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

    Gene ID: 7428, updated on 18-Apr-2024

    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; AllianceGenome:HGNC:12687
    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
    This gene encodes a component of a ubiquitination complex. The encoded 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. In addition to oxygen-related gene expression, this protein plays a role in many other cellular processes including cilia formation, cytokine signaling, regulation of senescence, and formation of the extracellular matrix. Variants of this gene are associated with von Hippel-Lindau syndrome, pheochromocytoma, erythrocytosis, renal cell carcinoma, and cerebellar hemangioblastoma. [provided by RefSeq, Jun 2022]
    Expression
    Ubiquitous expression in lymph node (RPKM 12.2), spleen (RPKM 10.0) and 25 other tissues See more
    Orthologs
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    Location:
    3p25.3
    Exon count:
    4
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (10141778..10153667)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (10134670..10146564)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (10183462..10195351)

    Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene 3p25 BRK1 Alu-mediated recombination region Neighboring gene small nucleolar RNA U13 Neighboring gene uncharacterized LOC124906359 Neighboring gene 3p25 von Hippel-Lindau tumor suppressor, E3 ubiquitin protein ligase Alu-mediated recombination region Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:10184379-10184912 Neighboring gene 3p25 IRAK2 Alu-mediated recombination region Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14055 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14056 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr3:10210671-10211181 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19418 Neighboring gene interleukin 1 receptor associated kinase 2 Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:10227030-10227530 Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:10227531-10228031 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19419 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19420 Neighboring gene Sharpr-MPRA regulatory region 12699 Neighboring gene U6 spliceosomal RNA Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:10266988-10267770 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19421 Neighboring gene Sharpr-MPRA regulatory region 8698 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:10275792-10276394 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14057 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14058 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:10290711-10291579 Neighboring gene 3p25 TatD DNase domain containing 2 Alu-mediated recombination region Neighboring gene TatD DNase domain containing 2 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14059 Neighboring gene microRNA 12127

    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

    Associated conditions

    Description Tests
    Chuvash polycythemia
    MedGen: C1837915 OMIM: 263400 GeneReviews: Not available
    Compare labs
    Nonpapillary renal cell carcinoma
    MedGen: CN074294 OMIM: 144700 GeneReviews: Not available
    Compare labs
    Pheochromocytoma Compare labs
    Von Hippel-Lindau syndrome
    MedGen: C0019562 OMIM: 193300 GeneReviews: Von Hippel-Lindau Syndrome
    Compare labs

    Copy number response

    Description
    Copy number response
    Triplosensitivity

    No evidence available (Last evaluated 2022-05-11)

    ClinGen Genome Curation Page
    Haploinsufficency

    Sufficient evidence for dosage pathogenicity (Last evaluated 2022-05-11)

    ClinGen Genome Curation PagePubMed

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Gene Ontology Provided by GOA

    Process Evidence Code Pubs
    involved_in amyloid fibril formation EXP
    Inferred from Experiment
    more info
    PubMed 
    involved_in amyloid fibril formation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in cell morphogenesis NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in cellular response to hypoxia TAS
    Traceable Author Statement
    more info
     
    involved_in negative regulation of TORC1 signaling IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in negative regulation of apoptotic process NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in negative regulation of autophagy IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in negative regulation of cell population proliferation IDA
    Inferred from Direct Assay
    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 signal transduction EXP
    Inferred from Experiment
    more info
    PubMed 
    involved_in negative regulation of transcription by RNA polymerase II IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in negative regulation of transcription elongation by RNA polymerase II IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of DNA-templated transcription IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of cell differentiation NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in proteasome-mediated ubiquitin-dependent protein catabolic process IDA
    Inferred from Direct Assay
    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 DNA-templated transcription IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in regulation of cellular response to hypoxia EXP
    Inferred from Experiment
    more info
    PubMed 
    involved_in regulation of gene expression EXP
    Inferred from Experiment
    more info
    PubMed 
    involved_in regulation of gene expression IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in regulation of gene expression IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    Component Evidence Code Pubs
    located_in cytosol TAS
    Traceable Author Statement
    more info
     
    is_active_in endoplasmic reticulum IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in endoplasmic reticulum NAS
    Non-traceable Author Statement
    more info
    PubMed 
    is_active_in intracellular non-membrane-bounded organelle EXP
    Inferred from Experiment
    more info
    PubMed 
    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 
    located_in plasma membrane IEA
    Inferred from Electronic Annotation
    more info
     

    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
      B2RE45, P40337, Q13599, Q6PDA9
      UniProtKB/TrEMBL
      A0A024R2F2, A0A0S2Z4I2, A0A8Q3SIA6
      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
      Consensus CDS
      CCDS93209.1
      UniProtKB/TrEMBL
      A0A8Q3WL21
      Related
      ENSP00000512435.1, ENST00000696143.1
      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/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)

    RNA

    1. NR_176335.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC034193

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000003.12 Reference GRCh38.p14 Primary Assembly

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

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060927.1 Alternate T2T-CHM13v2.0

      Range
      10134670..10146564
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)