VAV3

vav guanine nucleotide exchange factor 3, the group of Pleckstrin homology domain containing|MicroRNA protein coding host genes|Dbl family Rho GEFs|SH2 domain containing

Basic information

Region (hg38): 1:107571160-107965180

Links

ENSG00000134215 ∙ NCBI:10451 ∙ OMIM:605541 ∙ HGNC:12659 ∙ Uniprot:Q9UKW4 ∙ 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 VAV3 gene.

• Inborn genetic diseases (29 variants)
• not provided (19 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the VAV3 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				6	5	11
missense			29	4	1	34
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					2	2
non coding					1	1
Total	0	0	29	10	7

Variants in VAV3

This is a list of pathogenic ClinVar variants found in the VAV3 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-107574039-C-T			Benign (Dec 31, 2019)
1-107574093-G-A			Likely benign (May 21, 2018)
1-107574133-C-G		not specified	Uncertain significance (Apr 24, 2023)
1-107574166-C-T		not specified	Uncertain significance (Jul 14, 2021)
1-107574167-G-A			Likely benign (Apr 01, 2024)
1-107574170-G-A			Likely benign (May 21, 2018)
1-107596235-C-T		not specified	Uncertain significance (Nov 15, 2021)
1-107596271-A-T		not specified	Uncertain significance (Jan 23, 2023)
1-107602455-A-G		not specified	Uncertain significance (Oct 12, 2022)
1-107603039-C-A			Benign (Apr 10, 2018)
1-107603081-T-C		not specified	Uncertain significance (Oct 14, 2023)
1-107603117-T-G		not specified	Uncertain significance (Jun 02, 2023)
1-107603138-G-T		not specified	Uncertain significance (Dec 01, 2022)
1-107609935-G-T			Likely benign (Aug 01, 2018)
1-107617578-G-C		not specified	Uncertain significance (Jan 30, 2024)
1-107642621-G-C		not specified	Uncertain significance (Oct 10, 2023)
1-107642638-G-A		not specified	Uncertain significance (Dec 22, 2023)
1-107642641-T-C		not specified	Uncertain significance (Dec 22, 2023)
1-107642692-C-T		not specified	Uncertain significance (Apr 22, 2022)
1-107642705-C-T		not specified	Uncertain significance (Feb 27, 2024)
1-107642723-A-G		not specified	Uncertain significance (Dec 14, 2021)
1-107683515-G-C		not specified	Uncertain significance (Dec 19, 2022)
1-107688398-T-C		not specified	Uncertain significance (Feb 05, 2024)
1-107705049-T-C			Benign (Jul 10, 2018)
1-107749046-T-C		not specified	Uncertain significance (Aug 28, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
VAV3	protein_coding	protein_coding	ENST00000370056	27	393985

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.45e-14	1.00	125679	0	69	125748	0.000274

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.13	370	437	0.847	0.0000214	5583
Missense in Polyphen		145	191.12	0.75869		2494
Synonymous	-1.20	172	153	1.12	0.00000759	1493
Loss of Function	3.26	31	57.8	0.537	0.00000310	697

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000693	0.000693
Ashkenazi Jewish	0.000298	0.000298
East Asian	0.000109	0.000109
Finnish	0.000185	0.000185
European (Non-Finnish)	0.000284	0.000273
Middle Eastern	0.000109	0.000109
South Asian	0.000366	0.000359
Other	0.000165	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Exchange factor for GTP-binding proteins RhoA, RhoG and, to a lesser extent, Rac1. Binds physically to the nucleotide-free states of those GTPases. Plays an important role in angiogenesis. Its recruitment by phosphorylated EPHA2 is critical for EFNA1- induced RAC1 GTPase activation and vascular endothelial cell migration and assembly (By similarity). May be important for integrin-mediated signaling, at least in some cell types. In osteoclasts, along with SYK tyrosine kinase, required for signaling through integrin alpha-v/beta-1 (ITAGV-ITGB1), a crucial event for osteoclast proper cytoskeleton organization and function. This signaling pathway involves RAC1, but not RHO, activation. Necessary for proper wound healing. In the course of wound healing, required for the phagocytotic cup formation preceding macrophage phagocytosis of apoptotic neutrophils. Responsible for integrin beta-2 (ITGB2)-mediated macrophage adhesion and, to a lesser extent, contributes to beta-3 (ITGB3)- mediated adhesion. Does not affect integrin beta-1 (ITGB1)- mediated adhesion (By similarity). {ECO:0000250}.
• Pathway: Focal adhesion - Homo sapiens (human);T cell receptor signaling pathway - Homo sapiens (human);B cell receptor signaling pathway - Homo sapiens (human);Fc epsilon RI signaling pathway - Homo sapiens (human);Fc gamma R-mediated phagocytosis - Homo sapiens (human);Chemokine signaling pathway - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);cAMP signaling pathway - Homo sapiens (human);Natural killer cell mediated cytotoxicity - Homo sapiens (human);Leukocyte transendothelial migration - Homo sapiens (human);Fc Epsilon Receptor I Signaling in Mast Cells;Integrin-mediated Cell Adhesion;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;Mesodermal Commitment Pathway;Apoptosis-related network due to altered Notch3 in ovarian cancer;Focal Adhesion;Chemokine signaling pathway;Microglia Pathogen Phagocytosis Pathway;EGF-EGFR Signaling Pathway;T-Cell antigen Receptor (TCR) Signaling Pathway;Developmental Biology;Signaling by GPCR;Signal Transduction;DAP12 signaling;DAP12 interactions;VEGFA-VEGFR2 Pathway;Fcgamma receptor (FCGR) dependent phagocytosis;EPH-Ephrin signaling;FCERI mediated MAPK activation;FCERI mediated Ca+2 mobilization;Fc epsilon receptor (FCERI) signaling;TCR;Innate Immune System;Immune System;EPH-ephrin mediated repulsion of cells;Rho GTPase cycle;GPVI-mediated activation cascade;Platelet activation, signaling and aggregation;Signaling by Rho GTPases;BDNF;EGFR1;Regulation of RAC1 activity;Hemostasis;Coregulation of Androgen receptor activity;NRAGE signals death through JNK;Regulation of actin dynamics for phagocytic cup formation;Death Receptor Signalling;p75 NTR receptor-mediated signalling;Signaling by VEGF;Axon guidance;G alpha (12/13) signalling events;Signaling by Receptor Tyrosine Kinases;GPCR downstream signalling;Osteopontin-mediated events;Regulation of CDC42 activity;Cell death signalling via NRAGE, NRIF and NADE;EPHA2 forward signaling;Integrins in angiogenesis;EPHA forward signaling;Regulation of RhoA activity;VEGFR2 mediated vascular permeability (Consensus)

Recessive Scores

• pRec: 0.236

Intolerance Scores

• loftool: 0.484
• rvis_EVS: -0.46
• rvis_percentile_EVS: 23.66

Haploinsufficiency Scores

• pHI: 0.704
• hipred: Y
• hipred_score: 0.652
• ghis: 0.530

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.802

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Vav3
• Phenotype: vision/eye phenotype; digestive/alimentary 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); renal/urinary system phenotype; immune system phenotype; hematopoietic system phenotype; 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); normal phenotype; muscle phenotype; homeostasis/metabolism phenotype; cellular phenotype; endocrine/exocrine gland phenotype

Gene ontology

• Biological process: angiogenesis;vesicle fusion;cellular response to DNA damage stimulus;G protein-coupled receptor signaling pathway;integrin-mediated signaling pathway;small GTPase mediated signal transduction;regulation of cell size;positive regulation of signal transduction;lamellipodium assembly;platelet activation;neutrophil chemotaxis;positive regulation of B cell proliferation;regulation of Rho protein signal transduction;Fc-epsilon receptor signaling pathway;Fc-gamma receptor signaling pathway involved in phagocytosis;response to drug;positive regulation of apoptotic process;regulation of GTPase activity;positive regulation of GTPase activity;positive regulation of phosphatidylinositol 3-kinase activity;positive regulation of cell adhesion;vascular endothelial growth factor receptor signaling pathway;ephrin receptor signaling pathway;B cell receptor signaling pathway;regulation of small GTPase mediated signal transduction
• Cellular component: cytosol;plasma membrane
• Molecular function: SH3/SH2 adaptor activity;guanyl-nucleotide exchange factor activity;Rho guanyl-nucleotide exchange factor activity;GTPase activator activity;epidermal growth factor receptor binding;protein binding;Rac guanyl-nucleotide exchange factor activity;metal ion binding