IL1R2
protein-codinginterleukin 1 receptor type 2, the group of Immunoglobulin like 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 protein binds interleukin alpha (IL1A), interleukin beta (IL1B), and interleukin 1 receptor, type I(IL1R1/IL1RA), and acts as a decoy receptor that inhibits the activity of its ligands. Interleukin 4 (IL4) is reported to antagonize the activity of interleukin 1 by inducing the expression and release of this cytokine. This gene and three other genes form a cytokine receptor gene cluster on chromosome 2q12. Alternative splicing results in multiple transcript variants and protein isoforms. Alternative splicing produces both membrane-bound and soluble proteins. A soluble protein is also produced by proteolytic cleavage. [provided by RefSeq, May 2012]
- IL1RB
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~36.6 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 IL1R2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004633.4. 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 | 2 | 1 | 4 | ||
| missense | 62 | 11 | 1 | 74 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 65 | 13 | 2 | 80 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004624.1 | 8 | MANE Select | |
| Ensembl | ENSP00000330959.3 | 8 | MANE Select | |
| RefSeq | NP_001248348.1 | 6 | Standard | |
| Ensembl | ENSP00000377066.2 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- HTLV-I infection - Homo sapiens (human)
- Amoebiasis - Homo sapiens (human)
- Prostate cancer - Homo sapiens (human)
- Fluid shear stress and atherosclerosis - Homo sapiens (human)
- Transcriptional misregulation in cancer - Homo sapiens (human)
Biological Process
- immune response
- negative regulation of protein processing
- cytokine-mediated signaling pathway
- negative regulation of interleukin-1 alpha secretion
- interleukin-1-mediated signaling pathway
Molecular Function
- interleukin-1 receptor activity
- interleukin-1, type II, blocking receptor activity
- protein binding
- interleukin-1 binding
Cellular Component
- extracellular region
- cytoplasm
- plasma membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000332549
- Coding exons
- 8
- Length
- 36701
- Individuals with no LoFs
- 125643
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 105
- Defined
- 125748
- p
- 0.000418
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.111 | 242 | 237 | 1.02 | 0.0000139 | 2576 |
| Missense (PolyPhen) | 71 | 67.738 | 1.0482 | 787 | ||
| Synonymous | 0.353 | 87 | 91.3 | 0.953 | 0.00000530 | 796 |
| Loss of Function | -0.676 | 20 | 17.0 | 1.18 | 7.20e-7 | 214 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00031 | 0.00031 | rare |
| Latino/Admixed American | 0.00015 | 0.00014 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0.000092 | 0.000092 | rare |
| European (Non-Finnish) | 0.00073 | 0.00073 | rare |
| South Asian | 0.00016 | 0.00016 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Non-signaling receptor for IL1A, IL1B and IL1RN. Reduces IL1B activities. Serves as a decoy receptor by competetive binding to IL1B and preventing its binding to IL1R1. Also modulates cellular response through non-signaling association with IL1RAP after binding to IL1B. IL1R2 (membrane and secreted forms) preferentially binds IL1B and poorly IL1A and IL1RN. The secreted IL1R2 recruits secreted IL1RAP with high affinity; this complex formation may be the dominant mechanism for neutralization of IL1B by secreted/soluble receptors. {ECO:0000269|PubMed:10975853, ECO:0000269|PubMed:12530978, ECO:0000269|PubMed:7989776, ECO:0000269|PubMed:9862719}.;
Recessive Scores
- pRec
- 0.270
Intolerance Scores
- LoFtool
- 0.892
- RVIS EVS
- -0.71
- RVIS percentile EVS
- 14.57
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.889
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |