IL36RN

interleukin 36 receptor antagonist, the group of Interleukins

Basic information

Region (hg38): 2:113058638-113065382

Previous symbols: [ "IL1F5" ]

Links

ENSG00000136695 ∙ NCBI:26525 ∙ OMIM:605507 ∙ HGNC:15561 ∙ Uniprot:Q9UBH0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• psoriasis 14, pustular (Strong), mode of inheritance: AR
• psoriasis 14, pustular (Strong), mode of inheritance: AR
• pustulosis palmaris et plantaris (Supportive), mode of inheritance: AD
• psoriasis 14, pustular (Supportive), mode of inheritance: AR
• psoriasis 14, pustular (Supportive), mode of inheritance: AR
• psoriasis 14, pustular (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Psoriasis 14, pustular	AR	General	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	Allergy/Immunology/Infectious; Dermatologic	21848462; 21839423; 22903787; 23698098

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IL36RN gene.

• Generalized pustular psoriasis (3 variants)
• Acrodermatitis continua suppurativa of Hallopeau (1 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IL36RN gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	26		27
missense	1		51	1		53
nonsense	1	1	1			3
start loss						0
frameshift	1		3			4
inframe indel						0
splice donor/acceptor (+/-2bp)		3	1			4
splice region			6	5		11
non coding			31	20	17	68
Total	3	4	88	47	17

Highest pathogenic variant AF is 0.0000197

Variants in IL36RN

This is a list of pathogenic ClinVar variants found in the IL36RN region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-113059094-G-A		Generalized pustular psoriasis	Uncertain significance (Jun 14, 2016)
2-113059113-G-C		Generalized pustular psoriasis	Uncertain significance (Jan 13, 2018)
2-113059222-G-A		Generalized pustular psoriasis	Uncertain significance (Jan 13, 2018)
2-113059242-G-A		Generalized pustular psoriasis • Acrodermatitis continua suppurativa of Hallopeau	Uncertain significance (Apr 21, 2022)
2-113059363-C-G		not specified	Benign (Nov 12, 2023)
2-113059365-A-C		not specified	Benign (Nov 12, 2023)
2-113059444-C-T		Generalized pustular psoriasis • Autoinflammatory syndrome	Conflicting classifications of pathogenicity (Jul 01, 2024)
2-113059446-T-C		Generalized pustular psoriasis	Uncertain significance (Jun 13, 2022)
2-113059455-C-T		Generalized pustular psoriasis	Uncertain significance (May 17, 2022)
2-113059456-G-A		Generalized pustular psoriasis	Likely benign (Jan 31, 2024)
2-113059466-C-T		Generalized pustular psoriasis • Acrodermatitis continua suppurativa of Hallopeau	Uncertain significance (Mar 18, 2016)
2-113059467-G-A		Generalized pustular psoriasis • Autoinflammatory syndrome	Uncertain significance (Aug 25, 2020)
2-113059468-G-A		Generalized pustular psoriasis	Likely pathogenic (Dec 22, 2022)
2-113059470-G-A		Autoinflammatory syndrome	Uncertain significance (Dec 01, 2019)
2-113059472-G-A		Generalized pustular psoriasis	Uncertain significance (Jan 13, 2018)
2-113059473-T-C		Generalized pustular psoriasis	Uncertain significance (Jul 14, 2023)
2-113059474-G-A		Generalized pustular psoriasis	Likely benign (Dec 02, 2021)
2-113059482-C-A		Generalized pustular psoriasis	Likely benign (Jul 01, 2021)
2-113059482-C-G		Generalized pustular psoriasis	Likely benign (Sep 19, 2022)
2-113059604-C-T		not specified	Benign (Nov 12, 2023)
2-113060834-C-A		Generalized pustular psoriasis	Likely benign (Nov 27, 2023)
2-113060838-T-A		Generalized pustular psoriasis	Uncertain significance (Jan 12, 2018)
2-113060839-C-T		Generalized pustular psoriasis	Likely benign (Jan 09, 2024)
2-113060840-C-T		Generalized pustular psoriasis	Likely benign (Jan 04, 2024)
2-113060850-A-G		Generalized pustular psoriasis	Likely pathogenic (May 29, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IL36RN	protein_coding	protein_coding	ENST00000393200	4	6745

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.39e-8	0.0539	125730	0	18	125748	0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.427	100	88.7	1.13	0.00000535	996
Missense in Polyphen		37	33.921	1.0908		396
Synonymous	-0.101	41	40.2	1.02	0.00000271	318
Loss of Function	-0.858	10	7.47	1.34	4.08e-7	78

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000616	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.0000880	0.0000879
Middle Eastern	0.000163	0.000163
South Asian	0.000131	0.000131
Other	0.00	0.00

dbNSFP

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.
• Pathway: Signaling by Interleukins;Cytokine Signaling in Immune system;Immune System;Interleukin-36 pathway;Interleukin-1 family signaling (Consensus)

Recessive Scores

• pRec: 0.128

Intolerance Scores

• rvis_EVS: 0.04
• rvis_percentile_EVS: 56.92

Haploinsufficiency Scores

• pHI: 0.152
• hipred: N
• hipred_score: 0.170
• ghis: 0.531

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Il1f5
• Phenotype: homeostasis/metabolism phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; immune system phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: negative regulation of cytokine-mediated signaling pathway;inflammatory response;regulation of signaling receptor activity;cytokine-mediated signaling pathway;antifungal humoral response;neutrophil chemotaxis;negative regulation of interleukin-17 production;negative regulation of interleukin-6 production;positive regulation of interleukin-6 production;positive regulation of I-kappaB kinase/NF-kappaB signaling;innate immune response;positive regulation of JNK cascade;cellular response to lipopolysaccharide;negative regulation of interferon-gamma secretion
• Cellular component: extracellular region;extracellular space
• Molecular function: cytokine activity;interleukin-1 receptor binding;interleukin-1 receptor antagonist activity;protein binding