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Genetics Home Reference: your guide to understanding genetic conditions
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WAS

Reviewed February 2013

What is the official name of the WAS gene?

The official name of this gene is “Wiskott-Aldrich syndrome.”

WAS is the gene's official symbol. The WAS gene is also known by other names, listed below.

What is the normal function of the WAS gene?

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 activates the cell when it is needed and triggers its movement (motility) and attachment 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).

How are changes in the WAS gene related to health conditions?

Wiskott-Aldrich syndrome - caused by mutations in the WAS gene

More than 350 mutations in the WAS gene have been found to cause Wiskott-Aldrich syndrome, a condition characterized by a reduced ability to form blood clots and abnormal immune system function (immune deficiency). Most of these 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, leading to a reduction in platelet size and early cell death. The impairments of white blood cells and platelets are largely responsible for the immune deficiency and bleeding problems characteristic of Wiskott-Aldrich syndrome.

X-linked thrombocytopenia - caused by mutations in the WAS gene

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.

other disorders - caused by mutations in the WAS gene

Mutations in the WAS gene can cause a condition called severe congenital neutropenia, which is characterized by low levels of white blood cells (neutropenia) and decreased survival of hematopoietic stem cells. People with this condition tend to have immune deficiency resulting in recurrent infections. WAS gene mutations that cause severe congenital neutropenia lead to a change in a region of WASP known as the Cdc42 binding site. This site must attach (bind) to a protein called Cdc42 in order to turn on (activate) WASP. The mutations that cause severe congenital neutropenia lead to a WASP that is always active (constitutively active), even in the absence of the Cdc42 protein. It is not fully understood how a constitutively active WASP leads to the signs and symptoms of severe congenital neutropenia.

Where is the WAS gene located?

Cytogenetic Location: Xp11.4-p11.21

Molecular Location on the X chromosome: base pairs 48,683,796 to 48,691,426

The WAS gene is located on the short (p) arm of the X chromosome between positions 11.4 and 11.21.

The WAS gene is located on the short (p) arm of the X chromosome between positions 11.4 and 11.21.

More precisely, the WAS gene is located from base pair 48,683,796 to base pair 48,691,426 on the X chromosome.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about WAS?

You and your healthcare professional may find the following resources about WAS helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the WAS gene or gene products?

  • IMD2
  • WASP
  • WASP_HUMAN
  • Wiskott-Aldrich syndrome (eczema-thrombocytopenia)
  • Wiskott-Aldrich syndrome protein

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding WAS?

acids ; actin ; cell ; cell membrane ; congenital ; cytoskeleton ; deficiency ; eczema ; gene ; hematopoietic ; immune system ; infection ; neutropenia ; platelets ; protein ; stem cells ; susceptibility ; synapse ; syndrome ; thrombocytopenia ; white blood cells

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).

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. Epub 2006 Jun 27. (http://www.ncbi.nlm.nih.gov/pubmed/16804117?dopt=Abstract)
  • 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. Review. (http://www.ncbi.nlm.nih.gov/pubmed/21178275?dopt=Abstract)
  • Devriendt K, Kim AS, Mathijs G, Frints SG, Schwartz M, Van Den Oord JJ, Verhoef GE, Boogaerts MA, Fryns JP, You D, Rosen MK, Vandenberghe P. Constitutively activating mutation in WASP causes X-linked severe congenital neutropenia. Nat Genet. 2001 Mar;27(3):313-7. (http://www.ncbi.nlm.nih.gov/pubmed/11242115?dopt=Abstract)
  • 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. Epub 2003 Sep 11. (http://www.ncbi.nlm.nih.gov/pubmed/12969986?dopt=Abstract)
  • Lutskiy MI, Rosen FS, Remold-O'Donnell E. Genotype-proteotype linkage in the Wiskott-Aldrich syndrome. J Immunol. 2005 Jul 15;175(2):1329-36. (http://www.ncbi.nlm.nih.gov/pubmed/16002738?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/7454)
  • Notarangelo LD, Ochs HD. Wiskott-Aldrich Syndrome: a model for defective actin reorganization, cell trafficking and synapse formation. Curr Opin Immunol. 2003 Oct;15(5):585-91. Review. (http://www.ncbi.nlm.nih.gov/pubmed/14499269?dopt=Abstract)
  • Ochs HD, Notarangelo LD. Structure and function of the Wiskott-Aldrich syndrome protein. Curr Opin Hematol. 2005 Jul;12(4):284-91. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15928485?dopt=Abstract)
  • 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. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19082760?dopt=Abstract)
  • OMIM: WAS GENE (http://omim.org/entry/300392)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: February 2013
Published: July 21, 2014