IL18
protein-codinginterleukin 18, the group of Interleukins
Gene summary
The protein encoded by this gene is a proinflammatory cytokine of the IL-1 family that is constitutively found as a precursor within the cytoplasm of a variety of cells including macrophages and keratinocytes. The inactive IL-18 precursor is processed to its active form by caspase-1, and is capable of stimulating interferon gamma production, and of regulating both T helper (Th) 1 and Th2 responses. This cytokine has been implicated in the injury of different organs, and in potentially fatal conditions characterized by a cytokine storm. In humans, IL-18 gene is located on chromosome 11. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Aug 2020]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~20.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to IL18 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001562.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 7 | 3 | 10 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 8 | 4 | 0 | 12 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001553.1 | 5 | MANE Select | |
| Ensembl | ENSP00000280357.7 | 5 | MANE Select | |
| RefSeq | NP_001230140.1 | 4 | Standard | |
| RefSeq | NP_001373349.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Salmonella infection - Homo sapiens (human)
- Legionellosis - Homo sapiens (human)
- Influenza A - Homo sapiens (human)
- Inflammatory bowel disease (IBD) - Homo sapiens (human)
- African trypanosomiasis - Homo sapiens (human)
Biological Process
- MAPK cascade
- angiogenesis
- inflammatory response
- cell-cell signaling
- cell population proliferation
Molecular Function
- cytokine activity
- protein binding
- interleukin-18 receptor binding
Cellular Component
- extracellular region
- extracellular space
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000280357
- Coding exons
- 5
- Length
- 20867
- Individuals with no LoFs
- 124501
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 3
- Defined
- 124504
- p
- 0.0000120
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.52 | 51 | 92.0 | 0.554 | 0.00000433 | 1312 |
| Missense (PolyPhen) | 10 | 24.439 | 0.40919 | 402 | ||
| Synonymous | 0.665 | 25 | 29.6 | 0.844 | 0.00000146 | 316 |
| Loss of Function | 1.13 | 3 | 5.99 | 0.501 | 2.50e-7 | 97 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000027 | 0.000027 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: A proinflammatory cytokine primarily involved in polarized T-helper 1 (Th1) cell and natural killer (NK) cell immune responses (Probable). Upon binding to IL18R1 and IL18RAP, forms a signaling ternary complex which activates NF-kappa-B, triggering synthesis of inflammatory mediators (PubMed:14528293, PubMed:25500532). Synergizes with IL12/interleukin-12 to induce IFNG synthesis from T-helper 1 (Th1) cells and natural killer (NK) cells (Probable) (PubMed:10653850). {ECO:0000269|PubMed:10653850, ECO:0000269|PubMed:14528293, ECO:0000269|PubMed:25500532, ECO:0000305}.;
Recessive Scores
- pRec
- 0.550
Intolerance Scores
- LoFtool
- 0.585
- RVIS EVS
- -0.01
- RVIS percentile EVS
- 52.85
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.376
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Low | Low | Low |
| Primary Immunodeficiency | Low | Low | Low |
| Cancer | Low | Low | Low |