IL1RAPL2

Chr X

interleukin 1 receptor accessory protein like 2

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

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.

Summary from RefSeq
Research Assistant →
0
Active trials
5
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.29
LOEUF· LoF intol.
Multiple*
Mechanism· predicted
Clinical SummaryIL1RAPL2
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.29LOEUF
pLI 0.984
Z-score 3.89
OE 0.09 (0.040.29)
Highly constrained

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

Missense Constraint
2.00Z-score
OE missense 0.64 (0.560.73)
157 obs / 245.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.09 (0.040.29)
00.351.4
Missense OE0.64 (0.560.73)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 2 / 21.4Missense obs/exp: 157 / 245.1Syn Z: 0.08
DN
0.4686th %ile
GOF
0.6541th %ile
LOF
0.55top 25%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). The Badonyi & Marsh model scores gain-of-function highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOFLOEUF 0.29
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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

IL1RAPL2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 results · since 2015Search PubMed ↗