VEGFB

Chr 11

vascular endothelial growth factor B

Also known as: VEGFL, VRF

NCBI Gene: 7423ENSG00000173511UniProt: P49765

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]

72
ClinVar variants
8
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— VEGFB
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
8 Pathogenic / Likely Pathogenic· 56 VUS of 72 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.71Z-score
OE missense 1.18 (1.03–1.34)
152 obs / 129.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.1.31 (0.83–1.87)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.18 (1.03–1.34)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.22
0≤1.21.6
LoF obs/exp: 12 / 9.2Missense obs/exp: 152 / 129.3Syn Z: -1.30

ClinVar Variant Classifications

72 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6
Likely Pathogenic2
VUS56
Likely Benign4
Benign4
6
Pathogenic
2
Likely Pathogenic
56
VUS
4
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
6
0
6
Likely Pathogenic
0
0
2
0
2
VUS
0
53
3
0
56
Likely Benign
0
4
0
0
4
Benign
0
2
0
2
4
Total05911272

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

VEGFB · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Biology and therapeutic targeting of vascular endothelial growth factor A.
Pérez-Gutiérrez L et al.·Nat Rev Mol Cell Biol
2023Review
Microglial control of astrocytes in response to microbial metabolites.
Rothhammer V et al.·Nature
2018
Inhibition of VEGF-B signaling prevents non-alcoholic fatty liver disease development by targeting lipolysis in the white adipose tissue.
Falkevall A et al.·J Hepatol
2023
Design and Characterization of a Novel Intravitreal Dual-Transgene Genetic Medicine for Neovascular Retinopathies.
Calton MA et al.·Invest Ophthalmol Vis Sci
2024
FLT1 and its ligands VEGFB and PlGF: drug targets for anti-angiogenic therapy?
Fischer C et al.·Nat Rev Cancer
2008Review
Sexually dimorphic differences in angiogenesis markers are associated with brain aging trajectories in humans.
Torres-Espin A et al.·Sci Transl Med
2024
Basophils in Tumor Microenvironment and Surroundings.
Marone G et al.·Adv Exp Med Biol
2020Review
VEGFB(167) drives tumor progression by modulating the immune microenvironment.
Zheng Y et al.·Int Immunopharmacol
2025
Vasoregulatory Autoantibodies and Clinical Outcome After Ischemic Stroke-PROSCIS-B.
Liman TG et al.·J Am Heart Assoc
2023
Gene Therapy for Heart Failure.
Wang H et al.·J Cardiovasc Transl Res
2026Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Preeclampsia (PE)Intrauterine Growth Restriction (IUGR)Placental Insufficiency

Statin Intervention for Severe Early-Onset Placental Insufficiency. (STATIN-PRE Trial)

RECRUITING
NCT07098975Phase PHASE2Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant PauStarted 2026-01-14
Pravastatin 40 mgPlacebo

External Resources

Links to major genomics databases and tools