• 1
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
VEGFA (HGNC:12680) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
vascular endothelial growth factor A
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
VEGF
Alias symbols
VEGF-A, VPF
%HI
0.1(Read more about the DECIPHER Haploinsufficiency Index)
pLI
0(Read more about gnomAD pLI score)
LOEUF
0.84(Read more about gnomAD LOEUF score)
Cytoband
6p21.1
Genomic Coordinates
GRCh37/hg19: chr6:43737946-43754224 NCBI Ensembl UCSC
GRCh38/hg38: chr6:43770211-43786487 NCBI Ensembl UCSC
MANE Select Transcript
NM_003376.6 ENST00000672860.3 (Read more about MANE Select)
Function
[N-VEGF]: Participates in the induction of key genes involved in the response to hypoxia and in the induction of angiogenesis such as HIF1A (PubMed:35455969). Involved in protecting cells from hypoxia- mediated cell death (By similarity). {ECO:0000250|UniProtKB:Q00731, ECO:0000269|PubMed:35455969}. [VEGFA]: Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth. Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis and induces permeabilizat... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-12210
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Little Evidence for Haploinsufficiency (1)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
08/23/2023

Haploinsufficiency (HI) Score Details

HI Score:
1
HI Evidence Strength:
Little Evidence for Haploinsufficiency (Disclaimer)
HI Evidence:
  • PUBMED: PMID:20420808
    Zhao et al. (2010; PMID: 20420808) report three variants in VEGFA in a cohort of 192 individuals with left ventricular outflow tract obstruction (LVOTO). One variant was a nonsense alteration (p.R152*), one mutation was a missense mutation, and one mutation was an internal tandem duplication resulting in a frameshift (p.(Thr8Argfs*78) and a premature stop codon. All of these mutations were inherited by unaffected family members suggesting either incomplete penetrance or an oligogenic etiology of LVOTO. The VEGFA gene was the only gene examined in this study, so the possibility that these mutations are not associated with disease cannot be formally excluded.
  • PUBMED: 22067973
    In a separate publication, Zhao et al (2012; PMID: 22067973 – Cardiology in the Young) identified heterozygous nonsense variant , (p.Arg325*), by full gene Sanger sequencing of VEGFA in a patient with an isolated tricuspid aortic valve stenosis. This variant was inherited from a father with normal cardiac phenotype. The authors suggests that the p.Arg325* variant and the gene-disease phenotype could be incompletely penetrant.
  • PUBMED: 29261186
    Boissel et al (PMID: 29261186 ; 2018) identified a heterozygous de novo stop gain variant in a fetus; (NM_003376; c.C789A:p.C263X), which is likely inducing nonsense-mediated decay of the transcript of VEGFA (Table 4 and Supplementary Table S3). The authors mention that the loss of a single Vegfa allele is lethal in mouse embryos between days 11 and 12. These embryos show impaired early vascular development and multiple structural anomalies, which remain poorly characterized because of the early lethality. The authors also note that some of the defects observed in the fetus might be explained by a defect of blood vessel development but detailed phenotype information was not available at the time of testing in the fetus.
  • PUBMED: 30232381
    Reuter et al (2019; PMID: 30232381) in Genetics in Medicine performed genome sequencing involving 175 adults with tetralogy of Fallot from a single site. The group identified a stop gain variant, c.115G>T, p.(Glu39*), in VEGFA in a 29 y.o. with Tetralogy of Fallot, other cardiac abnormalities as well as learning difficulties and short stature. This variant is predicted to affect all isoforms. Inheritance information was not provided.
HI Evidence Comments:
VEGFA loss of function variants are detected, to date, in five unrelated probands, with most cases being inherited (three of 5 inherited, one known de novo identified prenatally, and one inheritance unknown). It is hypothesized that VEGFA may be a potential candidate gene associated with the spectrum of Left ventricular outflow tract obstruction lesions (PMID: 20420808). Loss of function mutation frequency in this gene is still overall low (PMID: 20420808, 30232381, 22067973). VEGFA appears to be tolerant of loss of function variation (pLI = 0 per gnomAD v2.1.1), and there are no entries in GENCC for this gene as of the date of this review. There are also several disease-associated polymorphisms noted in this gene related to diabetic retinopathy and other phenotypes, e.g. cancer associations (PMID: 11978667, PMID: 23404364).

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Evidence Comments:
Known focal duplications of VEGFA not reported to date.

Genomic View

Select assembly: (NC_000006.11) (NC_000006.12)