HNF1B
Overview
HNF1B (Hepatocyte Nuclear Factor 1 Beta) is a transcription factor with established roles in proximal tubule and renal development. In clear cell renal cell carcinoma biology, HNF1B binding sites are enriched at HIF2A-specific (but not HIF1A-specific) VHL-dependent gene loci, positioning it as a mediator of HIF2A’s tissue-restricted, dedifferentiation-linked transcriptional output following VHL loss.
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
- Cross-referenced in the context of a prior 17q12/HNF1B GWAS study as background for the NOL10-USF1 rs4519489 eQTL axis in prostate cancer; not directly assayed in this study PMID:28927585
Cancer types (linked)
- CCRCC: HNF1B binding-site enrichment at HIF2A-regulated loci supports a role in the tissue-specific transcriptional rewiring that precedes malignant transformation after VHL loss.
Co-occurrence and mutual exclusivity
- HNF1B co-enriched with HNF4A 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; its role as a downstream mediator of HIF2A activity may be relevant to understanding resistance or response patterns to belzutifan (HIF2A inhibitor) in VHL disease.
Open questions
- Whether HNF1B binding at HIF2A target loci is required for ccRCC initiation or is a passenger of HIF2A-driven dedifferentiation remains to be tested functionally PMID:23797736
Sources
This page was processed by crosslinker on 2026-05-09. - PMID:28927585
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