WASF2
protein-codingWASP family member 2, the group of Wiskott-Aldrich Syndrome protein family
Gene summary
This gene encodes a member of the Wiskott-Aldrich syndrome protein family. The gene product is a protein that forms a multiprotein complex that links receptor kinases and actin. Binding to actin occurs through a C-terminal verprolin homology domain in all family members. The multiprotein complex serves to tranduce signals that involve changes in cell shape, motility or function. The published map location (PMID:10381382) has been changed based on recent genomic sequence comparisons, which indicate that the expressed gene is located on chromosome 1, and a pseudogene may be located on chromosome X. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~85.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to WASF2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006990.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 1 | 3 | |||
| missense | 63 | 4 | 67 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 66 | 5 | 0 | 71 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_008921.1 | 8 | MANE Select | |
| Ensembl | ENSP00000483313.1 | 8 | MANE Select | |
| RefSeq | NP_001188333.1 | 7 | Standard | |
| Ensembl | ENSP00000439883.1 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Fc gamma R-mediated phagocytosis - Homo sapiens (human)
- Salmonella infection - Homo sapiens (human)
- Choline metabolism in cancer - Homo sapiens (human)
- Adherens junction - Homo sapiens (human)
- Regulation of actin cytoskeleton - Homo sapiens (human)
Biological Process
- angiogenesis
- ameboidal-type cell migration
- adenylate cyclase-modulating G protein-coupled receptor signaling pathway
- positive regulation of lamellipodium assembly
- viral process
Molecular Function
- actin binding
- protein binding
- SH3 domain binding
- cadherin binding
- protein kinase A binding
Cellular Component
- ruffle
- early endosome
- cytosol
- cell-cell junction
- actin cytoskeleton
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000430629
- Coding exons
- 8
- Length
- 85940
- Individuals with no LoFs
- 125741
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 7
- Defined
- 125748
- p
- 0.0000278
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.77 | 206 | 291 | 0.708 | 0.0000161 | 3220 |
| Missense (PolyPhen) | 21 | 34.554 | 0.60775 | 301 | ||
| Synonymous | 0.299 | 107 | 111 | 0.964 | 0.00000660 | 1058 |
| Loss of Function | 3.76 | 2 | 20.2 | 0.0988 | 0.00000108 | 232 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000035 | 0.000035 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Downstream effector molecule involved in the transmission of signals from tyrosine kinase receptors and small GTPases to the actin cytoskeleton. Promotes formation of actin filaments. Part of the WAVE complex that regulates lamellipodia formation. The WAVE complex regulates actin filament reorganization via its interaction with the Arp2/3 complex. {ECO:0000269|PubMed:10381382, ECO:0000269|PubMed:16275905}.;
Recessive Scores
- pRec
- 0.181
Intolerance Scores
- LoFtool
- 0.309
- RVIS EVS
- 0
- RVIS percentile EVS
- 53.73
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.674
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |