VHL
Summary: Von Hippel-Lindau syndrome (VHL) is a dominantly inherited familial cancer syndrome predisposing to a variety of malignant and benign tumors. A germline mutation of this gene is the basis of familial inheritance of VHL syndrome. The protein encoded by this gene is a component of the protein complex that includes elongin B, elongin C, and cullin-2, and possesses ubiquitin ligase E3 activity. This protein is involved in the ubiquitination and degradation of hypoxia-inducible-factor (HIF), which is a transcription factor that plays a central role in the regulation of gene expression by oxygen. RNA polymerase II subunit POLR2G/RPB7 is also reported to be a target of this protein. Alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008].
| Name | OMIM ID | Ensembl ID | HGNC ID | PHARMGKB ID | Map Location |
|---|---|---|---|---|---|
| von Hippel-Lindau tumor suppressor | MIM:608537 | Ensembl:ENSG00000134086 | HGNC:HGNC:12687 | PA37307 | 3p25.3 |
GO terms in VHL
| Term Type | Evidence Type | GO Term ID | GO Des. |
|---|---|---|---|
| MF | TAS | GO:0004842 | ubiquitin-protein transferase activity |
| MF | IPI | GO:0005515 | protein binding |
| MF | IPI | GO:0008134 | transcription factor binding |
| MF | IPI | GO:0019899 | enzyme binding |
| MF | IBA | GO:0061630 | ubiquitin protein ligase activity |
| MF | IDA | GO:0061630 | ubiquitin protein ligase activity |
| BP | TAS | GO:0000122 | negative regulation of transcription by RNA polymerase II |
| BP | NAS | GO:0000902 | cell morphogenesis |
| BP | IMP | GO:0006355 | regulation of transcription, DNA-templated |
| BP | TAS | GO:0006508 | proteolysis |
| BP | IMP | GO:0008285 | negative regulation of cell proliferation |
| BP | IMP | GO:0010629 | negative regulation of gene expression |
| BP | IBA | GO:0016567 | protein ubiquitination |
| BP | IDA | GO:0016567 | protein ubiquitination |
| BP | IEA | GO:0016567 | protein ubiquitination |
| BP | IMP | GO:0016567 | protein ubiquitination |
| BP | NAS | GO:0043066 | negative regulation of apoptotic process |
| BP | TAS | GO:0043687 | post-translational protein modification |
| BP | NAS | GO:0045597 | positive regulation of cell differentiation |
| BP | IMP | GO:0045893 | positive regulation of transcription, DNA-templated |
| BP | IMP | GO:0046426 | negative regulation of JAK-STAT cascade |
| BP | NAS | GO:0050821 | protein stabilization |
| BP | TAS | GO:0061418 | regulation of transcription from RNA polymerase II promoter in response to hypoxia |
| BP | IDA | GO:0061428 | negative regulation of transcription from RNA polymerase II promoter in response to hypoxia |
| CC | IBA | GO:0005634 | nucleus |
| CC | TAS | GO:0005634 | nucleus |
| CC | IDA | GO:0005654 | nucleoplasm |
| CC | TAS | GO:0005654 | nucleoplasm |
| CC | NAS | GO:0005739 | mitochondrion |
| CC | NAS | GO:0005783 | endoplasmic reticulum |
| CC | TAS | GO:0005829 | cytosol |
| CC | IEA | GO:0016020 | membrane |
| CC | IBA | GO:0030891 | VCB complex |
Gene expression in normal tissue: VHL
Gene-model tissue-cancer distribution: Bubble Plot
Gene-drug pathway distribution
Pathways in VHL
| Database | Pathway ID | Pathway Des. |
|---|---|---|
| reactome | R-HSA-1234174 | Regulation of Hypoxia-inducible Factor (HIF) by oxygen |
| reactome | R-HSA-1234174 | Regulation of Hypoxia-inducible Factor (HIF) by oxygen |
| reactome | R-HSA-1234176 | Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha |
| reactome | R-HSA-1234176 | Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha |
| reactome | R-HSA-1280218 | Adaptive Immune System |
| reactome | R-HSA-168256 | Immune System |
| reactome | R-HSA-2262749 | Cellular response to hypoxia |
| reactome | R-HSA-2262749 | Cellular response to hypoxia |
| reactome | R-HSA-2262752 | Cellular responses to stress |
| reactome | R-HSA-2262752 | Cellular responses to stress |
| reactome | R-HSA-2990846 | SUMOylation |
| reactome | R-HSA-3108232 | SUMO E3 ligases SUMOylate target proteins |
| reactome | R-HSA-3232142 | SUMOylation of ubiquitinylation proteins |
| reactome | R-HSA-392499 | Metabolism of proteins |
| reactome | R-HSA-597592 | Post-translational protein modification |
| reactome | R-HSA-8951664 | Neddylation |
| reactome | R-HSA-8953897 | Cellular responses to external stimuli |
| reactome | R-HSA-8953897 | Cellular responses to external stimuli |
| reactome | R-HSA-983168 | Antigen processing: Ubiquitination & Proteasome degradation |
| reactome | R-HSA-983169 | Class I MHC mediated antigen processing & presentation |
| biocarta | hifpathway | hypoxia-inducible factor in the cardivascular system |
| biocarta | vegfpathway | vegf hypoxia and angiogenesis |
| kegg | hsa04066 | HIF-1 signaling pathway - Homo sapiens (human) |
| kegg | hsa04120 | Ubiquitin mediated proteolysis - Homo sapiens (human) |
| kegg | hsa05200 | Pathways in cancer - Homo sapiens (human) |
| kegg | hsa05211 | Renal cell carcinoma - Homo sapiens (human) |
| pid | hif1apathway | Hypoxic and oxygen homeostasis regulation of HIF-1-alpha |
| pid | hif2pathway | HIF-2-alpha transcription factor network |
| wikipathways | WP1993 | Angiogenesis overview |
| wikipathways | WP3678 | Amplification and Expansion of Oncogenic Pathways as Metastatic Traits |
| wikipathways | WP4018 | Pathways in clear cell renal cell carcinoma |
| wikipathways | WP4241 | Type 2 papillary renal cell carcinoma |
Gene-Drug: Aster Plot
| Drug ID | Drug Name | Model Num. |
|---|---|---|
| iGMDRD190 | Nilotinib | 1 |
| iGMDRD454 | JNK Inhibitor VIII | 1 |
| iGMDRD399 | Selumetinib | 1 |
| iGMDRD284 | Palbociclib | 1 |
| iGMDRD309 | 17AAG | 1 |
| iGMDRD574 | Ruxolitinib | 1 |
| iGMDRD759 | PFI-1 | 1 |
| iGMDRD474 | Avrainvillamide | 2 |
| iGMDRD134 | Sorafenib | 1 |
| iGMDRD568 | SCHEMBL15005512 | 1 |
| iGMDRD280 | CYTOCHALASIN B | 2 |
| iGMDRD401 | Afatinib | 2 |
| iGMDRD470 | Trametinib | 1 |
| iGMDRD218 | XAV 939 | 1 |
| iGMDRD634 | SCHEMBL2608041 | 2 |
| iGMDRD152 | 179324-69-7 | 1 |
| iGMDRD397 | Pazopanib | 1 |
| iGMDRD283 | Bosutinib | 1 |
| iGMDRD313 | Axitinib | 1 |
| iGMDRD136 | Nutlin-3 | 1 |
| iGMDRD387 | CHIR-99021 | 1 |
| iGMDRD889 | Compound 7d-cis | 4 |
| iGMDRD300 | Tozasertib | 3 |
| iGMDRD872 | BRD7137 | 2 |
| iGMDRD119 | Temsirolimus | 1 |
| iGMDRD837 | Bevacizumab | 1 |
| iGMDRD241 | Sunitinib | 1 |
| iGMDRD293 | Bleomycin | 1 |
| iGMDRD467 | Motesanib | 1 |
| iGMDRD450 | JNJ-26854165 | 1 |
| iGMDRD536 | PLX-4720 | 1 |
| iGMDRD352 | PD-0325901 | 1 |
| iGMDRD150 | RITA | 2 |
| iGMDRD792 | Cetuximab | 1 |
Gene in drug-gene network: Network Plot
Gene-drug targets distribution
Gene Structure: PDB
Models in VHL
CLASSFICATION
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