RXRA
Overview
RXRA encodes retinoid X receptor alpha, a nuclear receptor that forms obligate heterodimers with other nuclear receptors (including PPARG, RAR, and VDR) to regulate transcription of genes involved in lipid metabolism, differentiation, and cell growth. Hotspot mutations in the ligand-binding domain occur in bladder cancer and are associated with constitutive transcriptional activation of adipogenesis and lipid-metabolism programs.
Alterations observed in the corpus
- Mutations in 9% of bladder urothelial carcinomas (BLCA); 7 of 12 mutations at hotspot S427 (5 S427F, 2 S427Y) in the ligand-binding domain; mutant tumors showed elevated adipogenesis/lipid-metabolism gene expression, suggesting constitutive activation PMID:24476821
Cancer types (linked)
- BLCA: recurrent hotspot mutations at S427 (ligand-binding domain); 9% prevalence in TCGA BLCA cohort; associated with altered lipid-metabolism transcriptional program PMID:24476821
Co-occurrence and mutual exclusivity
- No specific co-mutation or mutual-exclusivity relationships noted in this corpus.
Therapeutic relevance
- Hotspot S427 mutations in the ligand-binding domain may confer ligand-independent constitutive activity, suggesting potential susceptibility to retinoid-based or PPARG-targeted therapies; clinical validation not yet established in this corpus.
Open questions
- Whether RXRA S427 hotspot mutations function as oncogenic drivers or modifiers of differentiation state in bladder cancer requires functional validation.
Sources
This page was processed by crosslinker on 2026-05-09.