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Normal Function
The WAS gene provides instructions for making a protein called WASP. This protein is found in all blood cells. WASP is involved in relaying signals from the surface of blood cells to the actin cytoskeleton, which is a network of fibers that make up the cell's structural framework. WASP signaling triggers the cell to move and attach to other cells and tissues (adhesion). In white blood cells, which protect the body from infection, this signaling allows the actin cytoskeleton to establish the interaction between cells and the foreign invaders that they target (immune synapse).
Health Conditions Related to Genetic Changes
Wiskott-Aldrich syndrome
More than 350 mutations in the WAS gene have been found to cause Wiskott-Aldrich syndrome, a condition characterized by abnormal immune system function (immune deficiency) and a reduced ability to form blood clots leading to prolonged bleeding episodes.
Most of the mutations lead to the production of an abnormally short, nonfunctional version of WASP or prevent the production of any WASP. As a result, WASP cannot relay signals, which disrupts the function of the actin cytoskeleton in developing blood cells.
White blood cells that lack WASP have a decreased ability to respond to their environment and form immune synapses. As a result, white blood cells are less able to respond to foreign invaders, causing many of the immune problems related to Wiskott-Aldrich syndrome. Similarly, when cells that aid blood clot formation (platelets) lack functional WASP, their development is impaired. A reduction in platelet size and early cell death leads to the bleeding problems in affected individuals. The impairments of white blood cells and platelets are largely responsible for the immune deficiency and bleeding problems characteristic of Wiskott-Aldrich syndrome.
More About This Health ConditionX-linked thrombocytopenia
More than 60 mutations in the WAS gene have been found to cause X-linked thrombocytopenia, a blood disorder characterized by a decrease in the amount and size of platelets, leading to prolonged bleeding episodes. Immune problems such as an increased susceptibility to infections may also occur.
Most of these WAS gene mutations change single protein building blocks (amino acids) in WASP. Mutations typically lead to the production of an altered protein that cannot efficiently relay signals from the cell membrane to the actin cytoskeleton. In people with X-linked thrombocytopenia, these signaling problems primarily affect the development of platelets. In some cases, white blood cells are affected. When WASP function is impaired in white blood cells, these cells are less able to respond to foreign invaders and immune disorders are more likely to occur.
Some WAS gene mutations cause X-linked thrombocytopenia in some individuals and a related condition called Wiskott-Aldrich syndrome (described above) in others. These mutations usually prevent the production of any WASP. It is unknown why some people with these mutations have the relatively mild features of X-linked thrombocytopenia and others have the severe symptoms of Wiskott-Aldrich syndrome. Because they have overlapping features and the same genetic cause, Wiskott-Aldrich syndrome, X-linked thrombocytopenia, and severe congenital neutropenia are sometimes collectively referred to as WAS-related disorders.
More About This Health ConditionSevere congenital neutropenia
MedlinePlus Genetics provides information about Severe congenital neutropenia
More About This Health ConditionOther Names for This Gene
- IMD2
- WASP
- WASP_HUMAN
- WASPA
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Ancliff PJ, Blundell MP, Cory GO, Calle Y, Worth A, Kempski H, Burns S, Jones GE, Sinclair J, Kinnon C, Hann IM, Gale RE, Linch DC, Thrasher AJ. Two novel activating mutations in the Wiskott-Aldrich syndrome protein result in congenital neutropenia. Blood. 2006 Oct 1;108(7):2182-9. doi: 10.1182/blood-2006-01-010249. Epub 2006 Jun 27. Citation on PubMed
- Bhattacharya K, Swaminathan K, Peche VS, Clemen CS, Knyphausen P, Lammers M, Noegel AA, Rastetter RH. Novel Coronin7 interactions with Cdc42 and N-WASP regulate actin organization and Golgi morphology. Sci Rep. 2016 May 4;6:25411. doi: 10.1038/srep25411. Citation on PubMed or Free article on PubMed Central
- Blundell MP, Worth A, Bouma G, Thrasher AJ. The Wiskott-Aldrich syndrome: The actin cytoskeleton and immune cell function. Dis Markers. 2010;29(3-4):157-75. doi: 10.3233/DMA-2010-0735. Citation on PubMed or Free article on PubMed Central
- Imai K, Morio T, Zhu Y, Jin Y, Itoh S, Kajiwara M, Yata J, Mizutani S, Ochs HD, Nonoyama S. Clinical course of patients with WASP gene mutations. Blood. 2004 Jan 15;103(2):456-64. doi: 10.1182/blood-2003-05-1480. Epub 2003 Sep 11. Citation on PubMed
- Looi CY, Sasahara Y, Watanabe Y, Satoh M, Hakozaki I, Uchiyama M, Wong WF, Du W, Uchiyama T, Kumaki S, Tsuchiya S, Kure S. The open conformation of WASP regulates its nuclear localization and gene transcription in myeloid cells. Int Immunol. 2014 Jun;26(6):341-52. doi: 10.1093/intimm/dxt072. Epub 2014 Jan 8. Citation on PubMed
- Ochs HD, Notarangelo LD. Structure and function of the Wiskott-Aldrich syndrome protein. Curr Opin Hematol. 2005 Jul;12(4):284-91. doi: 10.1097/01.moh.0000168520.98990.19. Citation on PubMed
- Ochs HD. Mutations of the Wiskott-Aldrich Syndrome Protein affect protein expression and dictate the clinical phenotypes. Immunol Res. 2009;44(1-3):84-8. doi: 10.1007/s12026-008-8084-3. Citation on PubMed
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