IFNAR1 Gene

The protein encoded by the IFNAR1 gene (IFNAR1 stands for "interferon alpha and beta receptor subunit 1") is a type I membrane protein that forms one of the two chains of a receptor for interferons alpha and beta . It is located on chromosome 21q22.11 and belongs to the type II cytokine receptor family.

Phyiological binding of interferon type I to the receptor protein activates the JAK-STAT signaling cascade and triggers tyrosine phosphorylation of a number of proteins, including JAKs, TYK2, STAT proteins, and the IFNR alpha and beta subunits themselves. The receptor protein functions as an antiviral factor.

Associated signaling pathways include Toll-Like receptor signaling pathways and cytokine signaling pathways in the immune system.

The "Interferon Alpha and Beta Receptor Subunit 1" encoded by this gene generally functions as a heterodimer with IFNAR2. Remarkably, the encoded protein itself can form an active IFNB1 receptor and activate a signaling cascade that does not involve activation of the JAK-STAT pathway.

It appears that IFN-alpha receptor expression plays a role in the development of CIN, as women without CIN or HPV had higher IFN-alpha receptor expression than those with CIN (Tirone NR et al 2009).

Mutations in the IFNAR1 gene are associated with severe viral infections (Bastard P et al 2021). The nonsense IFNAR1 variant/p.Glu386* encodes a truncated protein that is absent and functionless at the cell surface. Patients' fibroblasts do not respond to type I IFNs (IFN-α2, IFN-ω, or IFN-β). Inherited IFNAR1 deficiency is observed clustered in individuals of Polynesian descent (Bastard P et al. 2022).

Furthermore, a mutation in the IFNAR1 gene appears to play an etiologic role in a vascular systemic disease, Köhlmeier-Degos disease.

1. Bastard P et al (2021) Herpes simplex encephalitis in a patient with a distinctive form of inherited IFNAR1 deficiency. J Clin Invest 131:e139980.
2. Bastard P et al (2022) A loss-of-function IFNAR1 allele in Polynesia underlies severe viral diseases in homozygotes. J Exp Med 219:e20220028.
3. Bucciol G et al (2023) Human inherited complete STAT2 deficiency underlies inflammatory viral diseases. J Clin Invest 133:e168321.
4. Uzé G et al (1990) Genetic transfer of a functional human interferon alpha receptor into mouse cells: cloning and expression of its cDNA. Cell 60:225-234.