Seroatlas · Human Serome Atlas

VEGFA

Vascular endothelial growth factor A, long form

Also known as: VEGF, VEGF-A, VEGFA_HUMAN, VPF

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

Protein identityUniProt · HPA

UniProt accession
P15692
Gene
VEGFA
Ensembl
ENSG00000112715
Chromosome
6
Canonical length
395 aa
Protein class
Cancer-related genes, Candidate cardiovascular disease genes, Disease related genes, FDA approved drug targets, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Predicted membrane proteins, Predicted secreted proteins, RAS pathway related proteins
Secretome location
Secreted to blood
Quaternary structure
Homodimer

OverviewNCBI Gene

This gene is a member of the PDGF/VEGF growth factor family. It encodes a heparin-binding protein, which exists as a disulfide-linked homodimer. This growth factor induces proliferation and migration of vascular endothelial cells, and is essential for both physiological and pathological angiogenesis. Disruption of this gene in mice resulted in abnormal embryonic blood vessel formation. This gene is upregulated in many known tumors and its expression is correlated with tumor stage and progression. Elevated levels of this protein are found in patients with POEMS syndrome, also known as Crow-Fukase syndrome. Allelic variants of this gene have been associated with microvascular complications of diabetes 1 (MVCD1) and atherosclerosis. Alternatively spliced transcript variants encoding different isoforms have been described. There is also evidence for alternative translation initiation from upstream non-AUG (CUG) codons resulting in additional isoforms. A recent study showed that a C-terminally extended isoform is produced by use of an alternative in-frame translation termination codon via a stop codon readthrough mechanism, and that this isoform is antiangiogenic. Expression of some isoforms derived from the AUG start codon is regulated by a small upstream open reading frame, which is located within an internal ribosome entry site. The levels of VEGF are increased during infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), thus promoting inflammation by facilitating recruitment of inflammatory cells, and by increasing the level of angiopoietin II (Ang II), one of two products of the SARS-CoV-2 binding target, angiotensin-converting enzyme 2 (ACE2). In turn, Ang II facilitates the elevation of VEGF, thus forming a vicious cycle in the release of inflammatory cytokines. [provided by RefSeq, Jun 2020]

Canonical amino-acid sequenceUniProt

395 residues, UniProt reviewed canonical sequence.

>P15692|VEGFA
     1  MTDRQTDTAP SPSYHLLPGR RRTVDAAASR GQGPEPAPGG GVEGVGARGV ALKLFVQLLG
    61  CSRFGGAVVR AGEAEPSGAA RSASSGREEP QPEEGEEEEE KEEERGPQWR LGARKPGSWT
   121  GEAAVCADSA PAARAPQALA RASGRGGRVA RRGAEESGPP HSPSRRGSAS RAGPGRASET
   181  MNFLLSWVHW SLALLLYLHH AKWSQAAPMA EGGGQNHHEV VKFMDVYQRS YCHPIETLVD
   241  IFQEYPDEIE YIFKPSCVPL MRCGGCCNDE GLECVPTEES NITMQIMRIK PHQGQHIGEM
   301  SFLQHNKCEC RPKKDRARQE KKSVRGKGKG QKRKRKKSRY KSWSVPCGPC SERRKHLFVQ
   361  DPQTCKCSCK NTDSRCKARQ LELNERTCRC DKPRR

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against VEGFA 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
Secreted
Secreted
Yes
Transmembrane segments
0
Mean surface accessibility (rSASA)
0.59
Highest tissue expression
256 nTPM

Expression across tissuesHPA

Tissue

  • thyroid gland: 256 nTPM
  • retina: 213 nTPM
  • skeletal muscle: 212 nTPM
  • heart muscle: 203 nTPM
  • liver: 202 nTPM
  • tongue: 144 nTPM

Single-cell type

  • podocytes: 1,272 nCPM
  • prostatic glandular cells: 359 nCPM
  • alveolar cells type 1: 343 nCPM
  • foveolar cells: 301 nCPM
  • müller glia: 301 nCPM
  • prostatic hillock cells: 281 nCPM

Immune cell

  • eosinophil: 0.3 nTPM
  • classical monocyte: 0.2 nTPM
  • basophil: 0 nTPM
  • gdT-cell: 0 nTPM
  • intermediate monocyte: 0 nTPM
  • MAIT T-cell: 0 nTPM

Brain region

  • choroid plexus: 98 nTPM
  • midbrain: 79 nTPM
  • cerebellum: 69 nTPM
  • thalamus: 66 nTPM
  • cerebral cortex: 58 nTPM
  • medulla oblongata: 56 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about VEGFA.

Disease | AllUniProt

Conditions VEGFA is implicated in, by any mechanism.

  • Microvascular complications of diabetes 1 (MVCD1) MIM:603933

Disease | GeneticClinVar

2 pathogenic / likely-pathogenic of 110 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

  • VEGFA-related disorder

ReferencesPubMed · IEDB

Publications for VEGFA from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Reference: AutoantibodyPubMed

3 publications

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

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)
0.84
gnomAD pLI
0
gnomAD missense Z
0.47
DepMap mean gene effect
-0.04
DepMap dependency class
none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% 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 VEGFA 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 VEGFA as an antibody target. Whether an autoantibody or antibody against VEGFA could matter depends on whether native VEGFA is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

VEGFA is annotated as secreted, so native VEGFA circulates and is directly accessible to antibodies. Secreted and cell-surface proteins are the autoantibody targets most likely to act like drugs, blocking or depleting the native protein.

Annotation status

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

Canonical record: https://seroatlas.com/gene/VEGFA. 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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