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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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IL1RAPL1
interleukin 1 receptor accessory protein like 1
Chromosome X Β· Xp21.3-p21.2
NCBI Gene: 11141Ensembl: ENSG00000169306.11HGNC: HGNC:5996UniProt: Q9NZN1
50PubMed Papers
21Diseases
0Drugs
31Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedReceptor
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
interleukin-1 bindingprotein bindingnegative regulation of exocytosisregulation of postsynapse organizationintellectual disability, X-linked 21X-linked non-syndromic intellectual disabilitynon-syndromic X-linked intellectual disabilityIntellectual disability
✦AI Summary

IL1RAPL1 is an X-linked synaptic adhesion molecule localized at the postsynaptic membrane that plays critical roles in neuronal development and synapse formation 1. The protein regulates dendrite morphology through its extracellular domain, with IL1RAPL1 loss-of-function mutations resulting in increased dendritic branching and simplified neuronal arborization 2. IL1RAPL1 mediates IL-1Ξ² activity on dendrite formation 2 and regulates glutamatergic synapse formation and stabilization through the Mcf2l-RhoA-ROCK signaling pathway, affecting AMPA receptor trafficking 3. Mutations and deletions of IL1RAPL1 are associated with X-linked intellectual disability (ID), autism spectrum disorder (ASD), and dysmorphic features 45. Genetic variation in IL1RAPL1 correlates with cognitive abilities, particularly memory and concentration, with the protein highly expressed in hippocampus and other memory-associated brain regions 6. Rare variants in IL1RAPL1 have also been identified in patients with treatment-resistant schizophrenia 7. These findings establish IL1RAPL1 as essential for normal cognitive development through regulation of dendritic architecture and synaptic plasticity.

Sources cited
1
IL1RAPL1 is a postsynaptic synaptic adhesion molecule; mutations cause ID and ASD
PMID: 30548231
2
IL1RAPL1 regulates dendrite morphology via extracellular domain; mediates IL-1Ξ² activity on dendrites
PMID: 28576939
3
IL1RAPL1 regulates glutamatergic synapse formation through Mcf2l-RhoA-ROCK pathway and AMPA receptor trafficking
PMID: 23785489
4
IL1RAPL1 deletions cause X-linked ID with dysmorphic features; highly expressed in hippocampus
PMID: 21933724
5
Intragenic IL1RAPL1 deletions are associated with X-linked mental retardation
PMID: 21271657
6
IL1RAPL1 genetic variants correlate with cognitive ability, memory, and concentration; expressed in memory-associated brain regions
PMID: 18467032
7
Rare IL1RAPL1 variants identified in treatment-resistant schizophrenia
PMID: 36318984
Disease Associationsβ“˜21
intellectual disability, X-linked 21Open Targets
0.73Strong
X-linked non-syndromic intellectual disabilityOpen Targets
0.66Moderate
non-syndromic X-linked intellectual disabilityOpen Targets
0.48Moderate
Intellectual disabilityOpen Targets
0.41Moderate
genetic disorderOpen Targets
0.34Weak
schizophreniaOpen Targets
0.30Weak
severe acute respiratory syndromeOpen Targets
0.28Weak
VitiligoOpen Targets
0.26Weak
COVID-19Open Targets
0.25Weak
ventral herniaOpen Targets
0.21Weak
developmental disorder of mental healthOpen Targets
0.12Weak
neoplasmOpen Targets
0.08Suggestive
breast neoplasmOpen Targets
0.07Suggestive
chronic rhinosinusitis with nasal polypsOpen Targets
0.05Suggestive
Nasal Cavity PolypOpen Targets
0.03Suggestive
diffuse large B-cell lymphomaOpen Targets
0.03Suggestive
breast cancerOpen Targets
0.03Suggestive
experimental autoimmune encephalomyelitisOpen Targets
0.03Suggestive
Abnormal sperm morphologyOpen Targets
0.02Suggestive
medulloblastomaOpen Targets
0.02Suggestive
Intellectual developmental disorder, X-linked 21UniProt
Pathogenic Variants31
NM_014271.4(IL1RAPL1):c.148C>T (p.Arg50Ter)Pathogenic
Intellectual disability, X-linked 21|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 50
NM_014271.4(IL1RAPL1):c.1054C>T (p.Arg352Ter)Pathogenic
not provided|Intellectual disability, X-linked 21
β˜…β˜…β˜†β˜†2023β†’ Residue 352
NM_014271.4(IL1RAPL1):c.660T>A (p.Tyr220Ter)Pathogenic
Inborn genetic diseases
β˜…β˜†β˜†β˜†2025β†’ Residue 220
NM_014271.4(IL1RAPL1):c.1670dup (p.Tyr557Ter)Likely pathogenic
Intellectual disability, X-linked 21
β˜…β˜†β˜†β˜†2025β†’ Residue 557
NM_014271.4(IL1RAPL1):c.1027C>T (p.Arg343Ter)Pathogenic
Intellectual disability, X-linked 21
β˜…β˜†β˜†β˜†2025β†’ Residue 343
NM_014271.4(IL1RAPL1):c.230_243del (p.Tyr77fs)Likely pathogenic
Intellectual disability, X-linked 21
β˜…β˜†β˜†β˜†2025β†’ Residue 77
NM_014271.4(IL1RAPL1):c.1118_1173dup (p.His392delinsValTrpTer)Likely pathogenic
Intellectual disability, X-linked 21
β˜…β˜†β˜†β˜†2025β†’ Residue 392
NM_014271.4(IL1RAPL1):c.1743_1744del (p.Phe581fs)Likely pathogenic
Intellectual disability, X-linked 21
β˜…β˜†β˜†β˜†2024β†’ Residue 581
NM_014271.4(IL1RAPL1):c.849G>C (p.Trp283Cys)Likely pathogenic
Intellectual disability, X-linked 21
β˜…β˜†β˜†β˜†2024β†’ Residue 283
NM_014271.4(IL1RAPL1):c.1133_1136dup (p.Cys380fs)Likely pathogenic
Intellectual disability, X-linked 21
β˜…β˜†β˜†β˜†2024β†’ Residue 380
NM_014271.4(IL1RAPL1):c.82+2T>CLikely pathogenic
Intellectual disability, X-linked 21
β˜…β˜†β˜†β˜†2024
NM_014271.4(IL1RAPL1):c.1460G>A (p.Trp487Ter)Likely pathogenic
Intellectual disability, X-linked 21
β˜…β˜†β˜†β˜†2023β†’ Residue 487
NM_014271.4(IL1RAPL1):c.366_379delinsGTAACAAAG (p.Asn122_Met127delinsLysTer)Likely pathogenic
Intellectual disability, X-linked 21
β˜…β˜†β˜†β˜†2023β†’ Residue 122
NM_014271.4(IL1RAPL1):c.555C>A (p.Cys185Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2022β†’ Residue 185
NM_014271.4(IL1RAPL1):c.375C>G (p.Tyr125Ter)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2022β†’ Residue 125
NM_014271.4(IL1RAPL1):c.1354_1355del (p.Asp452fs)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2022β†’ Residue 452
NM_014271.4(IL1RAPL1):c.1227dup (p.Ser410fs)Likely pathogenic
Intellectual disability, X-linked 21
β˜…β˜†β˜†β˜†2021β†’ Residue 410
NM_014271.4(IL1RAPL1):c.1075del (p.Glu359fs)Likely pathogenic
Intellectual disability, X-linked 21
β˜…β˜†β˜†β˜†2021β†’ Residue 359
NM_014271.4(IL1RAPL1):c.1372+1G>TLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2021
NM_014271.4(IL1RAPL1):c.1046T>C (p.Leu349Pro)Likely pathogenic
See cases
β˜…β˜†β˜†β˜†2021β†’ Residue 349
View on ClinVar β†—
Related Genes
NCS1Protein interaction98%IL1F10Protein interaction96%TUSC3Protein interaction90%DLG4Protein interaction86%MAPK8Protein interaction77%PTPRSProtein interaction77%
Tissue Expression6 tissues
Brain
100%
Heart
33%
Ovary
4%
Bone Marrow
1%
Liver
0%
Lung
0%
Gene Interaction Network
Click a node to explore
IL1RAPL1NCS1IL1F10TUSC3DLG4MAPK8PTPRS
PROTEIN STRUCTURE
Preparing viewer…
PDB4M92 Β· 1.60 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.16Highly Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.06 [0.03–0.16]
RankingsWhere IL1RAPL1 stands among ~20K protein-coding genes
  • #8,827of 20,598
    Most Researched50
  • #1,785of 5,498
    Most Pathogenic Variants31
  • #257of 17,882
    Most Constrained (LOEUF)0.16 Β· top 5%
Genes detectedIL1RAPL1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
The Synaptic and Neuronal Functions of the X-Linked Intellectual Disability Protein Interleukin-1 Receptor Accessory Protein Like 1 (IL1RAPL1).
PMID: 30548231
Dev Neurobiol Β· 2019
1.00
2
A study on the correlation between IL1RAPL1 and human cognitive ability.
PMID: 18467032
Neurosci Lett Β· 2008
0.90
3
IL1RAPL1 gene deletion as a cause of X-linked intellectual disability and dysmorphic features.
PMID: 21933724
Eur J Med Genet Β· 2012
0.80
4
Intragenic deletions of IL1RAPL1: Report of two cases and review of the literature.
PMID: 21271657
Am J Med Genet A Β· 2011
0.70
5
The X-Linked Intellectual Disability Protein IL1RAPL1 Regulates Dendrite Complexity.
PMID: 28576939
J Neurosci Β· 2017
0.60