IL1RAPL2

Chr X

interleukin 1 receptor accessory protein like 2

Also known as: IL-1R9, IL1R9, IL1RAPL-2, TIGIRR-1

NCBI Gene: 26280 ENSG00000189108 UniProt: Q9NP60 OMIM: 300277

The encoded protein is a member of the interleukin 1 receptor family, most closely related to interleukin 1 receptor accessory protein-like 1. Mutations cause X-linked non-syndromic intellectual disability. The gene is highly constrained against loss-of-function variants (pLI 0.98, LOEUF 0.29), indicating intolerance to protein-disrupting mutations.

OMIM ResearchSummary from RefSeq

The protein encoded by this gene is a member of the interleukin 1 receptor family. This protein is similar to the interleukin 1 accessory proteins, and is most closely related to interleukin 1 receptor accessory protein-like 1 (IL1RAPL1). This gene and IL1RAPL1 are located at a region on chromosome X that is associated with X-linked non-syndromic cognitive disability. [provided by RefSeq, Jul 2008]

OMIM 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

0.29

LOEUF· LoF intol.

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — X-linked: males carry a single copy

LoF Constraint?

0.29LOEUF

pLI 0.984

Z-score 3.89

OE 0.09 (0.04–0.29)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

2.00Z-score

OE missense 0.64 (0.56–0.73)

157 obs / 245.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.09 (0.04–0.29)

0≤0.351.4

Missense OE?0.64 (0.56–0.73)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 2 / 21.4Missense obs/exp: 157 / 245.1Syn Z: 0.08

Background carrier burden — how many people carry a rare variant somewhere in IL1RAPL2?

gnomAD v4 · ~732k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 230

427 rare PASS variants

Rare truncating (LoF)

1 in 12,000

15 rare PASS variants

Rare synonymous (reference)

1 in 560

199 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for IL1RAPL2. 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)	~561k	1 in 250	1 in 22,000
South Asian	~36k	1 in 280	≈ 1 in 33,000
Remaining (unassigned)	~31k	1 in 170	none seen
European (Finnish)	~27k	1 in 340	1 in 4,100
Admixed American	~23k	1 in 190	none seen
African / African American	~21k	1 in 150	≈ 1 in 10,000
East Asian	~20k	1 in 190	1 in 2,400
Ashkenazi Jewish	~13k	1 in 580	≈ 1 in 13,000
Middle Eastern	~2,758	1 in 200	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.