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

    Gene ID: 7428, updated on 11-Jul-2021

    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
    NEW
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    Genomic context

    See VHL in Genome Data Viewer
    Location:
    3p25.3
    Exon count:
    4
    Annotation release Status Assembly Chr Location
    109.20210514 current GRCh38.p13 (GCF_000001405.39) 3 NC_000003.12 (10141778..10153667)
    105.20201022 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (10183462..10195351)

    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 subunit of SCAR/WAVE actin nucleating complex 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 Apr 4 07:08:55 2018

    Bibliography

    GeneRIFs: Gene References Into Functions

    What'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 PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables enzyme binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables transcription factor binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables ubiquitin ligase-substrate adaptor activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables ubiquitin-protein transferase activity TAS
    Traceable Author Statement
    more info
     
    Process Evidence Code Pubs
    involved_in cell morphogenesis NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in negative regulation of apoptotic process NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in negative regulation of cell population proliferation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in negative regulation of gene expression IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in negative regulation of receptor signaling pathway via JAK-STAT IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in negative regulation of transcription by RNA polymerase II TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in negative regulation of transcription from RNA polymerase II promoter in response to hypoxia IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of cell differentiation NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in positive regulation of transcription, DNA-templated IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in protein stabilization NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in protein ubiquitination IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in protein ubiquitination IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in protein ubiquitination IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in proteolysis TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in regulation of transcription from RNA polymerase II promoter in response to hypoxia TAS
    Traceable Author Statement
    more info
     
    involved_in regulation of transcription, DNA-templated IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    Component Evidence Code Pubs
    located_in cytosol TAS
    Traceable Author Statement
    more info
     
    located_in endoplasmic reticulum NAS
    Non-traceable Author Statement
    more info
    PubMed 
    located_in membrane IEA
    Inferred from Electronic Annotation
    more info
     
    located_in mitochondrion NAS
    Non-traceable Author Statement
    more info
    PubMed 
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
     
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
     
    located_in nucleus TAS
    Traceable Author Statement
    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)

    NEW Try the new Transcript table

    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_000551.4NP_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
      Consensus CDS
      CCDS2597.1
      UniProtKB/Swiss-Prot
      P40337
      UniProtKB/TrEMBL
      A0A024R2F2
      Related
      ENSP00000256474.3, ENST00000256474.3
      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_001354723.2NP_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
      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_198156.3NP_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
      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 Updated Annotation Release 109.20210514

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

    Reference GRCh38.p13 Primary Assembly

    Genomic

    1. NC_000003.12 Reference GRCh38.p13 Primary Assembly

      Range
      10141778..10153667
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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