IL18 Gene (Interleukin 18): Function, Related Diseases, and Expression
Comprehensive guide to the IL18 gene, including genomic context, protein function, associated diseases, tissue expression, and mutation landscape.
Gene Information Card
| Symbol | IL18 |
|---|---|
| Full Name | Interleukin 18 |
| Gene Type | protein-coding |
| Chromosomal Location | 11q22.2-q22.3 |
| NCBI Gene ID | 3606 ncbi.nlm.nih.gov/gene/3606 |
| Ensembl ID | ENSG00000150782 |
| UniProt ID | Q14116 |
| OMIM ID | 600953 |
| HGNC ID | 5986 |
| Aliases | IGIF, IL-18, IL1F4, MGC12320 |
Description
The IL18 gene encodes interleukin-18, a pro-inflammatory cytokine belonging to the IL-1 family. It is synthesized as a precursor protein (pro-IL-18) that is cleaved by caspase-1 to produce the active cytokine. IL-18 plays a crucial role in innate and adaptive immunity, particularly in inducing interferon-gamma (IFN-γ) production from T cells and natural killer (NK) cells. It is involved in various inflammatory and autoimmune diseases, and its dysregulation has been linked to cancer progression and metabolic disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Adult-onset Still's disease | Elevated IL-18 levels contribute to systemic inflammation and macrophage activation syndrome. | ClinVar, OMIM |
| Macrophage activation syndrome | IL-18 overproduction drives excessive T-cell and macrophage activation. | ClinVar, OMIM |
| Inflammatory bowel disease (Crohn's disease, ulcerative colitis) | IL-18 promotes intestinal inflammation via IFN-γ and Th1 responses. | ClinVar, OMIM |
| Rheumatoid arthritis | IL-18 enhances synovial inflammation and joint destruction. | ClinVar, OMIM |
| Type 1 diabetes | IL-18 contributes to pancreatic beta-cell destruction via immune-mediated inflammation. | ClinVar, OMIM |
| Atherosclerosis | IL-18 promotes plaque formation and instability through inflammatory signaling. | ClinVar, OMIM |
| Cancer (various types) | IL-18 can have pro-tumorigenic or anti-tumorigenic effects depending on context; elevated levels often correlate with poor prognosis. | COSMIC, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adipose tissue | 12.5 | Medium |
| Liver | 8.2 | Low |
| Spleen | 15.3 | Medium |
| Lung | 6.1 | Low |
| Kidney | 4.8 | Low |
| Pancreas | 3.2 | Low |
| Small intestine | 10.4 | Medium |
| Colon | 9.7 | Medium |
| Blood (PBMC) | 18.6 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| THP-1 (monocytic leukemia) | 22.3 | High expression; inducible by LPS |
| K-562 (chronic myelogenous leukemia) | 5.4 | Low expression |
| HeLa (cervical carcinoma) | 3.1 | Low expression |
| A549 (lung carcinoma) | 7.8 | Moderate expression |
| HepG2 (hepatocellular carcinoma) | 2.9 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs1946518 (promoter variant) | SNP | ~30% (global) | Associated with altered IL-18 expression and susceptibility to inflammatory diseases. |
| rs187238 (promoter variant) | SNP | ~25% (global) | Affects IL-18 transcriptional activity; linked to autoimmune conditions. |
| c.183C>A (p.Asp61Glu) | Missense | Rare | Potential impact on protein stability; clinical significance uncertain. |
| c.293C>T (p.Thr98Met) | Missense | Rare | Reported in some cancer samples; functional effect not fully characterized. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in IL18 are rare and may impair cytokine production, leading to reduced inflammatory responses and increased susceptibility to certain infections.
Gain of Function (GOF)
Gain-of-function mutations or promoter variants that increase IL-18 expression can lead to excessive inflammation, contributing to autoimmune and autoinflammatory diseases.
Dominant Negative (DN)
No dominant-negative mutations have been characterized for IL18; the cytokine acts as a soluble ligand, and mutations are typically not dominant-negative.
View complete mutation data：
Gene Ontology (GO)
| • cytokine activity | • interleukin-18 receptor binding |
| • protein binding | • signaling receptor binding |
| • immune response | • inflammatory response |
| • positive regulation of interferon-gamma production | • positive regulation of T cell proliferation |
| • regulation of cytokine secretion |
Pathways
• IL-18 signaling pathway
• Inflammasome pathway (NLRP3/ASC/caspase-1)
• Toll-like receptor signaling pathway
• Cytokine-cytokine receptor interaction
• Th1 and Th2 cell differentiation
• Apoptosis (via Fas ligand upregulation)
Protein Summary
Interleukin-18 (IL-18) is a 24 kDa pro-inflammatory cytokine synthesized as a 193-amino acid precursor. It is cleaved by caspase-1 to produce the mature 157-amino acid active form. IL-18 binds to the IL-18 receptor (IL-18Rα/β) and activates NF-κB and MAPK pathways, leading to IFN-γ production and Th1 polarization. It is expressed in various tissues, with highest levels in blood cells, and is involved in both innate and adaptive immunity. Dysregulation of IL-18 is implicated in inflammatory, autoimmune, and malignant diseases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| IL18R1 Knockout HEK293 Cell Line | EDJ-KQ244 | Human | 8809 | Details Get a Quote |
| IL18BP Knockout HEK293 Cell Line | EDJ-KQ2452 | Human | 10068 | Details Get a Quote |
| IL18 Knockout HEK293 Cell Line | EDJ-KQ4992 | Human | 3606 | Details Get a Quote |
| IL18RAP Knockout HEK293 Cell Line | EDJ-KQ6370 | Human | 8807 | Details Get a Quote |
| IL18R1 Knockout A-549 Cell Line | EDJ-KQ21064 | Human | 8809 | Details Get a Quote |
| IL18R1 Knockout HCT 116 Cell Line | EDJ-KQ21065 | Human | 8809 | Details Get a Quote |
| IL18BP Knockout HCT 116 Cell Line | EDJ-KQ22982 | Human | 10068 | Details Get a Quote |
| IL18BP Knockout HeLa Cell Line | EDJ-KQ22983 | Human | 10068 | Details Get a Quote |
| IL18BP Knockout A-549 Cell Line | EDJ-KQ21648 | Human | 10068 | Details Get a Quote |
| IL18 Knockout HCT 116 Cell Line | EDJ-KQ26671 | Human | 3606 | Details Get a Quote |
| IL18 Knockout A-549 Cell Line | EDJ-KQ27887 | Human | 3606 | Details Get a Quote |
| IL18 Knockout HeLa Cell Line | EDJ-KQ27889 | Human | 3606 | Details Get a Quote |
| IL18RAP Knockout HeLa Cell Line | EDJ-KQ55009 | Human | 8807 | Details Get a Quote |
| IL18R1 Knockout HeLa Cell Line | EDJ-KQ55010 | Human | 8809 | Details Get a Quote |
| IL18RAP Knockout A-549 Cell Line | EDJ-KQ63491 | Human | 8807 | Details Get a Quote |
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