Gene Variant Detail

Gene FBXW7
Variant R505C
Impact List missense
Protein Effect loss of function
Gene Variant Descriptions FBXW7 R505C lies within the WD 4 repeat region of the Fbxw7 protein (UniProt.org). R505C confers a loss of FBXW7-substrate interation and impairs substrate degradation by FBXW7, resulting in sustained NICD and MYC expression (PMID: 17646409) and also has impaired degradation of Klf5 (PMID: 2896335).
Associated Drug Resistance

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Transcript NM_033632
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_011532083 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
XM_011532084 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
XM_017008362 chr4:g.152326137G>A c.1513C>T p.R505C RefSeq GRCh38/hg38

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

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Molecular Profile Protein Effect Treatment Approaches
FBXW7 R505C loss of function mTORC1 Inhibitor
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
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 T-cell adult acute lymphocytic leukemia resistant MRK-003 Preclinical Actionable In a preclinical study, FBXW7 R505C conferred resistance to gamma secretase inhibitor, MRK-300, 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 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