IFNLR1 (Interferon Lambda Receptor 1): Structure, Function, and Clinical Significance
A comprehensive overview of the IFNLR1 gene, encoding the ligand-binding subunit of the type III interferon receptor, with emphasis on its role in antiviral immunity, disease associations, and therapeutic relevance.
Gene Information Card
| Symbol | IFNLR1 |
|---|---|
| Full Name | Interferon Lambda Receptor 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 1p36.11 |
| NCBI Gene ID | 163702 ncbi.nlm.nih.gov/gene/163702 |
| Ensembl ID | ENSG00000185436 |
| UniProt ID | Q8IU57 |
| OMIM ID | 607404 |
| HGNC ID | 18584 |
| Aliases | IL28RA, CRF2-12, LICR2 |
Description
IFNLR1 encodes the ligand-binding subunit of the type III interferon receptor, which forms a heterodimeric complex with IL10RB to mediate signaling by interferon lambda (IFN-λ) cytokines (IFN-λ1/IL-29, IFN-λ2/IL-28A, IFN-λ3/IL-28B, and IFN-λ4). This receptor is primarily expressed on epithelial cells and hepatocytes, and its activation triggers the JAK-STAT pathway, leading to antiviral and immunomodulatory responses. IFNLR1 is critical for host defense against mucosal and hepatic viral infections, and its genetic variants have been associated with treatment outcomes in hepatitis C and other diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hepatitis C Virus Infection | IFNLR1 variants (e.g., rs10903092) influence IFN-λ signaling efficacy, affecting viral clearance and response to pegylated IFN-α/ribavirin therapy. | ClinVar, PMID: 22045340 |
| Inflammatory Bowel Disease | Altered IFNLR1 expression may modulate epithelial barrier function and mucosal immune responses, contributing to IBD susceptibility. | UniProt, PMID: 28067908 |
| Respiratory Viral Infections (e.g., Influenza) | IFNLR1 mediates IFN-λ responses in airway epithelium, influencing viral control and inflammation. | PMID: 28202771 |
| Cancer (various) | Differential IFNLR1 expression in tumors may affect anti-tumor immunity and response to immunotherapy. | COSMIC, PMID: 29593335 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 10.2 | Medium |
| Lung | 8.5 | Medium |
| Small Intestine | 12.3 | High |
| Colon | 9.8 | Medium |
| Kidney | 6.4 | Low |
| Skin | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.2 | Hepatocellular carcinoma cell line; high expression |
| A549 | 12.8 | Lung carcinoma; moderate expression |
| Caco-2 | 18.5 | Colorectal adenocarcinoma; high expression |
| MCF7 | 3.2 | Breast cancer; low expression |
| K562 | 1.5 | Chronic myelogenous leukemia; very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs10903092 (G/A) | SNP (intronic) | Minor allele frequency ~0.3 (global) | Associated with reduced IFN-λ signaling and poorer HCV clearance |
| c.113A>G (p.Asn38Ser) | Missense | Rare (<0.01) | Potential impact on ligand binding; clinical significance uncertain |
| c.457C>T (p.Arg153Trp) | Missense | Rare (<0.01) | May affect receptor dimerization; reported in ClinVar as uncertain significance |
| c.784G>A (p.Val262Ile) | Missense | Rare (<0.01) | No known functional effect; benign polymorphism |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in IFNLR1 are rare and may impair IFN-λ signaling, leading to increased susceptibility to viral infections, particularly in epithelial tissues. Examples include frameshift or nonsense variants that truncate the protein, though such variants are not well-documented in major databases.
Gain of Function (GOF)
No gain-of-function mutations have been reported for IFNLR1. Constitutive activation is not observed; the receptor requires ligand binding for signaling.
Dominant Negative (DN)
Dominant-negative effects are theoretically possible if a mutant subunit forms non-functional heterodimers with IL10RB, but no such variants have been characterized in the literature.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Interferon lambda signaling pathway (Reactome: R-HSA-909733)
• Cytokine-cytokine receptor interaction (KEGG: hsa04060)
• JAK-STAT signaling pathway (KEGG: hsa04630)
• Influenza A (KEGG: hsa05164)
• Hepatitis C (KEGG: hsa05160)
Protein Summary
IFNLR1 is a type I transmembrane protein of 520 amino acids, belonging to the class II cytokine receptor family. It consists of an extracellular domain with two fibronectin type III domains, a transmembrane region, and an intracellular domain containing conserved Box1 and Box2 motifs for JAK association. Upon binding IFN-λ, IFNLR1 forms a complex with IL10RB, activating JAK1 and TYK2, which phosphorylate STAT1 and STAT2, leading to ISGF3 formation and induction of interferon-stimulated genes. The protein is glycosylated and expressed predominantly on epithelial cells, hepatocytes, and some immune cells. Its expression is regulated by inflammatory stimuli and can be modulated by viral infections.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| IFNLR1 Knockout HEK293 Cell Line | EDJ-KQ2161 | Human | 163702 | Details Get a Quote |
| IFNLR1 Knockout A-549 Cell Line | EDJ-KQ22358 | Human | 163702 | Details Get a Quote |
| IFNLR1 Knockout HCT 116 Cell Line | EDJ-KQ22359 | Human | 163702 | Details Get a Quote |
| IFNLR1 Knockout HeLa Cell Line | EDJ-KQ22360 | Human | 163702 | Details Get a Quote |
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