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FBXW7 R505C - Gene Variant Detail

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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

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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

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  • Use quotes to match on a longer phrase with spaces (i.e. "mtor c1483f")

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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