Involved in the ubiquitination and subsequent proteasomal degradation via the von Hippel-Lindau ubiquitination complex (PubMed:10944113, PubMed:17981124, PubMed:19584355). Seems to act as a target recruitment subunit in the E3 ubiquitin ligase complex and recruits hydroxylated hypoxia-inducible factor (HIF) under normoxic conditions (PubMed:10944113, PubMed:17981124). Involved in transcriptional repression through interaction with HIF1A, HIF1AN and histone deacetylases (PubMed:10944113, PubMed:17981124).
Ubiquitinates, in an oxygen-responsive manner, ADRB2 (PubMed:19584355). Acts as a negative regulator of mTORC1 by promoting ubiquitination and degradation of RPTOR (PubMed:34290272)
Component of the VCB (VHL-Elongin BC-CUL2) complex; this complex acts as a ubiquitin-ligase E3 and directs proteasome-dependent degradation of targeted proteins. Interacts with CUL2; this interaction is dependent on the integrity of the trimeric VCB complex. Interacts (via the beta domain) with HIF1A (via the NTAD domain); this interaction mediates degradation of HIF1A in normoxia and, in hypoxia, prevents ubiquitination and degradation of HIF1A by mediating hypoxia-induced translocation to the nucleus, a process which requires a hypoxia-dependent regulatory signal.
Interacts with ADRB2; the interaction, in normoxia, is dependent on hydroxylation of ADRB2 and the subsequent VCB-mediated ubiquitination and degradation of ADRB2. Under hypoxia, hydroxylation, interaction with VHL, ubiquitination and subsequent degradation of ADRB2 are dramatically decreased. Interacts with RNF139, USP33 and JADE1.
Found in a complex composed of LIMD1, VHL, EGLN1/PHD2, ELOB and CUL2. Isoform 1 and isoform 3 interact with LIMD1 (via LIM zinc-binding 2), AJUBA (via LIM domains) and WTIP (via LIM domains). Interacts with EPAS1.
Interacts with CARD9. Interacts with DCUN1D1 independently of CUL2; this interaction engages DCUN1D1 in the VCB complex and triggers CUL2 neddylation and consequently cullin ring ligase (CRL) substrates polyubiquitylation (PubMed:23401859). Interacts with ALAS1 (hydroxylated form) (PubMed:16234850).
Interacts with IGFBP1 (By similarity)
Expressed in the adult and fetal brain and kidney
The Elongin BC complex binding domain is also known as BC-box with the consensus [APST]-L-x(3)-C-x(3)-[AILV]
A catecholamine-producing tumor of chromaffin tissue of the adrenal medulla or sympathetic paraganglia. The cardinal symptom, reflecting the increased secretion of epinephrine and norepinephrine, is hypertension, which may be persistent or intermittent.
VHLD is a dominantly inherited familial cancer syndrome predisposing to a variety of malignant and benign neoplasms, most frequently retinal, cerebellar and spinal hemangioblastoma, renal cell carcinoma (RCC), pheochromocytoma, and pancreatic tumors. VHL type 1 is without pheochromocytoma, type 2 is with pheochromocytoma. VHL type 2 is further subdivided into types 2A (pheochromocytoma, retinal angioma, and hemangioblastomas without renal cell carcinoma and pancreatic cyst) and 2B (pheochromocytoma, retinal angioma, and hemangioblastomas with renal cell carcinoma and pancreatic cyst).
An autosomal recessive disorder characterized by an increase in serum red blood cell mass, hypersensitivity of erythroid progenitors to erythropoietin, increased erythropoietin serum levels, and normal oxygen affinity. Patients with ECYT2 carry a high risk for peripheral thrombosis and cerebrovascular events.
Renal cell carcinoma is a heterogeneous group of sporadic or hereditary carcinoma derived from cells of the proximal renal tubular epithelium. It is subclassified into clear cell renal carcinoma (non-papillary carcinoma), papillary renal cell carcinoma, chromophobe renal cell carcinoma, collecting duct carcinoma with medullary carcinoma of the kidney, and unclassified renal cell carcinoma. Clear cell renal cell carcinoma is the most common subtype.
Click a pathway to open the interactive Reactome viewer.
Genes with an experimentally identified or computationally predicted synthetic-lethal relationship to VHL, aggregated across our SSL data sources. Click any partner node to view that gene’s page.
Nodes and edges are coloured by the SSL data source. Partners appearing in more than one source are shown in grey.
Total Trials Found: 70
| NCT ID | Condition | Brief Title | Phase | Status |
|---|---|---|---|---|
| NCT03979833 | Von Hippel-Lindau Disease | Drivers of Hypoxia-induced Angiogenesis in Tumor Development | N/A | UNKNOWN |
| NCT03749980 | Von Hippel-Lindau Disease, Hereditary Leiomyomatosis and Renal Cell Cancer, Birt-Hogg-Dube Syndrome, SDHB Gene Mutation | MyVHL: Patient Natural History Study | N/A | RECRUITING |
| NCT00330564 | Von Hippel-Lindau Syndrome, Renal Cell Carcinoma, Hemangioblastoma | Evaluation of Sunitinib Malate in Patients With Von Hippel-Lindau Syndrome (VHL) Who Have VHL Lesions to Follow | PHASE2 | TERMINATED |
| NCT06523582 | Neuroendocrine Neoplasm, Neuroendocrine Neoplasm of Gastrointestinal Tract, Neuroendocrine Neoplasm of Lung, Thymic Neuroendocrine Neoplasm, Neuroendocrine Tumor of Pancreas, Gastrointestinal Stromal Tumors, Medullary Thyroid Cancer, Paraganglioma, Pheochromocytoma, Primary Hyperparathyroidism, Pituitary Tumor, Multiple Endocrine Neoplasia Type 1, Multiple Endocrine Neoplasia Type 2, Multiple Endocrine Neoplasia Type 4, Carney Complex, Carney Stratakis Dyad, Carney Triad, Cowden Syndrome, DICER1 Syndrome, Li-Fraumeni Syndrome, Lynch Syndrome, Von Hippel-Lindau Disease, Familial Isolated Pituitary Adenoma, X-Linked Acrogigantism, Neurofibromatosis 1, Tuberous Sclerosis | Genetic Bases of Neuroendocrine Neoplasms in Mexican Patients | N/A | RECRUITING |
| NCT06553339 | Von Hippel Lindau-Deficient Clear Cell Renal Cell Carcinoma | A Study of HS-10516 in Patients With VHL Syndrome Associated Tumors | PHASE1 | RECRUITING |
| NCT04458935 | Retinal Hemangioblastoma, Von Hippel-Lindau Disease | Retrospective Case Series of Trans-scleral Cryotherapy for Retinal Hemangioblastoma | N/A | ACTIVE_NOT_RECRUITING |
| NCT00001703 | Renal Cell Carcinoma | Vaccine Therapy With Tumor Specific Mutated VHL Peptides in Adult Cancer Patients With Renal Cell Carcinoma | PHASE2 | TERMINATED |
| NCT01436227 | Von Hippel-Lindau Syndrome | Pazopanib Hydrochloride in Treating Patients With Von Hippel-Lindau Syndrome | PHASE2 | COMPLETED |
| NCT07300241 | Clear Cell Renal Cell Carcinoma, Renal Cell Carcinoma, RCC, Clear Cell Renal Cell Carcinoma Metastatic, ccRCC, VHL-Associated Clear Cell Renal Cell Carcinoma, VHL-Associated Renal Cell Carcinoma, Kidney Cancer Metastatic, Kidney Cancers | Open-Label Phase 1/2 Study of NEO-811 in Subjects With Locally Advanced or Metastatic Non-Resectable Clear Cell Renal Cell Carcinoma | PHASE1 | RECRUITING |
| NCT05941637 | Clear Cell Kidney Cancer, Kidney Cancer, Kidney Cancer With PBRM1/BAP1/VHL/SETD2 Mutations | An Expanded Access Program to Axitinib is Available for Patients With Advanced Forms of Kidney Cancer (Ductal; Papillary; Chromophobic; Oncocytic) With Mutations in VHL, PBRM1 / BAP1, SETD2, VEGF) | N/A | NO_LONGER_AVAILABLE |