Alt. symbols: IMD2 | THC | WASP | WASPA

Approved name: WASP actin nucleation promoting factor
Alt. names: thrombocytopenia 1 (X-linked), Wiskott-Aldrich syndrome (eczema-thrombocytopenia), Wiskott-Aldrich syndrome | eczema-thrombocytopenia

Location: Xp11.23: 48676596 - 48691431 (+)
Gene type: protein_coding, 9 transcripts.

Scores: LoFtool: | pLI: 0.99120208 | LOEUF: 0.149

HGNC: 12731

NCBI: 7454, RefSeq: NG_007877.1

Ensembl: ENSG00000015285.12

LRG_125 | Status: public

OMIM: 300392

Expression | ProteinAtlas

WAS encodes the Wiskott-Aldrich syndrome (WAS) protein (WASP), which serves as a critical mediator of signal transduction and actin cytoskeletal organization in hematopoietic cells (PMID: 14499269). Thus, WASP signaling is important for hematopoietic cell migration, anchoring, and localization (PMID: 15774550), as well as immune synapse formation (PMID: 12177428) and platelet production and turnover (PMID: 18854955). WASP activity is regulated by interaction with activated guanosine triphosphate (GTP)-loaded Cdc42 (PMID: 16246732) and post-translational modification (e.g., phosphorylation) (PMID: 14707117).

Hemizygous mutations in the gene are associated with at least 3 conditions collectively known as the WAS-related disorders: X-linked Thrombocytopenia (XLT) [OMIM: 313900], Wiskott-Aldrich syndrome (WAS) [OMIM: 301000], and X-linked Neutropenia (XLN) [OMIM: 300299]. Affected males with WAS have microthrombocytopenia with intermittent mucosal bleeding, bloody diarrhea, and intermittent or chronic petechiae and purpura; eczema; and recurrent bacterial and viral infections (GeneReviews). At least 40 % of those who survive the early complications develop autoimmune and/or autoinflammatory manifestations, such as hemolytic anemia, immune thrombocytopenic purpura, immune-mediated neutropenia, rheumatoid arthritis, vasculitis, and immune-mediated kidney and liver damage. Patients are also at increased risk of developing lymphomas, especially if exposed to EBV infection. XLT patients, who usually harbor milder allelic variants, share the microthrombocytopenia seen in WAS, but other complications such as eczema and immune dysfunction are usually mild or absent. XLN patients present with congenital neutropenia, myeloid dysplasia, and lymphocyte abnormalities. More than 350 pathogenic WAS variants have been published thus far. These have been found in all 12 exons, as well as noncoding regions. About half are missense variants that interfere with protein function or nonsense variants that lead to protein truncation. The remainder are splice site changes, small or large deletions/insertions, and complex rearrangements. Female carriers tend in general to be asymptomatic as a consequence of positive selection of cells with an active normal X chromosome, which results in a non-random inactivation of the mutated gene in affected cell lineages. [Load More]