VEGFB

Chr 11

vascular endothelial growth factor B

Also known as: VEGFL, VRF

NCBI Gene: 7423 ENSG00000173511 UniProt: P49765 OMIM: 601398

The protein is a growth factor for endothelial cells that binds to VEGFR-1 and neuropilin-1 receptors and specifically controls endothelial uptake of fatty acids. Mutations cause microphthalmia with coloboma and are inherited in an autosomal dominant pattern. This gene shows very low constraint against loss-of-function variants, indicating tolerance to such mutations in the general population.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the PDGF (platelet-derived growth factor)/VEGF (vascular endothelial growth factor) family. The VEGF family members regulate the formation of blood vessels and are involved in endothelial cell physiology. This member is a ligand for VEGFR-1 (vascular endothelial growth factor receptor 1) and NRP-1 (neuropilin-1). Studies in mice showed that this gene was co-expressed with nuclear-encoded mitochondrial genes and the encoded protein specifically controlled endothelial uptake of fatty acids. Alternatively spliced transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, Sep 2011]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.87

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.87LOEUF

pLI 0.000

Z-score -0.86

OE 1.31 (0.83–1.87)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.71Z-score

OE missense 1.18 (1.03–1.34)

152 obs / 129.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.31 (0.83–1.87)

0≤0.351.4

Missense OE?1.18 (1.03–1.34)

0≤0.61.4

Synonymous OE?1.22

0≤1.21.6

LoF obs/exp: 12 / 9.2Missense obs/exp: 152 / 129.3Syn Z: -1.30

Background carrier burden — how many people carry a rare variant somewhere in VEGFB?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 70

423 rare PASS variants

Rare truncating (LoF)

1 in 950

90 rare PASS variants

Rare synonymous (reference)

1 in 330

130 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for VEGFB. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 110	1 in 1,500
South Asian	~43k	1 in 130	1 in 500
Remaining (unassigned)	~30k	1 in 72	1 in 640
European (Finnish)	~27k	1 in 210	1 in 4,200
Admixed American	~22k	1 in 89	1 in 1,300
African / African American	~21k	1 in 100	1 in 350
East Asian	~20k	1 in 78	1 in 440
Ashkenazi Jewish	~13k	1 in 470	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 93	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 5 of 6 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: 5 of 6 (exon 5 below).? see exons ↓