VEGFB

Summary

VEGFB (vascular endothelial growth factor B, HGNC:12681) is a protein-coding gene on chromosome 11q13.1, encoding Vascular endothelial growth factor B (P49765). Growth factor for endothelial cells.

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.

Source: NCBI Gene 7423 — RefSeq curated summary.

At a glance

• GWAS associations: 22
• Clinical variants (ClinVar): 80 total
• Druggable target: yes
• MANE Select transcript: NM_003377

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12681
Approved symbol	VEGFB
Name	vascular endothelial growth factor B
Location	11q13.1
Locus type	gene with protein product
Status	Approved
Aliases	VEGFL
Ensembl gene	ENSG00000173511
Ensembl biotype	protein_coding
OMIM	601398
Entrez	7423

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 8 protein_coding, 1 retained_intron

ENST00000309422, ENST00000426086, ENST00000541681, ENST00000543462, ENST00000868565, ENST00000970131, ENST00000970132, ENST00000970133, ENST00000970134

RefSeq mRNA: 2 — MANE Select: NM_003377 NM_001243733, NM_003377

CCDS: CCDS58144, CCDS8062

Canonical transcript exons

ENST00000309422 — 7 exons

Exon	Start	End
ENSE00001195925	64237187	64237222
ENSE00001195931	64236254	64236327
ENSE00001195939	64235813	64236009
ENSE00001238372	64235458	64235500
ENSE00001238383	64237420	64237655
ENSE00002297940	64234584	64234893
ENSE00003751370	64238356	64239264

Expression profiles

Bgee: expression breadth ubiquitous, 250 present calls, max score 99.40.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 40.9126 / max 351.9427, expressed in 1814 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
114891	25.4319	1797
114890	14.8532	1779
114892	0.4365	218
114894	0.1008	11
114893	0.0902	16

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	99.40	gold quality
right atrium auricular region	UBERON:0006631	98.90	gold quality
right coronary artery	UBERON:0001625	98.78	gold quality
left coronary artery	UBERON:0001626	98.61	gold quality
popliteal artery	UBERON:0002250	98.60	gold quality
tibial artery	UBERON:0007610	98.60	gold quality
descending thoracic aorta	UBERON:0002345	98.57	gold quality
ascending aorta	UBERON:0001496	98.52	gold quality
thoracic aorta	UBERON:0001515	98.52	gold quality
omental fat pad	UBERON:0010414	98.37	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.35	gold quality
aorta	UBERON:0000947	98.32	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.31	gold quality
adenohypophysis	UBERON:0002196	98.29	gold quality
endocervix	UBERON:0000458	98.26	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.24	gold quality
peritoneum	UBERON:0002358	98.22	gold quality
lower esophagus	UBERON:0013473	98.18	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.18	gold quality
adipose tissue of abdominal region	UBERON:0007808	98.06	gold quality
right lobe of thyroid gland	UBERON:0001119	97.93	gold quality
left lobe of thyroid gland	UBERON:0001120	97.71	gold quality
endometrium epithelium	UBERON:0004811	97.67	gold quality
left uterine tube	UBERON:0001303	97.64	gold quality
right frontal lobe	UBERON:0002810	97.61	gold quality
body of uterus	UBERON:0009853	97.61	gold quality
anterior cingulate cortex	UBERON:0009835	97.59	gold quality
body of pancreas	UBERON:0001150	97.57	gold quality
metanephros cortex	UBERON:0010533	97.55	gold quality
mucosa of stomach	UBERON:0001199	97.53	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-8498	yes	12.13
E-ANND-3	yes	11.12

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FLCN, FOXM1, FOXO3, HDGF, HIF1A, STAT3, TEAD4, WT1, YY1

miRNA regulators (miRDB)

39 targeting VEGFB, 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-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-3934-5P	99.67	64.04	846
HSA-MIR-6751-5P	99.56	64.99	1145
HSA-MIR-12122	99.56	69.33	1672
HSA-MIR-642A-5P	99.51	65.10	1152
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4687-3P	99.48	66.41	968
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-130A-5P	99.33	70.26	2623
HSA-MIR-6803-5P	99.19	63.90	1026
HSA-MIR-5190	99.15	67.76	1234
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-371A-5P	99.08	66.51	1914
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-4738-3P	98.98	67.98	1846
HSA-MIR-374A-3P	98.87	67.82	1531

Literature-anchored findings (GeneRIF, showing 40)

• TIMP3 blocks the binding of VEGF to VEGF receptor-2 and inhibits downstream signaling and angiogenesis. (PMID:12652295)
• VEGF family proteins regulate wound healing, chronic inflammation and tumour angiogenesis and lymphangiogenesis in fibroblasts. (PMID:15009103)
• Results describe the crystal structure of human vascular endothelial growth factor-B (VEGF-B) and present a predicted model for the association of VEGF-B with the second domain of its receptor, VEGFR-1. (PMID:16616187)
• iodide at high concentration decreases the expression of the angiogenic factors VEGF-A, VEGF-B, and PG (PMID:16839256)
• Basophils could play a role in angiogenesis and inflammation through the expression of several forms of VEGF-B and their receptors. (PMID:17082651)
• VEGFB, and receptor were highly expressed in dysplastic neurons. IR in astroglial and balloon cells was observed for VEGFA and its receptors Double-labeling also showed expression of VEGFA, VEGFB and VEGFR-1 in cells of the microglia/macrophage lineage. (PMID:18317782)
• VEGF-B appears to have a relatively restricted angiogenic activity in the ischemic heart. (PMID:18511699)
• Increased VEGFB expression is associated with hepatocellular carcinoma (PMID:18537151)
• Overexpression of vascular endothelial growth factor-B in mouse heart alters cardiac lipid metabolism and induces myocardial hypertrophy. (PMID:18757827)
• The structural features of the ‘highly ordered’ interaction of the Fab fragment of the antibody (Fab-2H10) with VEGF-B, is presented. (PMID:18930733)
• VEGF-B mRNA was not expressed either in normal urothelium or in bladder cancer. (PMID:19424629)
• studies of up-regulation of VEGF in endometrial stromal cells: possible role of retinoic acid as endogenous co-regulator (PMID:19910455)
• analysis of binding of vascular endothelial growth factor-B by VEGFR-1(D2) (PMID:20501651)
• In systemic sclerosis, a switch from proangiogenic to antiangiogenic VEGF isoforms may have a crucial role in the insufficient angiogenic response to chronic ischemia. (PMID:21636803)
• In WT1 mutant cells, reduced VEGF(165)b was due to lack of WT1-mediated transcriptional repression of the splicing-factor kinase SRPK1 (PMID:22172722)
• VEGF-A has a tendency to over-express in gastro-oesophageal cancers, while VEGF-B does not seem involved in these tumours. (PMID:22872519)
• Expression of VEGF-B genes in glioma cell lines U87 is significantly changed under hypoxia and ischemic conditions. (PMID:23350126)
• VEGF-B might be an important ligand in the signalling between the tumor and preexisting blood vessels to ensure a functional blood supply for tumor survival. (PMID:23417498)
• Studies indicate that as a decoy VEGF receptor, aflibercept (VEGF-Trap) has binding affinity for VEGF-A, VEGF-B and placenta growth factor PGF. (PMID:23444216)
• High VEGFB expression is associated with bone marrow metastasis in neuroblastoma. (PMID:23553333)
• Data indicate that three miRs (miR-484, -642, and -217) were able to predict chemoresistance and vasculature of serous epithelial ovarian carcinomas through the regulation of the VEGFB and VEGFR2 pathways. (PMID:23697367)
• we report significant associations with overall survival and distant failure for certain VEGF(VEGF-B) family members. (PMID:23728940)
• Low VEGFB and VEGFD gene expression is associated with early-stage non-small cell lung cancer. (PMID:24145997)
• Our study suggested that VEGF-B was an angiogenesis factor in vitro and that ERK1/2 and p38-related signaling pathways were involved in these VEGF-B activities. (PMID:24374930)
• VEGF-B has possible roles in cardiac protection, energy metabolism support, and neuroprotectin [review] (PMID:24987005)
• Roles of vascular endothelial growth factor in amyotrophic lateral sclerosis. (PMID:24987705)
• High VEGF-B levels might correlate with the presence of hyperlipidemia and target organ damage in type 2 diabetic patients. (PMID:25001655)
• MMP9 may activate VEGF-B via PI3K/Akt signaling pathway. (PMID:25424698)
• fluid shear stress induces the synthesis of Insulin growth factor-2 and vascular endothelial growth factor (VEGF) B and D, which in turn transactivate MMP-12. (PMID:25435370)
• Frameshift mutations of VEGFB gene is associated with stomach and colorectal cancers. (PMID:25633991)
• plasma VEGF levels before treatment were lower in patients with schizophrenia and that their VEGF levels increased after treatment. (PMID:25977072)
• Data show that metformin treatment reduces serum vascular endothelial growth factor B (VEGF-B) levels and ameliorates insulin resistance. (PMID:26387747)
• VEGFA and VEGFB associated sub-network, kinase insert domain receptor (KDR), fibronectin 1 (FN1), transforming growth factor beta induced (TGFBI) and proliferating cell nuclear antigen (PCNA) found to interact with at least two of the three hub genes. (PMID:26422603)
• Cardiac transgenic vascular endothelial growth factor-B overexpression failed to protect heart transplants from ischemia-reperfusion injury. (PMID:27588416)
• renal VEGF-B expression correlates with the severity of Diabetic Kidney Disease. (PMID:28190774)
• High plasma VEGF-B levels are associated with type 2 diabetes mellitus. (PMID:28523459)
• Data from clinical studies point out the changes in circulating or tissue expression levels of VEGF-B in obese compared with lean patients. (PMID:28798193)
• vitreous levels increased in neovascular retinal diseases (PMID:29969324)
• Results found that VEGF-B expressions levels were higher in Behcet’s disease (BD) patients than those in the healthy group, but this difference did not reach statistical significance. Also, VEGF-B gene expression is significantly higher in patients with vascular involvement (DVT/thrombophlebitis). (PMID:30420902)
• Molecular docking, synthesis and biological evaluation of Vascular Endothelial Growth Factor (VEGF) B based peptide as antiangiogenic agent targeting the second domain of the Vascular Endothelial Growth Factor Receptor 1 (VEGFR1D2) for anticancer application. (PMID:32499505)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	vegfba	ENSDARG00000090997
danio_rerio	vegfbb	ENSDARG00000092480
mus_musculus	Vegfb	ENSMUSG00000024962
rattus_norvegicus	Vegfb	ENSRNOG00000021156

Paralogs (4): VEGFA (ENSG00000112715), PGF (ENSG00000119630), VEGFC (ENSG00000150630), VEGFD (ENSG00000165197)

Protein

Protein identifiers

Vascular endothelial growth factor B — P49765 (reviewed: P49765)

Alternative names: VEGF-related factor

All UniProt accessions (3): P49765, H0YGB6, Q7LAP4

UniProt curated annotations — full annotation on UniProt →

Function. Growth factor for endothelial cells. VEGF-B167 binds heparin and neuropilin-1 whereas the binding to neuropilin-1 of VEGF-B186 is regulated by proteolysis.

Subunit / interactions. Homodimer; disulfide-linked. Can also form heterodimer with VEGF.

Subcellular location. Secreted.

Tissue specificity. Expressed in all tissues except liver. Highest levels found in heart, skeletal muscle and pancreas.

Post-translational modifications. VEGF-B186 is O-glycosylated.

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

Isoforms (2)

UniProt ID	Names	Canonical?
P49765-1	VEGF-B186	yes
P49765-2	VEGF-B167

RefSeq proteins (2): NP_001230662, NP_003368* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF00341

UniProt features (21 total): strand 6, disulfide bond 5, splice variant 2, turn 2, compositionally biased region 2, signal peptide 1, chain 1, helix 1, region of interest 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
6TKK	X-RAY DIFFRACTION	1.06
2C7W	X-RAY DIFFRACTION	2.48
2XAC	X-RAY DIFFRACTION	2.71
2VWE	X-RAY DIFFRACTION	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P49765-F1	74.85	0.37

Antibody-complex structures (SAbDab): 1 — 2VWE

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): 47–89, 72, 78–122, 81, 82–124

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: 280 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_VASCULAR_ENDOTHELIAL_GROWTH_FACTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_WOUND_HEALING, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CORONARY_VASCULATURE_DEVELOPMENT, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_CELL_CHEMOTAXIS, GOBP_REGULATION_OF_PHOSPHORYLATION, GOCC_SECRETORY_GRANULE, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, GCANCTGNY_MYOD_Q6, GOBP_POSITIVE_REGULATION_OF_VASCULATURE_DEVELOPMENT, GOBP_VASCULAR_ENDOTHELIAL_GROWTH_FACTOR_RECEPTOR_SIGNALING_PATHWAY

GO Biological Process (23): response to hypoxia (GO:0001666), positive regulation of endothelial cell proliferation (GO:0001938), sprouting angiogenesis (GO:0002040), protein O-linked glycosylation (GO:0006493), positive regulation of cell population proliferation (GO:0008284), negative regulation of gene expression (GO:0010629), positive regulation of vascular endothelial growth factor receptor signaling pathway (GO:0030949), positive regulation of vascular wound healing (GO:0035470), vascular endothelial growth factor signaling pathway (GO:0038084), negative regulation of apoptotic process (GO:0043066), negative regulation of neuron apoptotic process (GO:0043524), vascular endothelial growth factor receptor signaling pathway (GO:0048010), positive regulation of peptidyl-tyrosine phosphorylation (GO:0050731), induction of positive chemotaxis (GO:0050930), positive regulation of cell division (GO:0051781), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), cardiac muscle contraction (GO:0060048), positive regulation of mast cell chemotaxis (GO:0060754), coronary vasculature development (GO:0060976), positive regulation of ERK1 and ERK2 cascade (GO:0070374), signal transduction (GO:0007165), heart development (GO:0007507), positive chemotaxis (GO:0050918)

GO Molecular Function (8): vascular endothelial growth factor receptor binding (GO:0005172), growth factor activity (GO:0008083), heparin binding (GO:0008201), chemoattractant activity (GO:0042056), identical protein binding (GO:0042802), vascular endothelial growth factor receptor 1 binding (GO:0043183), 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
positive regulation of cellular process	2
cell surface receptor protein tyrosine kinase signaling pathway	2
receptor ligand activity	2
cellular anatomical structure	2
response to stress	1
response to decreased oxygen levels	1
endothelial cell proliferation	1
regulation of endothelial cell proliferation	1
positive regulation of epithelial cell proliferation	1
angiogenesis	1
glycoprotein biosynthetic process	1
cell population proliferation	1
regulation of cell population proliferation	1
gene expression	1
regulation of gene expression	1
negative regulation of macromolecule biosynthetic process	1
positive regulation of signal transduction	1
regulation of vascular endothelial growth factor receptor signaling pathway	1
vascular endothelial growth factor receptor signaling pathway	1
positive regulation of angiogenesis	1
vascular wound healing	1
regulation of vascular wound healing	1
positive regulation of wound healing	1
cellular response to vascular endothelial growth factor stimulus	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
negative regulation of apoptotic process	1
regulation of neuron apoptotic process	1
neuron apoptotic process	1
positive regulation of protein phosphorylation	1
peptidyl-tyrosine phosphorylation	1
regulation of peptidyl-tyrosine phosphorylation	1
positive regulation of positive chemotaxis	1
cell division	1
regulation of cell division	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
positive regulation of intracellular signal transduction	1
striated muscle contraction	1

Protein interactions and networks

STRING

1811 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VEGFB	FLT1	P16057	999
VEGFB	FLT4	P35916	998
VEGFB	KDR	P35968	998
VEGFB	NRP1	O14786	996
VEGFB	PGF	P49763	888
VEGFB	VEGFD	O43915	883
VEGFB	PDGFC	Q9NRA1	811
VEGFB	DNAJC4	Q9NNZ3	782
VEGFB	NRP2	O60462	766
VEGFB	FGF1	P05230	747
VEGFB	ZFPL1	O95159	736
VEGFB	VEGFC	P49767	720
VEGFB	ANGPT1	Q15389	709
VEGFB	ADRB2	P07550	701
VEGFB	ANGPT2	O15123	696

IntAct

19 interactions, top by confidence:

A	B	Type	Score
VEGFB	KLHL12	psi-mi:“MI:0915”(physical association)	0.670
ADAM21	PLXNA2	psi-mi:“MI:0914”(association)	0.530
NOTCH2	ZNF316	psi-mi:“MI:0914”(association)	0.530
VEGFB	LAMB2	psi-mi:“MI:0914”(association)	0.530
rep	VEGFB	psi-mi:“MI:0915”(physical association)	0.490
VEGFB	VEGFA	psi-mi:“MI:0914”(association)	0.480
VEGFB	VEGFA	psi-mi:“MI:2364”(proximity)	0.480
VEGFB	VEGFB	psi-mi:“MI:0407”(direct interaction)	0.440
ST14	LIPT2	psi-mi:“MI:0914”(association)	0.350
LY86	PLXNB2	psi-mi:“MI:0914”(association)	0.350
EFNA2	C1QL1	psi-mi:“MI:0914”(association)	0.350
VEGFB	NPC1	psi-mi:“MI:0914”(association)	0.350
VEGFB	KLHL12	psi-mi:“MI:0915”(physical association)	0.000
ftsK	VEGFB	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (46): KLHL12 (Two-hybrid), FAT1 (Affinity Capture-MS), NUDT16L1 (Affinity Capture-MS), TRIM68 (Affinity Capture-MS), VEGFA (Affinity Capture-MS), HAL (Affinity Capture-MS), COL6A2 (Affinity Capture-MS), ALOXE3 (Affinity Capture-MS), LRFN3 (Affinity Capture-MS), VEGFA (Co-localization), TRIM68 (Affinity Capture-MS), VEGFB (Affinity Capture-MS), VEGFA (Affinity Capture-MS), HAL (Affinity Capture-MS), NUDT16L1 (Affinity Capture-MS)

ESM2 similar proteins: O08999, O35485, O35806, O43278, O89103, O95428, P13207, P23943, P35054, P49765, P49766, P59383, P97766, P98153, P98154, Q00918, Q14766, Q14767, Q16610, Q28019, Q2Q0I9, Q2TAL6, Q3U515, Q4ZHG4, Q5BIR3, Q5HZW5, Q5NRP8, Q5NRQ0, Q61508, Q61810, Q62894, Q765Z5, Q7TQH7, Q7Z4F1, Q867D0, Q86T13, Q86VZ4, Q8BH27, Q8C8N3, Q8CB67

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

3 interactions.

A	Effect	B	Mechanism
Aflibercept	“down-regulates activity”	VEGFB	“chemical inhibition”
bevacizumab	“down-regulates activity”	VEGFB	binding
VEGFB	up-regulates	Angiogenesis

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	50
Likely benign	4
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

896 predictions. Top by Δscore:

Variant	Effect	Δscore
11:64234894:GTAC:G	donor_loss	1.0000
11:64234895:T:G	donor_loss	1.0000
11:64235812:GTGGT:G	acceptor_gain	1.0000
11:64237179:C:G	acceptor_gain	1.0000
11:64237185:A:AG	acceptor_gain	1.0000
11:64237186:G:GG	acceptor_gain	1.0000
11:64235799:C:A	acceptor_gain	0.9900
11:64235809:CCAG:C	acceptor_loss	0.9900
11:64235811:A:AG	acceptor_gain	0.9900
11:64235811:A:AT	acceptor_loss	0.9900
11:64235811:AGT:A	acceptor_gain	0.9900
11:64235811:AGTG:A	acceptor_gain	0.9900
11:64235812:G:GT	acceptor_gain	0.9900
11:64235812:GT:G	acceptor_gain	0.9900
11:64235812:GTG:G	acceptor_gain	0.9900
11:64235812:GTGG:G	acceptor_gain	0.9900
11:64236007:CAGG:C	donor_loss	0.9900
11:64236008:AGG:A	donor_loss	0.9900
11:64236009:GGTAC:G	donor_loss	0.9900
11:64236010:GTA:G	donor_loss	0.9900
11:64236011:T:G	donor_loss	0.9900
11:64236223:A:AG	acceptor_gain	0.9900
11:64236224:C:G	acceptor_gain	0.9900
11:64236245:T:TA	acceptor_gain	0.9900
11:64236302:G:GT	donor_gain	0.9900
11:64236316:GT:G	donor_gain	0.9900
11:64237174:T:G	acceptor_gain	0.9900
11:64237178:A:AG	acceptor_gain	0.9900
11:64237185:A:AC	acceptor_loss	0.9900
11:64237186:GA:G	acceptor_gain	0.9900

AlphaMissense

1322 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:64235823:G:C	W38C	0.999
11:64235823:G:T	W38C	0.999
11:64235974:T:A	C89S	0.999
11:64235975:G:C	C89S	0.999
11:64235918:C:A	P70H	0.998
11:64235941:T:A	C78S	0.998
11:64235942:G:C	C78S	0.998
11:64235974:T:C	C89R	0.998
11:64236317:T:A	C122S	0.998
11:64236318:G:C	C122S	0.998
11:64235821:T:A	W38R	0.997
11:64235821:T:C	W38R	0.997
11:64235848:T:A	C47S	0.997
11:64235849:G:A	C47Y	0.997
11:64235849:G:C	C47S	0.997
11:64235939:G:C	R77P	0.997
11:64236323:T:A	C124S	0.997
11:64236324:G:C	C124S	0.997
11:64235848:T:C	C47R	0.996
11:64235917:C:T	P70S	0.996
11:64235941:T:C	C78R	0.996
11:64235942:G:A	C78Y	0.996
11:64235947:G:T	G80C	0.996
11:64235953:T:A	C82S	0.996
11:64235953:T:C	C82R	0.996
11:64235954:G:C	C82S	0.996
11:64235976:T:G	C89W	0.996
11:64235850:C:G	C47W	0.995
11:64235918:C:G	P70R	0.995
11:64235942:G:T	C78F	0.995

dbSNP variants (sampled 300 via entrez): RS1000078381 (11:64236664 C>T), RS1000475163 (11:64233150 G>A), RS1000548533 (11:64232920 C>T), RS1000579773 (11:64232713 AC>A,ACC), RS1000845623 (11:64238529 T>C), RS1002009338 (11:64233237 CT>C,CTT), RS1002281578 (11:64239338 T>G), RS1002312467 (11:64239189 G>A), RS1002622092 (11:64237092 A>C,G,T), RS1002747513 (11:64234487 G>A,C), RS1002880503 (11:64235256 G>A), RS1002943686 (11:64234836 G>A), RS1003015350 (11:64234485 C>A,G), RS1003590881 (11:64238294 ATG>A), RS1004398367 (11:64238472 C>G)

Disease associations

OMIM: gene MIM:601398 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

22 associations (top):

Study	Trait	p-value
GCST002782_96	Waist-to-hip ratio adjusted for body mass index	3.000000e-11
GCST002782_97	Waist-to-hip ratio adjusted for body mass index	4.000000e-08
GCST002782_98	Waist-to-hip ratio adjusted for body mass index	6.000000e-10
GCST002782_99	Waist-to-hip ratio adjusted for body mass index	8.000000e-07
GCST004132_98	Crohn’s disease	5.000000e-06
GCST004505_77	Waist-to-hip ratio adjusted for BMI (adjusted for smoking behaviour)	3.000000e-06
GCST004505_78	Waist-to-hip ratio adjusted for BMI (adjusted for smoking behaviour)	1.000000e-06
GCST006613_18	Triglycerides	1.000000e-16
GCST010136_47	Fruit consumption	9.000000e-10
GCST010241_24	Apolipoprotein A1 levels	2.000000e-17
GCST010242_478	HDL cholesterol levels	3.000000e-34
GCST010244_46	Triglyceride levels	8.000000e-44
GCST012229_142	Hip index	3.000000e-08
GCST90002381_512	Eosinophil count	7.000000e-13
GCST90002382_386	Eosinophil percentage of white cells	2.000000e-12
GCST90002403_202	Red blood cell count	1.000000e-12
GCST90020024_387	A body shape index	3.000000e-24
GCST90020025_1865	Waist-to-hip ratio adjusted for BMI	9.000000e-44
GCST90020026_780	Hip index	1.000000e-19
GCST90020027_1486	Waist-hip index	5.000000e-44
GCST90020028_1985	Hip circumference adjusted for BMI	2.000000e-14
GCST90020029_318	Waist circumference adjusted for body mass index	5.000000e-24

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0004318	smoking behavior
EFO:0004530	triglyceride measurement
EFO:0008111	diet measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0008039	BMI-adjusted hip circumference
EFO:0004842	eosinophil count
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004305	erythrocyte count
EFO:0007789	BMI-adjusted waist circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3580488 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs12366035	Toxicity	3	sorafenib	Drug Toxicity

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs12366035	VEGFB	3	1.50	1	sorafenib

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Arsenic	affects expression, increases expression, affects cotreatment, increases abundance	4
sodium arsenite	increases abundance, increases expression, decreases expression, affects cotreatment	3
perfluorooctane sulfonic acid	decreases expression, increases expression	2
Bortezomib	decreases expression, increases expression	2
Oxygen	increases expression	2
Tobacco Smoke Pollution	decreases expression	2
Valproic Acid	affects cotreatment, increases expression, increases methylation	2
GSK-J4	increases expression	1
bisphenol F	increases expression	1
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate	decreases expression	1
chloroacetaldehyde	increases expression	1
pirinixic acid	increases expression, affects binding, increases activity	1
bisphenol A	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
tetrathiomolybdate	decreases expression	1
perfluorooctanoic acid	decreases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
phenanthrene	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
yessotoxin	increases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Rosiglitazone	increases expression	1
Resveratrol	increases expression	1
Pioglitazone	increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	affects cotreatment, decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E0SU	Ubigene HeLa VEGFB KO	Cancer cell line	Female
CVCL_TX41	HAP1 VEGFB (-) 1	Cancer cell line	Male
CVCL_TX42	HAP1 VEGFB (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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