# VHL

Source: https://onco.cc/targets/vhl/  
OnCo record `vhl` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

VHL (von Hippel-Lindau disease tumour suppressor) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Renal cell carcinoma, Neuroendocrine tumours, Breast cancer and 5 more.

## Summary

Involved in the ubiquitination and subsequent proteasomal degradation via the von Hippel-Lindau ubiquitination complex. Seems to act as a target recruitment subunit in the E3 ubiquitin ligase complex and recruits hydroxylated hypoxia-inducible factor (HIF) under normoxic conditions. Involved in transcriptional repression through interaction with HIF1A, HIF1AN and histone deacetylases.

CIViC holds 2913 clinical evidence items and 6 assertions across 885 variants, naming Pazopanib, Anti-VEGF Monoclonal Antibody, Temsirolimus and Everolimus and others. Open Targets scores its association with cancer at 0.83 (direct and indirect evidence; datatypes genetic literature 0.83, affected pathway 0.87, literature 1.00, genetic association 0.79, somatic mutation 0.87, animal model 0.81). IntOGen calls it a driver in 6 cohorts (1 activating, 5 loss-of-function), covering Renal Clear Cell Carcinoma, Paraganglioma, Renal Cell Carcinoma.

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: von Hippel-Lindau tumor suppressor; von Hippel-Lindau disease tumor suppressor; VHL1
- Tags: cancer-genes-wave
- Symbol: VHL
- Class: tumor-suppressor
- Biology: Involved in the ubiquitination and subsequent proteasomal degradation via the von Hippel-Lindau ubiquitination complex. Seems to act as a target recruitment subunit in the E3 ubiquitin ligase complex and recruits hydroxylated hypoxia-inducible factor (HIF) under normoxic conditions. Involved in transcriptional repression through interaction with HIF1A, HIF1AN and histone deacetylases. Ubiquitinates, in an oxygen-responsive manner, ADRB2. Acts as a negative regulator of mTORC1 by promoting ubiquitination and degradation of RPTOR. Location: Cytoplasm; Cell membrane; Endoplasmic reticulum; Nucleus (UniProt). Locus 3p25.3 (HGNC).
- Where found: Renal cell carcinoma: Open Targets association 0.81 with renal cell carcinoma (MONDO_0005086); CIViC evidence names this disease; Neuroendocrine tumours: Open Targets association 0.77 with neuroendocrine neoplasm (MONDO_0019496); Breast cancer: CIViC evidence names this disease; Pancreatic ductal adenocarcinoma: CIViC evidence names this disease; Pheochromocytoma and paraganglioma: IntOGen driver in 1 cohort (PGNG); Clear cell renal cell carcinoma: CIViC evidence names this disease; IntOGen driver in 4 cohorts (CCRCC)

## Notes

- Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: CIViC lists 7 therapies; IntOGen calls it an activating (Act) driver in 1 cohort; IntOGen calls it a loss-of-function (LoF) driver in 5 cohorts; CIViC holds 2913 clinical evidence items on its variants. Evidence tier "clinical-evidence" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.
- Diseases the sources name that have no OnCo cancer page yet, so they are not linked: Von Hippel-Lindau Disease; Renal Carcinoma; Chuvash Polycythemia; Adrenal Gland Pheochromocytoma; Polycythemia; Splenomegaly.

## Sources

- HGNC HGNC:12687: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:12687
- UniProt P40337: https://www.uniprot.org/uniprotkb/P40337/entry
- NCBI Gene 7428: https://www.ncbi.nlm.nih.gov/gene/7428
- Ensembl ENSG00000134086: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000134086

## Connected records

- collections: [CIViC](https://onco.cc/collections/civic/), [IntOGen](https://onco.cc/collections/intogen/), [Open Targets Platform](https://onco.cc/collections/open-targets/)
- cancers: [Breast cancer (all types)](https://onco.cc/cancers/breast-cancer/), [Chromophobe renal cell carcinoma](https://onco.cc/cancers/chromophobe-rcc/), [Clear cell renal cell carcinoma](https://onco.cc/cancers/clear-cell-rcc/), [Neuroendocrine tumours](https://onco.cc/cancers/neuroendocrine/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/), [Pheochromocytoma and paraganglioma (PPGL)](https://onco.cc/cancers/pheochromocytoma-paraganglioma/), [Polycythaemia vera (PV)](https://onco.cc/cancers/polycythaemia-vera/), [Renal cell carcinoma](https://onco.cc/cancers/rcc/)
- pathways: [Renal cell carcinoma (KEGG map)](https://onco.cc/pathways/renal-cell-carcinoma-signalling/), [Ubiquitin-proteasome system & protein homeostasis](https://onco.cc/pathways/ubiquitin-proteasome-system/), [VHL / HIF oxygen sensing](https://onco.cc/pathways/hif-vhl/)
- trials: [Belzutifan/MK-6482 for the Treatment of Advanced Pheochromocytoma/Paraganglioma (PPGL), Pancreatic Neuroendocrine Tumor (pNET), Von Hippel-Lindau (VHL](https://onco.cc/trials/nct04924075/)

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JSON: https://onco.cc/api/v1/entities/vhl.json