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Aliases for VHL Gene

Aliases for VHL Gene

  • Von Hippel-Lindau Tumor Suppressor 2 3
  • Von Hippel-Lindau Tumor Suppressor, E3 Ubiquitin Protein Ligase 2 3 5
  • Protein G7 3 4
  • PVHL 3 4
  • Von Hippel-Lindau Syndrome 2
  • Elongin Binding Protein 3
  • HRCA1 3
  • RCA1 3
  • VHL1 3

External Ids for VHL Gene

Previous GeneCards Identifiers for VHL Gene

  • GC03P010112
  • GC03P010175
  • GC03P010158
  • GC03P010183
  • GC03P010119
  • GC03P010185
  • GC03P010200
  • GC03P010144
  • GC03P010145

Summaries for VHL Gene

Entrez Gene Summary for VHL Gene

  • 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]

GeneCards Summary for VHL Gene

VHL (Von Hippel-Lindau Tumor Suppressor) is a Protein Coding gene. Diseases associated with VHL include von hippel-lindau syndrome and erythrocytosis, familial, 2. Among its related pathways are Immune System and Cellular Senescence. GO annotations related to this gene include enzyme binding and ubiquitin-protein transferase activity. An important paralog of this gene is VHLL.

UniProtKB/Swiss-Prot for VHL Gene

  • 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.

Gene Wiki entry for VHL Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for VHL Gene

Genomics for VHL Gene

Regulatory Elements for VHL Gene

Promoters for VHL Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around VHL on UCSC Golden Path with GeneCards custom track

Genomic Location for VHL Gene

Chromosome:
3
Start:
10,141,008 bp from pter
End:
10,153,670 bp from pter
Size:
12,663 bases
Orientation:
Plus strand

Genomic View for VHL Gene

Genes around VHL on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
VHL Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for VHL Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for VHL Gene

Proteins for VHL Gene

  • Protein details for VHL Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P40337-VHL_HUMAN
    Recommended name:
    Von Hippel-Lindau disease tumor suppressor
    Protein Accession:
    P40337
    Secondary Accessions:
    • B2RE45
    • Q13599
    • Q6PDA9

    Protein attributes for VHL Gene

    Size:
    213 amino acids
    Molecular mass:
    24153 Da
    Quaternary structure:
    • 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 VBC complex. Interacts (via the beta domain) with HIF1A (via the NTAD domain); this interaction mediates degradation of HIF1A in normoxia and, in hypoxia, prevents ubiqitination 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, TCEB2 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.

    Three dimensional structures from OCA and Proteopedia for VHL Gene

    Alternative splice isoforms for VHL Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for VHL Gene

Proteomics data for VHL Gene at MOPED

Post-translational modifications for VHL Gene

  • Ubiquitination at Lys 196
  • Modification sites at PhosphoSitePlus

Other Protein References for VHL Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for VHL (VHL)

No data available for DME Specific Peptides for VHL Gene

Domains & Families for VHL Gene

Protein Domains for VHL Gene

Graphical View of Domain Structure for InterPro Entry

P40337

UniProtKB/Swiss-Prot:

VHL_HUMAN :
  • The Elongin BC complex binding domain is also known as BC-box with the consensus [APST]-L-x(3)-C-x(3)-[AILV].
  • Belongs to the VHL family.
Domain:
  • The Elongin BC complex binding domain is also known as BC-box with the consensus [APST]-L-x(3)-C-x(3)-[AILV].
Family:
  • Belongs to the VHL family.
genes like me logo Genes that share domains with VHL: view

No data available for Gene Families for VHL Gene

Function for VHL Gene

Molecular function for VHL Gene

GENATLAS Biochemistry:
Tumor suppressor protein,complexing with CUL2,elongin B,elongin C Rbx/ROC1 and an ubiquitin conjugating enzyme other than CDC34,either UBE2B,2D1,L6 or others to form an active E3 ubiquitin ligase complex named the VCB-CUL2 complex,targetting and regulating the hypoxia inducible protein HIF in normoxic conditions,also involved in cell cycle regulation exit of cell cycle upon serum withdrawal and in extracellular matrix formation through interaction with fibronectin may be an inhibitor of the transcriptor elongation factor B (SIII) through competition to binding TCEB1 and TCEBD
UniProtKB/Swiss-Prot Function:
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.

Gene Ontology (GO) - Molecular Function for VHL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004842 ubiquitin-protein transferase activity TAS --
genes like me logo Genes that share ontologies with VHL: view
genes like me logo Genes that share phenotypes with VHL: view

Human Phenotype Ontology for VHL Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for VHL Gene

MGI Knock Outs for VHL:

Animal Model Products

Inhibitory RNA Products

In Situ Assay Products

Flow Cytometry Products

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for VHL Gene

Localization for VHL Gene

Subcellular locations from UniProtKB/Swiss-Prot for VHL Gene

Isoform 1: Cytoplasm. Membrane; Peripheral membrane protein. Nucleus. Note=Found predominantly in the cytoplasm and with less amounts nuclear or membrane-associated. Colocalizes with ADRB2 at the cell membrane.
Isoform 3: Cytoplasm. Nucleus. Note=Equally distributed between the nucleus and the cytoplasm but not membrane-associated.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for VHL Gene COMPARTMENTS Subcellular localization image for VHL gene
Compartment Confidence
cytosol 5
endoplasmic reticulum 5
mitochondrion 5
nucleus 5
cytoskeleton 3
extracellular 1

Gene Ontology (GO) - Cellular Components for VHL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005829 cytosol TAS --
genes like me logo Genes that share ontologies with VHL: view

Pathways & Interactions for VHL Gene

genes like me logo Genes that share pathways with VHL: view

UniProtKB/Swiss-Prot P40337-VHL_HUMAN

  • Pathway: Protein modification; protein ubiquitination.

SIGNOR curated interactions for VHL Gene

Inactivates:
Is activated by:

Gene Ontology (GO) - Biological Process for VHL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000902 cell morphogenesis NAS 12169691
GO:0006355 regulation of transcription, DNA-templated IMP 15824735
GO:0006508 proteolysis TAS 10353251
GO:0043066 negative regulation of apoptotic process NAS 12169691
GO:0045893 positive regulation of transcription, DNA-templated IMP 17973242
genes like me logo Genes that share ontologies with VHL: view

Drugs & Compounds for VHL Gene

(41) Drugs for VHL Gene - From: Novoseek and ClinicalTrials

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Sunitinib Approved, Investigational Pharma VEGFR/PDGFRβ/ KIT/ FLT3/RET/CSF-1R inhibitor, RTK inhibitor, Kinase Inhibitors, Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) inhibitors, Potent VEGFR, PDGFRbeta and KIT inhibitor 486
Bevacizumab Approved, Investigational Pharma VEGF antagonist, Therapeutic Antibodies, Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) inhibitors 1875
Everolimus Approved Pharma mTOR inhibitor, mTOR Inhibitors, Kinase Inhibitors, Mammalian target of rapamycin (mTOR) inhibitors 1797
Miconazole Approved, Investigational Pharma Antagonist, Pore Blocker 3026
Pancrelipase Approved Pharma 880

(14) Additional Compounds for VHL Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with VHL: view

Transcripts for VHL Gene

Unigene Clusters for VHL Gene

Von Hippel-Lindau tumor suppressor, E3 ubiquitin protein ligase:
Representative Sequences:

Inhibitory RNA Products

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for VHL Gene

ExUns: 1a · 1b · 1c ^ 2 ^ 3 ^ 4
SP1: -
SP2: - -
SP3:

Relevant External Links for VHL Gene

GeneLoc Exon Structure for
VHL
ECgene alternative splicing isoforms for
VHL

Expression for VHL Gene

mRNA expression in normal human tissues for VHL Gene

Protein differential expression in normal tissues from HIPED for VHL Gene

This gene is overexpressed in Testis (42.8), Fetal ovary (13.7), and Peripheral blood mononuclear cells (7.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MOPED, and MaxQB for VHL Gene



SOURCE GeneReport for Unigene cluster for VHL Gene Hs.517792

mRNA Expression by UniProt/SwissProt for VHL Gene

P40337-VHL_HUMAN
Tissue specificity: Expressed in the adult and fetal brain and kidney.
genes like me logo Genes that share expression patterns with VHL: view

Protein tissue co-expression partners for VHL Gene

Primer Products

In Situ Assay Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and mRNA differential expression in normal tissues for VHL Gene

Orthologs for VHL Gene

This gene was present in the common ancestor of chordates.

Orthologs for VHL Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia VHL 36
  • 97 (a)
OneToOne
cow
(Bos Taurus)
Mammalia VHL 36
  • 87 (a)
OneToOne
VHL 35
  • 89.43 (n)
  • 93.9 (a)
dog
(Canis familiaris)
Mammalia VHL 35
  • 89.73 (n)
  • 89.57 (a)
mouse
(Mus musculus)
Mammalia Vhl 16
Vhl 36
  • 85 (a)
OneToMany
Vhl 35
  • 83.33 (n)
  • 86.36 (a)
oppossum
(Monodelphis domestica)
Mammalia -- 36
  • 68 (a)
ManyToMany
-- 36
  • 69 (a)
ManyToMany
rat
(Rattus norvegicus)
Mammalia Vhl 35
  • 86.5 (n)
  • 93.04 (a)
chicken
(Gallus gallus)
Aves VHL 35
  • 71.39 (n)
  • 71.63 (a)
-- 36
  • 56 (a)
OneToMany
lizard
(Anolis carolinensis)
Reptilia -- 36
  • 68 (a)
OneToMany
tropical clawed frog
(Silurana tropicalis)
Amphibia Str.17385 35
vhl 35
  • 68.31 (n)
  • 66.2 (a)
zebrafish
(Danio rerio)
Actinopterygii vhl 36
  • 47 (a)
OneToMany
vhl 35
  • 55.94 (n)
  • 54.11 (a)
Species with no ortholog for VHL:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • platypus (Ornithorhynchus anatinus)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for VHL Gene

ENSEMBL:
Gene Tree for VHL (if available)
TreeFam:
Gene Tree for VHL (if available)

Paralogs for VHL Gene

Paralogs for VHL Gene

(1) SIMAP similar genes for VHL Gene using alignment to 5 proteins:

genes like me logo Genes that share paralogs with VHL: view

Variants for VHL Gene

Sequence variations from dbSNP and Humsavar for VHL Gene

SNP ID Clin Chr 03 pos Sequence Context AA Info Type
VAR_005670 Von Hippel-Lindau disease (VHLD)
VAR_005671 Von Hippel-Lindau disease (VHLD)
VAR_005672 Von Hippel-Lindau disease (VHLD)
VAR_005673 Von Hippel-Lindau disease (VHLD)
VAR_005675 Pheochromocytoma (PCC)

Structural Variations from Database of Genomic Variants (DGV) for VHL Gene

Variant ID Type Subtype PubMed ID
dgv809e201 CNV Deletion 23290073
nsv436362 CNV Deletion 17901297
nsv436869 CNV Insertion 17901297
esv4117 CNV Complex 18987735
nsv3693 CNV Insertion 18451855
esv2662777 CNV Deletion 23128226

Variation tolerance for VHL Gene

Residual Variation Intolerance Score: 32% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.49; 10.64% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for VHL Gene

HapMap Linkage Disequilibrium report
VHL
Human Gene Mutation Database (HGMD)
VHL

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for VHL Gene

Disorders for VHL Gene

MalaCards: The human disease database

(30) MalaCards diseases for VHL Gene - From: OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
von hippel-lindau syndrome
  • von hippel-lindau syndrome, modifier of
erythrocytosis, familial, 2
  • chuvash polycythemia
pheochromocytoma
  • pheochromocytoma, modifier of
renal cell carcinoma
  • renal cell carcinoma, clear cell, somatic
vhl-related pheochromocytoma
- elite association - COSMIC cancer census association via MalaCards
Search VHL in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

VHL_HUMAN
  • Pheochromocytoma (PCC) [MIM:171300]: 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. {ECO:0000269 PubMed:12000816, ECO:0000269 PubMed:14500403, ECO:0000269 PubMed:9663592}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
  • von Hippel-Lindau disease (VHLD) [MIM:193300]: 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). {ECO:0000269 PubMed:10408776, ECO:0000269 PubMed:10533030, ECO:0000269 PubMed:10627136, ECO:0000269 PubMed:10635329, ECO:0000269 PubMed:16502427, ECO:0000269 PubMed:7728151, ECO:0000269 PubMed:7987306, ECO:0000269 PubMed:8493574, ECO:0000269 PubMed:8592333, ECO:0000269 PubMed:8634692, ECO:0000269 PubMed:8730290, ECO:0000269 PubMed:8825918, ECO:0000269 PubMed:8956040, ECO:0000269 PubMed:9452032, ECO:0000269 PubMed:9452106, ECO:0000269 PubMed:9829911, ECO:0000269 PubMed:9829912, ECO:0000269 Ref.41}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Erythrocytosis, familial, 2 (ECYT2) [MIM:263400]: 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. {ECO:0000269 PubMed:12393546, ECO:0000269 PubMed:12844285}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Renal cell carcinoma (RCC) [MIM:144700]: 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. {ECO:0000269 PubMed:11986208}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Relevant External Links for VHL

Genetic Association Database (GAD)
VHL
Human Genome Epidemiology (HuGE) Navigator
VHL
Tumor Gene Database (TGDB):
VHL
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
VHL
genes like me logo Genes that share disorders with VHL: view

No data available for Genatlas for VHL Gene

Publications for VHL Gene

  1. Mutations of von Hippel-Lindau tumor-suppressor gene and congenital polycythemia. (PMID: 12844285) Pastore Y.D. … Prchal J.T. (Am. J. Hum. Genet. 2003) 3 4 23 48 67
  2. A second major native von Hippel-Lindau gene product, initiated from an internal translation start site, functions as a tumor suppressor. (PMID: 9671762) Schoenfeld A. … Burk R.D. (Proc. Natl. Acad. Sci. U.S.A. 1998) 2 3 23
  3. Genetic analysis of von Hippel-Lindau disease. (PMID: 20151405) Nordstrom-O'Brien M. … Giles R.H. (Hum. Mutat. 2010) 3 23
  4. TP53, EGFR, and KRAS mutations in relation to VHL inactivation and lifestyle risk factors in renal-cell carcinoma from central and eastern Europe. (PMID: 20137853) SzymaA8ska K. … Brennan P. (Cancer Lett. 2010) 3 23
  5. Von Hippel-Lindau gene product modulates TIS11B expression in renal cell carcinoma: impact on vascular endothelial growth factor expression in hypoxia. (PMID: 19801654) Sinha S. … Mukhopadhyay D. (J. Biol. Chem. 2009) 3 23

Products for VHL Gene

Sources for VHL Gene

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