GeneBe

IL36RN

protein-coding

interleukin 36 receptor antagonist, the group of Interleukins

Gene summary

The protein encoded by this gene is a member of the interleukin 1 cytokine family. This cytokine was shown to specifically inhibit the activation of NF-kappaB induced by interleukin 1 family, member 6 (IL1F6). This gene and eight other interleukin 1 family genes form a cytokine gene cluster on chromosome 2. Two alternatively spliced transcript variants encoding the same protein have been reported. [provided by RefSeq, Jul 2008]

Previous symbols:
  • IL1F5

MANE transcript

NM_012275.3

Inheritance

AR, AD, SD

ClinVar variants

P:18U:63B:44

Top phenotype

Psoriasis 14, pustular

gnomAD constraint

pLI —, LoF o/e 1.34

Max pathogenic AF

—

Genomic locus

chr2:113,058,638-113,065,382

External References & Databases

Ensembl (ENSG00000136695)NCBI Gene (26525)OMIM (605507)HGNC:15561GenCCUniProt (Q9UBH0)AlphaFoldClinVar (IL36RN)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~6.7 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

psoriasis 14, pustularSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0013626

Submitter: Orphanet

psoriasis 14, pustularLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0013626

Submitter: G2P

psoriasis 14, pustularSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013626

Submitter: Labcorp Genetics (formerly Invitae)

psoriasis 14, pustularSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0013626

Submitter: Orphanet

palmoplantar pustulosisSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0015597

Submitter: Orphanet

autoinflammatory syndromeSTRONG

Inheritance Pattern: SD

Disease ID:MONDO:0019751

Submitter: PanelApp Australia

psoriasis 14, pustularSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0013626

Submitter: Orphanet

psoriasis 14, pustularSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013626

Submitter: Genomics England PanelApp

Clinical Genomic Database (CGD)

Psoriasis 14, pustularAR

Manifestation: Allergy/Immunology/Infectious; Dermatologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 21848462; 21839423; 22903787; 23698098Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to IL36RN variants in ClinVar

10 Conditions Cataloged
Generalized pustular psoriasisTotal: 136
not providedTotal: 25
Autoinflammatory syndromeTotal: 21
Acrodermatitis continua suppurativa of HallopeauTotal: 18
not specifiedTotal: 14
Inborn genetic diseasesTotal: 14
IL36RN-related disorderTotal: 7
IL36RN-related disordersTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_012275.3. 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.

EffectPLPVUSLBBSum
synonymous
2
clinvar
38
clinvar
 40
missense
2
clinvar
5
clinvar
57
clinvar
6
clinvar
 70
nonsense
2
clinvar
2
clinvar
 4
start loss
0
frameshift
4
clinvar
3
clinvar
 7
splice donor/acceptor (+/-2bp)
3
clinvar
1
clinvar
 4
Total81063440125

Highest pathogenic variant AF is 0.0033623201

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_012275.3RefSeqNP_036407.14MANE Select
ENST00000393200.7EnsemblENSP00000376896.24MANE Select
NM_173170.1RefSeqNP_775262.14Standard
ENST00000346807.7EnsemblENSP00000259212.34Standard

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

  • negative regulation of cytokine-mediated signaling pathway
  • inflammatory response
  • regulation of signaling receptor activity
  • cytokine-mediated signaling pathway
  • antifungal humoral response

Molecular Function

  • cytokine activity
  • interleukin-1 receptor binding
  • interleukin-1 receptor antagonist activity
  • protein binding

Cellular Component

  • extracellular region
  • extracellular space

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000393200
Coding exons
4
Length
6745
Individuals with no LoFs
125730
Homozygous LoFs
0
Heterozygous LoFs
18
Defined
125748
p
0.0000716
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense-0.42710088.71.130.00000535996
Missense (PolyPhen)3733.9211.0908396
Synonymous-0.1014140.21.020.00000271318
Loss of Function-0.858107.471.344.08e-778

Population LoF Frequency

PopulationCAFp-valueStatus
African0.0000620.000062rare
Latino/Admixed American00.0absent
Ashkenazi Jewish00.0absent
East Asian0.000160.00016rare
Finnish00.0absent
European (Non-Finnish)0.0000880.000088rare
South Asian0.000130.00013rare
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Inhibits the activity of interleukin-36 (IL36A,IL36B and IL36G) by binding to receptor IL1RL2 and preventing its association with the coreceptor IL1RAP for signaling. 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. Proposed to play a role in skin inflammation. May be involved in the innate immune response to fungal pathogens, such as Aspergillus fumigatus. May activate an anti-inflammatory signaling pathway by recruiting SIGIRR. {ECO:0000269|PubMed:11466363, ECO:0000269|PubMed:21965679, ECO:0000269|PubMed:23147407}.;
Disease
DISEASE: Psoriasis 14, pustular (PSORS14) [MIM:614204]: A life- threatening disease defined by repeated flares of sudden onset consisting of diffuse erythematous skin eruption characterized by rapid coverage with pustules, high-grade fever, asthenia, marked leukocytosis, and elevated serum levels of C-reactive protein. {ECO:0000269|PubMed:21839423, ECO:0000269|PubMed:21848462, ECO:0000269|PubMed:22903787}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.128

Intolerance Scores

RVIS EVS
0.04
RVIS percentile EVS
56.92

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
N
Indispensability score
0.114

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
Feedback | API | MCP | Annotate VCF | Sitemap | About | Privacy & Terms
For research and educational, non-commercial use only. Not for clinical or diagnostic use. GeneBe does not provide medical advice. Data use for AI modeling is prohibited: if used, the cost is $0.001 per byte of downloaded uncompressed data.