Human Gene Module / Chromosome 2 / IL1R2

IL1R2interleukin 1 receptor, type II

Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
2 / 6
Rare Variants / Common Variants
2 / 0
IL1R2, IL1RB,  CD121b
Associated Syndromes
Genetic Category
Rare Single Gene Mutation
Chromosome Band
Associated Disorders
Relevance to Autism

Rare mutations in the IL1R2 gene have been identified with autism (O'Roak et al., 2011; Sanders et al., 2012).

Molecular Function

Receptor for interleukin-1 alpha, beta, and interleukin-1 receptor antagonist protein.

Reports related to IL1R2 (6 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Recent Recommendation Alternate splicing of interleukin-1 receptor type II (IL1R2) in vitro correlates with clinical glucocorticoid responsiveness in patients with AIED. Vambutas A , et al. (2009) No -
2 Recent Recommendation Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47. Anderson CA , et al. (2011) No -
3 Primary Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations. O'Roak BJ , et al. (2011) Yes -
4 Support De novo mutations revealed by whole-exome sequencing are strongly associated with autism. Sanders SJ , et al. (2012) Yes -
5 Recent Recommendation De Novo Synonymous Mutations in Regulatory Elements Contribute to the Genetic Etiology of Autism and Schizophrenia. Takata A , et al. (2016) No -
6 Highly Cited Interleukin-1 type II receptor: a decoy target for IL-1 that is regulated by IL-4. Colotta F , et al. (1993) No -
Rare Variants   (2)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.90T>C p.Phe30%3D synonymous_variant De novo NA - 21572417 O'Roak BJ , et al. (2011)
c.90T>C p.Phe30%3D synonymous_variant De novo NA Simplex 22495306 Sanders SJ , et al. (2012)
Common Variants  

No common variants reported.

SFARI Gene score

Suggestive Evidence

A single de novo synonymous SNP in the IL1R2 gene was identified with autism through exome sequencing (O'Roak et al., 2011).

Score Delta: Score remained at 4


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.


Decreased from 4 to 3

New Scoring Scheme

A single de novo synonymous SNP in the IL1R2 gene was identified with autism through exome sequencing (O'Roak et al., 2011).

Reports Added
[New Scoring Scheme]
No data

Increased from No data to 4


A single de novo synonymous SNP in the IL1R2 gene was identified with autism through exome sequencing (O'Roak et al., 2011).

No data

Increased from No data to 4


A single de novo synonymous SNP in the IL1R2 gene was identified with autism through exome sequencing (O'Roak et al., 2011).

Krishnan Probability Score

Score 0.41234413131203

Ranking 22131/25841 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: A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at
ExAC Score

Score 1.9524279172041E-7

Ranking 15518/18225 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 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: aned_exac_nonTCGA_z_pli_rec_null_data.txt
Sanders TADA Score

Score 0.94992155798038

Ranking 18286/18665 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
Larsen Cumulative Evidence Score

Score 5

Ranking 285/461 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 -0.58303933184141

Ranking 19808/20870 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.