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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.
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.
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.
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.
Involved in the ubiquitination and subsequent proteasomal degradation via the von Hippel-Lindau ubiquitination complex.
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).
Tumour-specific alteration: the catalogues call it an oncogene driver (IntOGen cohort analysis finds it activated more often than chance) and a tumour suppressor (IntOGen finds it knocked out more often than chance), so the direction differs between cohorts but the alteration is somatic either way; what a medicine would aim at or exploit is the altered form or its loss, absent from normal cells; no corpus medicine is aimed at it yet. HPA VHL: RNA low tissue specificity; high antibody staining in 25 normal tissues; highest cancer staining head and neck cancer (4 of 4 high). Distribution: 6 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Renal cell carcinoma, Neuroendocrine tumours, Breast cancer (all types), Pancreatic ductal adenocarcinoma, Pheochromocytoma and paraganglioma (PPGL), Myeloid neoplasms); Open Targets associates it with 6 specific cancer types at or above 0.5 (pheochromocytoma, hereditary pheochromocytoma-paraganglioma, clear cell renal carcinoma, nonpapillary renal cell carcinoma, hereditary neoplastic syndrome, renal cell carcinoma). (Rule 6 of scripts/fetch-target-specificity.ts.)
Sources: UniProt P40337; CIViC gene VHL; IntOGen VHL; Human Protein Atlas VHL tissue; Open Targets ENSG00000134086 associations
First described 1993. Earliest sequence paper UniProt cites for the protein: Latif et al, Science, 1993, "Identification of the von Hippel-Lindau disease tumor suppressor gene". Source.
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)
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).
RNA: low tissue specificity, detected in all normal tissues.
Medium: Adrenal gland, Bone marrow, Breast, Cerebral cortex, Fallopian tube, Hippocampus, Kidney, Ovary.
Medium only: glioma, lymphoma.
HPA VHL tissue · HPA VHL pathology · HPA protein class: Essential proteins
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
Query 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.
Shares Clear cell renal cell carcinoma, Renal cell carcinoma, CIViC, IntOGen.
Shares Pheochromocytoma and paraganglioma (PPGL), Clear cell renal cell carcinoma, Renal cell carcinoma, IntOGen.
Shares Clear cell renal cell carcinoma, Renal cell carcinoma, CIViC, IntOGen.
Shares Clear cell renal cell carcinoma, Renal cell carcinoma, IntOGen, Breast cancer (all types).
Shares Chromophobe renal cell carcinoma, Renal cell carcinoma, CIViC, IntOGen.
Shares Ubiquitin-proteasome system & protein homeostasis, IntOGen, Breast cancer (all types), Open Targets Platform.
Shares Clear cell renal cell carcinoma, Renal cell carcinoma, IntOGen, Breast cancer (all types).
Shares Clear cell renal cell carcinoma, Renal cell carcinoma, IntOGen, Breast cancer (all types).