IFNAR2 (Interferon Alpha and Beta Receptor Subunit 2): Gene, Function, and Clinical Significance
A comprehensive overview of IFNAR2, a key mediator of type I interferon signaling, including its genomic context, expression, disease associations, and mutation landscape.
Gene Information Card
| Symbol | IFNAR2 |
|---|---|
| Full Name | Interferon Alpha and Beta Receptor Subunit 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 21q22.11 |
| NCBI Gene ID | 3455 ncbi.nlm.nih.gov/gene/3455 |
| Ensembl ID | ENSG00000159110 |
| UniProt ID | P48551 |
| OMIM ID | 602376 |
| HGNC ID | 5433 |
| Aliases | IFNABR, IFNARB, IFN-R, IFNAR2-1, IFNAR2-2 |
Description
IFNAR2 encodes the beta subunit of the type I interferon receptor. This receptor is a heterodimer composed of IFNAR1 and IFNAR2, and it is essential for mediating the biological activities of type I interferons (IFN-alpha and IFN-beta). IFNAR2 is involved in signal transduction via the JAK-STAT pathway, leading to the expression of interferon-stimulated genes that regulate antiviral, antiproliferative, and immunomodulatory responses. The gene is located on chromosome 21 and is expressed in various tissues and cell types.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Immunodeficiency 44 | Loss-of-function mutations in IFNAR2 impair type I interferon signaling, leading to increased susceptibility to viral infections, particularly severe influenza and herpes simplex encephalitis. | ClinVar, OMIM |
| Systemic lupus erythematosus (SLE) | Polymorphisms in IFNAR2 have been associated with altered type I interferon signaling, contributing to the autoimmune pathogenesis of SLE. | ClinVar, literature |
| Viral infections (e.g., COVID-19) | Deficient IFNAR2 expression or function may lead to inadequate antiviral responses, increasing severity of viral infections. | ClinVar, literature |
| Cancer (various) | Altered IFNAR2 expression or mutations may affect tumor immune surveillance and response to interferon-based therapies. | COSMIC, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 11.2 | Medium |
| Spleen | 9.8 | Medium |
| Liver | 8.5 | Low |
| Kidney | 7.9 | Low |
| Brain | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 12.3 | Cervical cancer cell line; high expression |
| A549 | 10.5 | Lung carcinoma; moderate expression |
| HepG2 | 8.2 | Liver cancer; low expression |
| K562 | 7.4 | Chronic myelogenous leukemia; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1084C>T (p.Arg362Ter) | Nonsense | Rare | Loss of function; leads to immunodeficiency 44 |
| c.731G>A (p.Arg244His) | Missense | Rare | Impaired receptor signaling; associated with viral susceptibility |
| c.1123A>G (p.Thr375Ala) | Missense | Low frequency | Potential impact on protein stability; clinical significance uncertain |
| c.1450G>A (p.Val484Ile) | Missense | Low frequency | Benign polymorphism; no known disease association |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in IFNAR2, such as nonsense or frameshift variants, result in truncated or absent protein, leading to defective type I interferon signaling and increased susceptibility to viral infections.
Gain of Function (GOF)
Gain-of-function mutations in IFNAR2 are rare and not well-documented; however, constitutive activation of the receptor could lead to excessive interferon signaling, potentially contributing to autoimmune or inflammatory conditions.
Dominant Negative (DN)
Dominant-negative mutations in IFNAR2 may produce a defective subunit that interferes with the function of the wild-type receptor, impairing signal transduction even in the presence of a normal allele.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Interferon alpha/beta signaling (Reactome: R-HSA-909733)
• JAK-STAT signaling pathway (KEGG: hsa04630)
• Cytokine-cytokine receptor interaction (KEGG: hsa04060)
Protein Summary
IFNAR2 is a type I membrane glycoprotein that forms a heterodimeric receptor with IFNAR1. It binds type I interferons (IFN-alpha, IFN-beta, and others) and activates the JAK-STAT signaling cascade, leading to the transcription of interferon-stimulated genes. The protein has multiple isoforms generated by alternative splicing, which may have distinct functions. IFNAR2 is critical for innate immunity against viral infections and also plays roles in cell growth regulation and immune modulation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| IFNAR2 Knockout HEK293 Cell Line | EDJ-KQ50384 | Human | 3455 | Details Get a Quote |
| IFNAR2 Knockout HeLa Cell Line | EDJ-KQ53619 | Human | 3455 | Details Get a Quote |
| IFNAR2 Knockout A-549 Cell Line | EDJ-KQ62089 | Human | 3455 | Details Get a Quote |
| IFNAR2 Knockout HCT 116 Cell Line | EDJ-KQ70573 | Human | 3455 | Details Get a Quote |
