WAS
Chr XXLRWASP actin nucleation promoting factor
Also known as: IMD2, SCNX, THC, THC1, WASP, WASPA
The WAS protein regulates actin cytoskeleton dynamics in hematopoietic cells by transducing signals from cell surface receptors and interacting with Cdc42 and the Arp2/3 complex. Mutations cause X-linked recessive disorders including classic Wiskott-Aldrich syndrome with immune dysregulation and microthrombocytopenia, as well as isolated X-linked thrombocytopenia and severe congenital neutropenia. The gene is highly constrained against loss-of-function variants, reflecting its essential role in hematopoietic cell function.
Definitive — sufficient evidence for diagnostic panels
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Mild missense constraint
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
257 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 41 | 13 | 50 | 0 | 104 |
Likely Pathogenic | 11 | 13 | 3 | 0 | 27 |
VUS | 2 | 37 | 14 | 2 | 55 |
Likely Benign | 0 | 5 | 10 | 14 | 29 |
Benign | 0 | 3 | 1 | 0 | 4 |
Conflicting | — | 10 | |||
| Total | 54 | 71 | 78 | 16 | 229 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
WAS · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Biologic Therapy to Prevent Osteoarthritis After ACL Injury
RECRUITINGTesting Trastuzumab and Pertuzumab in Patients With Higher Than Normal Copies of the HER2 Gene Found in Their Tumors (MATCH - Subprotocol J)
ACTIVE NOT RECRUITINGTEMPO Study: Trimethoprim-Sulfamethoxazole in Granulomatosis With Polyangiitis
ACTIVE NOT RECRUITINGNeoadjuvant Intense Endocrine Therapy for High Risk and Locally Advanced Prostate Cancer
RECRUITINGEfficacy and Safety of Ensartinib in Neoadjuvant Therapy for Stage IIA - IIIB (Operable or Potentially Operable) ALK-Positive Lung Adenocarcinoma ：A Multicenter, Real-World Clinical Study
NOT YET RECRUITINGLong-term Follow-up of Study Participant Treated With Lentiviral-Based Genetically Modified Autologous Cell Product ,AGT103-T
ENROLLING BY INVITATIONGenetic Modifiers of Cystic Fibrosis (CF) Liver Disease
ACTIVE NOT RECRUITINGAvo In R/R And Previously Untreated MCL
RECRUITINGStudy to Evaluate Safety and Antitumor Activity of Lete-Cel (GSK3377794) in HLA-A2+ Participants With NY-ESO-1 Positive Previously Treated Advanced (Metastatic or Unresectable) Synovial Sarcoma or Myxoid/Round Cell Liposarcoma
ACTIVE NOT RECRUITINGDefined Fecal Microbiota Transplantation for Clostridium Difficile Diarrhea
ENROLLING BY INVITATIONAnalysis of Deoxyribonucleic Acid and Ribonucleic Acid Next-Generation Sequencing in Non-Small Cell Lung Cancer Patients Without Pathological Complete Response Following Neoadjuvant Immunotherapy
NOT YET RECRUITINGOpen-label Study of Asciminib for CML-CP or CML-AP Patients With T315I Mutation Who Are Resistant, Intolerant or Ineligible to Ponatinib.
RECRUITINGExternal Resources
Links to major genomics databases and tools