Human Gene Module / Chromosome 6 / JARID2

JARID2jumonji and AT-rich interaction domain containing 2

Strong Candidate Criteria 2.1
Autism Reports / Total Reports
8 / 11
Rare Variants / Common Variants
5 / 3
Associated Syndromes
Genetic Category
Rare Single Gene Mutation, Syndromic, Genetic Association
Chromosome Band
Associated Disorders
Relevance to Autism

Two separate association studies using families from AGRE in the discovery cohort identified two different SNPs in the JARID2 gene that demonstrated association with ASD (Weiss et al., 2009; Ramos et al., 2012).

Molecular Function

This gene encodes a Jumonji- and AT-rich interaction domain (ARID)-domain-containing protein that functions as a transcriptional repressor. This protein interacts with the Polycomb repressive complex 2 (PRC2) which plays an essential role in regulating gene expression during embryonic development. During embryogenesis, JARID2 is predominantly expressed in neurons and particularly in dorsal root ganglion cells. Association studies have identified JARID2 as a possible susceptibility gene in schizophrenia (Pedrosa et al., 2007; Liu et al., 2009).

Reports related to JARID2 (11 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Positive Association Positive association of schizophrenia to JARID2 gene. Pedrosa E , et al. (2006) No -
2 Primary A genome-wide linkage and association scan reveals novel loci for autism. Weiss LA , et al. (2009) Yes -
3 Positive Association Whole genome association study in a homogenous population in Shandong peninsula of China reveals JARID2 as a susceptibility gene for schizophrenia. Liu Y , et al. (2009) No -
4 Support Immune function genes CD99L2, JARID2 and TPO show association with autism spectrum disorder. Ramos PS , et al. (2012) Yes -
5 Support Exome sequencing of extended families with autism reveals genes shared across neurodevelopmental and neuropsychiatric disorders. Cukier HN , et al. (2014) Yes -
6 Support Synaptic, transcriptional and chromatin genes disrupted in autism. De Rubeis S , et al. (2014) Yes -
7 Positive Association Genome-wide Association Study of Autism Spectrum Disorder in the East Asian Populations. Liu X , et al. (2015) Yes -
8 Support Genome-wide characteristics of de novo mutations in autism. Yuen RK , et al. (2016) Yes -
9 Support High diagnostic yield of syndromic intellectual disability by targeted next-generation sequencing. Martnez F , et al. (2016) No Autistic behavior, stereotypic behavior
10 Support Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder. Lim ET , et al. (2017) Yes -
11 Negative Association A study of single nucleotide polymorphisms in CD157, AIM2 and JARID2 genes in Han Chinese children with autism spectrum disorder. Mo W , et al. (2017) Yes -
Rare Variants   (5)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.66G>A p.(=) synonymous_variant De novo - Simplex 28714951 Lim ET , et al. (2017)
c.2255C>T p.Pro752Leu missense_variant De novo - - 27620904 Martnez F , et al. (2016)
3539+GATGTACC (delGATGTACC) 1180-! frameshift_variant De novo - - 25363760 De Rubeis S , et al. (2014)
c.2480G>A;c.1964G>A p.Arg827Gln;p.Arg655Gln missense_variant De novo - Simplex 27525107 Yuen RK , et al. (2016)
c.1474C>T p.Arg492Cys missense_variant Familial - Extended multiplex (at least one pair of ASD affec 24410847 Cukier HN , et al. (2014)
Common Variants   (3)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.-471-28343C>A;c.46-28343C>A;c.-329-28343C>A - intron_variant - - - 22681640 Ramos PS , et al. (2012)
c.-472+18856C>T;c.45+21236C>T;c.-472+19761C>T;c.-330+18856C>T - intron_variant - - - 19812673 Weiss LA , et al. (2009)
c.155-6435C>T;c.671-6435C>T;c.557-6435C>T;c.860-6435C>T;c.716-6435C>T;c.263-6435C>T - intron_variant - - - 26314684 Liu X , et al. (2015)
SFARI Gene score

Strong Candidate

Two separate association studies using families from AGRE in the discovery cohort identified two different SNPs in the JARID2 gene that demonstrated association with ASD (Weiss et al., 2009; Ramos et al., 2012). Association of the JARID2 gene with autism was observed in a family-based analysis of Japanese ASD families in Liu et al., 2016; however, this variant failed to replicate association with ASD in a Japanese case-control dataset or in a Taiwanese TDT dataset. JARID2 also failed to demonstrate association with ASD in a case-control analysis in a Han Chinese cohort (Mo et al., 2017). JARID2 has also been reported to associate with schizophrenia (Pedrosa et al., 2007; Liu et al., 2009). A de novo loss-of-function variant was observed in the JARID2 gene in an ASD proband from the Autism Sequencing Consortium (De Rubeis et al., 2014), while de novo missense variants predicted in silico to be damaging have been observed in an ASD proband from a cohort of 200 Canadian ASD trio families (Yuen et al., 2017) and in a male proband from DECIPHER presenting with intellectual disability and autistic behavior (Martinez et al., 2017).

Score Delta: Score remained at 3


Strong Candidate

See all Category 2 Genes

We 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.

Krishnan Probability Score

Score 0.53367692816158

Ranking 1504/25841 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 0.99986219301105

Ranking 730/18225 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 0.62190358533827

Ranking 785/18665 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 286/461 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 0.60352648119087

Ranking 79/20870 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.
Submit New Gene

Report an Error