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VHL von Hippel-Lindau tumor suppressor [ Homo sapiens (human) ]

Gene ID: 7428, updated on 5-Dec-2018

Summary

Official Symbol
VHLprovided by HGNC
Official Full Name
von Hippel-Lindau tumor suppressorprovided by HGNC
Primary source
HGNC:HGNC:12687
See related
Ensembl:ENSG00000134086 MIM:608537
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
RCA1; VHL1; pVHL; HRCA1
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]
Expression
Ubiquitous expression in lymph node (RPKM 12.2), spleen (RPKM 10.0) and 25 other tissues See more
Orthologs

Genomic context

See VHL in Genome Data Viewer
Location:
3p25.3
Exon count:
4
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 3 NC_000003.12 (10141635..10153670)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (10183319..10195354)

Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene FA complementation group D2 Neighboring gene FANCD2 opposite strand Neighboring gene 3p25 BRK1 Alu-mediated recombination region Neighboring gene 3p25 von Hippel-Lindau tumor suppressor, E3 ubiquitin protein ligase Alu-mediated recombination region Neighboring gene BRICK1, SCAR/WAVE actin nucleating complex subunit Neighboring gene 3p25 IRAK2 Alu-mediated recombination region Neighboring gene interleukin 1 receptor associated kinase 2 Neighboring gene 3p25 TatD DNase domain containing 2 Alu-mediated recombination region Neighboring gene TatD DNase domain containing 2

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Jun 15 11:32:44 2016

Bibliography

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Phenotypes

Professional guidelines

Description
Professional guideline
ACMG 2013

The ACMG recommends that laboratories performing clinical sequencing seek and report mutations in VHL that are pathogenic or expected to be pathogenic.

GuidelinePubMed

Copy number response

Description
Copy number response
Triplosensitivity

No evidence available (Last evaluated (2017-06-28)

ClinGen Genome Curation Page
Haploinsufficency

Sufficient evidence for dosage pathogenicity (Last evaluated (2017-06-28)

ClinGen Genome Curation PagePubMed

Pathways from BioSystems

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enzyme binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
transcription factor binding IPI
Inferred from Physical Interaction
more info
PubMed 
ubiquitin protein ligase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
ubiquitin protein ligase activity IDA
Inferred from Direct Assay
more info
PubMed 
ubiquitin-protein transferase activity TAS
Traceable Author Statement
more info
 
Process Evidence Code Pubs
cell morphogenesis NAS
Non-traceable Author Statement
more info
PubMed 
negative regulation of JAK-STAT cascade IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of apoptotic process NAS
Non-traceable Author Statement
more info
PubMed 
negative regulation of cell proliferation IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of gene expression IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of transcription by RNA polymerase II TAS
Traceable Author Statement
more info
PubMed 
negative regulation of transcription from RNA polymerase II promoter in response to hypoxia IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of cell differentiation NAS
Non-traceable Author Statement
more info
PubMed 
positive regulation of transcription, DNA-templated IMP
Inferred from Mutant Phenotype
more info
PubMed 
post-translational protein modification TAS
Traceable Author Statement
more info
 
protein stabilization NAS
Non-traceable Author Statement
more info
PubMed 
protein ubiquitination IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
protein ubiquitination IDA
Inferred from Direct Assay
more info
PubMed 
protein ubiquitination IEA
Inferred from Electronic Annotation
more info
 
protein ubiquitination IMP
Inferred from Mutant Phenotype
more info
PubMed 
proteolysis TAS
Traceable Author Statement
more info
PubMed 
regulation of transcription from RNA polymerase II promoter in response to hypoxia TAS
Traceable Author Statement
more info
 
regulation of transcription, DNA-templated IMP
Inferred from Mutant Phenotype
more info
PubMed 
Component Evidence Code Pubs
VCB complex IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
cytosol TAS
Traceable Author Statement
more info
 
endoplasmic reticulum NAS
Non-traceable Author Statement
more info
PubMed 
membrane IEA
Inferred from Electronic Annotation
more info
 
mitochondrion NAS
Non-traceable Author Statement
more info
PubMed 
nucleoplasm IDA
Inferred from Direct Assay
more info
 
nucleoplasm TAS
Traceable Author Statement
more info
 
nucleus IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 

General protein information

Preferred Names
von Hippel-Lindau disease tumor suppressor
Names
elongin binding protein
protein G7
von Hippel-Lindau tumor suppressor, E3 ubiquitin protein ligase

NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_008212.3 RefSeqGene

    Range
    5001..17036
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_322

mRNA and Protein(s)

  1. NM_000551.3NP_000542.1  von Hippel-Lindau disease tumor suppressor isoform 1

    See identical proteins and their annotated locations for NP_000542.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longest isoform (1).
    Source sequence(s)
    AC034193, AK315799, BC058831, D58014, L15409
    Consensus CDS
    CCDS2597.1
    UniProtKB/Swiss-Prot
    P40337
    UniProtKB/TrEMBL
    A0A024R2F2
    Related
    ENSP00000256474.2, ENST00000256474.2
    Conserved Domains (2) summary
    cd05468
    Location:64203
    pVHL; von Hippel-Landau (pVHL) tumor suppressor protein
    cl25865
    Location:786
    Trypan_PARP; Procyclic acidic repetitive protein (PARP)
  2. NM_001354723.1NP_001341652.1  von Hippel-Lindau disease tumor suppressor isoform 3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) lacks an alternate in-frame exon and contains another alternate exon compared to variant 1. The resulting isoform (3) has a shorter and distinct C-terminus compared to variant 1.
    Source sequence(s)
    AC034193, HY256093
    Conserved Domains (2) summary
    cl03381
    Location:63113
    pVHL; von Hippel-Landau (pVHL) tumor suppressor protein
    cl25865
    Location:786
    Trypan_PARP; Procyclic acidic repetitive protein (PARP)
  3. NM_198156.2NP_937799.1  von Hippel-Lindau disease tumor suppressor isoform 2

    See identical proteins and their annotated locations for NP_937799.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an in-frame coding exon compared to variant 1. The resulting isoform (2) lacks an internal region, as compared to isoform 1.
    Source sequence(s)
    AC034193, AK315799, BC058831, D58014, L15409
    Consensus CDS
    CCDS2598.1
    UniProtKB/Swiss-Prot
    P40337
    UniProtKB/TrEMBL
    A0A0S2Z4K1
    Related
    ENSP00000344757.2, ENST00000345392.2
    Conserved Domains (3) summary
    pfam17211
    Location:114163
    VHL_C; VHL box domain
    cl03381
    Location:63113
    pVHL; von Hippel-Landau (pVHL) tumor suppressor protein
    cl25865
    Location:786
    Trypan_PARP; Procyclic acidic repetitive protein (PARP)

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...Open this link in a new tab

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000003.12 Reference GRCh38.p12 Primary Assembly

    Range
    10141635..10153670
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
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