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25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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VEGFD
vascular endothelial growth factor D
Chromosome X · Xp22.2
NCBI Gene: 2277Ensembl: ENSG00000165197.6HGNC: HGNC:3708UniProt: O43915
159PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
RESEARCH IMPACT
Trending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
positive regulation of mast cell chemotaxisinduction of positive chemotaxischemoattractant activityprotein bindingneoplasmlymphangioleiomyomatosislung adenocarcinomaatrial fibrillation
✦AI Summary

VEGFD (vascular endothelial growth factor D) is a growth factor that promotes angiogenesis and lymphangiogenesis by binding and activating VEGFR-2 and VEGFR-3 receptors on endothelial cells 1. VEGFD stimulates endothelial cell proliferation and migration while increasing vascular permeability 1. The protein functions in forming venous and lymphatic vascular systems during embryogenesis and maintains differentiated lymphatic endothelium in adults. In pathological contexts, VEGFD plays a critical role in cancer progression. Tumor-secreted VEGFD promotes lymphangiogenesis in tumor-draining lymph nodes and induces dedifferentiation of high endothelial venules via VEGFR2 signaling, impairing lymphocyte homing and facilitating lymph node metastasis 2. The S100A6 protein upregulates VEGFD expression in lymphatic endothelial cells through the RAGE/NF-κB pathway, promoting lymphatic metastasis in liver cancer 3. SIRT2 modulates VEGFD expression by deacetylating EPAS1, suggesting potential therapeutic targets for inhibiting tumor lymphangiogenesis 4. Beyond vascular biology, VEGFD contributes to neural differentiation, where it functions alongside SDF1α and sFRP1 as a stromal-derived inducing activity factor promoting dopaminergic neuron differentiation from human pluripotent stem cells 5, with potential therapeutic applications for Parkinson's disease.

Sources cited
1
VEGFD is a member of the VEGF family with pro-angiogenic activity; binds VEGFR-2 and VEGFR-3; promotes endothelial cell proliferation and migration; increases vascular permeability
PMID: 30173249
2
SIRT2 regulates VEGFD expression and lymphangiogenesis by deacetylating EPAS1 in head and neck cancer under hypoxic conditions
PMID: 32965071
3
S100A6 upregulates VEGFD expression in lymphatic endothelial cells via RAGE/NF-κB pathway to promote lymphatic metastasis in liver cancer
PMID: 38350547
4
VEGFD binds VEGFR2 on high endothelial venule endothelial cells, inducing their dedifferentiation and impairing lymphocyte homing, facilitating lymph node metastasis
PMID: 40693467
5
VEGFD functions as a stromal-derived inducing activity factor promoting dopaminergic neuron differentiation from human pluripotent stem cells
PMID: 22535492
6
VEGFD is a ligand for VEGFR-3 involved in lymphangiogenesis and tumor-associated lymphatic vessel development
PMID: 19482087
Disease Associationsⓘ20
neoplasmOpen Targets
0.11Weak
lymphangioleiomyomatosisOpen Targets
0.11Weak
lung adenocarcinomaOpen Targets
0.10Suggestive
atrial fibrillationOpen Targets
0.09Suggestive
acute myeloid leukemiaOpen Targets
0.08Suggestive
chronic kidney diseaseOpen Targets
0.07Suggestive
tuberous sclerosisOpen Targets
0.07Suggestive
chondrosarcomaOpen Targets
0.06Suggestive
gastric cancerOpen Targets
0.06Suggestive
diabetic nephropathyOpen Targets
0.06Suggestive
breast carcinomaOpen Targets
0.06Suggestive
non-small cell lung carcinomaOpen Targets
0.05Suggestive
systemic sclerodermaOpen Targets
0.04Suggestive
cancerOpen Targets
0.04Suggestive
Kleine-Levin SyndromeOpen Targets
0.04Suggestive
hypersensitivity pneumonitisOpen Targets
0.04Suggestive
papillary thyroid carcinomaOpen Targets
0.04Suggestive
endometrial cancerOpen Targets
0.04Suggestive
carcinomaOpen Targets
0.04Suggestive
lung cancerOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
NTRK1Protein interaction100%ERBB4Protein interaction100%NRP2Protein interaction99%NTRK2Protein interaction99%PDGFRBProtein interaction99%EGFRProtein interaction99%
Tissue Expression6 tissues
Lung
100%
Heart
13%
Ovary
13%
Liver
6%
Brain
2%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
VEGFDNTRK1ERBB4NRP2NTRK2PDGFRBEGFR
PROTEIN STRUCTURE
Preparing viewer…
PDB2XV7 · 2.90 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.29LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.93 [0.68–1.29]
RankingsWhere VEGFD stands among ~20K protein-coding genes
  • #2,839of 20,598
    Most Researched159 · top quartile
  • #13,554of 17,882
    Most Constrained (LOEUF)1.29
Genes detectedVEGFD
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
Vascular endothelial growth factor (VEGF) - key factor in normal and pathological angiogenesis.
PMID: 30173249
Rom J Morphol Embryol · 2018
1.00
2
SIRT2 modulates VEGFD-associated lymphangiogenesis by deacetylating EPAS1 in human head and neck cancer.
PMID: 32965071
Mol Carcinog · 2020
0.90
3
S100A6 drives lymphatic metastasis of liver cancer via activation of the RAGE/NF-kB/VEGF-D pathway.
PMID: 38350547
Cancer Lett · 2024
0.80
4
Endometrial lymphangiogensis.
PMID: 17981324
Placenta · 2008
0.70
5
Emerging biomarkers of lymphangioleiomyomatosis.
PMID: 29171770
Expert Rev Respir Med · 2018
0.60