Information on VAV1
Basic details
Alt. symbols: VAV
Approved name: vav guanine nucleotide exchange factor 1
Alt. names: vav 1 oncogene, vav 1 guanine nucleotide exchange factor
Location: 19p13.3: 6772708 - 6857366 (+)
Gene type: protein_coding, 10 transcripts.
Scores: LoFtool: 0.199000 | pLI: 0.99999306 | LOEUF: 0.226
Normal function
VAV1 encodes a member of a tripartite family of guanine nucleotide exchange factors (GEFs) active in hematopoiesis and cellular immunity. Its GEF activity toward a range of small GTPases including RAC1 is activated through phosphorylation at three tyrosine residues (PMID: 8990121, 31654719). VAV1 activity promotes the formation of immunological synapses by T and B lymphocytes, as well as complement-induced phagocytosis and NK cell cytotoxicty (PMID: 26353933). VAV1 operates downstream of T-cell receptors (TCRs) during T-cell maturation to promote TCR-induced calcium influx and NFAT-dependent transcription (PMID: 7700360 , 10938113, 15886116). It couples signaling from TCRs and CD28 to intracellular pathways such as MAPK and cytoskeletal reorganization. Likewise, stimulation of IgM B-cell receptors activates VAV1 downstream of BTK signaling (PMID: 1375396, 19109164). Double knockout of VAV1 in mice leads to insufficient positive thymic selection of CD4+ and CD8+ T lymphocytes (PMID: 7700360).
Dysfunction and disease
A heterozygous VAV1 deletion spanning exons 2–27 has been associated with autosomal dominant common variable immunodeficiency with T cell deficiency (T-CVID) via a haploinsufficiency mechanism (PMID: 23058036). Even prior to the identification of this VAV1 mutation, defective Vav expression was found to correlate with defective F-actin reorganization in response to TCR/CD28 co-engagement in patients with T-CVID (PMID: 15817684). This was also associated with the impaired ability of helper T cell s to express IL-4 upon an anti-CD3 challenge, leading to a Th1-polarized state (PMID: 20638113). Reconstituted VAV1 expression in deficient patient T cells restored their ability to provide B-cell help. [Load More]
[Reviewed by Xiao P. Peng on 2022-07-08 04:41:28]
Associated conditions
| Acronym | Condition's_name | MOI | Mode_of_action |
OMIM_ID | No.cases |
|---|---|---|---|---|---|
CVID23 |
Immunodeficiency, common variable, 23 | AD |
- | 0 (0 fams) |
Please mind that full curation (inclusion of all published patients) of this gene has not started yet. Please contact us if you want to volunteer.
Transcripts of VAV1
| Name | ENSEMBL_ID | LRG_ID | CCDS_ID | MANE | Transcript.type | Exons | Canonical | CDS_length | REFSEQ_ID |
|---|---|---|---|---|---|---|---|---|---|
| 201 | ENST00000304076.6 | CCDS59341 | protein_coding | 26 | No | 2825 | NM_001258206 | ||
| 210 | ENST00000602142.6 | CCDS12174 | Select | protein_coding | 27 | Yes | 2892 | NM_005428 | |
| 204 | ENST00000596764.5 | CCDS59342 | protein_coding | 26 | No | 2775 | NM_001258207 |
Published variants
Found 0 variants
| Var.name | Exon/Intron | cDNA_pos. | CDS_change | Prot.change | Var.type | Var.class. | Patients |
|---|
Please mind that full curation (inclusion of all published variants) of this gene has not started yet. Please contact us if you want to volunteer.
Diagnostic pitfalls & paradigms
Considerations to take into account when analyzing this gene
| Year | Paradigm ⓘ | PMID | Notes |
|---|---|---|---|
| - | Regions of Homology | - | |
| - | Cryptic splicing | - | Unreported or not recorded in our DB. |
| - | Uniparental disomy | - | Unreported or not recorded in our DB. |
| - | Mosaicism | - | Unreported or not recorded in our DB. |
| - | Incomplete penetrance | - | Unreported or not recorded in our DB. |
| - | Di-/oligo-genic inheritance | - | Unreported or not recorded in our DB. |
| - | Somatic reversion | - | Unreported or not recorded in our DB. |
References linked to variants in VAV1
| ID | Year | Title | Journal | PMID | Variants |
|---|