VAV1

protein-coding

vav guanine nucleotide exchange factor 1, the group of SH2 domain containing|Pleckstrin homology domain containing|Dbl family Rho GEFs

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. The encoded protein is important in hematopoiesis, playing a role in T-cell and B-cell development and activation. The encoded protein has been identified as the specific binding partner of Nef proteins from HIV-1. Coexpression and binding of these partners initiates profound morphological changes, cytoskeletal rearrangements and the JNK/SAPK signaling cascade, leading to increased levels of viral transcription and replication. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Apr 2012]

Previous symbols:

MANE transcript

NM_005428.4

Inheritance

ClinVar variants

U:262B:161

Top phenotype

VAV1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.12

Max pathogenic AF

—

Genomic locus

chr19:6,772,708-6,857,366

External References & Databases

Ensembl (ENSG00000141968)

Transcript & Mutation Effects

hg38 • Region Span ~84.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

common variable immunodeficiencyLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0015517

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to VAV1 variants in ClinVar

14 Conditions Cataloged

not providedTotal: 590

not specifiedTotal: 77

VAV1-related disorderTotal: 11

Pes planusTotal: 1

TremorTotal: 1

HyperactivityTotal: 1

Expressive language delayTotal: 1

Attention deficit hyperactivity disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005428.4. 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			6 clinvar	148 clinvar	8 clinvar	162
missense			238 clinvar	5 clinvar		243
nonsense			4 clinvar			4
start loss						0
frameshift			4 clinvar			4
splice donor/acceptor (+/-2bp)			10 clinvar			10
Total	0	0	262	153	8	423

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 21 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005428.4	RefSeq	NP_005419.2	27	MANE Select
ENST00000602142.6	Ensembl	ENSP00000472929.1	27	MANE Select
NM_001258206.2	RefSeq	NP_001245135.1	26	Standard
NM_001258207.2	RefSeq	NP_001245136.1	26	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

regulation of transcription, DNA-templated
immune response
G protein-coupled receptor signaling pathway
integrin-mediated signaling pathway
small GTPase mediated signal transduction

Molecular Function

phosphotyrosine residue binding
DNA-binding transcription factor activity
guanyl-nucleotide exchange factor activity
Rho guanyl-nucleotide exchange factor activity
protein binding

Cellular Component

cytosol
plasma membrane
cell-cell junction

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000602142
Coding exons: 27
Length: 84653
Individuals with no LoFs: 125738
Homozygous LoFs: 0
Heterozygous LoFs: 10
Defined: 125748
p: 0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.86	270	517	0.522	0.0000313	5558
Missense (PolyPhen)		72	223.03	0.32283		2336
Synonymous	0.895	183	199	0.919	0.0000122	1551
Loss of Function	6.22	7	58.2	0.120	0.00000318	619

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.000054	0.000054	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000053	0.000053	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Couples tyrosine kinase signals with the activation of the Rho/Rac GTPases, thus leading to cell differentiation and/or proliferation.;

Recessive Scores

pRec: 0.538

Intolerance Scores

LoFtool: 0.199
RVIS EVS: -0.78
RVIS percentile EVS: 12.97

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.741

Gene Damage Prediction

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