IFNG

Description

The IFNG (interferon gamma) is a protein-coding gene located on chromosome 12.

Interferon gamma (IFNG or IFN-γ) is a dimerized soluble cytokine that is the only member of the type II class of interferons. The existence of this interferon, which early in its history was known as immune interferon, was described by E. F. Wheelock as a product of human leukocytes stimulated with phytohemagglutinin, and by others as a product of antigen-stimulated lymphocytes. It was also shown to be produced in human lymphocytes. or tuberculin-sensitized mouse peritoneal lymphocytes challenged with Mantoux test (PPD); the resulting supernatants were shown to inhibit growth of vesicular stomatitis virus. Those reports also contained the basic observation underlying the now widely employed interferon gamma release assay used to test for tuberculosis. In humans, the IFNG protein is encoded by the IFNG gene. Through cell signaling, interferon gamma plays a role in regulating the immune response of its target cell. A key signaling pathway that is activated by type II IFN is the JAK-STAT signaling pathway. IFNG plays an important role in both innate and adaptive immunity. Type II IFN is primarily secreted by CD4+ T helper 1 (Th1) cells, natural killer (NK) cells, and CD8+ cytotoxic T cells.

Type II interferon produced by immune cells such as T-cells and NK cells that plays crucial roles in antimicrobial, antiviral, and antitumor responses by activating effector immune cells and enhancing antigen presentation (PubMed:16914093, PubMed:8666937). Primarily signals through the JAK-STAT pathway after interaction with its receptor IFNGR1 to affect gene regulation (PubMed:8349687). Upon IFNG binding, IFNGR1 intracellular domain opens out to allow association of downstream signaling components JAK2, JAK1 and STAT1, leading to STAT1 activation, nuclear translocation and transcription of IFNG-regulated genes. Many of the induced genes are transcription factors such as IRF1 that are able to further drive regulation of a next wave of transcription (PubMed:16914093). Plays a role in class I antigen presentation pathway by inducing a replacement of catalytic proteasome subunits with immunoproteasome subunits (PubMed:8666937). In turn, increases the quantity, quality, and repertoire of peptides for class I MHC loading (PubMed:8163024). Increases the efficiency of peptide generation also by inducing the expression of activator PA28 that associates with the proteasome and alters its proteolytic cleavage preference (PubMed:11112687). Up-regulates as well MHC II complexes on the cell surface by promoting expression of several key molecules such as cathepsins B/CTSB, H/CTSH, and L/CTSL (PubMed:7729559). Participates in the regulation of hematopoietic stem cells during development and under homeostatic conditions by affecting their development, quiescence, and differentiation (By similarity). {ECO:0000250|UniProtKB:P01580, ECO:0000269|PubMed:11112687, ECO:0000269|PubMed:16914093, ECO:0000269|PubMed:7729559, ECO:0000269|PubMed:8163024, ECO:0000269|PubMed:8349687, ECO:0000269|PubMed:8666937}.

IFNG is also known as IFG, IFI, IMD69.

Associated Diseases

Comprehensive carrier screening

WES Whole Exome Sequencing

Clinical Exome Sequencing