IL1RAPL1interleukin 1 receptor accessory protein-like 1
Autism Reports / Total Reports
11 / 28Rare Variants / Common Variants
31 / 0Aliases
IL1RAPL1, IL1R8, MRX21, MRX34, OPHN4, IL1RAPL, TIGIRR-2Associated Syndromes
-Chromosome Band
Xp21.3-p21.2Associated Disorders
DD/NDD, ID, ASD, EPSRelevance to Autism
Studies have found rare mutations in the IL1RAPL1 gene that are associated with autism (e.g. Bhat et al., 2008) as well as with developmental delay and intellectual disability (Mikhail et al., 2011).
Molecular Function
This protein may regulate calcium-dependent exocytosis.
External Links
SFARI Genomic Platforms
Reports related to IL1RAPL1 (28 Reports)
| # | Type | Title | Author, Year | Autism Report | Associated Disorders |
|---|---|---|---|---|---|
| 1 | Highly Cited | IL1 receptor accessory protein like, a protein involved in X-linked mental retardation, interacts with Neuronal Calcium Sensor-1 and regulates exocytosis | Bahi N , et al. (2003) | No | - |
| 2 | Recent Recommendation | IL1-receptor accessory protein-like 1 (IL1RAPL1), a protein involved in cognitive functions, regulates N-type Ca2+-channel and neurite elongation | Gambino F , et al. (2007) | No | - |
| 3 | Primary | Disruption of the IL1RAPL1 gene associated with a pericentromeric inversion of the X chromosome in a patient with mental retardation and autism | Bhat SS , et al. (2007) | Yes | - |
| 4 | Recent Recommendation | A study on the correlation between IL1RAPL1 and human cognitive ability | Gao X , et al. (2008) | No | - |
| 5 | Support | Mutations in the calcium-related gene IL1RAPL1 are associated with autism | Piton A , et al. (2008) | Yes | MR |
| 6 | Recent Recommendation | A postsynaptic signaling pathway that may account for the cognitive defect due to IL1RAPL1 mutation | Pavlowsky A , et al. (2010) | No | - |
| 7 | Support | Functional impact of global rare copy number variation in autism spectrum disorders | Pinto D , et al. (2010) | Yes | - |
| 8 | Support | Direct measure of the de novo mutation rate in autism and schizophrenia cohorts | Awadalla P , et al. (2010) | Yes | - |
| 9 | Recent Recommendation | Clinically relevant single gene or intragenic deletions encompassing critical neurodevelopmental genes in patients with developmental delay, mental retardation, and/or autism spectrum disorders | Mikhail FM , et al. (2011) | No | ID |
| 10 | Support | A discovery resource of rare copy number variations in individuals with autism spectrum disorder | Prasad A , et al. (2013) | Yes | - |
| 11 | Support | Intragenic ILRAPL1 deletion in a male patient with intellectual disability, mild dysmorphic signs, deafness, and behavioral problems | Barone C , et al. (2013) | No | ASD |
| 12 | Recent Recommendation | IL1RAPL1 associated with mental retardation and autism regulates the formation and stabilization of glutamatergic synapses of cortical neurons through RhoA signaling pathway | Hayashi T , et al. (2013) | No | - |
| 13 | Support | Somatic mosaicism detected by exon-targeted, high-resolution aCGH in 10,362 consecutive cases | Pham J , et al. (2014) | Yes | - |
| 14 | Support | Etiological yield of SNP microarrays in idiopathic intellectual disability | Utine GE , et al. (2014) | No | ASD or autistic features, epilepsy |
| 15 | Support | Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing | Redin C , et al. (2014) | No | - |
| 16 | Recent Recommendation | Novel IL1RAPL1 mutations associated with intellectual disability impair synaptogenesis | Ramos-Brossier M , et al. (2014) | No | DD |
| 17 | Support | Whole exome sequencing in females with autism implicates novel and candidate genes | Butler MG , et al. (2015) | Yes | - |
| 18 | Support | X-linked intellectual disability related genes disrupted by balanced X-autosome translocations | Moyss-Oliveira M , et al. (2015) | No | - |
| 19 | Support | The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies | Redin C , et al. (2016) | No | - |
| 20 | Recent Recommendation | The X-Linked Intellectual Disability Protein IL1RAPL1 Regulates Dendrite Complexity | Montani C , et al. (2017) | No | - |
| 21 | Support | Genetic Diagnostic Evaluation of Trio-Based Whole Exome Sequencing Among Children With Diagnosed or Suspected Autism Spectrum Disorder | Du X , et al. (2018) | Yes | DD/ID, epilepsy/seizures |
| 22 | Support | Breakpoint mapping at nucleotide resolution in X-autosome balanced translocations associated with clinical phenotypes | Moyss-Oliveira M , et al. (2019) | No | - |
| 23 | Recent Recommendation | Genome-wide detection of tandem DNA repeats that are expanded in autism | Trost B et al. (2020) | Yes | - |
| 24 | Support | - | Rasheed M et al. (2021) | No | - |
| 25 | Support | - | N.Y.) (07/2) | No | - |
| 26 | Support | - | Miyake N et al. (2023) | Yes | - |
| 27 | Support | - | Spataro N et al. (2023) | No | Autistic features |
| 28 | Recent recommendation | - | Taehwan Shin et al. (2024) | Yes | - |
Rare Variants (31)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| - | - | translocation | De novo | - | - | 27841880 | Redin C , et al. (2016) | |
| - | - | copy_number_gain | De novo | - | - | 24508361 | Utine GE , et al. (2014) | |
| - | - | inversion | Familial | Maternal | - | 18005360 | Bhat SS , et al. (2007) | |
| - | - | minisatellite | Unknown | - | Unknown | 32717741 | Trost B et al. (2020) | |
| - | - | copy_number_loss | Unknown | - | Unknown | 24398791 | Pham J , et al. (2014) | |
| - | - | translocation | De novo | - | - | 26290131 | Moyss-Oliveira M , et al. (2015) | |
| - | - | translocation | De novo | - | - | 30700833 | Moyss-Oliveira M , et al. (2019) | |
| c.263C>T | p.Pro88Leu | missense_variant | De novo | - | - | 35901164 | N.Y.) (07/2) | |
| - | - | copy_number_gain | Unknown | - | Unknown | 23275889 | Prasad A , et al. (2013) | |
| - | - | copy_number_loss | Unknown | - | Unknown | 23275889 | Prasad A , et al. (2013) | |
| - | - | copy_number_loss | De novo | - | Simplex | 23613341 | Barone C , et al. (2013) | |
| - | - | copy_number_loss | Familial | Maternal | - | 22031302 | Mikhail FM , et al. (2011) | |
| - | - | copy_number_loss | Familial | Maternal | Multiplex | 18801879 | Piton A , et al. (2008) | |
| - | - | copy_number_gain | Familial | Maternal | Multiplex | 20531469 | Pinto D , et al. (2010) | |
| - | - | copy_number_loss | Familial | Maternal | Multiplex | 20531469 | Pinto D , et al. (2010) | |
| c.1489C>T | p.Arg497Ter | stop_gained | De novo | - | Simplex | 30555518 | Du X , et al. (2018) | |
| - | - | copy_number_loss | Familial | Maternal | Multiplex | 34452636 | Rasheed M et al. (2021) | |
| c.779-65850del | - | frameshift_variant | De novo | - | - | 20797689 | Awadalla P , et al. (2010) | |
| c.1046T>C | p.Leu349Pro | missense_variant | De novo | - | - | 36980980 | Spataro N et al. (2023) | |
| c.1136A>G | p.Lys379Arg | missense_variant | Familial | Maternal | - | 18801879 | Piton A , et al. (2008) | |
| c.1854A>T | p.Gln618His | missense_variant | Familial | Maternal | - | 18801879 | Piton A , et al. (2008) | |
| A>G | - | intergenic_variant | Familial | Both parents | Unknown | 39019033 | Taehwan Shin et al. (2024) | |
| G>A | - | intergenic_variant | Familial | Both parents | Unknown | 39019033 | Taehwan Shin et al. (2024) | |
| c.1433C>A | p.Thr478Asn | missense_variant | Unknown | - | Multiplex | 25574603 | Butler MG , et al. (2015) | |
| c.83-25209G>A | - | intron_variant | Familial | Both parents | Unknown | 39019033 | Taehwan Shin et al. (2024) | |
| c.1918C>T | p.Leu640Phe | missense_variant | Familial | Maternal | Simplex | 36973392 | Miyake N et al. (2023) | |
| c.1730del | p.Glu577GlyfsTer24 | frameshift_variant | De novo | - | Simplex | 18801879 | Piton A , et al. (2008) | |
| c.91T>C | p.Cys31Arg | missense_variant | Familial | Maternal | Multiplex | 25305082 | Ramos-Brossier M , et al. (2014) | |
| c.894_903del | p.Trp299ThrfsTer18 | frameshift_variant | Familial | Maternal | Multiplex | 25167861 | Redin C , et al. (2014) | |
| c.703+99897_778+59920del | p.Ala235_Leu259del | copy_number_loss | Familial | Maternal | Multiplex | 25305082 | Ramos-Brossier M , et al. (2014) | |
| c.1213_1287del | p.Tyr405_Phe429del | copy_number_loss | Familial | Maternal and paternal | Multi-generational | 25305082 | Ramos-Brossier M , et al. (2014) |
Common Variants
No common variants reported.
SFARI Gene score
2
Strong Candidate
Studies have identified rare sequence variants in the IL1RAPL1 gene with autism (e.g. Bhat et al., 2008).
Score Delta: Score remained at 2
criteria met
See SFARI Gene'scoring criteriaWe considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.
4/1/2022
3
2
Decreased from 3 to 2
Description
Studies have identified rare sequence variants in the IL1RAPL1 gene with autism (e.g. Bhat et al., 2008).
7/1/2020
3
3
Decreased from 3 to 3
Description
Studies have identified rare sequence variants in the IL1RAPL1 gene with autism (e.g. Bhat et al., 2008).
10/1/2019
4
3
Decreased from 4 to 3
New Scoring Scheme
Description
Studies have identified rare sequence variants in the IL1RAPL1 gene with autism (e.g. Bhat et al., 2008).
Reports Added
[New Scoring Scheme]1/1/2019
4
4
Decreased from 4 to 4
Description
Studies have identified rare sequence variants in the IL1RAPL1 gene with autism (e.g. Bhat et al., 2008).
4/1/2017
4
4
Decreased from 4 to 4
Description
Studies have identified rare sequence variants in the IL1RAPL1 gene with autism (e.g. Bhat et al., 2008).
Reports Added
[Disruption of the IL1RAPL1 gene associated with a pericentromeric inversion of the X chromosome in a patient with mental retardation and autism.2007] [Mutations in the calcium-related gene IL1RAPL1 are associated with autism.2008] [Functional impact of global rare copy number variation in autism spectrum disorders.2010] [Direct measure of the de novo mutation rate in autism and schizophrenia cohorts.2010] [A discovery resource of rare copy number variations in individuals with autism spectrum disorder.2013] [Whole exome sequencing in females with autism implicates novel and candidate genes.2015] [Somatic mosaicism detected by exon-targeted, high-resolution aCGH in 10,362 consecutive cases.2014] [Clinically relevant single gene or intragenic deletions encompassing critical neurodevelopmental genes in patients with developmental delay, mental...2011] [Etiological yield of SNP microarrays in idiopathic intellectual disability.2014] [Intragenic ILRAPL1 deletion in a male patient with intellectual disability, mild dysmorphic signs, deafness, and behavioral problems.2013] [Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing.2014] [Novel IL1RAPL1 mutations associated with intellectual disability impair synaptogenesis.2014] [IL1 receptor accessory protein like, a protein involved in X-linked mental retardation, interacts with Neuronal Calcium Sensor-1 and regulates exoc...2003] [IL1-receptor accessory protein-like 1 (IL1RAPL1), a protein involved in cognitive functions, regulates N-type Ca2+channel and neurite elongation.2007] [A study on the correlation between IL1RAPL1 and human cognitive ability.2008] [A postsynaptic signaling pathway that may account for the cognitive defect due to IL1RAPL1 mutation.2010] [IL1RAPL1 associated with mental retardation and autism regulates the formation and stabilization of glutamatergic synapses of cortical neurons thro...2013] [X-linked intellectual disability related genes disrupted by balanced X-autosome translocations.2015] [The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies.2016] [The X-linked intellectual disability protein IL1RAPL1 regulates dendrite complexity.2017]10/1/2016
4
4
Decreased from 4 to 4
Description
Studies have identified rare sequence variants in the IL1RAPL1 gene with autism (e.g. Bhat et al., 2008).
1/1/2016
4
4
Decreased from 4 to 4
Description
Studies have identified rare sequence variants in the IL1RAPL1 gene with autism (e.g. Bhat et al., 2008).
Reports Added
[Disruption of the IL1RAPL1 gene associated with a pericentromeric inversion of the X chromosome in a patient with mental retardation and autism.2007] [Mutations in the calcium-related gene IL1RAPL1 are associated with autism.2008] [Functional impact of global rare copy number variation in autism spectrum disorders.2010] [Direct measure of the de novo mutation rate in autism and schizophrenia cohorts.2010] [A discovery resource of rare copy number variations in individuals with autism spectrum disorder.2013] [Whole exome sequencing in females with autism implicates novel and candidate genes.2015] [Somatic mosaicism detected by exon-targeted, high-resolution aCGH in 10,362 consecutive cases.2014] [Clinically relevant single gene or intragenic deletions encompassing critical neurodevelopmental genes in patients with developmental delay, mental...2011] [Etiological yield of SNP microarrays in idiopathic intellectual disability.2014] [Intragenic ILRAPL1 deletion in a male patient with intellectual disability, mild dysmorphic signs, deafness, and behavioral problems.2013] [Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing.2014] [Novel IL1RAPL1 mutations associated with intellectual disability impair synaptogenesis.2014] [IL1 receptor accessory protein like, a protein involved in X-linked mental retardation, interacts with Neuronal Calcium Sensor-1 and regulates exoc...2003] [IL1-receptor accessory protein-like 1 (IL1RAPL1), a protein involved in cognitive functions, regulates N-type Ca2+channel and neurite elongation.2007] [A study on the correlation between IL1RAPL1 and human cognitive ability.2008] [A postsynaptic signaling pathway that may account for the cognitive defect due to IL1RAPL1 mutation.2010] [IL1RAPL1 associated with mental retardation and autism regulates the formation and stabilization of glutamatergic synapses of cortical neurons thro...2013] [X-linked intellectual disability related genes disrupted by balanced X-autosome translocations.2015]1/1/2015
4
4
Decreased from 4 to 4
Description
Studies have identified rare sequence variants in the IL1RAPL1 gene with autism (e.g. Bhat et al., 2008).
10/1/2014
4
4
Decreased from 4 to 4
Description
Studies have identified rare sequence variants in the IL1RAPL1 gene with autism (e.g. Bhat et al., 2008).
7/1/2014
No data
4
Increased from No data to 4
Description
Studies have identified rare sequence variants in the IL1RAPL1 gene with autism (e.g. Bhat et al., 2008).
4/1/2014
No data
4
Increased from No data to 4
Description
Studies have identified rare sequence variants in the IL1RAPL1 gene with autism (e.g. Bhat et al., 2008).
Krishnan Probability Score
Score 0.58575496388076
Ranking 519/25841 scored genes
[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning
approach on a human brain-specific gene network. The method was first presented in Nat
Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed
in column G of supplementary table 3 (see:
http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser,
with the ability to view networks of associated ASD risk genes, can be found at
asd.princeton.edu.
ExAC Score
Score 0.99689367835644
Ranking 1375/18225 scored genes
[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has
been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by
Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at
exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of-
function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of-
function mutations in autism in such a gene would be more likely to confer risk. For a full list of
pLI scores see:
ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle
aned_exac_nonTCGA_z_pli_rec_null_data.txt
Sanders TADA Score
Score 0.94975040127291
Ranking 18217/18665 scored genes
[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013),
and is a statistic that integrates evidence from both de novo and transmitted mutations.
It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233
(2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper
(the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Larsen Cumulative Evidence Score
Score 20
Ranking 103/461 scored genes
[Show Scoring Methodology]
Larsen and colleagues generated gene scores based on the sum of evidence for all available
ASD-associated variants in a gene, with assessments based on mode of inheritance, effect size,
and variant frequency in the general population. The approach was first presented in Mol Autism
7:44 (2016), and scores for 461 genes can be found in column I in supplementary table 4 from
that paper.
Zhang D Score
Score 0.50848229013408
Ranking 459/20870 scored genes
[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures),
or D score, was developed to combine evidence from de novo loss-of- function mutation with
evidence from cell-type- specific gene expression in the mouse brain (specifically translational
profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with
positive D scores are more likely to be associated with autism risk, with higher-confidence genes
having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204-
215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in
supplementary table 2 from that paper.
External PIN Data
Interactome
- Protein Binding
- DNA Binding
- RNA Binding
- Protein Modification
- Direct Regulation
- ASD-Linked Genes
Interaction Table
| Interactor Symbol | Interactor Name | Interactor Organism | Interactor Type | Entrez ID | Uniprot ID |
|---|---|---|---|---|---|
| NCS-1 | neuronal calcium sensor 1 | Human | Protein Binding | 23413 | P62166 |