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IFNAR1
interferon alpha and beta receptor subunit 1
IFNAR1 is located on the long (q) arm of chromosome 21, at band 21q22.11. Arm ratio per GRCh38 - banding schematic.
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Overview
IFNAR1 (interferon alpha and beta receptor subunit 1) is located on chromosome 21 and encodes a transmembrane protein that serves as one half of the heterodimeric receptor for type I interferons. Type I interferons comprise a large family of cytokines, including multiple interferon-alpha subtypes and interferon-beta, which are produced by cells in response to viral infection, microbial products, and certain inflammatory signals.
When type I interferons bind to the IFNAR1/IFNAR2 receptor complex, they initiate a signalling cascade that activates hundreds of interferon-stimulated genes, leading to an antiviral state within the cell and coordination of broader immune responses. Genetic variation in IFNAR1 can influence individual differences in susceptibility to viral infections and inflammatory conditions.
What the gene does
The IFNAR1 protein is a type I transmembrane receptor that heterodimerises with IFNAR2 to form the functional type I interferon receptor. The extracellular portion of IFNAR1 contains four fibronectin type-III domains that participate in ligand recognition and binding. Upon interferon binding, the receptor complex undergoes conformational changes that bring together intracellular signalling molecules, particularly the tyrosine kinases JAK1 and TYK2, which associate with the cytoplasmic tails of IFNAR1 and IFNAR2 respectively.
Activation of these kinases leads to phosphorylation of STAT (signal transducer and activator of transcription) proteins, which then translocate to the nucleus and drive expression of interferon-stimulated genes. These genes encode proteins with antiviral functions, including those that degrade viral RNA, inhibit protein synthesis in infected cells, and enhance antigen presentation to immune cells. The IFNAR1 protein thus serves as a critical node connecting extracellular interferon signals to intracellular antiviral programmes.
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Chromosome location
IFNAR1 is located on the long arm of chromosome 21 at position 22.11 (21q22.11). The gene spans this chromosomal region on a segment of DNA that contains multiple genes involved in immune function. Chromosome 21 is the smallest human autosome, and the clustering of immune-related genes in this region has prompted research into potential contributions to immune variation and disease susceptibility.
Protein structure
The IFNAR1 protein comprises 557 amino acids and features a modular architecture typical of cytokine receptors. The extracellular region contains four fibronectin type-III domains: fibronectin type-III 1 spans amino acids 32 to 126, fibronectin type-III 2 extends from amino acids 127 to 227, fibronectin type-III 3 occupies positions 231 to 329, and fibronectin type-III 4 runs from amino acids 331 to 432. These domains adopt immunoglobulin-like folds that create a binding surface for interferon ligands.
The cytoplasmic tail contains a region from amino acids 491 to 500 that is important for interaction with the tyrosine kinase TYK2, which is essential for signal transduction following receptor activation. The C-terminal portion includes a disordered region spanning amino acids 516 to 557, which may provide flexibility for regulatory interactions or post-translational modifications that modulate receptor activity.
Key variants
Genetic variants in IFNAR1 can affect receptor expression levels, ligand-binding affinity, or signalling efficiency. Because the gene shows polygenic inheritance patterns, individual variants typically exert modest effects that may combine with variation in other interferon pathway genes to influence overall immune responsiveness. Variants have been investigated in the context of susceptibility to viral infections and inflammatory disease outcomes.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.750T>G | p.Tyr250Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Immunodeficiency 106, susceptibility to viral infections |
GRCh37/hg19 21q22.11(chr21:34701363-34752816)x1 | - | Pathogenic | ★☆☆☆ | not specified |
g.(?_34713285)_(34713500_?)del | - | Pathogenic | ★☆☆☆ | not provided |
g.(33336874_33344911)del | - | Pathogenic | ★☆☆☆ | Immunodeficiency 106, susceptibility to viral infections |
c.100C>T | p.Gln34Ter | Pathogenic | ★☆☆☆ | not provided |
c.1130_1134del | p.Thr377fs | Pathogenic | ★☆☆☆ | not provided |
c.1165del | p.Thr389fs | Pathogenic | ★☆☆☆ | not provided |
c.1241del | p.Lys414fs | Pathogenic | ★☆☆☆ | not provided |
c.227dup | p.Leu76fs | Pathogenic | ★☆☆☆ | not provided |
c.263_267del | p.Asn88fs | Pathogenic | ★☆☆☆ | not provided |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
IFNAR1 variation has been studied in relation to immune-mediated conditions and infectious disease susceptibility, though the gene is not currently associated with monogenic inherited disorders. Research into IFNAR1 genetics has focused on understanding individual differences in antiviral immunity and inflammatory responses. The gene's role in type I interferon signalling means that variants may contribute to variation in how individuals respond to viral pathogens or inflammatory challenges, though such effects are typically part of complex, multifactorial patterns rather than single-gene causation.
No disease links recorded for this gene in our reference set.
UK clinical status
IFNAR1 appears on two NHS Genomic Medicine Service gene panels. It is designated with green confidence status on the COVID-19 research panel, reflecting its role in interferon-mediated antiviral responses that have been investigated in relation to severe COVID-19 outcomes. The gene also holds green confidence status (R15 level) on the Primary immunodeficiency or monogenic inflammatory bowel disease panel, indicating evidence for its involvement in immune function relevant to clinical evaluation of these conditions.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What do type I interferons do?
Type I interferons are signalling proteins released by cells during viral infections and other immune challenges. They bind to the IFNAR1/IFNAR2 receptor complex and trigger cellular responses that inhibit viral replication, enhance immune cell activation, and coordinate tissue-wide antiviral defences.
Why is IFNAR1 on chromosome 21?
IFNAR1 is located at position 21q22.11 on chromosome 21, where it resides alongside other immune-related genes. The specific chromosomal location is a product of evolutionary history, and the clustering of immune genes in this region has prompted research into potential coordinated regulation.
How does IFNAR1 variation affect health?
Variation in IFNAR1 can influence how efficiently cells respond to type I interferons, potentially affecting individual susceptibility to viral infections and inflammatory conditions. Because IFNAR1 shows polygenic inheritance, effects are typically modest and interact with variation in other genes rather than causing single-gene disorders.