VAV3

protein-coding

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

Gene summary

This gene is a member of the VAV gene family. The VAV proteins are guanine nucleotide exchange factors (GEFs) for Rho family GTPases that activate pathways leading to actin cytoskeletal rearrangements and transcriptional alterations. This gene product acts as a GEF preferentially for RhoG, RhoA, and to a lesser extent, RAC1, and it associates maximally with the nucleotide-free states of these GTPases. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

MANE transcript

NM_006113.5

Inheritance

—

ClinVar variants

U:111B:20

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.54

Max pathogenic AF

—

Genomic locus

chr1:107,571,161-107,965,180

External References & Databases

Ensembl (ENSG00000134215)

Transcript & Mutation Effects

hg38 • Region Span ~394.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to VAV3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 105

not providedTotal: 20

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006113.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	9 clinvar	5 clinvar	15
missense			108 clinvar	5 clinvar	1 clinvar	114
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	111	14	6	131

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 26 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006113.5	RefSeq	NP_006104.4	27	MANE Select
ENST00000370056.9	Ensembl	ENSP00000359073.4	27	MANE Select
NM_001079874.2	RefSeq	NP_001073343.1	10	Standard
ENST00000415432.6	Ensembl	ENSP00000394897.2	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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)

Biological Process

angiogenesis
vesicle fusion
cellular response to DNA damage stimulus
G protein-coupled receptor signaling pathway
integrin-mediated signaling pathway

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

Cellular Component

cytosol
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000370056
Coding exons: 27
Length: 393985
Individuals with no LoFs: 125679
Homozygous LoFs: 0
Heterozygous LoFs: 69
Defined: 125748
p: 0.000274

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.13	370	437	0.847	0.0000214	5583
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00037	0.00037	rare
Latino/Admixed American	0.00032	0.00032	rare
Ashkenazi Jewish	0.00030	0.00030	rare
East Asian	0.00011	0.00011	rare
Finnish	0.00019	0.00018	rare
European (Non-Finnish)	0.00028	0.00027	rare
South Asian	0.00037	0.00036	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.236

Intolerance Scores

LoFtool: 0.484
RVIS EVS: -0.46
RVIS percentile EVS: 23.66

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.802

Gene Damage Prediction

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