WAS
WASP actin nucleation promoting factor, the group of Wiskott-Aldrich Syndrome protein family
Basic information
Region (hg38): X:48676596-48691431
Previous symbols: [ "IMD2", "THC" ]
Links
Phenotypes
GenCC
Source:
- Wiskott-Aldrich syndrome (Supportive), mode of inheritance: AD
- thrombocytopenia 1 (Supportive), mode of inheritance: XL
- X-linked severe congenital neutropenia (Supportive), mode of inheritance: XL
- Wiskott-Aldrich syndrome (Definitive), mode of inheritance: XL
- X-linked severe congenital neutropenia (Moderate), mode of inheritance: XL
- X-linked severe congenital neutropenia (Strong), mode of inheritance: XL
- Wiskott-Aldrich syndrome (Strong), mode of inheritance: XL
- X-linked severe congenital neutropenia (Definitive), mode of inheritance: XL
- Wiskott-Aldrich syndrome (Definitive), mode of inheritance: XL
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Wiskott-Aldrich syndrome; Thrombocytopenia 1; Neutropenia, severe congenital, X-linked | XL | Allergy/Immunology/Infectious; Hematologic; Pharmacogenomic | Prophylaxis and early and aggressive treatments for infections, and avoidance of circumstances that would result in severe bleeding, including certain medications, may be beneficial; HSCT, and genetically modified HSCT (gene therapy) have been described | Allergy/Immunology/Infectious; Dermatologic; Hematologic | 13133561; 4177931; 4177932; 3995178; 3284030; 1960605; 8279047; 8069912; 7795648; 7537115; 1611094; 7579347; 8682510; 10575547; 8931701; 10447259; 11242115; 11447283; 15142877; 11238097; 11242115; 16804117; 17065640; 17065636; 17250667; 19006568; 18724301; 18479478; 20301357; 21067383; 22052860; 22338148; 22426750; 22456069; 22523910; 23023736; 23237501; 23264593; 23343520; 23498591; 23527602; 23845947; 23943155; 37478401 |
| Individuals can have immune dysfunction, such as in SCNX, which is due to constitutively activating variants |
ClinVar
This is a list of variants' phenotypes submitted to
- Thrombocytopenia 1;Wiskott-Aldrich syndrome;X-linked severe congenital neutropenia (30 variants)
- not provided (29 variants)
- X-linked severe congenital neutropenia;Thrombocytopenia 1;Wiskott-Aldrich syndrome (23 variants)
- Wiskott-Aldrich syndrome (16 variants)
- Thrombocytopenia 1 (10 variants)
- X-linked severe congenital neutropenia;Wiskott-Aldrich syndrome;Thrombocytopenia 1 (6 variants)
- Wiskott-Aldrich syndrome;X-linked severe congenital neutropenia;Thrombocytopenia 1 (5 variants)
- Thrombocytopenia 1;X-linked severe congenital neutropenia;Wiskott-Aldrich syndrome (5 variants)
- WAS-related disorder (3 variants)
- X-linked severe congenital neutropenia (3 variants)
- Thrombocytopenia (2 variants)
- Wiskott-Aldrich syndrome;Thrombocytopenia 1;X-linked severe congenital neutropenia (2 variants)
- Inborn genetic diseases (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the WAS gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 133 | 12 | 148 | |||
| missense | 15 | 19 | 124 | 20 | 183 | |
| nonsense | 19 | 24 | ||||
| start loss | 1 | |||||
| frameshift | 44 | 15 | 59 | |||
| inframe indel | 12 | |||||
| splice donor/acceptor (+/-2bp) | 13 | |||||
| splice region | 3 | 1 | 14 | 25 | 2 | 45 |
| non coding | 62 | 73 | ||||
| Total | 89 | 45 | 137 | 215 | 27 |
Highest pathogenic variant AF is 0.00000895
Variants in WAS
This is a list of pathogenic ClinVar variants found in the WAS region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| WAS | protein_coding | protein_coding | ENST00000376701 | 12 | 14834 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.999 | 0.000994 | 0 | 0 | 0 | 0 | 0.00 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.98 | 129 | 209 | 0.616 | 0.0000174 | 3153 |
| Missense in Polyphen | 22 | 71.019 | 0.30978 | 1016 | ||
| Synonymous | 0.617 | 80 | 87.3 | 0.916 | 0.00000771 | 1103 |
| Loss of Function | 4.15 | 0 | 20.0 | 0.00 | 0.00000176 | 263 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00 | 0.00 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Effector protein for Rho-type GTPases that regulates actin filament reorganization via its interaction with the Arp2/3 complex (PubMed:12235133, PubMed:12769847, PubMed:16275905). Important for efficient actin polymerization (PubMed:8625410, PubMed:12235133, PubMed:16275905). Possible regulator of lymphocyte and platelet function (PubMed:9405671). Mediates actin filament reorganization and the formation of actin pedestals upon infection by pathogenic bacteria (PubMed:18650809). In addition to its role in the cytoplasmic cytoskeleton, also promotes actin polymerization in the nucleus, thereby regulating gene transcription and repair of damaged DNA (PubMed:20574068). Promotes homologous recombination (HR) repair in response to DNA damage by promoting nuclear actin polymerization, leading to drive motility of double-strand breaks (DSBs) (PubMed:29925947). {ECO:0000269|PubMed:12235133, ECO:0000269|PubMed:12769847, ECO:0000269|PubMed:16275905, ECO:0000269|PubMed:18650809, ECO:0000269|PubMed:20574068, ECO:0000269|PubMed:29925947, ECO:0000269|PubMed:8625410, ECO:0000269|PubMed:9405671}.;
- Disease
- DISEASE: Wiskott-Aldrich syndrome (WAS) [MIM:301000]: An X-linked recessive immunodeficiency characterized by eczema, thrombocytopenia, recurrent infections, and bloody diarrhea. Death usually occurs before age 10. {ECO:0000269|PubMed:10447259, ECO:0000269|PubMed:11793485, ECO:0000269|PubMed:20574068, ECO:0000269|PubMed:7753869, ECO:0000269|PubMed:8528198, ECO:0000269|PubMed:8528199, ECO:0000269|PubMed:8682510, ECO:0000269|PubMed:9098856, ECO:0000269|PubMed:9126958, ECO:0000269|PubMed:9445409, ECO:0000269|PubMed:9683546, ECO:0000269|PubMed:9713366}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Thrombocytopenia 1 (THC1) [MIM:313900]: Thrombocytopenia is defined by a decrease in the number of platelets in circulating blood, resulting in the potential for increased bleeding and decreased ability for clotting. {ECO:0000269|PubMed:10447259, ECO:0000269|PubMed:11167787, ECO:0000269|PubMed:11877312, ECO:0000269|PubMed:7795648, ECO:0000269|PubMed:8528199}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Neutropenia, severe congenital, X-linked (XLN) [MIM:300299]: A disorder of hematopoiesis characterized by maturation arrest of granulopoiesis at the level of promyelocytes with peripheral blood absolute neutrophil counts below 0.5 x 10(9)/l and early onset of severe bacterial infections. {ECO:0000269|PubMed:11242115}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- 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);Tight junction - Homo sapiens (human);Chemokine signaling pathway - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);Bacterial invasion of epithelial cells - Homo sapiens (human);Shigellosis - Homo sapiens (human);Pathogenic Escherichia coli infection - Homo sapiens (human);Pathogenic Escherichia coli infection;Human Complement System;Chemokine signaling pathway;Regulation of Actin Cytoskeleton;G13 Signaling Pathway;T-Cell antigen Receptor (TCR) Signaling Pathway;Signal Transduction;Generation of second messenger molecules;TCR signaling;Fcgamma receptor (FCGR) dependent phagocytosis;TCR;Innate Immune System;Immune System;RHO GTPases Activate WASPs and WAVEs;Adaptive Immune System;KitReceptor;RHO GTPase Effectors;Signaling by Rho GTPases;Regulation of actin dynamics for phagocytic cup formation;TCR signaling in naïve CD4+ T cells
(Consensus)
Recessive Scores
- pRec
- 0.559
Intolerance Scores
- loftool
- rvis_EVS
- 0.51
- rvis_percentile_EVS
- 80.01
Haploinsufficiency Scores
- pHI
- 0.845
- hipred
- Y
- hipred_score
- 0.775
- ghis
- 0.524
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.539
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Was
- Phenotype
- homeostasis/metabolism phenotype; cellular phenotype; endocrine/exocrine gland phenotype; hematopoietic system phenotype; digestive/alimentary phenotype; renal/urinary system phenotype; skeleton phenotype; immune system phenotype;
Gene ontology
- Biological process
- actin cortical patch assembly;regulation of T cell antigen processing and presentation;endocytosis;defense response;immune response;Rho protein signal transduction;blood coagulation;regulation of actin polymerization or depolymerization;actin polymerization or depolymerization;epidermis development;regulation of lamellipodium assembly;endosomal transport;actin filament polymerization;actin filament-based movement;Cdc42 protein signal transduction;Fc-gamma receptor signaling pathway involved in phagocytosis;T cell activation;positive regulation of transcription by RNA polymerase II;regulation of catalytic activity;T cell receptor signaling pathway;positive regulation of actin nucleation;regulation of stress fiber assembly;negative regulation of stress fiber assembly;actin cortical patch localization;protein-containing complex assembly;cellular response to interferon-gamma;positive regulation of double-strand break repair via homologous recombination;negative regulation of cell motility;positive regulation of Arp2/3 complex-mediated actin nucleation;regulation of double-strand break repair via nonhomologous end joining
- Cellular component
- nucleus;cytosol;actin filament;cell-cell junction;vesicle membrane;actin cytoskeleton;actin cortical patch;site of double-strand break;phagocytic vesicle;extracellular exosome
- Molecular function
- protein binding;SH3 domain binding;protein kinase binding;GTPase regulator activity;small GTPase binding;identical protein binding;phospholipase binding;Rac GTPase binding;actin filament binding