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Gene Review

IFNG  -  interferon, gamma

Homo sapiens

Synonyms: IFG, IFI, IFN-gamma, Immune interferon, Interferon gamma
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Disease relevance of IFNG


Psychiatry related information on IFNG


High impact information on IFNG

  • In addition to IFN-alpha/beta, a wide range of other innate cytokines can mediate biological functions regulating the NK cell responses of cytotoxicity, proliferation, and gamma interferon (IFN-gamma) production [12].
  • Certain, but not all, viral infections induce interleukin 12 (IL-12) to elicit NK cell IFN-gamma production and antiviral mechanisms [12].
  • Immune, type II, or gamma-interferon (IFN-gamma) is secreted by thymus-derived (T) cells under certain conditions of activation and by natural killer (NK) cells [13].
  • However, much of the cellular response to IFN-gamma can be described in terms of a set of integrated molecular programs underlying well-defined physiological systems, for example the induction of efficient antigen processing for MHC-mediated antigen presentation, which play clearly defined roles in pathogen resistance [13].
  • The Th1 subset of CD4+ T cells secretes cytokines usually associated with inflammation, such as IFN-gamma and TNF and induces cell-mediated immune responses [14].

Chemical compound and disease context of IFNG


Biological context of IFNG

  • Further, our data indicate that IFNG genotype may provide valuable information for both identifying transplant recipients at greater risk for PTLD and developing preventive and curative strategies [20].
  • This stage-specific susceptibility of progenitors to IFNG-induced cytotoxicity consisted of two components, delay in the G(1)/S transition of the cell cycle and increased cell death at least partly mediated by apoptosis, suggesting that progression of the cell cycle was tightly linked to this toxic mechanism [21].
  • Histone H3 acetylation of IFNG and TBET genes occurred with different kinetics, however, and was distinctively regulated by cytokines [22].
  • Interleukin (IL)-12 and IL-18 enhanced the histone acetylation of the IFNG gene [22].
  • 12-q23.3 region are contributing to the expression of the clinical phenotype asthma and the strongest evidence for linkage is in a region near the gene encoding IFNG and (2) a susceptibility locus for both asthma and allergic rhinitis maps to this region [23].

Anatomical context of IFNG

  • In examining the relationship between genotype and cytolytic T-lymphocyte (CTL) function, transforming growth factor beta (TGF-beta) inhibited restimulation of CTLs in PBLs with adenosine at IFNG base + 874, but not in PBLs homozygous for thymidine [20].
  • Among the three stages tested, IFNG had direct cytotoxic effects on actively proliferating oligodendrocyte progenitors but much less on immature oligodendrocytes and none on mature oligodendrocytes [21].
  • Within this region, a single-site nucleotide polymorphism, -179G/T, imparts tumor necrosis factor-alpha stimulation of IFNG in peripheral blood lymphocytes, and is linked with accelerated AIDS progression [24].
  • These results suggest that polymorphisms of the IFNG gene may modify the function of this proinflammatory mediator and the response to pancreatic islet beta cells [25].
  • Monocyte deactivation in septic patients: restoration by IFN-gamma treatment [26].

Associations of IFNG with chemical compounds


Physical interactions of IFNG


Enzymatic interactions of IFNG

  • We demonstrate that JAK2 and Stat1 are phosphorylated at tyrosine residues in a time- and concentration-dependent manner following exposure to IFN-gamma [36].

Regulatory relationships of IFNG


Other interactions of IFNG

  • The activated proteins then move into the nucleus and directly activate genes induced by IFN-alpha and IFN-gamma [45].
  • Although tyrosine phosphorylation was required for the assembly of each of these GRR binding complexes, only those formed as a result of treatment with IFN-gamma or IL-10 contained p91 [46].
  • Our data demonstrate a direct negative feedback of IFN-gamma on expression of the Th2 cytokine gene IL-4 and, thus, provide evidence for another important mechanism by which IFNgamma assists Th1 and attenuates Th2 responses [37].
  • GM-CSF was additive with IL-4 and low amounts (less than 3 U/ml) of IFN-gamma and synergistic with TNF-alpha [47].
  • This suppression occurs whether IL-2 is used alone, in costimulation with anti-mu antibody, or in synergy with IFN-gamma [48].
  • IL-17 and SLAM have opposing effects on IFN-gamma production through CREB activation in persons with tuberculosis [49].

Analytical, diagnostic and therapeutic context of IFNG

  • There was no functional difference in the signal transducers and activators of transcription (STAT) pathways between progenitors and mature oligodendrocytes as determined by induction of IRF1 mRNA in response to IFNG [21].
  • Polymorphisms in IFNG were characterized by restriction enzyme analysis or size-determination electrophoresis [50].
  • A large case-control study of severe malaria in a West Africa population identified several weak associations with individual single-nucleotide polymorphisms in the IFNG and IL22 genes, and defined two IL22 haplotypes that are, respectively, associated with resistance and susceptibility [51].
  • Duodenal biopsies were sampled across distinct histopathological stages of the disease, including refractory CD (RCD), and used to determine IFN-gamma gene (IFNG) expression by real-time RT-PCR [52].
  • Southern blot analysis of genomic DNA of the tumor revealed the amplification of the MDM2 gene together with the fragment locus, but not the IFNG gene [53].


  1. A tumor necrosis factor-alpha-inducible promoter variant of interferon-gamma accelerates CD4+ T cell depletion in human immunodeficiency virus-1-infected individuals. An, P., Vlahov, D., Margolick, J.B., Phair, J., O'Brien, T.R., Lautenberger, J., O'Brien, S.J., Winkler, C.A. J. Infect. Dis. (2003) [Pubmed]
  2. Linkage disequilibrium analysis of chromosome 12q14-15 in multiple sclerosis: delineation of a 118-kb interval around interferon-gamma (IFNG) that is involved in male versus female differential susceptibility. Goris, A., Heggarty, S., Marrosu, M.G., Graham, C., Billiau, A., Vandenbroeck, K. Genes Immun. (2002) [Pubmed]
  3. Cross-sectional study on cytokine polymorphisms, cytokine production after T-cell stimulation and clinical parameters in a random sample of a German population. Nieters, A., Brems, S., Becker, N. Hum. Genet. (2001) [Pubmed]
  4. Interferon-gamma and interferon-gamma receptor 1 and 2 gene polymorphisms and restenosis following coronary stenting. Tiroch, K., von Beckerath, N., Koch, W., Lengdobler, J., Joost, A., Schömig, A., Kastrati, A. Atherosclerosis (2005) [Pubmed]
  5. Functional IFNG polymorphism in intron 1 in association with an increased risk to promote sporadic breast cancer. Saha, A., Dhir, A., Ranjan, A., Gupta, V., Bairwa, N., Bamezai, R. Immunogenetics (2005) [Pubmed]
  6. How interferon-gamma keeps autoimmune diseases in check. Kelchtermans, H., Billiau, A., Matthys, P. Trends Immunol. (2008) [Pubmed]
  7. Sleep associated regulation of T helper 1/T helper 2 cytokine balance in humans. Dimitrov, S., Lange, T., Tieken, S., Fehm, H.L., Born, J. Brain Behav. Immun. (2004) [Pubmed]
  8. Increased intrathecal TGF-beta1, but not IL-12, IFN-gamma and IL-10 levels in Alzheimer's disease patients. Rota, E., Bellone, G., Rocca, P., Bergamasco, B., Emanuelli, G., Ferrero, P. Neurol. Sci. (2006) [Pubmed]
  9. Tumor necrosis factor-alpha: is there a continuum of liability between stress, anxiety states and anorexia nervosa? Holden, R.J., Pakula, I.S. Med. Hypotheses (1999) [Pubmed]
  10. Suppression of cellular immunity in men with a past history of posttraumatic stress disorder. Kawamura, N., Kim, Y., Asukai, N. The American journal of psychiatry. (2001) [Pubmed]
  11. Interferon gamma allelic variants: sex-biased multiple sclerosis susceptibility and gene expression. Kantarci, O.H., Hebrink, D.D., Schaefer-Klein, J., Sun, Y., Achenbach, S., Atkinson, E.J., Heggarty, S., Cotleur, A.C., de Andrade, M., Vandenbroeck, K., Pelfrey, C.M., Weinshenker, B.G. Arch. Neurol. (2008) [Pubmed]
  12. Natural killer cells in antiviral defense: function and regulation by innate cytokines. Biron, C.A., Nguyen, K.B., Pien, G.C., Cousens, L.P., Salazar-Mather, T.P. Annu. Rev. Immunol. (1999) [Pubmed]
  13. Cellular responses to interferon-gamma. Boehm, U., Klamp, T., Groot, M., Howard, J.C. Annu. Rev. Immunol. (1997) [Pubmed]
  14. Induction of Th1 and Th2 CD4+ T cell responses: the alternative approaches. Constant, S.L., Bottomly, K. Annu. Rev. Immunol. (1997) [Pubmed]
  15. Interferon gamma inhibits interleukin 10 production by monocytes. Chomarat, P., Rissoan, M.C., Banchereau, J., Miossec, P. J. Exp. Med. (1993) [Pubmed]
  16. Dampening of IFN-{gamma}-Inducible Gene Expression in Human Choriocarcinoma Cells Is Due to Phosphatase-Mediated Inhibition of the JAK/STAT-1 Pathway. Choi, J.C., Holtz, R., Petroff, M.G., Alfaidy, N., Murphy, S.P. J. Immunol. (2007) [Pubmed]
  17. Interleukin-1 inhibits gamma interferon-induced bacteriostasis in human uroepithelial cells. Däubener, W., Hucke, C., Seidel, K., Hadding, U., MacKenzie, C.R. Infect. Immun. (1999) [Pubmed]
  18. Bacillus Calmette Guerin triggers the IL-12/IFN-gamma axis by an IRAK-4- and NEMO-dependent, non-cognate interaction between monocytes, NK, and T lymphocytes. Feinberg, J., Fieschi, C., Doffinger, R., Feinberg, M., Leclerc, T., Boisson-Dupuis, S., Picard, C., Bustamante, J., Chapgier, A., Filipe-Santos, O., Ku, C.L., de Beaucoudrey, L., Reichenbach, J., Antoni, G., Baldé, R., Alcaïs, A., Casanova, J.L. Eur. J. Immunol. (2004) [Pubmed]
  19. Pentoxifylline, a phosphodiesterase inhibitor, induces immune deviation in patients with multiple sclerosis. Rieckmann, P., Weber, F., Günther, A., Martin, S., Bitsch, A., Broocks, A., Kitze, B., Weber, T., Börner, T., Poser, S. J. Neuroimmunol. (1996) [Pubmed]
  20. IFN-gamma gene polymorphisms associate with development of EBV+ lymphoproliferative disease in hu PBL-SCID mice. Dierksheide, J.E., Baiocchi, R.A., Ferketich, A.K., Roychowdhury, S., Pelletier, R.P., Eisenbeis, C.F., Caligiuri, M.A., VanBuskirk, A.M. Blood (2005) [Pubmed]
  21. MEK-ERK signaling is involved in interferon-gamma-induced death of oligodendroglial progenitor cells. Horiuchi, M., Itoh, A., Pleasure, D., Itoh, T. J. Biol. Chem. (2006) [Pubmed]
  22. Discrete roles for histone acetylation in human T helper 1 cell-specific gene expression. Morinobu, A., Kanno, Y., O'Shea, J.J. J. Biol. Chem. (2004) [Pubmed]
  23. Dense mapping of chromosome 12q13.12-q23.3 and linkage to asthma and atopy. Barnes, K.C., Freidhoff, L.R., Nickel, R., Chiu, Y.F., Juo, S.H., Hizawa, N., Naidu, R.P., Ehrlich, E., Duffy, D.L., Schou, C., Levett, P.N., Marsh, D.G., Beaty, T.H. J. Allergy Clin. Immunol. (1999) [Pubmed]
  24. An IFNG SNP with an estrogen-like response element selectively enhances promoter expression in peripheral but not lamina propria T cells. Gonsky, R., Deem, R.L., Bream, J.H., Young, H.A., Targan, S.R. Genes Immun. (2006) [Pubmed]
  25. A CA repeat polymorphism of the IFN-gamma gene is associated with susceptibility to type 1 diabetes. Jahromi, M., Millward, A., Demaine, A. J. Interferon Cytokine Res. (2000) [Pubmed]
  26. Monocyte deactivation in septic patients: restoration by IFN-gamma treatment. Döcke, W.D., Randow, F., Syrbe, U., Krausch, D., Asadullah, K., Reinke, P., Volk, H.D., Kox, W. Nat. Med. (1997) [Pubmed]
  27. Complementation by the protein tyrosine kinase JAK2 of a mutant cell line defective in the interferon-gamma signal transduction pathway. Watling, D., Guschin, D., Müller, M., Silvennoinen, O., Witthuhn, B.A., Quelle, F.W., Rogers, N.C., Schindler, C., Stark, G.R., Ihle, J.N. Nature (1993) [Pubmed]
  28. Interleukin 8 (IL-8) selectively inhibits immunoglobulin E production induced by IL-4 in human B cells. Kimata, H., Yoshida, A., Ishioka, C., Lindley, I., Mikawa, H. J. Exp. Med. (1992) [Pubmed]
  29. Two essential regulatory elements in the human interferon gamma promoter confer activation specific expression in T cells. Penix, L., Weaver, W.M., Pang, Y., Young, H.A., Wilson, C.B. J. Exp. Med. (1993) [Pubmed]
  30. Down-regulation of MHC II in mesenchymal stem cells at high IFN-gamma can be partly explained by cytoplasmic retention of CIITA. Tang, K.C., Trzaska, K.A., Smirnov, S.V., Kotenko, S.V., Schwander, S.K., Ellner, J.J., Rameshwar, P. J. Immunol. (2008) [Pubmed]
  31. The extracellular domain of the human interferon gamma receptor interacts with a species-specific signal transducer. Gibbs, V.C., Williams, S.R., Gray, P.W., Schreiber, R.D., Pennica, D., Rice, G., Goeddel, D.V. Mol. Cell. Biol. (1991) [Pubmed]
  32. Interferon-gamma enhances expression of cellular receptors for tumor necrosis factor. Tsujimoto, M., Yip, Y.K., Vilcek, J. J. Immunol. (1986) [Pubmed]
  33. A distal region in the interferon-gamma gene is a site of epigenetic remodeling and transcriptional regulation by interleukin-2. Bream, J.H., Hodge, D.L., Gonsky, R., Spolski, R., Leonard, W.J., Krebs, S., Targan, S., Morinobu, A., O'Shea, J.J., Young, H.A. J. Biol. Chem. (2004) [Pubmed]
  34. Inhibition of IL-10 expression by IFN-gamma up-regulates transcription of TNF-alpha in human monocytes. Donnelly, R.P., Freeman, S.L., Hayes, M.P. J. Immunol. (1995) [Pubmed]
  35. IL-12 induces monocyte IL-18 binding protein expression via IFN-gamma. Veenstra, K.G., Jonak, Z.L., Trulli, S., Gollob, J.A. J. Immunol. (2002) [Pubmed]
  36. Interferon-gamma-induced JAK2 and STAT1 signalling in a human salivary gland cell line. Wu, A.J., Chen, Z.J., Kan, E.C., Baum, B.J. J. Cell. Physiol. (1997) [Pubmed]
  37. IFN-gamma represses IL-4 expression via IRF-1 and IRF-2. Elser, B., Lohoff, M., Kock, S., Giaisi, M., Kirchhoff, S., Krammer, P.H., Li-Weber, M. Immunity (2002) [Pubmed]
  38. Regulation of cytokine production by soluble CD23: costimulation of interferon gamma secretion and triggering of tumor necrosis factor alpha release. Armant, M., Ishihara, H., Rubio, M., Delespesse, G., Sarfati, M. J. Exp. Med. (1994) [Pubmed]
  39. Interferon (IFN) beta acts downstream of IFN-gamma-induced class II transactivator messenger RNA accumulation to block major histocompatibility complex class II gene expression and requires the 48-kD DNA-binding protein, ISGF3-gamma. Lu, H.T., Riley, J.L., Babcock, G.T., Huston, M., Stark, G.R., Boss, J.M., Ransohoff, R.M. J. Exp. Med. (1995) [Pubmed]
  40. Apical role for BRG1 in cytokine-induced promoter assembly. Ni, Z., Karaskov, E., Yu, T., Callaghan, S.M., Der, S., Park, D.S., Xu, Z., Pattenden, S.G., Bremner, R. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  41. Secretory leucocyte protease inhibitor inhibits interferon-gamma-induced cathepsin S expression. Geraghty, P., Greene, C.M., O'Mahony, M., O'Neill, S.J., Taggart, C.C., McElvaney, N.G. J. Biol. Chem. (2007) [Pubmed]
  42. Induction of indoleamine 2,3-dioxygenase in vascular smooth muscle cells by interferon-gamma contributes to medial immunoprivilege. Cuffy, M.C., Silverio, A.M., Qin, L., Wang, Y., Eid, R., Brandacher, G., Lakkis, F.G., Fuchs, D., Pober, J.S., Tellides, G. J. Immunol. (2007) [Pubmed]
  43. Interferon-gamma reduces cell surface expression of annexin 2 and suppresses the invasive capacity of prostate cancer cells. Hastie, C., Masters, J.R., Moss, S.E., Naaby-Hansen, S. J. Biol. Chem. (2008) [Pubmed]
  44. Colocalization of the IL-12 receptor and FcgammaRIIIa to natural killer cell lipid rafts leads to activation of ERK and enhanced production of interferon-gamma. Kondadasula, S.V., Roda, J.M., Parihar, R., Yu, J., Lehman, A., Caligiuri, M.A., Tridandapani, S., Burry, R.W., Carson, W.E. Blood (2008) [Pubmed]
  45. Polypeptide signalling to the nucleus through tyrosine phosphorylation of Jak and Stat proteins. Shuai, K., Ziemiecki, A., Wilks, A.F., Harpur, A.G., Sadowski, H.B., Gilman, M.Z., Darnell, J.E. Nature (1993) [Pubmed]
  46. Tyrosine phosphorylation of DNA binding proteins by multiple cytokines. Larner, A.C., David, M., Feldman, G.M., Igarashi, K., Hackett, R.H., Webb, D.S., Sweitzer, S.M., Petricoin, E.F., Finbloom, D.S. Science (1993) [Pubmed]
  47. Cytokines in chronic inflammatory arthritis. IV. Granulocyte/macrophage colony-stimulating factor-mediated induction of class II MHC antigen on human monocytes: a possible role in rheumatoid arthritis. Alvaro-Gracia, J.M., Zvaifler, N.J., Firestein, G.S. J. Exp. Med. (1989) [Pubmed]
  48. Interleukin 4 counteracts the interleukin 2-induced proliferation of monoclonal B cells. Karray, S., DeFrance, T., Merle-Béral, H., Banchereau, J., Debré, P., Galanaud, P. J. Exp. Med. (1988) [Pubmed]
  49. IFN-gamma production during active tuberculosis is regulated by mechanisms that involve IL-17, SLAM, and CREB. Pasquinelli, V., Townsend, J.C., Jurado, J.O., Alvarez, I.B., Quiroga, M.F., Barnes, P.F., Samten, B., García, V.E. J. Infect. Dis. (2009) [Pubmed]
  50. Evidence that interferon-gamma plays a protective role during cerebral malaria. Cabantous, S., Poudiougou, B., Traore, A., Keita, M., Cisse, M.B., Doumbo, O., Dessein, A.J., Marquet, S. J. Infect. Dis. (2005) [Pubmed]
  51. Investigation of malaria susceptibility determinants in the IFNG/IL26/IL22 genomic region. Koch, O., Rockett, K., Jallow, M., Pinder, M., Sisay-Joof, F., Kwiatkowski, D. Genes Immun. (2005) [Pubmed]
  52. The interferon gamma gene in celiac disease: augmented expression correlates with tissue damage but no evidence for genetic susceptibility. Wapenaar, M.C., van Belzen, M.J., Fransen, J.H., Sarasqueta, A.F., Houwen, R.H., Meijer, J.W., Mulder, C.J., Wijmenga, C. J. Autoimmun. (2004) [Pubmed]
  53. Detection of DNA abnormalities by arbitrarily primed PCR fingerprinting: amplification of the MDM2 gene in a mediastinum fibrosarcoma. Kuchiki, H., Yasuda, J., Kayama, T., Murakami, Y., Sekiya, T. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
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