IL1R1

Chr 2AD

interleukin 1 receptor type 1

Also known as: CD121A, CRMO3, D2S1473, IL-1R-alpha, IL-1RT1, IL1R, IL1RA, P80

NCBI Gene: 3554 ENSG00000115594 OMIM: 147810

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]

OMIM Research

OMIM ResearchGenerating clinical summary…

MultiplemechanismADLOEUF 0.511 OMIM phenotype

Clinical Summary— IL1R1

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 38 VUS of 56 total submissions

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Clinical Trials

3 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.51LOEUF

pLI 0.151

Z-score 3.33

OE 0.26 (0.14–0.51)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.92Z-score

OE missense 0.69 (0.61–0.77)

205 obs / 298.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.26 (0.14–0.51)

0≤0.351.4

Missense OE?0.69 (0.61–0.77)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 6 / 23.4Missense obs/exp: 205 / 298.4Syn Z: -0.26

This gene — mechanism propensity

0.6647th %ile

GOF

0.7029th %ile

LOF

0.2581th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

56 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

VUS38

Likely Benign5

Benign2

Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Synonymous	Total
Pathogenic	0	1	0	1
Likely Pathogenic	0	0	0	0
VUS	0	38	0	38
Likely Benign	0	3	2	5
Benign	1	0	1	2
Total	1	42	3	46

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

15 pathogenic / likely-pathogenic (of 22) ClinVar copy-number / structural variants overlap IL1R1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →