Monogenic disorders of the IRF transcription factors

Interferon regulatory factors (IRFs) are a family of transcription factors essential for immune system development and host defense. Beyond immunity, IRF6 plays an indispensable role in craniofacial development. Inborn errors of IRFs (IE-IRFs) are a group of rare monogenic disorders caused by damaging variants in the IRF family of genes. In this review, we comprehensively discuss known IE-IRFs and how they contribute to our understanding of human biology, and provide a framework for their diagnosis and treatment. The IRF transcription factors mediate a wide range of biological functions. Accordingly, genetic defects in individual IRFs give rise to diverse human phenotypes, including increased susceptibility to infection, impaired immune development, and even congenital anatomical anomalies. Our collective understanding of IE-IRFs is a powerful example of how integration of clinical care with mechanistic translational research can transform the lives of patients while simultaneously advancing our fundamental understanding of human biology.