VAV2 Gene - Guanine Nucleotide Exchange Factor for Rho GTPases
VAV2: A Key Regulator of Cell Signaling, Adhesion, and Cancer Progression
Gene Information Card
| Symbol | VAV2 |
|---|---|
| Full Name | vav guanine nucleotide exchange factor 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 9q34.2 |
| NCBI Gene ID | 7410 ncbi.nlm.nih.gov/gene/7410 |
| Ensembl ID | ENSG00000136840 |
| UniProt ID | P52735 |
| OMIM ID | 600428 |
| HGNC ID | 12659 |
| Aliases | VAV-2, VAV2 oncogene |
Description
VAV2 is a member of the VAV family of guanine nucleotide exchange factors (GEFs) for Rho family GTPases. It catalyzes the exchange of GDP for GTP on RhoA, Rac1, and Cdc42, thereby activating downstream signaling pathways that regulate cytoskeletal organization, cell adhesion, migration, and proliferation. VAV2 is widely expressed and plays critical roles in immune cell function, neuronal development, and cancer metastasis. Its activity is regulated by tyrosine phosphorylation and interaction with adaptor proteins.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | VAV2 overexpression or gain-of-function mutations enhance Rac1 and RhoA signaling, promoting cell migration, invasion, and metastasis. | COSMIC; multiple studies in breast, lung, and colorectal cancers. |
| Charcot-Marie-Tooth disease (CMT) | Rare VAV2 missense variants may disrupt axonal transport and cytoskeletal dynamics in peripheral neurons. | ClinVar; limited case reports. |
| Immunodeficiency | VAV2 deficiency impairs T-cell and B-cell receptor signaling, leading to defective immune responses. | Mouse models; human data sparse. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Lung | 8.3 | Low |
| Breast | 6.7 | Low |
| Colon | 5.9 | Low |
| Ovary | 4.2 | Low |
| Testis | 3.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | High expression in embryonic kidney cells |
| HeLa | 9.8 | Moderate expression in cervical cancer cells |
| MCF7 | 7.4 | Moderate expression in breast cancer cells |
| A549 | 6.1 | Low expression in lung cancer cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1742G>A (p.Arg581His) | Missense | <0.1% | Potential gain-of-function; observed in colorectal cancer (COSMIC) |
| c.2150C>T (p.Thr717Met) | Missense | <0.1% | Unknown significance; reported in lung adenocarcinoma (COSMIC) |
| c.1123_1124insA (p.Thr375Asnfs*2) | Frameshift | <0.1% | Loss-of-function; rare in breast cancer (COSMIC) |
Mutation functional classification
Loss of Function (LOF)
Frameshift or nonsense mutations that truncate the protein, impairing GEF activity and downstream Rho GTPase signaling.
Gain of Function (GOF)
Missense mutations in the catalytic DH-PH domain that increase GEF activity, leading to enhanced cell migration and invasion.
Dominant Negative (DN)
Not well characterized; some mutations may interfere with wild-type VAV2 function in heterodimers.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Rho GTPase cycle (R-HSA-194840)
• Signaling by Rho family GTPases (R-HSA-194315)
• Rac1 signaling (R-HSA-9013405)
• VAV2-mediated activation of Rac1 (R-HSA-9013406)
Protein Summary
VAV2 is a 878-amino acid protein containing a calponin homology (CH) domain, a Dbl homology (DH) domain, a pleckstrin homology (PH) domain, a zinc finger, and multiple SH2/SH3 domains. The DH-PH tandem is responsible for its GEF activity toward Rho GTPases. VAV2 is activated by tyrosine phosphorylation (e.g., by Src family kinases) and interacts with adaptor proteins such as Grb2 and Nck. It localizes to the plasma membrane and focal adhesions, where it regulates actin dynamics and cell motility. Overexpression of VAV2 is oncogenic in several cancer types.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| VAV2 Knockout HEK293 Cell Line | EDJ-KQ1340 | Human | 7410 | Details Get a Quote |
| VAV2 Knockout A-549 Cell Line | EDJ-KQ20801 | Human | 7410 | Details Get a Quote |
| VAV2 Knockout HCT 116 Cell Line | EDJ-KQ20802 | Human | 7410 | Details Get a Quote |
| VAV2 Knockout HeLa Cell Line | EDJ-KQ20803 | Human | 7410 | Details Get a Quote |
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