IL1RAP

Chr 3

interleukin 1 receptor accessory protein

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

NCBI Gene: 3556 ENSG00000196083 UniProt: Q9NPH3

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]

Research

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.44

LOEUF

GOF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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

Background carrier burden — how many people carry a rare variant somewhere in IL1RAP?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 70

922 rare PASS variants

Rare truncating (LoF)

1 in 1,800

110 rare PASS variants

Rare synonymous (reference)

1 in 76

413 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for IL1RAP. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 94	1 in 1,800
South Asian	~43k	1 in 49	1 in 870
Remaining (unassigned)	~30k	1 in 59	1 in 2,300
European (Finnish)	~27k	1 in 170	1 in 3,300
Admixed American	~22k	1 in 65	1 in 1,700
African / African American	~21k	1 in 78	1 in 1,900
East Asian	~20k	1 in 77	1 in 990
Ashkenazi Jewish	~13k	1 in 380	≈ 1 in 6,000
Middle Eastern	~2,884	1 in 70	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 8 of 10 coding exons well covered in gnomAD exomes; exons 6, 7 marginal. Genomes: all 10.? see exons ↓