IL1RAP

Chr 3

interleukin 1 receptor accessory protein

Also known as: C3orf13, IL-1RAcP, IL1R3

NCBI Gene: 3556 ENSG00000196083 UniProt: Q9NPH3 OMIM: 602626

This gene encodes a component of the interleukin 1 receptor complex, which initiates signalling events that result in the activation of interleukin 1-responsive genes. Alternative splicing of this gene results in membrane-bound and soluble isoforms differing in their C-terminus. The ratio of soluble to membrane-bound forms increases during acute-phase induction or stress. [provided by RefSeq, Jul 2018]

OMIM Research

OMIM ResearchGenerating clinical summary…

GOFmechanismLOEUF 0.44

Clinical Summary— IL1RAP

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.

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ClinVar Variants

31 VUS of 62 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?

0.44LOEUF

pLI 0.258

Z-score 3.85

OE 0.24 (0.13–0.44)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.83Z-score

OE missense 0.74 (0.67–0.81)

277 obs / 376.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.24 (0.13–0.44)

0≤0.351.4

Missense OE?0.74 (0.67–0.81)

0≤0.61.4

Synonymous OE?0.88

0≤1.21.6

LoF obs/exp: 7 / 29.6Missense obs/exp: 277 / 376.7Syn Z: 1.05

This gene — mechanism propensity

0.6163th %ile

GOF

0.7029th %ile

LOF

0.3259th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction 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

62 submitted variants in ClinVar

ClinVar

Classification Summary

VUS31

Likely Benign4

Benign5

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	31	0	31
Likely Benign	1	3	4
Benign	1	4	5
Total	33	7	40

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

View in ClinVar →

39 pathogenic / likely-pathogenic (of 45) ClinVar copy-number / structural variants overlap IL1RAP — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →