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Aliases for VHL Gene

Aliases for VHL Gene

  • Von Hippel-Lindau Tumor Suppressor 2 3 5
  • 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 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
  • GC03P010147
  • GC03P010148
  • GC03P010152
  • GC03P010153

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]

CIViC summary for VHL Gene

  • Von Hippel-Lindau (VHL) disease is characterized by heterozygous germline mutation in VHL gene on chromosome 3p. Patients are predisposed to developing hemangioblastomas of the brain, spinal cord, and retina; renal cysts and clear cell renal cell carcinoma; pheochromocytoma, pancreatic cysts and neuroendocrine tumors; endolymphatic sac tumors; and epididymal and broad ligament cysts. Cerebellar hemangioblastomas may be associated with headache, vomiting, gait disturbances, or ataxia. Spinal hemangioblastomas and related syrinx usually present with pain. Sensory and motor loss may develop with cord compression. Retinal hemangioblastomas may be the initial manifestation of VHL disease and can cause vision loss. Renal cell carcinoma occurs in about 70% of individuals with VHL and is the leading cause of mortality. Pheochromocytomas can be asymptomatic but may cause sustained or episodic hypertension. Pancreatic lesions often remain asymptomatic and rarely cause endocrine or exocrine insufficiency. Endolymphatic sac tumors can cause hearing loss of varying severity, which can be a presenting symptom. Cystadenomas of the epididymis are relatively common. They rarely cause problems, unless bilateral, in which case they may result in infertility. The VHL gene product encodes pVHL, which binds to elongin C, elongin B, cullin-2 and Rbx1. This complex catalyzes the polyubiquitinylation of specific proteins and targets them for degradation by proteosomes. For example, under normoxic conditions, hydroxylated hypoxia-inducble factor alpha subunits (HIFα) binds pVHL targets HIFα for degradation. Under hypoxic conditions, HIF1α is not hydroxylated, pVHL does not bind, and HIF1α subunits accumulate. HIF1α forms heterodimers with HIF1β and activates transcription of a variety of hypoxia-inducible genes (i.e., VEGF, EPO, TGFα, PDGFβ). Likewise, when pVHL is absent or mutated, HIF1α subunits accumulate, resulting in cell proliferation and the neovascularization of tumors characteristic of VHL disease. Pathogenic variants in VHL either prevent its expression (i.e., deletions, frameshifts, nonsense mutations, and splice site mutations) or lead to the expression of an abnormal protein (i.e., missense mutations). Missense mutations that destabilize packing of the alpha-helical domains, decrease the stability of the alpha-beta domain interface, interfere with binding of elongin C and HIF1α, or disrupt hydrophobic core residues result in loss of HIF regulation and are more likely to result in VHL type 1 (no predisposition to pheochromocytoma). Missense mutations that result in pVHL that is normal with respect to HIF regulation are more likely to be associated with VHL with clinical pheochromocytoma. Acquired somatic pathogenic variants in VHL may give rise to sporadic VHL-type tumors (i.e., clear cell RCC and hemangioblastoma) without other associated tumors characteristic of the hereditary disease. It should be noted that >90% of the most common form of kidney cancer (clear cell renal cell carcinoma) are associated with bi-allelic somatic mutation in the VHL gene, and is the rationale for the anti-angiogenic therapy for RCC patients.

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 CDK-mediated phosphorylation and removal of Cdc6 and Cellular Senescence (REACTOME). 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

Additional gene information 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

Enhancers for VHL Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH03H010188 2.1 FANTOM5 Ensembl ENCODE dbSUPER 18.5 +53.8 53837 12 HDGF PKNOX1 FOXA2 ARNT ARID4B SIN3A ZNF2 ZBTB7B YY1 ZNF143 BRPF1 SETD5 IRAK2 GHRLOS LINC00852 TATDN2 FANCD2 BRK1 GHRL TTLL3
GH03H010201 1.9 FANTOM5 Ensembl ENCODE dbSUPER 15.5 +63.5 63514 6 FOXA2 ATF1 MLX ZFP64 ARID4B DMAP1 YY1 FOS REST PPARG IRAK2 TATDN2 VHL GHRLOS ARPC4 FANCD2OS GHRL SEC13 CAMK1 ARPC4-TTLL3
GH03H009975 1.6 Ensembl ENCODE dbSUPER 10.8 -162.8 -162795 4 HDGF PKNOX1 FOXA2 ARNT ARID4B SIN3A ZNF2 YY1 ZNF766 FOS BRPF1 TTLL3 SETD5 FANCD2 THUMPD3-AS1 BRK1 EMC3-AS1 PRRT3 CIDECP ENSG00000269894
GH03H010247 1.4 ENCODE dbSUPER 11.5 +108.2 108219 2 HDGF PKNOX1 FOXA2 ARNT ARID4B SIN3A DMAP1 ZNF2 YY1 CBX5 GHRLOS EMC3-AS1 SETD5 BRPF1 GHRL IRAK2 FANCD2OS VHL SEC13 IL17RE
GH03H010251 0.8 ENCODE dbSUPER 11.5 +110.1 110124 0 ZFHX2 SCRT2 ZKSCAN1 EGR2 GHRL VHL IRAK2 SEC13 FANCD2OS IL17RE PRRT3 ARPC4 ARPC4-TTLL3 TADA3
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around VHL on UCSC Golden Path with GeneCards custom track

Promoters for VHL Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000148356 1092 1401 HDGF PKNOX1 ARNT ARID4B SIN3A DMAP1 ZNF2 ZBTB7B YY1 SLC30A9

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 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.

    Three dimensional structures from OCA and Proteopedia for VHL Gene

    Alternative splice isoforms for VHL Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for VHL Gene

Post-translational modifications for VHL Gene

  • Ubiquitination at posLast=196196
  • Modification sites at PhosphoSitePlus

Other Protein References for VHL Gene

No data available for DME Specific Peptides for VHL Gene

Domains & Families for VHL Gene

Gene Families for VHL Gene

Human Protein Atlas (HPA):
  • Cancer-related genes
  • Disease related genes
  • Predicted intracellular proteins

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

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.

Phenotypes From GWAS Catalog for VHL Gene

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 10205047
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

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

CRISPR Products

Inhibitory RNA Products

Clone Products

  • Addgene plasmids for VHL
  • Applied Biological Materials Clones for VHL
  • Vectors and viruses for ORF, Lenti, Retro, Adenovirus, AAV, and more

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
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for VHL gene
Compartment Confidence
mitochondrion 5
nucleus 5
endoplasmic reticulum 5
cytosol 5
cytoskeleton 3
extracellular 2

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nucleoplasm (4)
  • Cytosol (3)
See all subcellular structures

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:0005737 cytoplasm IEA --
GO:0005739 mitochondrion NAS 12169691
GO:0005783 endoplasmic reticulum NAS 12169691
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: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 IMP 23338840
genes like me logo Genes that share ontologies with VHL: view

Drugs & Compounds for VHL Gene

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

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 514
Bevacizumab Approved, Investigational Pharma VEGF antagonist, Therapeutic Antibodies, Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) inhibitors 2052
Everolimus Approved Pharma mTOR inhibitor, mTOR Inhibitors, Kinase Inhibitors, Mammalian target of rapamycin (mTOR) inhibitors 1977
Miconazole Approved, Investigational, Vet_approved Pharma Antagonist, Pore Blocker 3778
Pancrelipase Approved Pharma 996

(12) 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:

CRISPR Products

Inhibitory RNA Products

Clone Products

  • Addgene plasmids for VHL
  • Applied Biological Materials Clones for VHL
  • Vectors and viruses for ORF, Lenti, Retro, Adenovirus, AAV, and more

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 from GTEx, Illumina, BioGPS, and CGAP SAGE 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, MaxQB, and MOPED for VHL Gene



Protein tissue co-expression partners for VHL Gene

NURSA nuclear receptor signaling pathways regulating expression of VHL Gene:

VHL

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.

Evidence on tissue expression from TISSUES for VHL Gene

  • Nervous system(4.5)
  • Pancreas(3.1)
  • Intestine(3)
  • Kidney(2.6)

Phenotype-based relationships between genes and organs from Gene ORGANizer for VHL Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • endocrine
  • immune
  • integumentary
  • nervous
  • reproductive
  • respiratory
  • skeletal muscle
  • skeleton
  • urinary
Organs:
Head and neck:
  • brain
  • cerebellum
  • cerebrospinal fluid
  • cranial nerve
  • ear
  • eye
  • head
  • meninges
  • neck
  • skull
Thorax:
  • esophagus
  • heart
  • heart valve
  • lung
Abdomen:
  • adrenal gland
  • intestine
  • kidney
  • large intestine
  • liver
  • pancreas
  • small intestine
  • spleen
  • stomach
Pelvis:
  • testicle
General:
  • blood
  • blood vessel
  • coagulation system
  • peripheral nerve
  • peripheral nervous system
  • red blood cell
  • skin
  • spinal cord
  • sweat gland
genes like me logo Genes that share expression patterns with VHL: view

Primer 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 34
  • 97 (a)
OneToOne
dog
(Canis familiaris)
Mammalia VHL 33
  • 89.73 (n)
cow
(Bos Taurus)
Mammalia VHL 33 34
  • 89.43 (n)
rat
(Rattus norvegicus)
Mammalia Vhl 33
  • 86.5 (n)
mouse
(Mus musculus)
Mammalia Vhl 33 16 34
  • 83.33 (n)
oppossum
(Monodelphis domestica)
Mammalia -- 34
  • 69 (a)
ManyToMany
-- 34
  • 68 (a)
ManyToMany
chicken
(Gallus gallus)
Aves VHL 33
  • 71.39 (n)
-- 34
  • 56 (a)
OneToMany
lizard
(Anolis carolinensis)
Reptilia -- 34
  • 68 (a)
OneToMany
tropical clawed frog
(Silurana tropicalis)
Amphibia vhl 33
  • 68.31 (n)
Str.17385 33
zebrafish
(Danio rerio)
Actinopterygii vhl 33 34
  • 55.94 (n)
Species where no ortholog for VHL was found in the sources mined by GeneCards:
  • 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
rs104893824 Pathogenic, Von Hippel-Lindau disease (VHLD) [MIM:193300], Von Hippel-Lindau disease (VHLD) [MIM:193300] 10,142,181(+) ACAGC(A/C/T)ACCGA reference, missense
rs104893825 Pathogenic, Von Hippel-Lindau disease (VHLD) [MIM:193300] 10,149,819(+) AGGTT(G/T)TCCGG reference, missense
rs104893826 Pathogenic, Pheochromocytoma (PCC) [MIM:171300] 10,142,038(+) GCTGC(A/C/G)CTCGG reference, missense
rs104893827 Pathogenic, Pheochromocytoma (PCC) [MIM:171300] 10,142,035(+) CGTGC(C/T)GCGCT reference, missense
rs104893830 Pathogenic, Erythrocytosis, familial, 2 (ECYT2) [MIM:263400], Von Hippel-Lindau disease (VHLD) [MIM:193300] 10,146,561(+) TTCTG(C/G)TTAAC intron-variant, reference, missense

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

Variant ID Type Subtype PubMed ID
dgv762e201 CNV deletion 23290073
esv2662777 CNV deletion 23128226
esv3595261 CNV loss 21293372
esv4117 OTHER complex 18987735
nsv1073204 CNV deletion 25765185
nsv1121603 CNV deletion 24896259
nsv3693 CNV insertion 18451855
nsv436362 CNV deletion 17901297
nsv436869 CNV insertion 17901297

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

Human Gene Mutation Database (HGMD)
VHL
SNPedia medical, phenotypic, and genealogical associations of SNPs for
VHL

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

Disorders for VHL Gene

MalaCards: The human disease database

(34) MalaCards diseases for VHL Gene - From: HGMD, 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
renal cell carcinoma
  • renal cell carcinoma, clear cell, somatic
pheochromocytoma
  • pheochromocytoma, modifier of
kidney cancer
  • malignant neoplasm of kidney except pelvis
- 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
  • 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.
  • 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.
  • 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.
  • 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.

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 … Prchal JT (American journal of human genetics 2003) 3 4 22 45 60
  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 RD (Proceedings of the National Academy of Sciences of the United States of America 1998) 2 3 4 22 60
  3. 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) Szymańska K … Brennan P (Cancer letters 2010) 3 22 45 60
  4. Head and neck paragangliomas in von Hippel-Lindau disease and multiple endocrine neoplasia type 2. (PMID: 19336503) Boedeker CC … Neumann HP (The Journal of clinical endocrinology and metabolism 2009) 3 22 45 60
  5. Oxygen-regulated beta(2)-adrenergic receptor hydroxylation by EGLN3 and ubiquitylation by pVHL. (PMID: 19584355) Xie L … Stamler JS (Science signaling 2009) 3 4 22 60

Products for VHL Gene

  • Addgene plasmids for VHL

Sources for VHL Gene

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