The SH2D1A gene (SH2D1A stands for "SH2 Domain Containing 1A") is a protein-coding gene located on chromosome Xq25. Several transcript variants encoding different isoforms have been found for this gene.
SH2D1A Gene
DefinitionThis section has been translated automatically.
General informationThis section has been translated automatically.
The SH2D1A gene encodes a protein (Signaling Lymphocytic Activation Molecule-Associated Protein) that plays an important role in stimulating T and B cells. The encoded protein contains an SH2 domain and a short tail. It associates with the signaling lymphocyte activation molecule and thereby acts as an inhibitor of this transmembrane protein by blocking the recruitment of the SH2 domain-containing signal transduction molecule SHP-2 to its docking site. The encoded protein can also bind to other related surface molecules expressed on activated T, B, and NK cells, thereby altering signal transduction pathways in these cells.
Clinical pictureThis section has been translated automatically.
Mutations in this gene cause lymphoproliferative syndrome X-lchromosomal type 1 (Duncan disease), a rare immunodeficiency characterized by extreme susceptibility to Epstein-Barr virus infections and symptoms such as severe mononucleosis and malignant lymphoma (see also Lymphoproliferative syndrome X-lchromosomal -Overview )
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The encoded protein is a cytoplasmic adaptor that regulates receptors of the signaling lymphocyte activation molecule (SLAM) family such as SLAMF1, CD244, LY9, CD84, SLAMF6, and SLAMF7. It further positively regulates CD244/2B4 and CD84-mediated natural killer (NK) cell functions. May also promote CD48-, SLAMF6-, LY9-, and SLAMF7-mediated NK cell activation. Enhances conjugate formation with target cells as part of NK cell-mediated cytotoxicity. May also regulate the activity of neurotrophin receptors NTRK1, NTRK2, and NTRK3.
LiteratureThis section has been translated automatically.
- Booth C et al (2011) X-linked lymphoproliferative disease due to SAP/SH2D1A deficiency: a multicenter study on the manifestations, management and outcome of the disease. Blood 117: 53-62.
- Brandau O et al (1999) Epstein-Barr virus-negative boys with non-Hodgkin lymphoma are mutated in the SH2D1A gene, as are patients with X-linked lymphoproliferative disease (XLP). Hum Molec Genet 8: 2407-2413.
- Purtilo DT et al (1974) Fatal infectious mononucleosis in familial lymphohistiocytosis. (Letter) New Eng J Med 291: 736.
- Purtilo DT et al (19991) Methods of detection of new families with X-linked lymphoproliferative disease. Cancer Genet Cytogenet 51: 143-153.
- Stepensky P et al (2011) IL-2-inducible T-cell kinase deficiency: clinical presentation and therapeutic approach. Haematologica 96: 472-476.
- Sumegi J et al (1999) The molecular genetics of X-linked lymphoproliferative (Duncan's) disease. Cancer J Sci Am 5: 57-62.