IL1R1

protein-coding

interleukin 1 receptor type 1, the group of CD molecules|Interleukin receptors|TIR domain containing|I-set domain containing

Gene summary

This gene encodes a cytokine receptor that belongs to the interleukin-1 receptor family. The encoded protein is a receptor for interleukin-1 alpha, interleukin-1 beta, and interleukin-1 receptor antagonist. It is an important mediator involved in many cytokine-induced immune and inflammatory responses. This gene is located in a cluster of related cytokine receptor genes on chromosome 2q12. [provided by RefSeq, Dec 2013]

Previous symbols:

IL1R
IL1RA

MANE transcript

NM_000877.4

Inheritance

ClinVar variants

P:1U:42B:8

Top phenotype

Chronic recurrent multifocal osteomyelitis 3

gnomAD constraint

pLI —, LoF o/e 0.26

Max pathogenic AF

—

Genomic locus

chr2:102,064,544-102,179,874

External References & Databases

Ensembl (ENSG00000115594)

Transcript & Mutation Effects

hg38 • Region Span ~115.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

chronic recurrent multifocal osteomyelitis 3LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0958177

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Chronic recurrent multifocal osteomyelitis 3AD

Manifestation: Allergy/Immunology/Infectious

Intervention: Allergy/Immunology/Infectious

Rationale: The condition can manifest with early-onset sterile osteomyelitis and medical management (eg, with monoclonal antibody against IL1B) has been reported as beneficial

Refs: 37315560

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to IL1R1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 42

not providedTotal: 4

Chronic recurrent multifocal osteomyelitis 3Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000877.4. 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 clinvar	3 clinvar	1 clinvar	5
missense	1 clinvar		39 clinvar	3 clinvar		43
nonsense						0
start loss						0
frameshift					1 clinvar	1
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	1	0	42	6	2	51

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 109 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000877.4	RefSeq	NP_000868.1	10	MANE Select
ENST00000410023.6	Ensembl	ENSP00000386380.1	10	MANE Select
NM_001288706.2	RefSeq	NP_001275635.1	10	Standard
NM_001320978.2	RefSeq	NP_001307907.1	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Inflammatory mediator regulation of TRP channels - Homo sapiens (human)
HTLV-I infection - Homo sapiens (human)
Amoebiasis - Homo sapiens (human)
Fluid shear stress and atherosclerosis - Homo sapiens (human)
Th17 cell differentiation - Homo sapiens (human)

Biological Process

inflammatory response
immune response
cell surface receptor signaling pathway
cytokine-mediated signaling pathway
positive regulation of interferon-gamma production

Molecular Function

protease binding
transmembrane signaling receptor activity
interleukin-1 receptor activity
interleukin-1, type I, activating receptor activity
platelet-derived growth factor receptor binding

Cellular Component

extracellular region
plasma membrane
integral component of plasma membrane
external side of plasma membrane
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000410023
Coding exons: 10
Length: 115331
Individuals with no LoFs: 125724
Homozygous LoFs: 0
Heterozygous LoFs: 9
Defined: 125733
p: 0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.92	205	298	0.687	0.0000147	3744
Missense (PolyPhen)		49	102.51	0.47799		1346
Synonymous	-0.263	113	110	1.03	0.00000591	1044
Loss of Function	3.33	6	23.4	0.256	9.80e-7	337

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.00013	0.000099	rare
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000026	0.000026	rare
South Asian	0.000066	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Receptor for IL1A, IL1B and IL1RN. After binding to interleukin-1 associates with the coreceptor IL1RAP to form the high affinity interleukin-1 receptor complex which mediates interleukin-1-dependent activation of NF-kappa-B, MAPK and other pathways. Signaling involves the recruitment of adapter molecules such as TOLLIP, MYD88, and IRAK1 or IRAK2 via the respective TIR domains of the receptor/coreceptor subunits. Binds ligands with comparable affinity and binding of antagonist IL1RN prevents association with IL1RAP to form a signaling complex. Involved in IL1B-mediated costimulation of IFNG production from T-helper 1 (Th1) cells (PubMed:10653850). {ECO:0000269|PubMed:10653850, ECO:0000269|PubMed:10671496}.;

Recessive Scores

pRec: 0.601

Intolerance Scores

LoFtool: 0.685
RVIS EVS: 0.09
RVIS percentile EVS: 60.47

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: E
Indispensability score: 0.960

Gene Damage Prediction

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