Common gamma chain

Common gamma chain
Interleukin 2 receptor, gamma (severe combined immunodeficiency)

Crystallographic structure of IL-2 (center alpha helices) complexed with the common gamma chain (IL2RG; 10 O'Clock to 1 O'Clock), IL2RA (4 O'Clock), and IL2RB (7 O'Clock to 9 O'Clock). Each protein is individually rainbow colored (N-terminus = blue, C-terminus = red).[1]
Symbols IL2RG; CD132; IMD4; SCIDX; SCIDX1
External IDs OMIM308380 MGI96551 HomoloGene172 GeneCards: IL2RG Gene
RNA expression pattern
PBB GE IL2RG 204116 at tn.png
More reference expression data
Species Human Mouse
Entrez 3561 16186
Ensembl ENSG00000147168 ENSMUSG00000031304
UniProt P31785 Q3UPA9
RefSeq (mRNA) NM_000206 NM_013563
RefSeq (protein) NP_000197 NP_038591
Location (UCSC) Chr X:
70.24 – 70.25 Mb
Chr X:
97.47 – 97.47 Mb
PubMed search [1] [2]

The common gamma chainc) (or CD132), also known as interleukin-2 receptor subunit gamma or IL-2RG, is a cytokine receptor sub-unit that is common to the receptor complexes for at least six different interleukin receptors: IL-2, IL-4,[2] IL-7,[3] IL-9, IL-15[4] and interleukin-21 receptor. The γc glycoprotein is a member of the type I cytokine receptor family expressed on most lymphocyte (white blood cell) populations, and its gene is found on the X-chromosome of mammals.

This protein is located on the surface of immature blood-forming cells in bone marrow. One end of the protein resides outside of the cell where it binds to cytokines and the other end of the protein resides in the interior of the cell where it transmits signals to the cell's nucleus. The common gamma chain partners with other proteins to direct blood-forming cells to form lymphocytes (a type of white blood cell). The receptor also directs the growth and maturation of lymphocyte subtypes: T cells, B cells, and natural killer cells. These cells kill viruses, make antibodies, and help regulate the entire immune system.



Cytokine receptor common subunit gamma also known as interleukin-2 receptor subunit gamma or IL-2RG is a protein that in humans is encoded by the IL2RG gene.[5] The human IL2RG gene is located on the long (q) arm of the X chromosome at position 13.1, from base pair 70,110,279 to base pair 70,114,423.

IL-7 receptor and signaling, common γ chain (blue) and IL-7 receptor-α (green)


The γc chain is an integral membrane protein that contains extracellular, transmembrane, and intracellular domains.


Lymphocytes expressing the common gamma chain can form functional receptors for these cytokine proteins, which transmit signals from one cell to another and direct programs of cellular differentiation.


The γc chain partners with other ligand-specific receptors to direct lymphocytes to respond to cytokines including IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21.[6]


IL2RG has been shown to interact with Janus kinase 3.[7][8]

Clinical significance

X-linked severe combined immunodeficiency

X-linked severe combined immunodeficiency is caused by mutations in the IL2RG gene[citation needed]. More than 200 different mutations in the IL2RG gene have been identified in people with X-linked severe combined immunodeficiency (SCID)[citation needed]. Most of these mutations involve changes in one or a few DNA building blocks (nucleotides) in the gene. These changes lead to the production of a nonfunctional version of the common gamma chain protein[citation needed] or no production of protein.[9] Without the common gamma chain, important chemical signals are not relayed to the nucleus and lymphocytes cannot develop normally. A lack of functional mature lymphocytes disrupts the immune system's ability to protect the body from infection. Sufferers have no functional immunity and can die within months after birth without successful bone marrow transplantation or alternatively, isolation from exposure to pathogens. Without important developmental signals from IL-7 and IL-15, T-cell and NK cell populations respectively fail to develop.

Experiments in animal models has shown X-SCID to occur similarly in dogs, but not in mice.[10]


  1. ^ PDB 2B5IWang X, Rickert M, Garcia KC (November 2005). "Structure of the quaternary complex of interleukin-2 with its alpha, beta, and gammac receptors". Science 310 (5751): 1159–63. doi:10.1126/science.1117893. PMID 16293754. 
  2. ^ Russell SM, Keegan AD, Harada N et al. (December 1993). "Interleukin-2 receptor gamma chain: a functional component of the interleukin-4 receptor". Science 262 (5141): 1880–3. doi:10.1126/science.8266078. PMID 8266078. 
  3. ^ Noguchi M, Nakamura Y, Russell SM et al. (1994). "Interleukin-2 receptor gamma chain: a functional component of the interleukin-7 receptor". Science 262 (5141): 1877–80. doi:10.1126/science.8266077. PMID 8266077. 
  4. ^ Giri JG, Kumaki S, Ahdieh M et al. (1995). "Identification and cloning of a novel IL-15 binding protein that is structurally related to the alpha chain of the IL-2 receptor". EMBO J. 14 (15): 3654–63. PMC 394440. PMID 7641685. 
  5. ^ Takeshita T, Asao H, Ohtani K, Ishii N, Kumaki S, Tanaka N, Munakata H, Nakamura M, Sugamura K (July 1992). "Cloning of the gamma chain of the human IL-2 receptor". Science 257 (5068): 379–82. doi:10.1126/science.1631559. PMID 1631559. 
  6. ^ Asao H, Okuyama C, Kumaki S, Ishii N, Tsuchiya S, Foster D, Sugamura K (July 2001). "Cutting edge: the common gamma-chain is an indispensable subunit of the IL-21 receptor complex". J. Immunol. 167 (1): 1–5. PMID 11418623. 
  7. ^ Miyazaki, T; Kawahara A, Fujii H, Nakagawa Y, Minami Y, Liu Z J, Oishi I, Silvennoinen O, Witthuhn B A, Ihle J N (Nov. 1994). "Functional activation of Jak1 and Jak3 by selective association with IL-2 receptor subunits". Science (UNITED STATES) 266 (5187): 1045–7. doi:10.1126/science.7973659. ISSN 0036-8075. PMID 7973659. 
  8. ^ Russell, S M; Johnston J A, Noguchi M, Kawamura M, Bacon C M, Friedmann M, Berg M, McVicar D W, Witthuhn B A, Silvennoinen O (Nov. 1994). "Interaction of IL-2R beta and gamma c chains with Jak1 and Jak3: implications for XSCID and XCID". Science (UNITED STATES) 266 (5187): 1042–5. doi:10.1126/science.7973658. ISSN 0036-8075. PMID 7973658. 
  9. ^ Schmalstieg FC, Leonard WJ, Noguchi M et al. (1995). "Missense mutation in exon 7 of the common gamma chain gene causes a moderate form of X-linked combined immunodeficiency". J. Clin. Invest. 95 (3): 1169–73. doi:10.1172/JCI117765. PMC 441454. PMID 7883965. 
  10. ^ Henthorn PS, Somberg RL, Fimiani VM, Puck JM, Patterson DF, Felsburg PJ (September 1994). "IL-2R gamma gene microdeletion demonstrates that canine X-linked severe combined immunodeficiency is a homologue of the human disease". Genomics 23 (1): 69–74. doi:10.1006/geno.1994.1460. PMID 7829104. 

Further reading

External links

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