Seroatlas · Human Serome Atlas

VHL

von Hippel-Lindau disease tumor suppressor

Also known as: VHL_HUMAN, VHL1

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession
P40337
Gene
VHL
Ensembl
ENSG00000134086
Chromosome
3
Canonical length
213 aa
Protein class
Cancer-related genes, Disease related genes, Human disease related genes, Predicted intracellular proteins
Subcellular location
Nucleoplasm,Primary cilium,Primary cilium tip,Cytosol

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

213 residues, UniProt reviewed canonical sequence.

>P40337|VHL
     1  MPRRAENWDE AEVGAEEAGV EEYGPEEDGG EESGAEESGP EESGPEELGA EEEMEAGRPR
    61  PVLRSVNSRE PSQVIFCNRS PRVVLPVWLN FDGEPQPYPT LPPGTGRRIH SYRGHLWLFR
   121  DAGTHDGLLV NQTELFVPSL NVDGQPIFAN ITLPVYTLKE RCLQVVRSLV KPENYRRLDI
   181  VRSLYEDLED HPNVQKDLER LTQERIAHQR MGD

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against VHL can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability
Cell surface
Secreted
No
Transmembrane segments
0
Mean surface accessibility (rSASA)
0.44
Highest tissue expression
26 nTPM

Expression across tissuesHPA

Tissue

  • lymph node: 26 nTPM
  • tonsil: 23 nTPM
  • bone marrow: 23 nTPM
  • cerebellum: 22 nTPM
  • spleen: 21 nTPM
  • amygdala: 18 nTPM

Single-cell type

  • neutrophils: 103 nCPM
  • neutrophil progenitors: 89 nCPM
  • monocytes: 87 nCPM
  • monocyte progenitors: 68 nCPM
  • platelets: 66 nCPM
  • kupffer cells: 66 nCPM

Immune cell

  • neutrophil: 5.4 nTPM
  • basophil: 4.5 nTPM
  • naive B-cell: 3.3 nTPM
  • classical monocyte: 3.2 nTPM
  • NK-cell: 3 nTPM
  • gdT-cell: 2.5 nTPM

Brain region

  • hypothalamus: 42 nTPM
  • cerebellum: 34 nTPM
  • white matter: 33 nTPM
  • cerebral cortex: 32 nTPM
  • hippocampal formation: 32 nTPM
  • amygdala: 31 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about VHL.

Disease | AllUniProt

Conditions VHL is implicated in, by any mechanism.

Disease | GeneticClinVar

448 pathogenic / likely-pathogenic of 2,147 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)
0.93
gnomAD pLI
0.08
gnomAD missense Z
-0.39
DepMap mean gene effect
-0.74
DepMap dependency class
common

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of VHL in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads VHL as an antibody target. Whether an autoantibody or antibody against VHL could matter depends on whether native VHL is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

VHL is annotated at the cell surface, where native VHL is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.

Annotation status

The present source text does not explicitly label VHL as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/VHL. Study-independent annotations aggregated from UniProt, Human Protein Atlas, PubMed, IEDB, Pfam, InterPro, Gene Ontology, AlphaFold, gnomAD, DepMap, ClinVar, TCGA. Catalog release seroatlas-reviewed-human-uniprot-20260313.

Seroatlas is the reference for exploring autoantibody and antibody serology at the human-protein level: the autoreactome and human serome, multiplex serology (HuProt, HuScan, VirScan, PhIP-Seq).

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