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VHL von Hippel-Lindau tumor suppressor, E3 ubiquitin protein ligase [ Homo sapiens (human) ]

Gene ID: 7428, updated on 15-Sep-2014
Official Symbol
VHLprovided by HGNC
Official Full Name
von Hippel-Lindau tumor suppressor, E3 ubiquitin protein ligaseprovided by HGNC
Primary source
HGNC:HGNC:12687
See related
HPRD:01905; 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]
Location:
3p25.3
Exon count:
3
Annotation release Status Assembly Chr Location
106 current GRCh38 (GCF_000001405.26) 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

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

Little evidence for dosage pathogenicity (Last evaluated (2012-07-06)

ISCA Genome Curation PagePubMed
Haploinsufficency

Sufficient evidence for dosage pathogenicity (Last evaluated (2012-07-06)

ISCA 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
 
ubiquitin-protein transferase activity TAS
Traceable Author Statement
more info
 
Component Evidence Code Pubs
cytosol TAS
Traceable Author Statement
more info
 
endoplasmic reticulum NAS
Non-traceable Author Statement
more info
PubMed 
intermediate filament cytoskeleton IDA
Inferred from Direct Assay
more info
 
membrane IEA
Inferred from Electronic Annotation
more info
 
mitochondrion NAS
Non-traceable Author Statement
more info
PubMed 
NOT nucleolus IDA
Inferred from Direct Assay
more info
 
nucleoplasm TAS
Traceable Author Statement
more info
 
nucleus IDA
Inferred from Direct Assay
more info
 
Preferred Names
von Hippel-Lindau disease tumor suppressor
Names
von Hippel-Lindau disease tumor suppressor
protein G7
elongin binding protein

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 

    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 proteins identical to 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/TrEMBL
    A0A024R2F2
    UniProtKB/Swiss-Prot
    P40337
    Conserved Domains (2) summary
    pfam05887
    Location:786
    Blast Score: 97
    Trypan_PARP; Procyclic acidic repetitive protein (PARP)
    cd05468
    Location:64203
    Blast Score: 414
    pVHL; von Hippel-Landau (pVHL) tumor suppressor protein
  2. NM_198156.2NP_937799.1  von Hippel-Lindau disease tumor suppressor isoform 2

    See proteins identical to 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
    Conserved Domains (2) summary
    pfam05887
    Location:786
    Blast Score: 91
    Trypan_PARP; Procyclic acidic repetitive protein (PARP)
    cd05468
    Location:64162
    Blast Score: 235
    pVHL; von Hippel-Landau (pVHL) tumor suppressor protein

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 106

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

Reference GRCh38 Primary Assembly

Genomic

  1. NC_000003.12 

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

Alternate HuRef

Genomic

  1. AC_000135.1 

    Range
    10119232..10131274
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.1

Genomic

  1. NC_018914.2 

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