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

Gene ID: 7428, updated on 12-Aug-2022

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
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Genomic context

See VHL in Genome Data Viewer
Location:
3p25.3
Exon count:
4
Annotation release Status Assembly Chr Location
110 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (10141778..10153667)
110 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 small nucleolar RNA U13 Neighboring gene 3p25 von Hippel-Lindau tumor suppressor, E3 ubiquitin protein ligase Alu-mediated recombination region Neighboring gene 3p25 IRAK2 Alu-mediated recombination region Neighboring gene interleukin 1 receptor associated kinase 2 Neighboring gene Sharpr-MPRA regulatory region 12699 Neighboring gene U6 spliceosomal RNA

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

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables DNA-binding transcription factor binding IPI
Inferred from Physical Interaction
more info
PubMed 
enables enzyme binding IPI
Inferred from Physical Interaction
more info
PubMed 
enables molecular adaptor activity EXP
Inferred from Experiment
more info
PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
enables transcription elongation factor activity IDA
Inferred from Direct Assay
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 DNA-templated transcription elongation IEA
Inferred from Electronic Annotation
more info
 
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 apoptotic process NAS
Non-traceable Author Statement
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 elongation by RNA polymerase II IDA
Inferred from Direct Assay
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 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 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 
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 
is_active_in intracellular non-membrane-bounded organelle EXP
Inferred from Experiment
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, Q6PDA9
    UniProtKB/TrEMBL
    A0A024R2F2, A0A0S2Z4I2
    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
    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/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)

RNA

  1. NR_176335.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC034193

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 110 details...Open this link in a new tab

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)