{"entity":{"id":"vhl","kind":"target","name":"VHL","aka":["von Hippel-Lindau tumor suppressor","von Hippel-Lindau disease tumor suppressor","VHL1"],"tldr":"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.\n\nCIViC 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.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:12687","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:12687"},{"label":"UniProt P40337","url":"https://www.uniprot.org/uniprotkb/P40337/entry"},{"label":"NCBI Gene 7428","url":"https://www.ncbi.nlm.nih.gov/gene/7428"},{"label":"Ensembl ENSG00000134086","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000134086"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets","intogen"],"cancers":["rcc","neuroendocrine","breast-cancer","pancreatic","pheochromocytoma-paraganglioma","clear-cell-rcc","polycythaemia-vera","chromophobe-rcc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["hif-vhl","renal-cell-carcinoma-signalling","ubiquitin-proteasome-system"],"terms":[],"trials":["nct04924075"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"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."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"VHL","role":["drug-target","oncogene-driver","tumour-suppressor","biomarker"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:12687","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:12687","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt P40337","url":"https://www.uniprot.org/uniprotkb/P40337/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene VHL","url":"https://civicdb.org/features/58","note":"2913 evidence items, 6 assertions, 885 variants; diseases: Von Hippel-Lindau Disease, Clear Cell Renal Cell Carcinoma, Renal Cell Carcinoma, Renal Carcinoma, Chuvash Polycythemia and 7 more (GraphQL API, CC0)"},{"label":"Open Targets ENSG00000134086","url":"https://platform.opentargets.org/target/ENSG00000134086/associations","note":"association with cancer (MONDO_0004992) 0.83; per-cancer scores at or above 0.5: renal cell carcinoma 0.81, neuroendocrine neoplasm 0.77 (GraphQL API, CC0)"},{"label":"IntOGen VHL","url":"https://www.intogen.org/search?gene=VHL","note":"driver in 6 cohorts (Act 1, LoF 5); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"hgnc":"HGNC:12687","ensembl":"ENSG00000134086","uniprot":"P40337","entrez":"7428","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).","whereFound":["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)"],"targetClass":"tumor-suppressor","prevalence":[]},"route":"/targets/vhl/","neighbours":{"collection":[{"id":"civic","kind":"collection","name":"CIViC","route":"/collections/civic/"},{"id":"intogen","kind":"collection","name":"IntOGen","route":"/collections/intogen/"},{"id":"open-targets","kind":"collection","name":"Open Targets Platform","route":"/collections/open-targets/"}],"cancer":[{"id":"breast-cancer","kind":"cancer","name":"Breast cancer (all types)","route":"/cancers/breast-cancer/"},{"id":"chromophobe-rcc","kind":"cancer","name":"Chromophobe renal cell carcinoma","route":"/cancers/chromophobe-rcc/"},{"id":"clear-cell-rcc","kind":"cancer","name":"Clear cell renal cell carcinoma","route":"/cancers/clear-cell-rcc/"},{"id":"neuroendocrine","kind":"cancer","name":"Neuroendocrine tumours","route":"/cancers/neuroendocrine/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"},{"id":"pheochromocytoma-paraganglioma","kind":"cancer","name":"Pheochromocytoma and paraganglioma (PPGL)","route":"/cancers/pheochromocytoma-paraganglioma/"},{"id":"polycythaemia-vera","kind":"cancer","name":"Polycythaemia vera (PV)","route":"/cancers/polycythaemia-vera/"},{"id":"rcc","kind":"cancer","name":"Renal cell carcinoma","route":"/cancers/rcc/"}],"pathway":[{"id":"renal-cell-carcinoma-signalling","kind":"pathway","name":"Renal cell carcinoma (KEGG map)","route":"/pathways/renal-cell-carcinoma-signalling/"},{"id":"ubiquitin-proteasome-system","kind":"pathway","name":"Ubiquitin-proteasome system & protein homeostasis","route":"/pathways/ubiquitin-proteasome-system/"},{"id":"hif-vhl","kind":"pathway","name":"VHL / HIF oxygen sensing","route":"/pathways/hif-vhl/"}],"trial":[{"id":"nct04924075","kind":"trial","name":"Belzutifan/MK-6482 for the Treatment of Advanced Pheochromocytoma/Paraganglioma (PPGL), Pancreatic Neuroendocrine Tumor (pNET), Von Hippel-Lindau (VHL","route":"/trials/nct04924075/"}]}}