IL1RAPL1

Chr XXLR

interleukin 1 receptor accessory protein like 1

Also known as: IL-1-RAPL-1, IL-1RAPL-1, IL1R8, IL1RAPL, IL1RAPL-1, MRX10, MRX21, MRX34

The protein functions as a synaptic organizer that regulates presynaptic differentiation by inhibiting N-type voltage-gated calcium channels and promotes neurite outgrowth and dendritic spine formation through trans-synaptic binding to protein tyrosine phosphatases. Mutations cause X-linked intellectual developmental disorder with inheritance following an X-linked recessive pattern. The gene is highly constrained against loss-of-function variants and shows high expression in postnatal hippocampal memory structures, consistent with its role in learning and memory processes.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismXLRLOEUF 0.201 OMIM phenotype
Clinical SummaryIL1RAPL1
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Gene-Disease Validity (ClinGen)
non-syndromic X-linked intellectual disability · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). 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
0.20LOEUF
pLI 0.999
Z-score 4.36
OE 0.04 (0.010.20)
Highly constrained

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

Missense Constraint
2.77Z-score
OE missense 0.52 (0.460.60)
140 obs / 267.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.04 (0.010.20)
00.351.4
Missense OE0.52 (0.460.60)
00.61.4
Synonymous OE1.00
01.21.6
LoF obs/exp: 1 / 24.1Missense obs/exp: 140 / 267.4Syn Z: -0.01
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveIL1RAPL1-related intellectual developmental disorderLOFXLR
DN
0.3196th %ile
GOF
0.5563th %ile
LOF
0.72top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.20

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

IL1RAPL1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

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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