Human Gene Module / Chromosome X / IL1RAPL2

IL1RAPL2interleukin 1 receptor accessory protein-like 2

Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
2 / 2
Rare Variants / Common Variants
1 / 3
Aliases
IL1RAPL2, IL-1R9,  IL1R9,  IL1RAPL-2,  TIGIRR-1
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation, Genetic Association
Chromosome Band
Xq22.3
Associated Disorders
-
Relevance to Autism

Genetic association has been found between the IL1RAPL2 gene and males with ASD in the HIHG/CHGR, AGRE and ACC cohorts (Chung et al., 2011).

Molecular Function

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 mental retardation.

Reports related to IL1RAPL2 (2 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary An X chromosome-wide association study in autism families identifies TBL1X as a novel autism spectrum disorder candidate gene in males. Chung RH , et al. (2011) Yes -
2 Support A discovery resource of rare copy number variations in individuals with autism spectrum disorder. Prasad A , et al. (2013) Yes -
Rare Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_gain Unknown - Unknown 23275889 Prasad A , et al. (2013)
Common Variants   (3)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.1049-4004T>C - intron_variant - - - 22050706 Chung RH , et al. (2011)
c.903-3035T>C C/T intron_variant - - - 22050706 Chung RH , et al. (2011)
c.1193-3016C>T T/C intron_variant - - - 22050706 Chung RH , et al. (2011)
SFARI Gene score
3

Suggestive Evidence

Genetic association has been found between the IL1RAPL2 gene and males with ASD in the HIHG/CHGR, AGRE and ACC cohorts (Chung et al., 2011). However, Piton et al. (2008) reported an absence of non-synonymous mutations in IL1RAPL2 in a screen of 142 individuals with ASD. Similarly, Kantoj?rvi et al. (2011) reported an absence of novel IL1RAPL2 mutations in a screen of 42 individuals with ASD.

Score Delta: Score remained at 4

3

Suggestive Evidence

See all Category 3 Genes

The literature is replete with relatively small studies of candidate genes, using either common or rare variant approaches, which do not reach the criteria set out for categories 1 and 2. Genes that had two such lines of supporting evidence were placed in category 3, and those with one line of evidence were placed in category 4. Some additional lines of "accessory evidence" (indicated as "acc" in the score cards) could also boost a gene from category 4 to 3.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Genetic association has been found between the IL1RAPL2 gene and males with ASD in the HIHG/CHGR, AGRE and ACC cohorts (Chung et al., 2011). However, Piton et al. (2008) reported an absence of non-synonymous mutations in IL1RAPL2 in a screen of 142 individuals with ASD. Similarly, Kantoj?rvi et al. (2011) reported an absence of novel IL1RAPL2 mutations in a screen of 42 individuals with ASD.

Reports Added
[New Scoring Scheme]
7/1/2014
No data
icon
4

Increased from No data to 4

Description

Genetic association has been found between the IL1RAPL2 gene and males with ASD in the HIHG/CHGR, AGRE and ACC cohorts (Chung et al., 2011). However, Piton et al. (2008) reported an absence of non-synonymous mutations in IL1RAPL2 in a screen of 142 individuals with ASD. Similarly, Kantoj?rvi et al. (2011) reported an absence of novel IL1RAPL2 mutations in a screen of 42 individuals with ASD.

4/1/2014
No data
icon
4

Increased from No data to 4

Description

Genetic association has been found between the IL1RAPL2 gene and males with ASD in the HIHG/CHGR, AGRE and ACC cohorts (Chung et al., 2011). However, Piton et al. (2008) reported an absence of non-synonymous mutations in IL1RAPL2 in a screen of 142 individuals with ASD. Similarly, Kantoj?rvi et al. (2011) reported an absence of novel IL1RAPL2 mutations in a screen of 42 individuals with ASD.

Krishnan Probability Score

Score 0.52430198895423

Ranking 1632/25841 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 0.97337947596316

Ranking 2290/18225 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 0.94840704757029

Ranking 17671/18665 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 3

Ranking 347/461 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 0.32303263052128

Ranking 2389/20870 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.
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SFARI Gene Update

We are pleased to announce some changes to the ongoing curation of the data in SFARI Gene. In the context of a continued effort to develop the human gene module and its manually curated list of autism risk genes, we are modifying other aspects of the site to focus on the information that is of greatest interest to the research community. The version of SFARI Gene that has been developed until now will be frozen and will remain available as “SFARI Gene Archive”. Please see the announcement for more details.
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