HNF4A
Overview
HNF4A (Hepatocyte Nuclear Factor 4 Alpha) is a nuclear receptor transcription factor with roles in hepatic, intestinal, and renal development. In the context of ccRCC initiation, HNF4A binding sites are enriched at HIF2A-specific (but not HIF1A-specific) VHL-dependent gene loci, suggesting it participates in the tissue-restricted transcriptional reprogramming driven by HIF2A stabilization after VHL loss in proximal tubule cells.
Alterations observed in the corpus
- Identified by LISA and ChEA3 (top 50 in both) as a transcription factor whose binding sites are enriched at HIF2A-specific VHL-dependent gene loci in a mouse VHL-knockout model of ccRCC initiation; proposed to mediate HIF2A’s dedifferentiation-linked transcriptional output in proximal tubule cells PMID:23797736
- Hepatobiliary master regulator implicated in bile salt export pump (BSEP/ABCB11) and bile acid homeostasis maintenance in cholangiocarcinoma PMID:25608663
Cancer types (linked)
- CCRCC: HNF4A binding-site enrichment at HIF2A-regulated loci in VHL-null proximal tubule cells; implicates HNF4A in the early transcriptional events that precede morphological transformation.
Co-occurrence and mutual exclusivity
- HNF4A co-enriched with HNF1B and FOXA2 at HIF2A-specific VHL-dependent loci; all three have established roles in proximal tubule/renal development PMID:23797736
Therapeutic relevance
- Not directly targeted in the corpus; relationship to HIF2A-driven programs may inform interpretation of HIF2A inhibitor (belzutifan) response in VHL disease.
Open questions
- Functional requirement for HNF4A at HIF2A target loci in ccRCC initiation vs. normal tubular differentiation has not been directly tested PMID:23797736
Sources
This page was processed by crosslinker on 2026-05-14. - PMID:25608663
This page was processed by crosslinker on 2026-05-14.