7s2r

Structural highlights

Disease

IL2RG_HUMAN Defects in IL2RG are the cause of severe combined immunodeficiency X-linked T-cell-negative/B-cell-positive/NK-cell-negative (XSCID) [MIM:300400; also known as agammaglobulinemia Swiss type. A form of severe combined immunodeficiency (SCID), a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients present in infancy recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T-cell development.^{[1] [2] [3] [4] [5] [6] [7] [8] [9] [10]} Defects in IL2RG are the cause of X-linked combined immunodeficiency (XCID) [MIM:312863. XCID is a less severe form of X-linked immunodeficiency with a less severe degree of deficiency in cellular and humoral immunity than that seen in XSCID.^{[11] [12]}

Function

IL2RG_HUMAN Common subunit for the receptors for a variety of interleukins.

References

1. ↑ Puck JM, Deschenes SM, Porter JC, Dutra AS, Brown CJ, Willard HF, Henthorn PS. The interleukin-2 receptor gamma chain maps to Xq13.1 and is mutated in X-linked severe combined immunodeficiency, SCIDX1. Hum Mol Genet. 1993 Aug;2(8):1099-104. PMID:8401490
2. ↑ DiSanto JP, Dautry-Varsat A, Certain S, Fischer A, de Saint Basile G. Interleukin-2 (IL-2) receptor gamma chain mutations in X-linked severe combined immunodeficiency disease result in the loss of high-affinity IL-2 receptor binding. Eur J Immunol. 1994 Feb;24(2):475-9. PMID:8299698
3. ↑ Markiewicz S, Subtil A, Dautry-Varsat A, Fischer A, de Saint Basile G. Detection of three nonsense mutations and one missense mutation in the interleukin-2 receptor gamma chain gene in SCIDX1 that differently affect the mRNA processing. Genomics. 1994 May 1;21(1):291-3. PMID:8088810 doi:http://dx.doi.org/10.1006/geno.1994.1265
4. ↑ Ishii N, Asao H, Kimura Y, Takeshita T, Nakamura M, Tsuchiya S, Konno T, Maeda M, Uchiyama T, Sugamura K. Impairment of ligand binding and growth signaling of mutant IL-2 receptor gamma-chains in patients with X-linked severe combined immunodeficiency. J Immunol. 1994 Aug 1;153(3):1310-7. PMID:8027558
5. ↑ DiSanto JP, Rieux-Laucat F, Dautry-Varsat A, Fischer A, de Saint Basile G. Defective human interleukin 2 receptor gamma chain in an atypical X chromosome-linked severe combined immunodeficiency with peripheral T cells. Proc Natl Acad Sci U S A. 1994 Sep 27;91(20):9466-70. PMID:7937790
6. ↑ Pepper AE, Buckley RH, Small TN, Puck JM. Two mutational hotspots in the interleukin-2 receptor gamma chain gene causing human X-linked severe combined immunodeficiency. Am J Hum Genet. 1995 Sep;57(3):564-71. PMID:7668284
7. ↑ Clark PA, Lester T, Genet S, Jones AM, Hendriks R, Levinsky RJ, Kinnon C. Screening for mutations causing X-linked severe combined immunodeficiency in the IL-2R gamma chain gene by single-strand conformation polymorphism analysis. Hum Genet. 1995 Oct;96(4):427-32. PMID:7557965
8. ↑ Puck JM, Pepper AE, Bedard PM, Laframboise R. Female germ line mosaicism as the origin of a unique IL-2 receptor gamma-chain mutation causing X-linked severe combined immunodeficiency. J Clin Invest. 1995 Feb;95(2):895-9. PMID:7860773 doi:http://dx.doi.org/10.1172/JCI117740
9. ↑ Stephan V, Wahn V, Le Deist F, Dirksen U, Broker B, Muller-Fleckenstein I, Horneff G, Schroten H, Fischer A, de Saint Basile G. Atypical X-linked severe combined immunodeficiency due to possible spontaneous reversion of the genetic defect in T cells. N Engl J Med. 1996 Nov 21;335(21):1563-7. PMID:8900089 doi:10.1056/NEJM199611213352104
10. ↑ Jones AM, Clark PA, Katz F, Genet S, McMahon C, Alterman L, Cant A, Kinnon C. B-cell-negative severe combined immunodeficiency associated with a common gamma chain mutation. Hum Genet. 1997 May;99(5):677-80. PMID:9150740
11. ↑ Schmalstieg FC, Leonard WJ, Noguchi M, Berg M, Rudloff HE, Denney RM, Dave SK, Brooks EG, Goldman AS. Missense mutation in exon 7 of the common gamma chain gene causes a moderate form of X-linked combined immunodeficiency. J Clin Invest. 1995 Mar;95(3):1169-73. PMID:7883965 doi:http://dx.doi.org/10.1172/JCI117765
12. ↑ Sharfe N, Shahar M, Roifman CM. An interleukin-2 receptor gamma chain mutation with normal thymus morphology. J Clin Invest. 1997 Dec 15;100(12):3036-43. PMID:9399950 doi:10.1172/JCI119858
13. ↑ Yen M, Ren J, Liu Q, Glassman CR, Sheahan TP, Picton LK, Moreira FR, Rustagi A, Jude KM, Zhao X, Blish CA, Baric RS, Su LL, Garcia KC. Facile discovery of surrogate cytokine agonists. Cell. 2022 Apr 14;185(8):1414-1430.e19. PMID:35325595 doi:10.1016/j.cell.2022.02.025