IL36G: Interleukin 36 Gamma – A Key Mediator in Skin Inflammation and Epithelial Defense
Comprehensive genomic and functional analysis of IL36G, a member of the IL-1 cytokine family implicated in psoriasis, pustular disorders, and epithelial immunity.
Gene Information Card
| Symbol | IL36G |
|---|---|
| Full Name | Interleukin 36 Gamma |
| Gene Type | Protein coding |
| Chromosomal Location | 2q14.1 |
| NCBI Gene ID | 56300 ncbi.nlm.nih.gov/gene/56300 |
| Ensembl ID | ENSG00000136688 |
| UniProt ID | Q9NZH8 |
| OMIM ID | 605542 |
| HGNC ID | 15741 |
| Aliases | IL1F9, IL-1F9, IL-1H1, IL-1RP2, IL36GAMMA, IL-36γ |
Description
IL36G (Interleukin 36 Gamma) is a member of the interleukin 1 (IL-1) cytokine family. It is primarily expressed in epithelial tissues, especially skin, and plays a crucial role in innate immune responses. IL36G signals through the IL-36 receptor (IL-36R/IL1RL2) and activates NF-κB and MAPK pathways, leading to the production of pro-inflammatory cytokines and antimicrobial peptides. Dysregulation of IL36G is strongly associated with inflammatory skin diseases such as psoriasis and generalized pustular psoriasis (GPP).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Psoriasis | Overexpression of IL36G in keratinocytes amplifies IL-36R signaling, driving chronic inflammation and neutrophil recruitment. | Multiple studies; ClinVar; OMIM #605542 |
| Generalized Pustular Psoriasis (GPP) | Gain-of-function mutations in IL36RN (IL-36Ra) lead to unopposed IL36G signaling; IL36G itself is upregulated in pustular lesions. | ClinVar; OMIM #614204 |
| Acrodermatitis Continua of Hallopeau | IL36G overexpression contributes to pustular inflammation in acral skin. | Case reports; ClinVar |
| Palmoplantar Pustulosis | Elevated IL36G expression in palmoplantar pustules drives local neutrophil infiltration. | ClinVar; literature review |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skin | 12.5 | High |
| Esophagus | 8.3 | Medium |
| Lung | 4.1 | Low |
| Tonsil | 3.9 | Low |
| Spleen | 1.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HaCaT (keratinocyte) | 15.2 | High baseline expression; upregulated by IL-17A and TNF-α |
| A549 (lung epithelial) | 6.8 | Moderate expression; induced by IL-1β |
| HEK293 (embryonic kidney) | 0.5 | Very low endogenous expression |
| THP-1 (monocyte) | 0.3 | Not expressed in monocytes |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | Rare | Likely loss-of-function; reported in ClinVar as uncertain significance |
| c.115C>T (p.Arg39Trp) | Missense | 0.001% (gnomAD) | Unknown functional effect; not associated with disease |
| c.338G>A (p.Arg113His) | Missense | 0.002% (gnomAD) | Reported in COSMIC in skin cancer; functional impact unclear |
Mutation functional classification
Loss of Function (LOF)
No confirmed loss-of-function mutations in IL36G are currently reported in ClinVar or COSMIC. The c.1A>G variant may affect translation initiation but lacks functional validation.
Gain of Function (GOF)
No gain-of-function mutations in IL36G have been described. Disease association is primarily through overexpression rather than activating mutations.
Dominant Negative (DN)
No dominant-negative mutations reported for IL36G.
View complete mutation data：
Gene Ontology (GO)
Pathways
• IL-1 family signaling (Reactome: R-HSA-446652)
• IL-36 pathway (Reactome: R-HSA-9014826)
• NF-κB signaling (KEGG: hsa04064)
• MAPK signaling (KEGG: hsa04010)
Protein Summary
IL36G encodes a 169-amino acid protein (17.5 kDa) that is secreted as a mature cytokine after N-terminal processing. It belongs to the IL-1 family and binds to the IL-36 receptor (IL-36R/IL1RL2) along with the co-receptor IL-1RAcP. The protein adopts a β-trefoil fold typical of IL-1 cytokines. IL36G is a potent agonist of the IL-36 pathway, inducing pro-inflammatory gene expression in keratinocytes, fibroblasts, and epithelial cells. Its activity is antagonized by the IL-36 receptor antagonist (IL-36Ra, encoded by IL36RN).
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| IL36G Knockout HEK293 Cell Line | EDJ-KQ13828 | Human | 56300 | Details Get a Quote |
| IL36G Knockout HeLa Cell Line | EDJ-KQ56731 | Human | 56300 | Details Get a Quote |
| IL36G Knockout A-549 Cell Line | EDJ-KQ65236 | Human | 56300 | Details Get a Quote |
| IL36G Knockout HCT 116 Cell Line | EDJ-KQ73675 | Human | 56300 | Details Get a Quote |
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