The IRAK1 gene (IRAK1 stands for "Interleukin 1 Receptor Associated Kinase 1") is a protein-coding gene that is loaclized on chromosome Xq28. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. The IRAK1 gene encodes interleukin-1 receptor-associated kinase 1, one of two putative serine/threonine kinases that associate with the interleukin-1 receptor (IL1R) upon stimulation. The IRAK1 gene is partially responsible for IL1-induced upregulation of the transcription factor NF-kappa B.
IRAK1 Gene
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Diseases associated with IRAK1 include:
- Lupus Erythematosus in both childhood and adulthood (see references below - Jacob CO et al 2009).
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- X-linked MECP2 defect syndrome due to large de novo Xq28 chromosomal deletion including MECP2 and IRAK1.
- Furthermore, mutations in IRAK1 (rs1059703 T allele) are associated with increased severity of rheumatoid arthritis (Hosseini N et al. 2021).
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The IRAKs (interleukin-1 receptor-associated kinases) are serine-threonine kinases, EC 2.7.11.1, which are essential regulators of IL-1R- and TLR-mediated signal transduction. To date, four IRAK isoforms have been identified: IRAK1, IRAK2, IRAK3 (IRAK-M), and IRAK4.
Inhibitors of IRAK1 show cytotoxic activity at single-digit micromolar concentrations in a group of WM, DLBCL, and lymphoma cell lines expressing MYD88.
Lupus erythematosus: In the study of approximately 5,000 subjects and healthy controls, 5 SNPs in the IRAK1 gene showed disease association in both adult and childhood SLE in 4 different ethnic groups, with a 4-SNP haplotype (GGGG) strongly associated with disease. The finding of a gene on the X chromosome as a disease susceptibility factor in human SLE suggests that the sex difference in SLE may be due in part to genes on the sex chromosome (Jacob CO et al 2009).
LiteratureThis section has been translated automatically.
- Hatcher JM et al (2020) Discovery of a Selective, Covalent IRAK1 Inhibitor with Antiproliferative Activity in MYD88 Mutated B-Cell Lymphoma. ACS Med Chem Lett 11:2238-2243
- Hosseini N et al (2021) IRAK1 gene polymorphism in rheumatoid arthritis. Immunol Invest 50:304-321.
- Jacob CO et al (2009) Identification of IRAK1 as a risk gene with critical role in the pathogenesis of systemic lupus erythematosus. Proc Natl Acad Sci U S A 106: 6256-6261.