IFNAR1

IFNAR1, or interferon alpha/beta receptor subunit 1, is a transmembrane protein that together with IFNAR2 forms the receptor for type I interferons, IFN-α and IFN-β. The IFNAR1 gene encodes this subunit in humans.

The receptor is a heterodimer consisting of IFNAR1 and IFNAR2. The extracellular domains bind the ligand, with IFNAR2 contributing higher affinity, and the intracellular tails associate with kinases JAK1 (to IFNAR1) and TYK2 (to IFNAR2). Upon ligand binding, receptor-associated kinases phosphorylate STAT1 and STAT2, which together with IRF9 form the ISGF3 complex that translocates to the nucleus to activate interferon-stimulated genes.

Signaling via the IFNAR1/IFNAR2 complex mediates antiviral, antiproliferative, and immunomodulatory effects. The response is rapid but tightly regulated to limit tissue damage; regulation occurs through receptor internalization and negative feedback by proteins such as SOCS1/3 and USP18.

Genetic or functional defects in IFNAR1 or the type I interferon signaling axis can cause increased susceptibility to viral infections. Conversely, altered signaling has been linked to autoimmune disease risk and modulated responses to interferon-based therapies. Given its central role in antiviral defense, IFNAR1 is a focus of study in virology, immunology, and cancer research.

IFNAR1 is conserved across vertebrates, reflecting its fundamental role in innate immunity.