WASL
protein-codingWASP like actin nucleation promoting factor, the group of Wiskott-Aldrich Syndrome protein family
Gene summary
This gene encodes a member of the Wiskott-Aldrich syndrome (WAS) protein family. Wiskott-Aldrich syndrome proteins share similar domain structure, and associate with a variety of signaling molecules to alter the actin cytoskeleton. The encoded protein is highly expressed in neural tissues, and interacts with several proteins involved in cytoskeletal organization, including cell division control protein 42 (CDC42) and the actin-related protein-2/3 (ARP2/3) complex. The encoded protein may be involved in the formation of long actin microspikes, and in neurite extension. [provided by RefSeq, Jul 2013]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~67.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0005180
Submitter: PanelApp Australia
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to WASL variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003941.4. 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 | 1 | 1 | 2 | |||
| missense | 48 | 1 | 49 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 7 | 7 | ||||
| Total | 0 | 0 | 56 | 2 | 0 | 58 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003932.3 | 11 | MANE Select | |
| Ensembl | ENSP00000223023.4 | 11 | MANE Select | |
| Ensembl | ENSP00000594402.1 | 11 | Standard | |
| Ensembl | ENSP00000594403.1 | 10 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| wasla | Danio rerio | Structure: thrombocyte Quality: decreased amount abnormal |
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)
- Endocytosis - Homo sapiens (human)
Biological Process
- actin cortical patch assembly
- endocytosis
- vesicle budding from membrane
- actin polymerization or depolymerization
- response to bacterium
Molecular Function
- protein binding
- GTPase regulator activity
- actin filament binding
Cellular Component
- nucleus
- cytosol
- actin filament
- plasma membrane
- actin cytoskeleton
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000223023
- Coding exons
- 11
- Length
- 67133
- Individuals with no LoFs
- 125740
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 7
- Defined
- 125747
- p
- 0.0000278
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.01 | 168 | 259 | 0.649 | 0.0000126 | 3243 |
| Missense (PolyPhen) | 24 | 33.51 | 0.7162 | 392 | ||
| Synonymous | -0.678 | 101 | 92.7 | 1.09 | 0.00000448 | 1032 |
| Loss of Function | 3.83 | 4 | 24.4 | 0.164 | 0.00000144 | 291 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00012 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000026 | 0.000026 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Regulates actin polymerization by stimulating the actin- nucleating activity of the Arp2/3 complex (PubMed:9422512, PubMed:16767080, PubMed:19366662, PubMed:19487689, PubMed:22847007, PubMed:22921828). Involved in various processes, such as mitosis and cytokinesis, via its role in the regulation of actin polymerization (PubMed:9422512, PubMed:19366662, PubMed:19487689, PubMed:22847007, PubMed:22921828). Together with CDC42, involved in the extension and maintenance of the formation of thin, actin-rich surface projections called filopodia (PubMed:9422512). In addition to its role in the cytoplasm, also plays a role in the nucleus by regulating gene transcription, probably by promoting nuclear actin polymerization (PubMed:16767080). Binds to HSF1/HSTF1 and forms a complex on heat shock promoter elements (HSE) that negatively regulates HSP90 expression (By similarity). Plays a role in dendrite spine morphogenesis (By similarity). {ECO:0000250|UniProtKB:Q91YD9, ECO:0000269|PubMed:16767080, ECO:0000269|PubMed:19366662, ECO:0000269|PubMed:19487689, ECO:0000269|PubMed:22847007, ECO:0000269|PubMed:22921828, ECO:0000269|PubMed:9422512}.;
Recessive Scores
- pRec
- 0.352
Intolerance Scores
- LoFtool
- 0.131
- RVIS EVS
- -0.69
- RVIS percentile EVS
- 14.97
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- H
- Indispensability pred.
- E
- Indispensability score
- 0.904
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |