The IFNGR1 gene (IFNGR1 stands for "Interferon Gamma Receptor 1") is a protein coding gene located at chromosome 6q23.3.
The IFNGR1 gene encodes the ligand-binding chain (alpha) of the gamma interferon receptor. The human interferon-gamma receptor is a heterodimer composed of the proteins IFNGR1 and the accessory transmembrane factor IFNGR2. When assembled, both proteins form a functional receptor.
The receptor subunit for interferon-gamma, plays a critical role in antimicrobial, antiviral and antitumor responses by activating effector immune cells and enhancing antigen presentation. Upon ligand binding, the intracellular domain of IFNGR1 opens and allows association of the downstream signaling components JAK1 and JAK2. Activated JAK1 in turn phosphorylates IFNGR1 to form a docking site for STAT1. Subsequent phosphorylation of STAT1 leads to dimerization, translocation to the nucleus, and stimulation of transcription of target genes. STAT3 can also be activated in a similar manner, although the activation appears to be weaker. Phosphorylation of the intracellular domain of IFNGR1 also provides a docking site for SOCS1, which regulates the JAK-STAT pathway by competing with STAT1 binding to IFNGR1.
Genetic variation in IFNGR1 is associated with susceptibility to Helicobacter pylori infection as well as systemic Listeria monocytogenes (Eshleman EM et al. 2017). In addition, defects in IFNGR1 are one of the causes of "Mendelian Susceptibility to Mycobacterial Diseases" (also referred to as "familial disseminated atypical mycobacterial infection").