IFNAR2

IFNAR2, or interferon alpha/beta receptor subunit 2, is a human gene that encodes a membrane-bound subunit of the type I interferon receptor. The functional receptor for type I interferons is a heterodimer composed of IFNAR1 and IFNAR2; IFNAR2 binds interferons such as IFN-α and IFN-β and contributes to ligand recognition and receptor activation. Upon ligand binding, the associated kinases JAK1 and TYK2 are activated, initiating a signaling cascade that leads to phosphorylation of STAT1 and STAT2. These form a complex with IRF9 to generate ISGF3, which translocates to the nucleus and drives expression of interferon-stimulated genes that mediate antiviral responses.

The IFNAR2 gene expresses multiple isoforms through alternative splicing. These include a full-length membrane-bound form that participates in signaling and soluble forms lacking transmembrane domains that can modulate signaling by binding extracellular interferons, acting as decoys or regulators of receptor activation.

Expression of IFNAR2 is widespread across hematopoietic and non-hematopoietic tissues. Type I interferon signaling via IFNAR2 plays a central role in antiviral defense and in the regulation of immune responses, with broader implications for chronic viral infections and cancer. Alterations in IFNAR2 expression or signaling can influence treatment responses and disease pathogenesis; genetic variation in components of the interferon receptor pathway has been linked to differences in susceptibility and severity of certain infections and autoimmune conditions.

In research and clinical contexts, IFNAR2 remains a focus for strategies aiming to modulate type I interferon signaling and its downstream effects.