VEGFA

vascular endothelial growth factor A, the group of VEGF family

Basic information

Region (hg38): 6:43770183-43786487

Previous symbols: [ "VEGF" ]

Links

ENSG00000112715 ∙ NCBI:7422 ∙ OMIM:192240 ∙ HGNC:12680 ∙ Uniprot:P15692 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the VEGFA gene.

• not provided (19 variants)
• Inborn genetic diseases (19 variants)
• Microvascular complications of diabetes, susceptibility to, 1 (1 variants)
• VEGFA-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the VEGFA gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				7	1	8
missense			12	8		20
nonsense			1			1
start loss						0
frameshift		2	1			3
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding					6	6
Total	0	2	14	15	7

Highest pathogenic variant AF is 0.0000328

Variants in VEGFA

This is a list of pathogenic ClinVar variants found in the VEGFA region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
6-43770613-C-G		Microvascular complications of diabetes, susceptibility to, 1	Benign (Jun 19, 2021)
6-43770712-G-GGA			Uncertain significance (Jul 03, 2023)
6-43770712-G-GGACA			Likely pathogenic (Jun 01, 2016)
6-43770770-C-T			Uncertain significance (-)
6-43770795-G-A		not specified	Uncertain significance (Sep 16, 2021)
6-43770835-G-A			Likely benign (Aug 08, 2018)
6-43770894-G-T		not specified	Uncertain significance (Oct 25, 2023)
6-43770897-T-C		not specified	Likely benign (Apr 07, 2023)
6-43770920-G-T		not specified	Uncertain significance (Aug 08, 2022)
6-43770928-C-G			Likely benign (Jul 21, 2018)
6-43770931-G-A			Benign (Sep 19, 2018)
6-43770941-G-A		not specified	Likely benign (Apr 07, 2023)
6-43770945-C-G		not specified	Likely benign (Apr 07, 2023)
6-43770980-C-T		not specified	Likely benign (Apr 07, 2023)
6-43770989-G-T			Uncertain significance (May 01, 2016)
6-43770994-G-A		VEGFA-related disorder	Likely benign (Jun 01, 2019)
6-43771000-A-G		VEGFA-related disorder	Likely benign (Jul 01, 2019)
6-43771029-A-G		not specified	Likely benign (Apr 07, 2023)
6-43771041-G-T		not specified	Uncertain significance (May 24, 2023)
6-43771043-G-T		not specified	Likely benign (Apr 07, 2023)
6-43771047-G-C		not specified	Uncertain significance (Nov 15, 2021)
6-43771104-C-A		not specified	Uncertain significance (Apr 07, 2023)
6-43771137-G-C		not specified	Likely benign (Apr 07, 2023)
6-43771140-G-C		not specified	Likely benign (Apr 07, 2023)
6-43771175-A-C		not specified	Uncertain significance (Jan 23, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
VEGFA	protein_coding	protein_coding	ENST00000372055	8	16304

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000241	0.982	125716	0	32	125748	0.000127

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.467	203	223	0.912	0.0000130	2628
Missense in Polyphen		45	66.213	0.67962		747
Synonymous	-0.819	99	89.2	1.11	0.00000528	827
Loss of Function	2.12	11	21.7	0.508	0.00000119	243

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000615	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000466	0.0000462
European (Non-Finnish)	0.000247	0.000246
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth. Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis and induces permeabilization of blood vessels. Binds to the FLT1/VEGFR1 and KDR/VEGFR2 receptors, heparan sulfate and heparin. NRP1/Neuropilin-1 binds isoforms VEGF-165 and VEGF-145. Isoform VEGF165B binds to KDR but does not activate downstream signaling pathways, does not activate angiogenesis and inhibits tumor growth. Binding to NRP1 receptor initiates a signaling pathway needed for motor neuron axon guidance and cell body migration, including for the caudal migration of facial motor neurons from rhombomere 4 to rhombomere 6 during embryonic development (By similarity). {ECO:0000250|UniProtKB:Q00731, ECO:0000269|PubMed:11427521, ECO:0000269|PubMed:16489009}.
• Disease: DISEASE: Microvascular complications of diabetes 1 (MVCD1) [MIM:603933]: Pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end- stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis. {ECO:0000269|PubMed:11978667}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);Focal adhesion - Homo sapiens (human);Relaxin signaling pathway - Homo sapiens (human);Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human);Renal cell carcinoma - Homo sapiens (human);VEGF signaling pathway - Homo sapiens (human);AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human);Bladder cancer - Homo sapiens (human);HIF-1 signaling pathway - Homo sapiens (human);Fluid shear stress and atherosclerosis - Homo sapiens (human);Rap1 signaling pathway - Homo sapiens (human);Ras signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);MicroRNAs in cancer - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Rheumatoid arthritis - Homo sapiens (human);Cytokine-cytokine receptor interaction - Homo sapiens (human);Pancreatic cancer - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Celecoxib Pathway, Pharmacodynamics;VEGF Signaling Pathway;Bevacizumab Action Pathway;Heart Development;Integrated Breast Cancer Pathway;Angiogenesis overview;Regulation of Hypoxia-inducible Factor (HIF) by oxygen;Allograft Rejection;Oncostatin M Signaling Pathway;Quercetin and Nf-kB- AP-1 Induced Cell Apoptosis;Aryl Hydrocarbon Receptor;Bladder Cancer;Differentiation Pathway;Focal Adhesion;NOTCH1 regulation of human endothelial cell calcification;miR-148a-miR-31-FIH1-HIF1α-Notch signaling in glioblastoma;Photodynamic therapy-induced HIF-1 survival signaling;Photodynamic therapy-induced NF-kB survival signaling;Hepatitis C and Hepatocellular Carcinoma;Amplification and Expansion of Oncogenic Pathways as Metastatic Traits;VEGFA-VEGFR2 Signaling Pathway;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;Robo4 and VEGF Signaling Pathways Crosstalk;Pathways in clear cell renal cell carcinoma;Interleukin-4 and 13 signaling;Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors;PI3K-Akt Signaling Pathway;Hereditary Leiomyomatosis and Renal Cell Carcinoma Pathway;Type 2 papillary renal cell carcinoma;Endochondral Ossification;Hypertrophy Model;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;Signal Transduction;Gene expression (Transcription);hypoxia-inducible factor in the cardivascular system;vegf hypoxia and angiogenesis;VEGFA-VEGFR2 Pathway;Generic Transcription Pathway;GPCR signaling-G alpha q;GPCR signaling-cholera toxin;GPCR signaling-pertussis toxin;RNA Polymerase II Transcription;HIF-2-alpha transcription factor network;actions of nitric oxide in the heart;GPCR signaling-G alpha s Epac and ERK;VEGF ligand-receptor interactions;Platelet degranulation ;Response to elevated platelet cytosolic Ca2+;Platelet activation, signaling and aggregation;GPCR signaling-G alpha s PKA and ERK;Beta3 integrin cell surface interactions;SHP2 signaling;Hemostasis;Signaling events mediated by TCPTP;VEGF binds to VEGFR leading to receptor dimerization;Signaling by VEGF;Plexin-D1 Signaling;TFAP2 (AP-2) family regulates transcription of growth factors and their receptors;Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors;GPCR signaling-G alpha i;Signaling by Receptor Tyrosine Kinases;VEGF;Alpha9 beta1 integrin signaling events;VEGF and VEGFR signaling network;Glypican 1 network;S1P1 pathway;Beta1 integrin cell surface interactions;S1P3 pathway;HIF-1-alpha transcription factor network;Signaling events mediated by VEGFR1 and VEGFR2;Integrins in angiogenesis;VEGFR1 specific signals;VEGFR2 mediated cell proliferation (Consensus)

Recessive Scores

• pRec: 0.0942

Haploinsufficiency Scores

• pHI: 0.272
• ghis: 0.540

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.792

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Vegfa
• Phenotype: embryo phenotype; liver/biliary system phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; reproductive system phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); neoplasm; digestive/alimentary phenotype; limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype; immune system phenotype; renal/urinary system phenotype; skeleton phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); endocrine/exocrine gland phenotype; muscle phenotype; craniofacial phenotype; homeostasis/metabolism phenotype; cellular phenotype

Zebrafish Information Network

• Gene name: vegfaa
• Affected structure: blood vessel endothelial cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;angiogenesis;ovarian follicle development;branching involved in blood vessel morphogenesis;vasculogenesis;response to hypoxia;in utero embryonic development;kidney development;positive regulation of protein phosphorylation;positive regulation of endothelial cell proliferation;sprouting angiogenesis;cell migration involved in sprouting angiogenesis;positive regulation of neuroblast proliferation;positive regulation of mesenchymal cell proliferation;positive regulation of receptor internalization;platelet degranulation;positive regulation of leukocyte migration;heart morphogenesis;outflow tract morphogenesis;coronary vein morphogenesis;regulation of transcription by RNA polymerase II;nervous system development;mesoderm development;lactation;positive regulation of cell population proliferation;regulation of cell shape;regulation of signaling receptor activity;positive regulation of endothelial cell migration;positive regulation of gene expression;negative regulation of gene expression;regulation of nitric oxide mediated signal transduction;cytokine-mediated signaling pathway;monocyte differentiation;macrophage differentiation;lung development;positive regulation of cell migration;epithelial cell differentiation;positive regulation of vascular endothelial growth factor receptor signaling pathway;post-embryonic camera-type eye development;positive regulation of protein complex assembly;positive regulation of protein autophosphorylation;activation of protein kinase activity;positive regulation of CREB transcription factor activity;positive regulation of peptidyl-serine phosphorylation;tube formation;endothelial cell chemotaxis;cellular response to vascular endothelial growth factor stimulus;lymph vessel morphogenesis;positive regulation of endothelial cell chemotaxis by VEGF-activated vascular endothelial growth factor receptor signaling pathway;vascular endothelial growth factor signaling pathway;positive regulation of cell proliferation by VEGF-activated platelet derived growth factor receptor signaling pathway;VEGF-activated neuropilin signaling pathway;eye photoreceptor cell development;positive regulation of tyrosine phosphorylation of STAT protein;negative regulation of apoptotic process;surfactant homeostasis;negative regulation of cysteine-type endopeptidase activity involved in apoptotic process;positive regulation of MAP kinase activity;positive regulation of blood vessel endothelial cell migration;positive regulation of angiogenesis;positive regulation of cell adhesion;positive regulation of transcription by RNA polymerase II;vascular endothelial growth factor receptor signaling pathway;cell maturation;camera-type eye morphogenesis;cardiac muscle fiber development;branching morphogenesis of an epithelial tube;positive regulation of axon extension involved in axon guidance;artery morphogenesis;positive regulation of epithelial cell proliferation;positive regulation of peptidyl-tyrosine phosphorylation;positive chemotaxis;positive regulation of positive chemotaxis;induction of positive chemotaxis;positive regulation of cellular component movement;positive regulation of cell division;positive regulation of focal adhesion assembly;primitive erythrocyte differentiation;mammary gland alveolus development;positive regulation of mast cell chemotaxis;cardiac vascular smooth muscle cell development;coronary artery morphogenesis;regulation of transcription from RNA polymerase II promoter in response to hypoxia;positive regulation of transcription from RNA polymerase II promoter in response to hypoxia;cellular response to hypoxia;dopaminergic neuron differentiation;commissural neuron axon guidance;positive regulation of protein kinase C signaling;positive regulation of cell migration involved in sprouting angiogenesis;positive regulation of branching involved in ureteric bud morphogenesis;regulation of retinal ganglion cell axon guidance;motor neuron migration;cellular stress response to acid chemical;positive regulation of cold-induced thermogenesis;positive regulation of peptidyl-tyrosine autophosphorylation;positive regulation of p38MAPK cascade;positive regulation of histone deacetylase activity;positive regulation of retinal ganglion cell axon guidance;positive regulation of protein kinase D signaling;positive regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis;positive regulation of sprouting angiogenesis
• Cellular component: extracellular region;extracellular space;cytoplasm;cell surface;membrane;secretory granule;extracellular matrix;platelet alpha granule lumen
• Molecular function: fibronectin binding;cytokine activity;platelet-derived growth factor receptor binding;vascular endothelial growth factor receptor binding;protein binding;growth factor activity;heparin binding;chemoattractant activity;identical protein binding;protein homodimerization activity;vascular endothelial growth factor receptor 1 binding;vascular endothelial growth factor receptor 2 binding;protein heterodimerization activity;receptor ligand activity;extracellular matrix binding