Interferon omega-1 is a protein that is encoded by the IFNW1 gene.

Interferon omega-1 (IFN-ω) is a subtype of the Interferon type I family. The Interferon Type 1 family is made up of cytokines (proteins used in cell signaling) which bind to the cell surface receptor IFNAR. They are found in mammals and play roles in immunoregulation, inflammation, T-cell response, and tumor cell identification. Type 1 interferons have also been found in birds, lizards, and turtles. Multiple subvariants of IFN-ω have been observed in non-primate mammals with placentas. IFN-ω has been linked to antitumor activity and protection against bacterial and parasitic pathogens.

Through genome sequence analysis, it is thought that the IFN-ω gene diverged from the IFN-α gene roughly 130 million years ago. Interferon omega-1 serves as a cytokine that promotes innate immunity against viruses and cancers. It is involved with almost every nucleated cell.

There are sixteen subtypes of interferon type I. Despite having roughly 20%-60% sequence identity, the subtypes each act on IFNAR1 or IFNAR2 subunits of the class two helical cytokine receptor family. Specifically, IFN-ω shares 33% sequence similarity with IFN-β and 62% sequence similarity with IFN-α. The IFNAR1 subunit contains an intracellular domain that is linked to tyrosine kinase 2 and the IFNAR2 subunit contains an intracellular domain that is linked to Janus kinase 1. Once bound to these tyrosine kinases, a [phosphorylation] cascade will progress and is regulated by the STAT protein. Different responses result from the binding of each type I Interferon, and evidence points to the cause being conformational differences in ligand-receptor binding. The receptor can bind each type I Interferon in unique ways, creating respective downstream effects for each variant.

Limited IFN-ω structures are publicly available. There has been a structure of the IFNω-IFNAR ternary complex which has been solved to a resolution of 3.5 angstroms via X-ray crystallography. From this structure, the protein consists of four long and aligned alpha helices and one short alpha-helix connection. It is bound to both subunits simultaneously and with each active site being at opposite ends of the protein. In this structure, there is a small molecule of NAG bound to IFNAR1 on the opposite side of IFN-ω binding.

The Arg35 residue in IFN-ω binds to the IFNAR2 subunit and is conserved across most IFN type I subvariants. Leu32 of IFN-ω is another conserved residue in the hydrophobic cluster involved in IFNAR2 binding. The Val80 residue of IFNAR2 is key in discriminating between Type 1 Interferon subtypes and has a large effect on IFN-ω binding.

For binding with the IFNAR1 subunit, the residue Phe67 of IFN-ω has key hydrophobic and aromatic interactions with the Leu134 residue of IFNAR1. Additional hotspot residues include Arg123 of IFN-ω and Tyr70 or the IFNAR1 subunit. A salt bridge is formed between Lys152 and Glu149 of IFN-ω and in a small distance from Glu77 of IFNAR1. When bound to IFN-ω, the SD1 of IFNAR1 undergoes a major conformational change that is not seen when unbound or bound to IFN-α2.

A study reported a correlation between a decreased level of interferon type I proteins and more severe COVID-19 cases that are not associated with detectable autoantibodies against IFN-ω or IFN-α.