VAV1 Gene
VAV Guanine Nucleotide Exchange Factor 1
Gene Information Card
| Symbol | VAV1 |
|---|---|
| Full Name | VAV guanine nucleotide exchange factor 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 19p13.3 |
| NCBI Gene ID | 7409 ncbi.nlm.nih.gov/gene/7409 |
| Ensembl ID | ENSG00000141968 |
| UniProt ID | P15498 |
| OMIM ID | 164875 |
| HGNC ID | 12659 |
| Aliases | VAV, VAV-1 |
Description
VAV1 is a proto-oncogene that encodes a guanine nucleotide exchange factor (GEF) for Rho family GTPases. It plays a critical role in T-cell and B-cell receptor signaling, cytoskeletal reorganization, and cell migration. VAV1 is predominantly expressed in hematopoietic cells and is involved in immune responses and cancer development.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| T-cell acute lymphoblastic leukemia (T-ALL) | Activating mutations in VAV1 lead to constitutive Rho GTPase signaling, promoting T-cell proliferation and survival. | ClinVar, COSMIC |
| Peripheral T-cell lymphoma (PTCL) | VAV1 fusions and mutations drive aberrant T-cell receptor signaling and lymphomagenesis. | COSMIC, NCBI |
| Immunodeficiency (e.g., combined immunodeficiency) | Loss-of-function mutations impair T-cell and B-cell activation, leading to immune defects. | OMIM, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Spleen | 42.3 | High |
| Lymph node | 38.1 | High |
| Bone marrow | 25.7 | Medium |
| Thymus | 20.4 | Medium |
| Whole blood | 12.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Jurkat (T-cell leukemia) | 85.2 | High expression; model for T-cell signaling |
| Raji (B-cell lymphoma) | 62.1 | High expression; B-cell line |
| K562 (chronic myeloid leukemia) | 18.4 | Moderate expression |
| HEK293 (embryonic kidney) | 2.1 | Low expression; non-hematopoietic |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1740_1741insG | Insertion | 0.5% in T-ALL | Frameshift; gain-of-function |
| p.Tyr174Cys | Missense | 0.2% in PTCL | Constitutive activation of GEF activity |
| p.Arg68Trp | Missense | 0.1% in immunodeficiency | Loss-of-function; impaired signaling |
Mutation functional classification
Loss of Function (LOF)
Rare missense or nonsense mutations in the DH or PH domains impair GEF activity, leading to defective T-cell and B-cell activation and immunodeficiency.
Gain of Function (GOF)
Insertions or missense mutations in the regulatory N-terminal region (e.g., c.1740_1741insG) cause constitutive activation of Rho GTPases, driving T-cell malignancies.
Dominant Negative (DN)
Not well characterized; some truncating mutations may exert dominant-negative effects by sequestering interacting partners.
View complete mutation data：
Gene Ontology (GO)
Pathways
• T cell receptor signaling pathway (KEGG: hsa04660)
• B cell receptor signaling pathway (KEGG: hsa04662)
• Rho GTPase cycle (Reactome: R-HSA-194840)
Protein Summary
VAV1 is a 845-amino acid protein containing multiple domains: calponin homology (CH), acidic region, Dbl homology (DH), pleckstrin homology (PH), zinc finger, and SH2/SH3 domains. It acts as a GEF for Rac1, RhoA, and Cdc42, linking receptor tyrosine kinases and immune receptors to cytoskeletal changes. VAV1 is autoinhibited in resting cells and activated upon tyrosine phosphorylation. Mutations disrupting autoinhibition are oncogenic.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| VAV1 Knockout HEK293 Cell Line | EDJ-KQ765 | Human | 7409 | Details Get a Quote |
| VAV1 Knockout A-549 Cell Line | EDJ-KQ20799 | Human | 7409 | Details Get a Quote |
| VAV1 Knockout HCT 116 Cell Line | EDJ-KQ20800 | Human | 7409 | Details Get a Quote |
| VAV1 Knockout HeLa Cell Line | EDJ-KQ54736 | Human | 7409 | Details Get a Quote |
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