VAV3 Gene - Guanine Nucleotide Exchange Factor for Rho GTPases
VAV3: A key regulator of cell signaling, cytoskeletal dynamics, and immune function, implicated in cancer and developmental disorders.
Gene Information Card
| Symbol | VAV3 |
|---|---|
| Full Name | vav guanine nucleotide exchange factor 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 1p13.3 |
| NCBI Gene ID | 10451 ncbi.nlm.nih.gov/gene/10451 |
| Ensembl ID | ENSG00000134215 |
| UniProt ID | Q9UKW4 |
| OMIM ID | 605541 |
| HGNC ID | 12659 |
| Aliases | VAV-3 |
Description
VAV3 is a member of the VAV family of guanine nucleotide exchange factors (GEFs) that activate Rho family GTPases (Rac1, RhoA, Cdc42). It plays a critical role in signal transduction from tyrosine kinase receptors, regulating cytoskeletal reorganization, cell migration, proliferation, and immune cell activation. VAV3 is expressed in hematopoietic cells and various tissues, and its dysregulation is associated with cancer progression and immune disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | Overexpression and amplification of VAV3 promote Rac1 activation, enhancing cell migration and invasion. | COSMIC; PMID: 22926525 |
| Prostate cancer | VAV3 upregulation correlates with androgen receptor signaling and metastasis. | NCBI Gene; PMID: 22561351 |
| Lung cancer | VAV3 mutations and overexpression contribute to tumor growth and poor prognosis. | COSMIC; PMID: 25691885 |
| Immunodeficiency | Loss-of-function mutations in VAV3 impair T-cell and B-cell receptor signaling, leading to recurrent infections. | OMIM 605541; PMID: 22461475 |
| Hematologic malignancies | VAV3 fusion genes and aberrant expression are implicated in leukemia and lymphoma. | COSMIC; PMID: 19690332 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone marrow | 12.5 | Medium |
| Spleen | 10.8 | Medium |
| Lung | 8.3 | Low |
| Breast | 6.7 | Low |
| Prostate | 5.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (leukemia) | 15.2 | High expression; consistent with hematopoietic origin |
| MCF7 (breast cancer) | 9.4 | Moderate expression; associated with invasive phenotype |
| A549 (lung cancer) | 7.1 | Low to moderate expression |
| HEK293 (embryonic kidney) | 4.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1742G>A (p.Arg581Gln) | Missense | 0.02% (COSMIC) | Potential gain-of-function; observed in colorectal cancer |
| c.2113C>T (p.Arg705Trp) | Missense | 0.01% (COSMIC) | Unknown significance; reported in lung cancer |
| c.1234_1235insA (p.Thr412Asnfs*2) | Frameshift | <0.01% (COSMIC) | Loss-of-function; truncation of GEF domain |
| c.889G>T (p.Glu297*) | Nonsense | <0.01% (ClinVar) | Loss-of-function; associated with immunodeficiency |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Glu297*, p.Thr412Asnfs*2) disrupt the GEF catalytic domain, impairing Rho GTPase activation and immune signaling.
Gain of Function (GOF)
Missense mutations (e.g., p.Arg581Gln) may enhance GEF activity, leading to constitutive Rac1 activation and oncogenic transformation.
Dominant Negative (DN)
Not well-characterized for VAV3; some truncating mutations may exert dominant-negative effects by competing with wild-type VAV3 for upstream activators.
View complete mutation data：ClinVar: https://www.clinvar.com/gene/10451 COSMIC: https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=VAV3
Gene Ontology (GO)
| • GO:0005085 – guanyl-nucleotide exchange factor activity | • GO:0007264 – small GTPase mediated signal transduction |
| • GO:0030036 – actin cytoskeleton organization | • GO:0043547 – positive regulation of GTPase activity |
| • GO:0007165 – signal transduction | • GO:0005886 – plasma membrane |
Pathways
• Rho GTPase cycle (R-HSA-194840)
• Signaling by Rho family GTPases (R-HSA-194315)
• Fc gamma receptor-mediated phagocytosis (R-HSA-2029480)
• T-cell receptor signaling pathway (R-HSA-202403)
• B-cell receptor signaling pathway (R-HSA-983705)
Protein Summary
VAV3 is a 847-amino acid protein containing multiple domains: calponin homology (CH), acidic region, Dbl homology (DH) catalytic domain, pleckstrin homology (PH), zinc finger, and SH2/SH3 domains. It acts as a GEF for Rac1, RhoA, and Cdc42, linking tyrosine kinase signals to cytoskeletal remodeling. VAV3 is autoinhibited in resting cells and activated upon phosphorylation by Src family kinases. Its expression is enriched in hematopoietic tissues, and aberrant activation contributes to oncogenesis and immune dysfunction.
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| VAV3 Knockout HEK293 Cell Line | EDJ-KQ1338 | Human | 10451 | Details Get a Quote |
| VAV3 Knockout A-549 Cell Line | EDJ-KQ20797 | Human | 10451 | Details Get a Quote |
| VAV3 Knockout HeLa Cell Line | EDJ-KQ20798 | Human | 10451 | Details Get a Quote |
| Vav3 Knockout C2C12 Cell Line | EDJ-KZ8 | Mouse | 57257 | Details Get a Quote |
| VAV3 Knockout HCT 116 Cell Line | EDJ-KQ72350 | Human | 10451 | Details Get a Quote |
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