VAV1

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

Basic information

Region (hg38): 19:6772708-6857366

Previous symbols: [ "VAV" ]

Links

ENSG00000141968 ∙ NCBI:7409 ∙ OMIM:164875 ∙ HGNC:12657 ∙ Uniprot:P15498 ∙ 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 VAV1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the VAV1 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			2	117	8	127
missense			149	3	1	153
nonsense				1		1
start loss						0
frameshift			4			4
inframe indel			2			2
splice donor/acceptor (+/-2bp)			2			2
splice region			19	33	6	58
non coding			1	103	8	112
Total	0	0	160	224	17

Variants in VAV1

This is a list of pathogenic ClinVar variants found in the VAV1 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-6772811-G-C			Uncertain significance (Aug 22, 2021)
19-6772828-C-T			Likely benign (Jan 25, 2024)
19-6772833-A-G			Uncertain significance (May 04, 2022)
19-6772840-C-T			Likely benign (Nov 02, 2023)
19-6772851-G-A			Uncertain significance (Feb 10, 2022)
19-6772852-G-A		VAV1-related disorder	Likely benign (Nov 07, 2023)
19-6772861-G-C		not specified • VAV1-related disorder	Benign (Feb 01, 2024)
19-6772861-G-T			Likely benign (Dec 27, 2023)
19-6772874-G-A			Uncertain significance (Jan 20, 2024)
19-6772878-C-T			Uncertain significance (Aug 29, 2023)
19-6772888-G-T			Likely benign (Apr 01, 2023)
19-6772921-G-A			Likely benign (Mar 30, 2023)
19-6772936-G-T			Likely benign (Jan 10, 2024)
19-6772943-C-T			Likely benign (Jan 04, 2024)
19-6772948-TAAC-T			Uncertain significance (Dec 18, 2020)
19-6772969-C-T			Likely benign (Jun 24, 2022)
19-6772975-C-T			Likely benign (Jan 31, 2024)
19-6772991-C-T			Likely benign (Dec 11, 2023)
19-6772994-C-T			Uncertain significance (Oct 27, 2021)
19-6772995-G-A			Uncertain significance (Dec 14, 2023)
19-6773002-G-A			Likely benign (Oct 17, 2022)
19-6773022-C-T			Likely benign (Dec 26, 2023)
19-6773023-G-A			Likely benign (Aug 15, 2021)
19-6773024-C-T			Likely benign (Jul 15, 2021)
19-6773025-G-A			Likely benign (Jan 27, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
VAV1	protein_coding	protein_coding	ENST00000602142	27	84653

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000655	125738	0	10	125748	0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.86	270	517	0.522	0.0000313	5558
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000615	0.0000615
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.0000463	0.0000462
European (Non-Finnish)	0.0000529	0.0000527
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Couples tyrosine kinase signals with the activation of the Rho/Rac GTPases, thus leading to cell differentiation and/or proliferation.
• 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);Prolactin Signaling Pathway;B Cell Receptor Signaling Pathway;JAK-STAT;Hematopoietic Stem Cell Differentiation;IL-3 Signaling Pathway;Kit receptor signaling pathway;Focal Adhesion;IL-6 signaling pathway;Chemokine signaling pathway;Microglia Pathogen Phagocytosis Pathway;EGF-EGFR Signaling Pathway;Regulation of Actin Cytoskeleton;Interferon type I signaling pathways;T-Cell antigen Receptor (TCR) Signaling Pathway;Signaling by GPCR;Antigen activates B Cell Receptor (BCR) leading to generation of second messengers;Disease;Signal Transduction;Signaling by Interleukins;ras signaling pathway;pkc-catalyzed phosphorylation of inhibitory phosphoprotein of myosin phosphatase;VEGFA-VEGFR2 Pathway;rho cell motility signaling pathway;ras-independent pathway in nk cell-mediated cytotoxicity;t cell receptor signaling pathway;bcr signaling pathway;rac1 cell motility signaling pathway;Prolactin;Cytokine Signaling in Immune system;B cell receptor signaling;CD28 dependent Vav1 pathway;CD28 co-stimulation;Costimulation by the CD28 family;Signaling by the B Cell Receptor (BCR);Fcgamma receptor (FCGR) dependent phagocytosis;FCERI mediated MAPK activation;FCERI mediated Ca+2 mobilization;Fc epsilon receptor (FCERI) signaling;TCR;Innate Immune System;Immune System;Adaptive Immune System;Rho GTPase cycle;BCR;GPVI-mediated activation cascade;Platelet activation, signaling and aggregation;Signaling by Rho GTPases;Integrin;fc epsilon receptor i signaling in mast cells;EGFR1;Regulation of RAC1 activity;CXCR4-mediated signaling events;Hemostasis;NRAGE signals death through JNK;PIP3 activates AKT signaling;IL2;Regulation of actin dynamics for phagocytic cup formation;Death Receptor Signalling;p75 NTR receptor-mediated signalling;PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling;Negative regulation of the PI3K/AKT network;Signaling by VEGF;G alpha (12/13) signalling events;Signaling by SCF-KIT;Constitutive Signaling by Aberrant PI3K in Cancer;PI3K/AKT Signaling in Cancer;IL6;Signaling by Receptor Tyrosine Kinases;GPCR downstream signalling;Intracellular signaling by second messengers;Diseases of signal transduction;Fc-epsilon receptor I signaling in mast cells;TCR signaling in naïve CD8+ T cells;Cell death signalling via NRAGE, NRIF and NADE;Signaling events mediated by Stem cell factor receptor (c-Kit);IL6-mediated signaling events;TCR signaling in naïve CD4+ T cells;Regulation of RhoA activity;VEGFR2 mediated vascular permeability;CD4 T cell receptor signaling;Regulation of signaling by CBL;Interleukin-3, 5 and GM-CSF signaling (Consensus)

Recessive Scores

• pRec: 0.538

Intolerance Scores

• loftool: 0.199
• rvis_EVS: -0.78
• rvis_percentile_EVS: 12.97

Haploinsufficiency Scores

• pHI: 0.698
• hipred: Y
• hipred_score: 0.775
• ghis: 0.577

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.741

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Vav1
• Phenotype: endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype; cellular phenotype; embryo phenotype; 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); digestive/alimentary phenotype; immune system phenotype

Gene ontology

• Biological process: regulation of transcription, DNA-templated;immune response;G protein-coupled receptor signaling pathway;integrin-mediated signaling pathway;small GTPase mediated signal transduction;regulation of cell size;cytokine-mediated signaling pathway;platelet activation;T cell differentiation;neutrophil chemotaxis;T cell costimulation;regulation of Rho protein signal transduction;Fc-epsilon receptor signaling pathway;Fc-gamma receptor signaling pathway involved in phagocytosis;positive regulation of apoptotic process;regulation of GTPase activity;positive regulation of GTPase activity;positive regulation of natural killer cell mediated cytotoxicity;positive regulation of Ras protein signal transduction;phosphatidylinositol phosphorylation;vascular endothelial growth factor receptor signaling pathway;regulation of small GTPase mediated signal transduction;positive regulation of protein kinase B signaling;reactive oxygen species metabolic process
• Cellular component: cytosol;plasma membrane;cell-cell junction
• Molecular function: phosphotyrosine residue binding;DNA-binding transcription factor activity;guanyl-nucleotide exchange factor activity;Rho guanyl-nucleotide exchange factor activity;protein binding;Rac guanyl-nucleotide exchange factor activity;metal ion binding;phosphatidylinositol-4,5-bisphosphate 3-kinase activity