VEGFD

Chr X

vascular endothelial growth factor D

Also known as: FIGF, VEGF-D

NCBI Gene: 2277 ENSG00000165197 UniProt: O43915

The encoded protein is a secreted growth factor that stimulates angiogenesis, lymphangiogenesis, and endothelial cell growth by binding and activating VEGFR-2 and VEGFR-3 receptors. Mutations cause autosomal recessive primary lymphedema with predominantly lower limb involvement. This gene shows low constraint against loss-of-function variants, consistent with its recessive inheritance pattern.

ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a member of the platelet-derived growth factor/vascular endothelial growth factor (PDGF/VEGF) family and is active in angiogenesis, lymphangiogenesis, and endothelial cell growth. This secreted protein undergoes a complex proteolytic maturation, generating multiple processed forms which bind and activate VEGFR-2 and VEGFR-3 receptors. This protein is structurally and functionally similar to vascular endothelial growth factor C. Read-through transcription has been observed between this locus and the upstream PIR (GeneID 8544) locus. [provided by RefSeq, Feb 2011]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.15

LOEUF

—

Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.15LOEUF

pLI 0.000

Z-score 1.16

OE 0.66 (0.40–1.15)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.50Z-score

OE missense 0.88 (0.76–1.02)

121 obs / 137.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.66 (0.40–1.15)

0≤0.351.4

Missense OE?0.88 (0.76–1.02)

0≤0.61.4

Synonymous OE?1.12

0≤1.21.6

LoF obs/exp: 9 / 13.6Missense obs/exp: 121 / 137.5Syn Z: -0.66

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

gnomAD v4 · ~732k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 320

317 rare PASS variants

Rare truncating (LoF)

1 in 3,600

46 rare PASS variants

Rare synonymous (reference)

1 in 430

102 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for VEGFD. 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)	~561k	1 in 300	1 in 5,800
South Asian	~36k	1 in 310	1 in 2,500
Remaining (unassigned)	~31k	1 in 170	1 in 5,000
European (Finnish)	~27k	1 in 920	≈ 1 in 27,000
Admixed American	~23k	1 in 370	1 in 2,100
African / African American	~21k	1 in 170	1 in 1,200
East Asian	~20k	1 in 160	1 in 3,900
Ashkenazi Jewish	~13k	1 in 720	none seen
Middle Eastern	~2,758	1 in 140	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): 6 of 7 coding exons well covered in gnomAD exomes; exon 5 marginal. Genomes: all 7.? see exons ↓