Normal Function
The SH2D1A gene provides instructions for making a protein called signaling lymphocyte activation molecule (SLAM) associated protein (SAP). SAP interacts with other proteins called SLAM family receptors to activate signaling pathways that are involved in the control of immune cells (lymphocytes). In particular, it helps regulate lymphocytes that destroy other cells (cytotoxic lymphocytes) and is necessary for the development of specialized lymphocytes called natural killer T cells. SAP also helps control immune reactions by triggering self-destruction (apoptosis) of lymphocytes when they are no longer needed.
Health Conditions Related to Genetic Changes
X-linked lymphoproliferative disease
More than 70 SH2D1A gene mutations have been identified in people with X-linked lymphoproliferative disease (XLP). Some SH2D1A gene mutations impair SAP function. Others result in an abnormally short protein that is unstable or nonfunctional, or prevent any SAP from being produced. The loss of functional SAP disrupts proper control of the immune system and may result in the life-threatening immune reaction to Epstein-Barr virus infection that occurs in this disorder. In addition, cancers of immune system cells (lymphomas) may develop in affected individuals when defective lymphocytes are not properly destroyed by apoptosis.
More About This Health ConditionOther Names for This Gene
- DSHP
- Duncan disease SH2-protein
- EBVS
- MTCP1
- SAP
- SH2 domain-containing protein 1A
- SH21A_HUMAN
- signaling lymphocyte activation molecule-associated protein
- SLAM-associated protein
- XLP
- XLPD
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Bassiri H, Janice Yeo WC, Rothman J, Koretzky GA, Nichols KE. X-linked lymphoproliferative disease (XLP): a model of impaired anti-viral, anti-tumor and humoral immune responses. Immunol Res. 2008;42(1-3):145-59. doi: 10.1007/s12026-008-8048-7. Citation on PubMed
- Latour S. Natural killer T cells and X-linked lymphoproliferative syndrome. Curr Opin Allergy Clin Immunol. 2007 Dec;7(6):510-4. doi: 10.1097/ACI.0b013e3282f1bad6. Citation on PubMed
- Nagy N, Klein E. Deficiency of the proapoptotic SAP function in X-linked lymphoproliferative disease aggravates Epstein-Barr virus (EBV) induced mononucleosis and promotes lymphoma development. Immunol Lett. 2010 May 4;130(1-2):13-8. doi: 10.1016/j.imlet.2010.01.002. Epub 2010 Jan 18. Citation on PubMed
- Nagy N, Matskova L, Hellman U, Klein G, Klein E. The apoptosis modulating role of SAP (SLAM associated protein) contributes to the symptomatology of the X linked lymphoproliferative disease. Cell Cycle. 2009 Oct 1;8(19):3086-90. doi: 10.4161/cc.8.19.9636. Epub 2009 Oct 27. Citation on PubMed
- Schuster V, Kreth HW. X-linked lymphoproliferative disease is caused by deficiency of a novel SH2 domain-containing signal transduction adaptor protein. Immunol Rev. 2000 Dec;178:21-8. doi: 10.1034/j.1600-065x.2000.17819.x. Citation on PubMed
- Snow AL, Marsh RA, Krummey SM, Roehrs P, Young LR, Zhang K, van Hoff J, Dhar D, Nichols KE, Filipovich AH, Su HC, Bleesing JJ, Lenardo MJ. Restimulation-induced apoptosis of T cells is impaired in patients with X-linked lymphoproliferative disease caused by SAP deficiency. J Clin Invest. 2009 Oct;119(10):2976-89. doi: 10.1172/JCI39518. Epub 2009 Sep 14. Citation on PubMed or Free article on PubMed Central
- Woon ST, Ameratunga R, Croxson M, Taylor G, Neas K, Edkins E, Browett P, Gane E, Munn S. Follicular lymphoma in a X-linked lymphoproliferative syndrome carrier female. Scand J Immunol. 2008 Aug;68(2):153-8. doi: 10.1111/j.1365-3083.2008.02128.x. Erratum In: Scand J Immunol. 2008 Sep;68(3):362. Citation on PubMed
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