IL1RN

interleukin 1 receptor antagonist, the group of Interleukins

Basic information

Region (hg38): 2:113099315-113134016

Links

ENSG00000136689 ∙ NCBI:3557 ∙ OMIM:147679 ∙ HGNC:6000 ∙ Uniprot:P18510 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• sterile multifocal osteomyelitis with periostitis and pustulosis (Strong), mode of inheritance: AR
• sterile multifocal osteomyelitis with periostitis and pustulosis (Moderate), mode of inheritance: AR
• sterile multifocal osteomyelitis with periostitis and pustulosis (Supportive), mode of inheritance: AR
• sterile multifocal osteomyelitis with periostitis and pustulosis (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Chronic recurrent multifocal osteomyelitis 2, with periostitis and pustulosis	AR	Allergy/Immunology/Infectious	Individuals may present in infancy with manifestations including rash, pain, and oral lesions, which may advance to more severe findings such as progressive skin lesions, vasculitis, skeletal lesions, pulmonary disease, and severe inflammatory response syndrome, and medical treatment (eg, with anakinra) has been described as effective	Allergy/Immunology/Infectious; Dermatologic	19494218; 19494219

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IL1RN gene.

• Sterile multifocal osteomyelitis with periostitis and pustulosis (6 variants)
• not provided (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IL1RN 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			3	36	2	41
missense			57	2		59
nonsense	4	1				5
start loss						0
frameshift	1	2	3			6
inframe indel	1					1
splice donor/acceptor (+/-2bp)		1				1
splice region			4	2	2	8
non coding			22	21	36	79
Total	6	4	85	59	38

Highest pathogenic variant AF is 0.00000657

Variants in IL1RN

This is a list of pathogenic ClinVar variants found in the IL1RN region.

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

Position	Type	Phenotype	Significance	ClinVar
2-113117640-A-C			Benign (Jun 19, 2021)
2-113117851-G-A			Benign (May 12, 2021)
2-113117924-C-G		Autoinflammatory syndrome	Uncertain significance (Jan 06, 2017)
2-113117932-G-A		Sterile multifocal osteomyelitis with periostitis and pustulosis • not specified	Benign (Nov 12, 2023)
2-113117936-G-A		Sterile multifocal osteomyelitis with periostitis and pustulosis	Likely benign (Jan 12, 2018)
2-113117948-A-G		Sterile multifocal osteomyelitis with periostitis and pustulosis	Uncertain significance (Jan 13, 2018)
2-113117988-A-G		Sterile multifocal osteomyelitis with periostitis and pustulosis • not specified	Benign (Nov 12, 2023)
2-113118007-G-C		Sterile multifocal osteomyelitis with periostitis and pustulosis • not specified	Benign (Nov 12, 2023)
2-113118022-G-A		Sterile multifocal osteomyelitis with periostitis and pustulosis	Uncertain significance (Jan 28, 2022)
2-113118022-G-T		Sterile multifocal osteomyelitis with periostitis and pustulosis	Uncertain significance (Mar 20, 2022)
2-113118030-T-C		Autoinflammatory syndrome	Likely pathogenic (Sep 17, 2020)
2-113118032-A-G		Sterile multifocal osteomyelitis with periostitis and pustulosis	Uncertain significance (May 14, 2022)
2-113118039-T-C		Sterile multifocal osteomyelitis with periostitis and pustulosis	Likely benign (Oct 01, 2022)
2-113118042-A-C		Sterile multifocal osteomyelitis with periostitis and pustulosis	Likely benign (Jan 29, 2024)
2-113118045-C-CT		Sterile multifocal osteomyelitis with periostitis and pustulosis	Likely benign (Jul 12, 2023)
2-113118054-T-C		not specified	Benign (Nov 12, 2023)
2-113118176-C-G			Benign (May 12, 2021)
2-113118196-A-G			Benign (May 12, 2021)
2-113119836-G-T			Benign (Jun 19, 2021)
2-113119918-G-T			Benign (Nov 12, 2018)
2-113119961-G-C		not specified	Benign (Jan 24, 2024)
2-113120049-C-T		Sterile multifocal osteomyelitis with periostitis and pustulosis	Likely benign (Dec 20, 2023)
2-113120050-A-C		Sterile multifocal osteomyelitis with periostitis and pustulosis	Likely benign (Feb 20, 2021)
2-113120071-T-G		Sterile multifocal osteomyelitis with periostitis and pustulosis	Uncertain significance (Oct 20, 2021)
2-113120073-G-T		Sterile multifocal osteomyelitis with periostitis and pustulosis	Uncertain significance (Nov 27, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IL1RN	protein_coding	protein_coding	ENST00000259206	6	26803

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0309	0.930	125725	0	23	125748	0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.00812	100	100	0.998	0.00000561	1187
Missense in Polyphen		28	34.166	0.81952		438
Synonymous	-0.797	43	36.8	1.17	0.00000235	326
Loss of Function	1.78	4	10.1	0.397	5.15e-7	122

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.000544	0.000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000106	0.000105
Middle Eastern	0.000544	0.000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Inhibits the activity of interleukin-1 by binding to receptor IL1R1 and preventing its association with the coreceptor IL1RAP for signaling. Has no interleukin-1 like activity. Binds functional interleukin-1 receptor IL1R1 with greater affinity than decoy receptor IL1R2; however, the physiological relevance of the latter association is unsure. {ECO:0000269|PubMed:7775431}.
• Disease: DISEASE: Interleukin 1 receptor antagonist deficiency (DIRA) [MIM:612852]: A rare autoinflammatory disease of skin and bone resulting in sterile multifocal osteomyelitis, periostitis, and pustulosis from birth. The term autoinflammatory disease describes a group of disorders characterized by attacks of seemingly unprovoked inflammation without significant levels of autoantibodies and autoreactive T-cells. {ECO:0000269|PubMed:19494218}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Leptin signaling pathway;JAK-STAT;Interleukin-10 signaling;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;Signaling by Interleukins;signal transduction through il1r;Cytokine Signaling in Immune system;Interleukin-1 signaling;Immune System;IL1;IL1-mediated signaling events;Interleukin-1 family signaling (Consensus)

Recessive Scores

• pRec: 0.711

Intolerance Scores

• loftool: 0.375
• rvis_EVS: -0.69
• rvis_percentile_EVS: 14.97

Haploinsufficiency Scores

• pHI: 0.0939
• hipred: N
• hipred_score: 0.145
• ghis: 0.515

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.838

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Il1rn
• Phenotype: skeleton phenotype; immune system phenotype; 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; 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); 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); reproductive system phenotype; homeostasis/metabolism phenotype; cellular phenotype

Gene ontology

• Biological process: lipid metabolic process;inflammatory response;immune response;regulation of signaling receptor activity;cytokine-mediated signaling pathway;insulin secretion;neutrophil chemotaxis;positive regulation of interleukin-6 production;negative regulation of heterotypic cell-cell adhesion;positive regulation of I-kappaB kinase/NF-kappaB signaling;positive regulation of JNK cascade;response to glucocorticoid;interleukin-1-mediated signaling pathway;cellular response to lipopolysaccharide;negative regulation of interleukin-1-mediated signaling pathway
• Cellular component: extracellular space;cytoplasm;plasma membrane;extracellular exosome
• Molecular function: cytokine activity;interleukin-1 receptor binding;interleukin-1, type I receptor binding;interleukin-1, type II receptor binding;interleukin-1 receptor antagonist activity;protein binding;interleukin-1 type I receptor antagonist activity;interleukin-1 type II receptor antagonist activity