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

    Gene ID: 7428, updated on 9-Jul-2017
    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; Vega:OTTHUMG00000128668
    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]
    Orthologs
    Location:
    3p25.3
    Exon count:
    3
    Annotation release Status Assembly Chr Location
    108 current GRCh38.p7 (GCF_000001405.33) 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 Fanconi anemia complementation group D2 Neighboring gene FANCD2 opposite strand Neighboring gene BRICK1, SCAR/WAVE actin nucleating complex subunit Neighboring gene interleukin 1 receptor associated kinase 2 Neighboring gene TatD DNase domain containing 2 Neighboring gene ghrelin opposite strand/antisense RNA

    • 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

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    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
    Products Interactant Other Gene Complex Source Pubs Description

    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 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 from RNA polymerase II promoter 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 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 
    protein ubiquitination TAS
    Traceable Author Statement
    more info
     
    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
     
    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 TAS
    Traceable Author Statement
    more info
    PubMed 
    Preferred Names
    von Hippel-Lindau disease tumor suppressor
    Names
    elongin binding protein
    protein G7
    von Hippel-Lindau tumor suppressor, E3 ubiquitin protein ligase

    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) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      AC034193, AK315799, BC058831, D58014, L15409
      Consensus CDS
      CCDS2597.1
      UniProtKB/Swiss-Prot
      P40337
      UniProtKB/TrEMBL
      A0A024R2F2
      Related
      ENSP00000256474.2, OTTHUMP00000158850, ENST00000256474.2, OTTHUMT00000250559
      Conserved Domains (2) summary
      pfam05887
      Location:786
      Trypan_PARP; Procyclic acidic repetitive protein (PARP)
      pfam01847
      Location:61205
      VHL; von Hippel-Lindau disease tumour suppressor protein
    2. 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, OTTHUMP00000158851, ENST00000345392.2, OTTHUMT00000250560
      Conserved Domains (2) summary
      pfam05887
      Location:786
      Trypan_PARP; Procyclic acidic repetitive protein (PARP)
      cl03381
      Location:61164
      pVHL; von Hippel-Landau (pVHL) tumor suppressor protein

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 108 details...Open this link in a new tab

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

    Reference GRCh38.p7 Primary Assembly

    Genomic

    1. NC_000003.12 Reference GRCh38.p7 Primary Assembly

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

    Alternate CHM1_1.1

    Genomic

    1. NC_018914.2 Alternate CHM1_1.1

      Range
      10133330..10145363
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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