IL4R Gene: Interleukin-4 Receptor, Key Mediator of Allergic Inflammation and Immune Regulation
Comprehensive genomic, functional, and clinical insights into IL4R, a critical cytokine receptor implicated in asthma, atopy, and cancer.
Gene Information Card
| Symbol | IL4R |
|---|---|
| Full Name | Interleukin 4 Receptor |
| Gene Type | protein-coding |
| Chromosomal Location | 16p12.1 |
| NCBI Gene ID | 3566 ncbi.nlm.nih.gov/gene/3566 |
| Ensembl ID | ENSG00000077238 |
| UniProt ID | P24394 |
| OMIM ID | 147781 |
| HGNC ID | 6014 |
| Aliases | IL4RA; CD124; IL-4R; IL4R1 |
Description
The IL4R gene encodes the alpha subunit of the interleukin-4 receptor, a type I transmembrane protein that binds interleukin-4 (IL-4) and, in complex with the common gamma chain (γc), mediates IL-4 signaling. IL4R is also a component of the type II receptor complex (with IL13RA1) that responds to IL-13. Activation of IL4R triggers JAK-STAT signaling, particularly STAT6, leading to Th2 differentiation, IgE class switching, and modulation of immune responses. IL4R is expressed on various immune and non-immune cells, and its dysregulation is linked to allergic diseases, asthma, and certain cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Asthma | IL4R variants alter receptor function, enhancing IL-4/IL-13 signaling and promoting Th2-mediated airway inflammation. | ClinVar, OMIM |
| Atopic dermatitis | Gain-of-function IL4R variants increase IgE production and skin inflammation. | ClinVar, OMIM |
| Allergic rhinitis | IL4R polymorphisms are associated with elevated IgE and nasal allergic responses. | ClinVar |
| Hyper-IgE syndrome (Job syndrome) | Rare IL4R mutations may contribute to elevated IgE and immune dysregulation. | OMIM |
| Cancer (e.g., breast, lung) | IL4R overexpression in tumor cells promotes survival and immune evasion via STAT6 activation. | COSMIC, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 5.2 | Medium |
| Spleen | 4.8 | Medium |
| Lymph node | 4.5 | Medium |
| Bone marrow | 3.9 | Low |
| Skin | 3.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| THP-1 (monocyte) | 12.5 | High expression |
| A549 (lung carcinoma) | 8.3 | Moderate expression |
| MCF7 (breast cancer) | 6.7 | Moderate expression |
| Jurkat (T cell) | 2.1 | Low expression |
| HepG2 (liver) | 1.0 | Very low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs1801275 (Q576R) | Missense | ~20% allele frequency | Gain-of-function; enhances STAT6 signaling, associated with asthma and atopy. |
| rs1805010 (I50V) | Missense | ~30% allele frequency | Alters receptor affinity; linked to allergic rhinitis. |
| rs1805015 (S478P) | Missense | ~10% allele frequency | May affect receptor stability; associated with asthma severity. |
| rs2239346 (5' UTR) | Regulatory | ~15% allele frequency | Affects gene expression; linked to asthma susceptibility. |
Mutation functional classification
Loss of Function (LOF)
Rare loss-of-function mutations impair IL-4/IL-13 signaling, reducing Th2 responses and IgE production, potentially leading to immunodeficiency.
Gain of Function (GOF)
Common gain-of-function variants (e.g., Q576R) enhance STAT6 phosphorylation, increasing IgE synthesis and promoting allergic inflammation.
Dominant Negative (DN)
Dominant-negative mutations are rare; they may interfere with receptor dimerization, reducing signaling but not completely abolishing it.
View complete mutation data：
Gene Ontology (GO)
| • interleukin-4 receptor activity | • interleukin-13 receptor activity |
| • cytokine receptor activity | • protein binding |
| • signal transduction | • JAK-STAT cascade |
| • immune response | • cell surface receptor signaling pathway |
Pathways
• IL-4 signaling pathway
• IL-13 signaling pathway
• JAK-STAT signaling pathway
• Th2 differentiation pathway
• IgE production pathway
Protein Summary
The IL4R protein (P24394) is a 140 kDa glycosylated type I membrane protein. It consists of an extracellular domain with fibronectin type III domains, a transmembrane region, and an intracellular domain containing Box1/Box2 motifs for JAK binding. Upon IL-4 binding, IL4R associates with the common gamma chain (γc) to form a high-affinity receptor complex, activating JAK1/JAK3 and STAT6. In type II receptor complexes, IL4R pairs with IL13RA1 to bind IL-13, also activating STAT6. IL4R signaling promotes Th2 cell differentiation, B-cell class switching to IgE, and upregulation of adhesion molecules. Soluble IL4R (sIL4R) can act as a decoy, modulating IL-4 activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| IL4R Knockout HEK293 Cell Line | EDJ-KQ496 | Human | 3566 | Details Get a Quote |
| IL4R Knockout HeLa Cell Line | EDJ-KQ17947 | Human | 3566 | Details Get a Quote |
| IL4R Knockout HCT 116 Cell Line | EDJ-KQ18009 | Human | 3566 | Details Get a Quote |
| IL4R Knockout A-549 Cell Line | EDJ-KQ18808 | Human | 3566 | Details Get a Quote |
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