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Aliases for VHL Gene

Aliases for VHL Gene

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

External Ids for VHL Gene

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, E3 Ubiquitin Protein Ligase) is a Protein Coding gene. Diseases associated with VHL include erythrocytosis, familial, 2 and vhl-related pheochromocytoma. Among its related pathways are Class I MHC mediated antigen processing and presentation and Pathways in cancer. GO annotations related to this gene include transcription factor binding and enzyme binding. 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 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

Genomic Location for VHL Gene

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

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for VHL Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for VHL Gene

Regulatory Elements 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

  • Modification sites at PhosphoSitePlus
  • Ubiquitination at Lys196

Other Protein References for VHL Gene

ENSEMBL proteins:
Reactome Protein details:
REFSEQ proteins:

No data available for DME Specific Peptides for VHL Gene

Domains for VHL Gene

Protein Domains for VHL Gene

UniProtKB/Swiss-Prot:

VHL_HUMAN
Domain:
  • The Elongin BC complex binding domain is also known as BC-box with the consensus [APST]-L-x(3)-C-x(3)-[AILV]:
    • P40337
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 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 --
GO:0005515 protein binding IPI 11292862
GO:0008134 transcription factor binding IPI 11641274
GO:0019899 enzyme binding IPI 11641274
GO:0061630 ubiquitin protein ligase activity IDA 24899725
genes like me logo Genes that share ontologies with VHL: view
genes like me logo Genes that share phenotypes with VHL: view

Animal Models for VHL Gene

MGI Knock Outs for VHL:

miRNA for VHL Gene

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targeting 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
endoplasmic reticulum 5
mitochondrion 5
nucleus 5
cytosol 4
cytoskeleton 1
extracellular 1

Gene Ontology (GO) - Cellular Components for VHL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus TAS 7604013
GO:0005654 nucleoplasm TAS --
GO:0005739 mitochondrion NAS 12169691
GO:0005783 endoplasmic reticulum NAS 12169691
GO:0005829 cytosol TAS --
genes like me logo Genes that share ontologies with VHL: view

Pathways 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

Gene Ontology (GO) - Biological Process for VHL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription from RNA polymerase II promoter TAS 7660122
GO:0000902 cell morphogenesis NAS 12169691
GO:0006355 regulation of transcription, DNA-templated IMP 15824735
GO:0006508 proteolysis TAS 10353251
GO:0008285 negative regulation of cell proliferation TAS 7660130
genes like me logo Genes that share ontologies with VHL: view

Compounds for VHL Gene

(35) Novoseek inferred chemical compound relationships for VHL Gene

Compound -log(P) Hits PubMed IDs
vegf 68.8 89
succinate 58.1 7
ehen 54.8 1
fumarate 54.5 4
oxygen 50.3 52
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:

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

Integrated Proteomics: protein expression 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 expressions with VHL: view

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 37
  • 97 (a)
OneToOne
cow
(Bos Taurus)
Mammalia VHL 36
  • 89.43 (n)
  • 93.9 (a)
VHL 37
  • 87 (a)
OneToOne
dog
(Canis familiaris)
Mammalia VHL 36
  • 89.73 (n)
  • 89.57 (a)
mouse
(Mus musculus)
Mammalia Vhl 36
  • 83.33 (n)
  • 86.36 (a)
Vhl 16
Vhl 37
  • 85 (a)
OneToMany
oppossum
(Monodelphis domestica)
Mammalia -- 37
  • 68 (a)
ManyToMany
-- 37
  • 69 (a)
ManyToMany
rat
(Rattus norvegicus)
Mammalia Vhl 36
  • 86.5 (n)
  • 93.04 (a)
chicken
(Gallus gallus)
Aves -- 37
  • 56 (a)
OneToMany
VHL 36
  • 71.39 (n)
  • 71.63 (a)
lizard
(Anolis carolinensis)
Reptilia -- 37
  • 68 (a)
OneToMany
tropical clawed frog
(Silurana tropicalis)
Amphibia Str.17385 36
vhl 36
  • 68.31 (n)
  • 66.2 (a)
zebrafish
(Danio rerio)
Actinopterygii vhl 36
  • 55.94 (n)
  • 54.11 (a)
vhl 37
  • 47 (a)
OneToMany
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

Selected 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 MAF
rs166484 -- 10,147,997(-) cacct(A/T)agcct intron-variant
rs187873 -- 10,148,011(-) tcaag(A/G)gatcc intron-variant
rs187874 -- 10,148,004(-) atcct(A/C)ccacc intron-variant
rs192374 -- 10,148,017(-) ctggg(C/T)tcaag intron-variant
rs271989 -- 10,148,464(+) cgccc(A/G)ccact intron-variant

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

Relevant External Links for VHL Gene

HapMap Linkage Disequilibrium report
VHL
Human Gene Mutation Database (HGMD)
VHL
Locus Specific Mutation Databases (LSDB)
VHL

Disorders for VHL Gene

(4) OMIM Diseases for VHL Gene (608537)

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.

(4) University of Copenhagen DISEASES for VHL Gene

(82) Novoseek inferred disease relationships for VHL Gene

Disease -log(P) Hits PubMed IDs
renal clear cell carcinoma 93.2 69
von hippel-lindau disease 93 66
carcinoma renal cell 89.9 139
hemangioblastoma 88.1 33
renal cancer 85.1 35

Relevant External Links for VHL

GeneTests
VHL
GeneReviews
VHL
Genetic Association Database (GAD)
VHL
Human Genome Epidemiology (HuGE) Navigator
VHL
Tumor Gene Database (TGDB):
VHL
genes like me logo Genes that share disorders with VHL: view

Publications for VHL Gene

  1. 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 4 23
  2. Germ-line mutations in nonsyndromic pheochromocytoma. (PMID: 12000816) Neumann H.P.H. … Eng C. (N. Engl. J. Med. 2002) 3 4 23 49
  3. 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 49
  4. Congenital disorder of oxygen sensing: association of the homozygous Chuvash polycythemia VHL mutation with thrombosis and vascular abnormalities but not tumors. (PMID: 14726398) Gordeuk V.R. … Polyakova L.A. (Blood 2004) 3 23 49
  5. Hypertension, antihypertensives and mutations in the Von Hippel-Lindau gene in renal cell carcinoma: results from the Netherlands Cohort Study. (PMID: 16208141) Schouten L.J. … van den Brandt P.A. (J. Hypertens. 2005) 3 23 49

Products for VHL Gene

  • Addgene plasmids for VHL

Sources for VHL Gene

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