VHL
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.
Overview
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.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · 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.
- 1 · What it is
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.
- 2 · What goes wrong in cancer
Involved in the ubiquitination and subsequent proteasomal degradation via the von Hippel-Lindau ubiquitination complex.
- 3 · How drugs use it
No product in this corpus aims at VHL yet. Because the protein is lost rather than overactive, drugs either restore its function or exploit the weakness its loss leaves (synthetic lethality).
External identifiers
Sources: HGNC HGNC:12687 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt P40337 (protein name, function text, keywords and locations (REST API)); CIViC gene VHL (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)); Open Targets ENSG00000134086 (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)); IntOGen VHL (driver in 6 cohorts (Act 1, LoF 5); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
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).
- 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
top- 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.
Latest papers
topQuery for this target: (TITLE:"VHL" OR ABSTRACT:"VHL" OR TITLE:"von Hippel-Lindau tumor suppressor" OR ABSTRACT:"von Hippel-Lindau tumor suppressor" OR TITLE:"von Hippel-Lindau disease tumor suppressor" OR ABSTRACT:"von Hippel-Lindau disease tumor suppressor" OR TITLE:"VHL1" OR ABSTRACT:"VHL1") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about VHL, not a curated reading list.
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