VEGFD

Summary

VEGFD (vascular endothelial growth factor D, HGNC:3708) is a protein-coding gene on chromosome Xp22.2, encoding Vascular endothelial growth factor D (O43915). Growth factor active in angiogenesis, lymphangiogenesis and endothelial cell growth, stimulating their proliferation and migration and also has effects on the permeability of blood vessels.

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.

Source: NCBI Gene 2277 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 3 total
• MANE Select transcript: NM_004469

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3708
Approved symbol	VEGFD
Name	vascular endothelial growth factor D
Location	Xp22.2
Locus type	gene with protein product
Status	Approved
Aliases	VEGF-D
Ensembl gene	ENSG00000165197
Ensembl biotype	protein_coding
OMIM	300091
Entrez	2277

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000297904, ENST00000488351, ENST00000948564

RefSeq mRNA: 1 — MANE Select: NM_004469 NM_004469

CCDS: CCDS14166

Canonical transcript exons

ENST00000297904 — 7 exons

Exon	Start	End
ENSE00001032213	15355150	15355298
ENSE00001091191	15383857	15384413
ENSE00001091192	15363109	15363319
ENSE00001127415	15345596	15346259
ENSE00001159565	15347164	15347359
ENSE00001159570	15353068	15353168
ENSE00001159585	15358003	15358193

Expression profiles

Bgee: expression breadth ubiquitous, 184 present calls, max score 92.95.

FANTOM5 (CAGE): breadth broad, TPM avg 1.0164 / max 96.4677, expressed in 188 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
198525	0.5604	137
198527	0.3248	123
198526	0.0937	48
209609	0.0375	26

Top tissues by expression

286 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lung	UBERON:0002167	92.95	gold quality
apex of heart	UBERON:0002098	89.83	gold quality
upper lobe of left lung	UBERON:0008952	88.78	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.40	gold quality
mammary duct	UBERON:0001765	88.30	gold quality
upper lobe of lung	UBERON:0008948	88.11	gold quality
lower lobe of lung	UBERON:0008949	87.50	gold quality
lung	UBERON:0002048	87.47	gold quality
epithelium of mammary gland	UBERON:0003244	87.17	gold quality
gastrocnemius	UBERON:0001388	86.88	gold quality
thoracic mammary gland	UBERON:0005200	86.23	gold quality
mammary gland	UBERON:0001911	85.75	gold quality
hindlimb stylopod muscle	UBERON:0004252	85.33	gold quality
muscle of leg	UBERON:0001383	85.19	gold quality
mucosa of stomach	UBERON:0001199	82.88	gold quality
right adrenal gland cortex	UBERON:0035827	81.15	gold quality
muscle organ	UBERON:0001630	80.58	gold quality
heart left ventricle	UBERON:0002084	80.02	gold quality
ectocervix	UBERON:0012249	80.01	gold quality
cardiac ventricle	UBERON:0002082	79.51	gold quality
adult organism	UBERON:0007023	79.03	gold quality
right adrenal gland	UBERON:0001233	78.88	gold quality
deltoid	UBERON:0001476	78.75	silver quality
esophagogastric junction muscularis propria	UBERON:0035841	78.53	gold quality
lower esophagus muscularis layer	UBERON:0035833	77.44	gold quality
lower esophagus	UBERON:0013473	77.42	gold quality
tibialis anterior	UBERON:0001385	77.11	silver quality
left adrenal gland	UBERON:0001234	77.08	gold quality
adipose tissue	UBERON:0001013	76.87	gold quality
right coronary artery	UBERON:0001625	76.78	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	12.79

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOS, HIF1A, HNF4A, JUN, NCOA2, NFKB1, NR3C1, RELA, STAT1

miRNA regulators (miRDB)

29 targeting VEGFD, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-4645-3P	99.76	69.33	993
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-4470	99.66	69.35	1767
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-6758-3P	99.57	67.55	1078
HSA-MIR-330-3P	99.41	69.95	2521
HSA-MIR-135A-5P	99.36	71.85	1601
HSA-MIR-135B-5P	99.36	71.63	1613
HSA-MIR-6853-3P	99.36	70.79	1558
HSA-MIR-2115-3P	99.31	69.68	2026
HSA-MIR-5190	99.15	67.76	1234
HSA-MIR-1257	98.97	68.02	1133
HSA-MIR-5585-3P	98.25	67.41	941
HSA-MIR-6765-3P	97.83	64.59	1165
HSA-MIR-320E	97.49	65.96	865
HSA-MIR-2277-3P	91.94	62.27	299

Literature-anchored findings (GeneRIF, showing 40)

• VEGF-D expression is associated with lymph node metastasis and may be a novel prognostic factor in breast cancer. (PMID:12576440)
• Increased expression of VEGF-C, VEGF-D and VEGFR-3 was significantly associated with lymph node metastasis and peritoneal metastasis from ovarian neoplasms (PMID:12610509)
• Using adenoviral gene transfer in rabbit hindlimb skeletal muscle, VEGF-D was the strongest angiogenic and lymphangiogenic effector among VEGFs delivered (PMID:12714562)
• VEGF-D-positive staining in 26 of the 83 carcinomas (31%): significant relationship between the presence of VEGF-D protein and the incidence of lymph node metastasis (p < 0.01). (PMID:12759540)
• study demonstrated that beta-catenin negative regulation is on the vascular endothelial growth factor-D messenger RNA 3’-untranslated region (PMID:12920128)
• Data show that the serine protease plasmin cleaved both propeptides from human vascular endothelial growth factor (VEGF)-D, generating mature forms, and also activated VEGF-C. (PMID:12963694)
• VEGF-C and VEGF-D are ligands for the integrin alpha9beta1 (PMID:15590642)
• High vascular endothelial growth factor D expression is associated with lymph node metastasis in human pancreatic cancer (PMID:15623620)
• Patients with primary lymphedema have serum level of VEGF-D significantly higher than controls.The increased levels of VEGF-D suggest that primary lymphedema may be based on defective stimulation of VEGFR-3. (PMID:15693535)
• High expression of VEGF-D was associated with advanced-stage metastatic prostate cancer. (PMID:15701844)
• Findings indicate that VEGF-D expression and increased lymph vessel density may have an important role for lymph node metastasis in papillary thyroid carcinoma. (PMID:15803188)
• VEGF-D levels were decreased in patients with cervical nodal metastasis as compared to patients with negative lymph node status (PMID:16049374)
• VEGF-D has a novel function as a survival factor of breast carcinoma cells in addition to its established functions as an angiogenic and lymphangiogenic fa (PMID:16152591)
• The VEGF-D expression was associated only with LVD(D2-40-positive vessels)and regulated . (PMID:16467091)
• VEGF-D/VEGFR-3 signaling plays a critical role in osteoblast maturation (PMID:16624815)
• VEGF-Dreacts with neuropilin 2 in a heparin-dependent way. (PMID:16816121)
• results suggest the presence of lymphatic capillaries throughout the skeletal muscle, and present the localisation of VEGF-C and -D in the muscles. (PMID:16924525)
• Serum VEGF-D levels may be a valuable surrogate marker for evaluating the disease severity in lymphangioleiomyomatosis (PMID:17034294)
• In nasopharyngeal carcinoma, positive expression of VEGF-D shows no correlation to regional lymph node metastasis, but is positively related to high expression of VEGF-C and closely correlated to 5-year survival rate. (PMID:17222375)
• in binding VEGFR-2, furin and PC5 promote cleavage of N-and C-terminal VEGF-D propeptides, whereas PC7 promotes cleavage of the C-terminal propeptide only (PMID:17242158)
• Expression of VEGF-D was found to be related to the presence of intralymphatic tumor cells. (PMID:17442484)
• Goal of study was to define role of VEGF-C, VEGF-D and Flt-4 with TMA technology for tumor biology of urothelial carcinoma of the bladder. (PMID:17676294)
• VEGF-D could contribute to leukemia and lymphoma growth via the induction of angiogenesis in bone marrow and lymphoid tissues (PMID:17917969)
• Expression of VEGF-C, VEGF-D and their receptor VEGFR-3 in diffuse large B-cell lymphomas. (PMID:17926187)
• The balance between expression of VEGF-C and VEGF-D at the invading colorectal tumour edge may enhance lymphatic metastasis, by promoting tumour lymphangiogenesis or by activation of pre-existing lymphatic vessels. (PMID:17931169)
• The expression of VEGF-D protein and mRNA levels in patients without lymph node metastasis were significantly higher than those with metastasis (p=0.013, p=0.0494, respectively). (PMID:17970036)
• the 936_C>T polymorphism appears to modify disease risks in BRCA1 carriers. (PMID:18171601)
• Regulation of vascular endothelial growth factor D by hepatocyte nuclear factor-4 alpha and chicken ovalbumin upstream promoter transcription factors 1 and 2. (PMID:18199540)
• Injection of a plasmid encoding VEGF-D through the portal vein is an effective method to induce the formation of fenestrae and decrease portal vein pressure in cirrhotic rats. (PMID:18416461)
• VEGF-C and VEGF-D play an important role in lymphangiogenesis making the carcinoma more aggressive and leading to a poor prognosis. (PMID:18512120)
• VEGF-C and VEGF-D expressions were associated with VEGFR-3 expression and were significantly correlated with both peritumoral lymphangiogenesis and lymph node metastasis. (PMID:18561194)
• Serum levels of VEGF-D were significantly higher in control subjects than in patients with gastric adenocarcinomas. (PMID:18609713)
• The expression of VEGF-D in rectal cancer was significantly higher than that in rectal polyps and normal rectal tissues. (PMID:18636361)
• in breast cancer, VEGF-C and VEGF-D are involved in lymphatic vessel invasion prior to lymph node metastasis, and their expression decreases after lymph node metastasis occurs (PMID:18717190)
• VEGF-D is involved in CD74-induced promotion of cell proliferation and invasion, as well as tumor-induced human umbilical vein endothelial cell migration in vitro. (PMID:18941249)
• Expression of angiogenic and lymphangiogenic factors (VEGF-A, IL-8, VEGF-C,and VEGF-D) is up-regulated directly or indirectly by altitude-dependent hypoxia. Both factors could be involved in a mechanism of adaptation to high altitudes. (PMID:18983460)
• Vascular endothelial growth factor-D transgenic mice show enhanced blood capillary density, improved postischemic muscle regeneration, and increased susceptibility to tumor formation. (PMID:19074006)
• An association between expression of HIF-1alpha and VEGF-D suggests that these two angiogenic factors are essential in progression of esophageal squamous cell carcinoma. (PMID:19096126)
• High expression of VEGF-D is associated with node micrometastasis in pN0 early gastric cancer (PMID:19117016)
• VEGF-D plays an essential role in tumoral lymphangiogenesis and lymphatic spread. VEGF-D expression, and the intratumoral lymphatics are indicators for prognostic evaluation in patients with epithelial ovarian carcinoma. (PMID:19226617)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	vegfd	ENSDARG00000056624
mus_musculus	Vegfd	ENSMUSG00000031380
rattus_norvegicus	Vegfd	ENSRNOG00000003587

Paralogs (4): VEGFA (ENSG00000112715), PGF (ENSG00000119630), VEGFC (ENSG00000150630), VEGFB (ENSG00000173511)

Protein

Protein identifiers

Vascular endothelial growth factor D — O43915 (reviewed: O43915)

Alternative names: c-Fos-induced growth factor

All UniProt accessions (1): O43915

UniProt curated annotations — full annotation on UniProt →

Function. Growth factor active in angiogenesis, lymphangiogenesis and endothelial cell growth, stimulating their proliferation and migration and also has effects on the permeability of blood vessels. May function in the formation of the venous and lymphatic vascular systems during embryogenesis, and also in the maintenance of differentiated lymphatic endothelium in adults. Binds and activates VEGFR-2 (KDR/FLK1) and VEGFR-3 (FLT4) receptors.

Subunit / interactions. Homodimer; non-covalent and antiparallel.

Subcellular location. Secreted.

Tissue specificity. Highly expressed in lung, heart, small intestine and fetal lung, and at lower levels in skeletal muscle, colon, and pancreas.

Post-translational modifications. Undergoes a complex proteolytic maturation which generates a variety of processed secreted forms with increased activity toward VEGFR-3 and VEGFR-2. VEGF-D first form an antiparallel homodimer linked by disulfide bonds before secretion. The fully processed VEGF-D is composed mostly of two VEGF homology domains (VHDs) bound by non-covalent interactions.

Similarity. Belongs to the PDGF/VEGF growth factor family.

RefSeq proteins (1): NP_004460* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000072	PDGF/VEGF_dom	Domain
IPR004153	CXCXC_repeat	Repeat
IPR023581	PD_growth_factor_CS	Conserved_site
IPR029034	Cystine-knot_cytokine	Homologous_superfamily
IPR050507	PDGF/VEGF_growth_factor	Family

Pfam: PF00341, PF03128

Enzyme classification (BRENDA):

• EC 3.4.21.46 — complement factor D (BRENDA: 9 organisms, 37 substrates, 121 inhibitors, 8 Km, 8 kcat entries)

Substrate kinetics (BRENDA)

1 substrates with measured Km, best-characterized 1. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
BENZYLOXYCARBONYL-LYS-THIOBENZYL ESTER	2.95–11.44	8

UniProt features (25 total): disulfide bond 5, strand 5, repeat 4, glycosylation site 3, helix 3, propeptide 2, signal peptide 1, chain 1, region of interest 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2XV7	X-RAY DIFFRACTION	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43915-F1	70.33	0.23

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (5): 111–153, 136, 142–189, 145, 146–191

Glycosylation sites (3): 185, 287, 155

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-114608	Platelet degranulation
R-HSA-194313	VEGF ligand-receptor interactions
R-HSA-195399	VEGF binds to VEGFR leading to receptor dimerization

MSigDB gene sets: 182 (showing top): MODULE_516, GOBP_VASCULAR_ENDOTHELIAL_GROWTH_FACTOR_SIGNALING_PATHWAY, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, GOCC_SECRETORY_GRANULE, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, GOBP_VASCULAR_ENDOTHELIAL_GROWTH_FACTOR_RECEPTOR_SIGNALING_PATHWAY, GOBP_INDUCTION_OF_POSITIVE_CHEMOTAXIS, GOBP_NEUROGENESIS, GOMF_GROWTH_FACTOR_ACTIVITY, GOBP_REGULATION_OF_POSITIVE_CHEMOTAXIS, GOBP_REGULATION_OF_LEUKOCYTE_MIGRATION, PID_INTEGRIN_A9B1_PATHWAY, GOBP_LEUKOCYTE_CHEMOTAXIS

GO Biological Process (14): response to hypoxia (GO:0001666), sprouting angiogenesis (GO:0002040), positive regulation of cell population proliferation (GO:0008284), response to bacterium (GO:0009617), vascular endothelial growth factor signaling pathway (GO:0038084), vascular endothelial growth factor receptor signaling pathway (GO:0048010), fibroblast proliferation (GO:0048144), induction of positive chemotaxis (GO:0050930), positive regulation of cell division (GO:0051781), positive regulation of mast cell chemotaxis (GO:0060754), dopaminergic neuron differentiation (GO:0071542), angiogenesis (GO:0001525), cell differentiation (GO:0030154), positive chemotaxis (GO:0050918)

GO Molecular Function (8): platelet-derived growth factor receptor binding (GO:0005161), vascular endothelial growth factor receptor binding (GO:0005172), growth factor activity (GO:0008083), chemoattractant activity (GO:0042056), identical protein binding (GO:0042802), vascular endothelial growth factor receptor 3 binding (GO:0043185), protein binding (GO:0005515), receptor ligand activity (GO:0048018)

GO Cellular Component (4): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), membrane (GO:0016020), platelet alpha granule lumen (GO:0031093)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Response to elevated platelet cytosolic Ca2+	1
Signaling by VEGF	1
VEGF ligand-receptor interactions	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell population proliferation	2
positive regulation of cellular process	2
cell surface receptor protein tyrosine kinase signaling pathway	2
growth factor receptor binding	2
receptor ligand activity	2
cellular anatomical structure	2
response to stress	1
response to decreased oxygen levels	1
angiogenesis	1
regulation of cell population proliferation	1
response to other organism	1
cellular response to vascular endothelial growth factor stimulus	1
positive regulation of positive chemotaxis	1
cell division	1
regulation of cell division	1
mast cell chemotaxis	1
positive regulation of leukocyte chemotaxis	1
regulation of mast cell chemotaxis	1
neuron differentiation	1
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
cellular developmental process	1
chemotaxis	1
cytokine receptor binding	1
positive chemotaxis	1
protein binding	1
vascular endothelial growth factor receptor binding	1
binding	1
signaling receptor binding	1
signal transduction	1
signaling receptor activator activity	1
platelet alpha granule	1
secretory granule lumen	1

Protein interactions and networks

STRING

1670 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VEGFD	FLT4	P35916	999
VEGFD	KDR	P35968	998
VEGFD	FLT1	P16057	998
VEGFD	NRP2	O60462	936
VEGFD	LYVE1	Q9Y5Y7	933
VEGFD	VEGFB	P49765	883
VEGFD	NRP1	O14786	850
VEGFD	PROX1	Q92786	843
VEGFD	FGF1	P05230	749
VEGFD	ANGPT2	O15123	742
VEGFD	VEGFC	P49767	728
VEGFD	FGFR1	P11362	678
VEGFD	FGF5	P12034	677
VEGFD	FGF3	P11487	666
VEGFD	FGF2	P09038	649

IntAct

11 interactions, top by confidence:

A	B	Type	Score
VEGFD	ADAM9	psi-mi:“MI:0914”(association)	0.640
VAMP3	VEGFD	psi-mi:“MI:0915”(physical association)	0.490
VEGFD	VAMP3	psi-mi:“MI:0915”(physical association)	0.490
VEGFD	ATP5F1B	psi-mi:“MI:0915”(physical association)	0.400
VEGFD	RPSA2	psi-mi:“MI:0914”(association)	0.350
CHST10	CLGN	psi-mi:“MI:0914”(association)	0.350
VEGFD	FBXO21	psi-mi:“MI:0914”(association)	0.350

BioGRID (50): UBR4 (Affinity Capture-MS), ZER1 (Affinity Capture-MS), ADAM9 (Affinity Capture-MS), BIRC6 (Affinity Capture-MS), KCMF1 (Affinity Capture-MS), TUBB8 (Affinity Capture-MS), MOCS3 (Affinity Capture-MS), OAF (Affinity Capture-MS), ADAM9 (Affinity Capture-MS), UBR4 (Affinity Capture-MS), BIRC6 (Affinity Capture-MS), KCMF1 (Affinity Capture-MS), FIGF (Two-hybrid), FLT4 (Reconstituted Complex), ZBTB25 (Affinity Capture-Luminescence)

ESM2 similar proteins: A0A060WQA3, A5PMY6, A8WGB1, B4HVU2, B4IXJ2, B4PD96, B4QMF4, D3YXF5, O18738, O35167, O35251, O35348, O43278, O43915, O75339, O89103, P06213, P10643, P13385, P21757, P21758, P51864, P51865, P97946, Q03637, Q05585, Q29243, Q3MI99, Q4LDE5, Q4ZJM7, Q58T08, Q5G872, Q5RAD0, Q5RBP1, Q62165, Q66K08, Q6NZL8, Q6UXH8, Q6UXI9, Q76LD0

Diamond homologs: B0VXV3, B0VXV4, C0HM96, C0K3N1, C0K3N2, C0K3N3, C0K3N4, C0K3N5, O35251, O35485, O35757, O43915, O73682, P0DL42, P0DW97, P0DW98, P15691, P15692, P16612, P26617, P49151, P49763, P49764, P49765, P49766, P49767, P50412, P52584, P52585, P67860, P67861, P67862, P67863, P67964, P67965, P82475, P83906, P83942, P97946, P97953

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
bevacizumab	“down-regulates activity”	VEGFD	binding
VEGFD	up-regulates	FLT4	binding
VEGFD	up-regulates	KDR	binding
VEGFD	up-regulates	Angiogenesis

Disease & clinical

Clinical variants and AI predictions

ClinVar

3 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	2
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

802 predictions. Top by Δscore:

Variant	Effect	Δscore
X:15347159:TTTAC:T	donor_loss	1.0000
X:15347160:TTAC:T	donor_loss	1.0000
X:15347161:TAC:T	donor_loss	1.0000
X:15347162:ACCT:A	donor_loss	1.0000
X:15347355:GTGGT:G	acceptor_gain	1.0000
X:15347356:TGGT:T	acceptor_gain	1.0000
X:15347357:GGT:G	acceptor_gain	1.0000
X:15347358:GT:G	acceptor_gain	1.0000
X:15347360:C:CC	acceptor_gain	1.0000
X:15352894:T:TC	acceptor_gain	1.0000
X:15353166:CAG:C	acceptor_gain	1.0000
X:15363106:TACC:T	donor_loss	1.0000
X:15363108:CCTTT:C	donor_loss	1.0000
X:15363318:CG:C	acceptor_gain	1.0000
X:15363318:CGCT:C	acceptor_gain	1.0000
X:15363320:C:CC	acceptor_gain	1.0000
X:15363321:T:C	acceptor_gain	1.0000
X:15363321:T:TC	acceptor_gain	1.0000
X:15346263:T:C	acceptor_gain	0.9900
X:15346263:T:TC	acceptor_gain	0.9900
X:15347162:A:AC	donor_gain	0.9900
X:15347163:C:CC	donor_gain	0.9900
X:15347163:CCTG:C	donor_gain	0.9900
X:15352884:CATTT:C	acceptor_gain	0.9900
X:15352888:T:C	acceptor_gain	0.9900
X:15352888:T:TC	acceptor_gain	0.9900
X:15352894:T:C	acceptor_gain	0.9900
X:15352896:G:C	acceptor_gain	0.9900
X:15353169:C:CC	acceptor_gain	0.9900
X:15354614:T:TG	acceptor_gain	0.9900

AlphaMissense

2359 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:15358163:C:G	C111S	0.999
X:15358164:A:T	C111S	0.999
X:15358177:C:A	W106C	0.999
X:15358177:C:G	W106C	0.999
X:15355225:C:G	C189S	0.998
X:15355226:A:T	C189S	0.998
X:15358073:C:G	R141P	0.998
X:15358096:C:A	K133N	0.998
X:15358096:C:G	K133N	0.998
X:15358164:A:G	C111R	0.998
X:15358037:C:G	C153S	0.997
X:15358038:A:T	C153S	0.997
X:15358070:C:G	C142S	0.997
X:15358071:A:G	C142R	0.997
X:15358071:A:T	C142S	0.997
X:15355219:C:G	C191S	0.996
X:15355220:A:G	C191R	0.996
X:15355220:A:T	C191S	0.996
X:15355226:A:G	C189R	0.996
X:15358036:A:C	C153W	0.996
X:15358037:C:T	C153Y	0.996
X:15358038:A:G	C153R	0.996
X:15358162:G:C	C111W	0.996
X:15358179:A:G	W106R	0.996
X:15358179:A:T	W106R	0.996
X:15355225:C:T	C189Y	0.995
X:15358057:G:C	C146W	0.995
X:15358058:C:G	C146S	0.995
X:15358058:C:T	C146Y	0.995
X:15358059:A:T	C146S	0.995

dbSNP variants (sampled 300 via entrez): RS1000334250 (X:15356973 T>C), RS1000386455 (X:15356387 T>TA), RS1000438451 (X:15365157 G>A), RS1000486561 (X:15357552 C>T), RS1000489001 (X:15363549 A>G), RS1000513826 (X:15354037 C>T), RS1000583608 (X:15355693 T>C), RS1000637417 (X:15362664 C>T), RS1000640538 (X:15380583 G>A), RS1000713775 (X:15380980 C>T), RS1000890354 (X:15382512 G>A), RS1000935087 (X:15369004 C>T), RS1001087791 (X:15382148 G>A), RS1001122473 (X:15373594 C>A,G,T), RS1001316432 (X:15363993 T>C)

Disease associations

OMIM: gene MIM:300091 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009571_2	vascular endothelial growth factor D levels	2.000000e-15

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010575	vascular endothelial growth factor D measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

50 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
methylmercuric chloride	decreases expression, increases expression, affects cotreatment	3
Dexamethasone	increases expression, affects cotreatment	2
2-methoxy-6-undecyl-1,4-benzoquinone	decreases expression	1
bisphenol A	increases expression	1
butyraldehyde	decreases expression	1
nickel chloride	increases expression	1
butylbenzyl phthalate	increases expression	1
nickel sulfate	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
cordycepin	increases secretion	1
azoxystrobin	decreases expression	1
deguelin	decreases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
clothianidin	decreases expression	1
thifluzamide	decreases expression	1
pyrachlostrobin	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
licochalcone B	increases expression	1
picoxystrobin	decreases expression	1
PCI 5002	affects cotreatment, increases expression	1
Atorvastatin	affects expression	1
Arsenic Trioxide	affects cotreatment, decreases expression	1
Benzalkonium Compounds	increases expression	1
Carbamazepine	affects expression	1
Cisplatin	affects cotreatment, increases expression	1
Cycloheximide	decreases expression, decreases reaction	1
Diethylhexyl Phthalate	decreases expression	1
Dinitrochlorobenzene	increases expression	1
Indomethacin	affects cotreatment, increases expression	1

Cellosaurus cell lines

2 cell lines: 1 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D8DD	Ubigene A-549 VEGFD KO	Cancer cell line	Male
CVCL_W713	VEGF-D 293 clone 11	Transformed cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.