IRF9 Gene

The IRF9 gene (IRF9 stands for"Interferon Regulatory Factor 9") is a protein-coding gene located on chromosome 14q12. The IRF9 gene encodes a member of the interferon regulatory factor (IRF) family, a group of transcription factors with diverse functions, including virus-mediated activation of interferon and modulation of cell growth, differentiation, apoptosis and immune system activities. Members of the IRF family are characterized by a conserved N-terminal DNA-binding domain containing tryptophan (W) repeats.

Mutations in this gene lead to the clinical picture

• Immunodeficiency 65 (mutation in the IRF9 gene)

IRF9 encodes a transcription factor that plays an essential role in antiviral immunity. This transcription factor mediates signal transduction by type I IFNs (IFN-alpha|IFN-beta). Upon binding of type I interferons to cell surface receptors, JAK kinases (TYK2 and JAK1) are activated, leading to tyrosine phosphorylation of STAT1 and STAT2.

IRF9 combines with the phosphorylated STAT1/STAT2 dimer to form a protein complex called transcription factor ISGF3 , which can enter the nucleus. ISGF3 binds to the IFN-stimulated response element(ISRE) to activate the transcription of interferon-stimulated genes that place the cell in an antiviral state. If this activation pathway is disturbed, the cell becomes susceptible to infection, especially against viral pathogens.

1. Akira S et al (2006) Pathogen recognition and innate immunity. Cell 124: 783-801
2. Bravo Garcia-Morato et al (2019) Impaired control of multiple viral infections in a family with complete IRF9 deficiency. J Allergy Clin Immun 144: 309-312.
3. Hernandez N et al (2018) Life-threatening influenza pneumonitis in a child with inherited IRF9 deficiency. J Exp Med 215: 2567-2585.
4. Manry J et al (2011) Evolutionary genetic dissection of human interferons. J Exp Med 208:2747-2759.
5. Michalska A et al (2018) A Positive Feedback Amplifier Circuit That Regulates Interferon (IFN)-Stimulated Gene Expression and Controls Type I and Type II IFN Responses. Front Immunol 9:1135.
6. Sheikh SZ et al (2011) Characterization of an interferon-stimulated response element (ISRE) in the Il23a promoter. J Biol Chem 286:1174-1180.