C | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
FBXW7 R505C | T-cell adult acute lymphocytic leukemia | resistant | MRK-003 | Preclinical | Actionable | In a preclinical study, FBXW7 R505C conferred resistance to gamma secretase inhibitor, MRK-003, by activation of the NOTCH pathway and stablization of MYC as demonstrated in T cell acute lymphoblastic leukemia (T-ALL) cell lines (PMID: 17646409). | 17646409 |
FBXW7 R505C | head and neck squamous cell carcinoma | sensitive | Vorinostat | Preclinical | Actionable | In a preclinical study, Zolinza (vorinostat) inhibited growth of a head and neck squamous cell carcinoma cell line harboring FBXW7 R505C in culture (PMID: 23274910). | 23274910 |
FBXW7 R505C | colorectal cancer | resistant | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, colorectal cell lines with FBXW7 R505C demonstrated acquired resistance in regorafenib (PMID: 27399335). | 27399335 |
FBXW7 R505C | melanoma | predicted - resistant | unspecified PD-1 antibody | Preclinical | Actionable | In a preclinical study, a melanoma cell line expressing FBXW7 R505C in a mouse model conferred resistance to treatment with an unspecified PD-1 antibody, demonstrating increased tumor volume and decreased survival compared to models with wild-type FBXW7 (PMID: 32371478). | 32371478 |
FBXW7 R505C | melanoma | predicted - resistant | Pembrolizumab | Case Reports/Case Series | Actionable | In a clinical case study, a melanoma patient treated with Keytruda (pembrolizumab) demonstrated a response in all lesions except one, which was found to harbor FBXW7 R505C (PMID: 32371478). | 32371478 |