IL18R1
protein-codinginterleukin 18 receptor 1, the group of Immunoglobulin like domain containing|TIR domain containing|CD molecules|Interleukin receptors
Gene summary
The protein encoded by this gene is a cytokine receptor that belongs to the interleukin 1 receptor family. This receptor specifically binds interleukin 18 (IL18), and is essential for IL18 mediated signal transduction. IFN-alpha and IL12 are reported to induce the expression of this receptor in NK and T cells. This gene along with four other members of the interleukin 1 receptor family, including IL1R2, IL1R1, ILRL2 (IL-1Rrp2), and IL1RL1 (T1/ST2), form a gene cluster on chromosome 2q. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~87.2 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 IL18R1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003855.5. 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 | 48 | 3 | 1 | 52 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 48 | 3 | 2 | 53 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003846.1 | 10 | MANE Select | |
| Ensembl | ENSP00000233957.1 | 10 | MANE Select | |
| RefSeq | NP_001269328.1 | 8 | Standard | |
| RefSeq | NP_001358347.1 | 10 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Inflammatory bowel disease (IBD) - Homo sapiens (human)
- TNF signaling pathway - Homo sapiens (human)
- Cytokine-cytokine receptor interaction - Homo sapiens (human)
- Signaling by Interleukins
- il12 and stat4 dependent signaling pathway in th1 development
Biological Process
- inflammatory response
- immune response
- signal transduction
- natural killer cell activation
- positive regulation of interferon-gamma production
Molecular Function
- interleukin-1 receptor activity
- protein binding
- signaling receptor activity
- interleukin-18 binding
- interleukin-18 receptor activity
Cellular Component
- plasma membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000409599
- Coding exons
- 10
- Length
- 87230
- Individuals with no LoFs
- 125720
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 27
- Defined
- 125747
- p
- 0.000107
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.974 | 233 | 279 | 0.836 | 0.0000137 | 3552 |
| Missense (PolyPhen) | 67 | 85.057 | 0.7877 | 1182 | ||
| Synonymous | -0.522 | 113 | 106 | 1.06 | 0.00000592 | 994 |
| Loss of Function | 2.17 | 12 | 23.3 | 0.514 | 0.00000114 | 329 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00018 | rare |
| Latino/Admixed American | 0.00015 | 0.00014 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.000047 | 0.000046 | rare |
| European (Non-Finnish) | 0.00013 | 0.00013 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Within the IL18 receptor complex, responsible for the binding of the proinflammatory cytokine IL18, but not IL1A nor IL1B (PubMed:8626725, PubMed:14528293, PubMed:25261253, PubMed:25500532). Involved in IL18-mediated IFNG synthesis from T- helper 1 (Th1) cells (PubMed:10653850). Contributes to IL18- induced cytokine production, either independently of SLC12A3, or as a complex with SLC12A3 (By similarity). {ECO:0000250|UniProtKB:Q61098, ECO:0000269|PubMed:10653850, ECO:0000269|PubMed:14528293, ECO:0000269|PubMed:25261253, ECO:0000269|PubMed:25500532, ECO:0000269|PubMed:8626725}.;
Recessive Scores
- pRec
- 0.186
Intolerance Scores
- LoFtool
- 0.831
- RVIS EVS
- 0.29
- RVIS percentile EVS
- 71.5
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.240
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |