IL36B
protein-codinginterleukin 36 beta, the group of Interleukins
Gene summary
The protein encoded by this gene is a member of the interleukin 1 cytokine family. Protein structure modeling indicated that this cytokine may contain a 12-stranded beta-trefoil structure that is conserved between IL1A (IL-A alpha) and IL1B (IL-1 beta). This gene and eight other interleukin 1 family genes form a cytokine gene cluster on chromosome 2. Two alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]
- IL1F8
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~30.8 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 IL36B variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_173178.3. 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 | 0 | |||||
| missense | 8 | 1 | 9 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 8 | 1 | 0 | 9 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_775270.1 | 4 | MANE Select | |
| Ensembl | ENSP00000328420.2 | 4 | MANE Select | |
| RefSeq | NP_055253.2 | 5 | Standard | |
| Ensembl | ENSP00000259213.4 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Signaling by Interleukins
- Cytokine Signaling in Immune system
- Immune System
- Interleukin-36 pathway
- Interleukin-1 family signaling
Biological Process
- inflammatory response
- immune response
- regulation of signaling receptor activity
- cytokine-mediated signaling pathway
- neutrophil chemotaxis
Molecular Function
- cytokine activity
- interleukin-1 receptor binding
Cellular Component
- extracellular region
- extracellular space
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000259213
- Coding exons
- 5
- Length
- 30777
- Individuals with no LoFs
- 125673
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 68
- Defined
- 125741
- p
- 0.000270
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.186 | 96 | 91.0 | 1.05 | 0.00000444 | 1089 |
| Missense (PolyPhen) | 15 | 17.361 | 0.86402 | 231 | ||
| Synonymous | 1.16 | 19 | 26.6 | 0.713 | 0.00000114 | 284 |
| Loss of Function | 1.18 | 5 | 8.78 | 0.569 | 5.38e-7 | 86 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00025 | 0.00025 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.00033 | 0.00032 | rare |
| European (Non-Finnish) | 0.00048 | 0.00047 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Cytokine that binds to and signals through the IL1RL2/IL-36R receptor which in turn activates NF-kappa-B and MAPK signaling pathways in target cells linked to a pro-inflammatory response. Part of the IL-36 signaling system that is thought to be present in epithelial barriers and to take part in local inflammatory response; similar to the IL-1 system with which it shares the coreceptor IL1RAP. Stimulates production of interleukin-6 and interleukin-8 in synovial fibrobasts, articular chondrocytes and mature adipocytes. Induces expression of a number of antimicrobial peptides including beta-defensins 4 and 103 as well as a number of matrix metalloproteases. Seems to be involved in skin inflammatory response by acting on keratinocytes, dendritic cells and indirectly on T-cells to drive tissue infiltration, cell maturation and cell proliferation. In cultured keratinocytes induces the expression of macrophage, T-cell, and neutrophil chemokines, such as CCL3, CCL4, CCL5, CCL2, CCL17, CCL22, CL20, CCL5, CCL2, CCL17, CCL22, CXCL8, CCL20 and CXCL1, and the production of proinflammatory cytokines such as TNF-alpha, IL- 8 and IL-6. {ECO:0000269|PubMed:16646978, ECO:0000269|PubMed:20300079, ECO:0000269|PubMed:21242515, ECO:0000269|PubMed:21881584, ECO:0000269|PubMed:21965679, ECO:0000269|PubMed:24829417}.;
Recessive Scores
- pRec
- 0.0794
Intolerance Scores
- RVIS EVS
- 0.39
- RVIS percentile EVS
- 76.05
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.114
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |