IL36RN Gene (Interleukin 36 Receptor Antagonist)
Key regulator of skin inflammation and pustular psoriasis
Gene Information Card
| Symbol | IL36RN |
|---|---|
| Full Name | Interleukin 36 Receptor Antagonist |
| Gene Type | Protein coding |
| Chromosomal Location | 2q14.1 |
| NCBI Gene ID | 26525 ncbi.nlm.nih.gov/gene/26525 |
| Ensembl ID | ENSG00000136695 |
| UniProt ID | Q9UBH0 |
| OMIM ID | 605507 |
| HGNC ID | 15561 |
| Aliases | IL1F5, IL1HY1, FIL1D, IL1RP3, IL-36Ra, IL36RA |
Description
The IL36RN gene encodes the interleukin-36 receptor antagonist (IL-36Ra), a member of the interleukin-1 cytokine family. IL-36Ra binds to the IL-36 receptor (IL-1Rrp2) and competitively inhibits the pro-inflammatory signaling of IL-36α, IL-36β, and IL-36γ. Loss-of-function mutations in IL36RN lead to unopposed IL-36 signaling, resulting in excessive cutaneous inflammation and the development of generalized pustular psoriasis (GPP).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Generalized pustular psoriasis (GPP) | Loss-of-function mutations impair IL-36Ra antagonism, leading to uncontrolled IL-36 receptor activation and neutrophil-driven pustular inflammation. | OMIM #614204; multiple case-control studies (Marrakchi et al. 2011, Onoufriadis et al. 2011) |
| Acrodermatitis continua of Hallopeau | Same mechanism as GPP; IL36RN mutations found in a subset of patients. | ClinVar; case reports (Sugiura et al. 2013) |
| Palmoplantar pustulosis | IL36RN mutations contribute to pustular inflammation in palms and soles. | ClinVar; association studies (Setta-Kaffetzi et al. 2013) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skin | 12.5 | Medium |
| Esophagus | 8.2 | Medium |
| Lung | 4.1 | Low |
| Spleen | 3.8 | Low |
| Bone marrow | 2.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Keratinocytes | 15.0 | Primary human keratinocytes; high expression |
| HaCaT | 12.3 | Immortalized keratinocyte line |
| THP-1 | 2.1 | Monocytic cell line; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.115+6T>C | Splice site | Common in East Asian populations (carrier frequency ~1-2%) | Loss of function; leads to exon skipping and reduced IL-36Ra |
| c.338C>T (p.Ser113Leu) | Missense | Rare; reported in European GPP patients | Loss of function; impaired secretion and antagonism |
| c.227C>T (p.Pro76Leu) | Missense | Rare; reported in Japanese GPP patients | Loss of function; reduced protein stability |
Mutation functional classification
Loss of Function (LOF)
Most IL36RN mutations are loss-of-function, reducing or abolishing IL-36Ra antagonistic activity, leading to unopposed IL-36 signaling.
Gain of Function (GOF)
No gain-of-function mutations have been reported for IL36RN.
Dominant Negative (DN)
No dominant-negative effects have been described; IL36RN mutations are typically recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• IL-36 signaling pathway (Reactome: R-HSA-9020958)
• Interleukin-1 family signaling (Reactome: R-HSA-446652)
• Cytokine-cytokine receptor interaction (KEGG: hsa04060)
Protein Summary
IL-36Ra is a 17 kDa secreted protein that belongs to the IL-1 cytokine family. It acts as a natural antagonist of the IL-36 receptor, blocking the pro-inflammatory effects of IL-36α, IL-36β, and IL-36γ. The protein is primarily expressed in skin keratinocytes and plays a critical role in maintaining immune homeostasis in the epidermis. Loss of IL-36Ra function results in unchecked IL-36 signaling, leading to neutrophil recruitment and pustular skin inflammation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| IL36RN Knockout HEK293 Cell Line | EDJ-KQ2688 | Human | 26525 | Details Get a Quote |
| IL36RN Knockout HeLa Cell Line | EDJ-KQ55944 | Human | 26525 | Details Get a Quote |
| IL36RN Knockout A-549 Cell Line | EDJ-KQ64431 | Human | 26525 | Details Get a Quote |
| IL36RN Knockout HCT 116 Cell Line | EDJ-KQ72886 | Human | 26525 | Details Get a Quote |
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