JARID2
<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">JARID2</th>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Jumonji and AT-Rich Interaction Domain Containing 2</td>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>JARID2</td>
</tr>
<tr>
<td class="label">Aliases</td>
<td>JMJ, JUMONJI</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>6p22.3</td>
</tr>
<tr>
<td class="label">Gene Type</td>
<td>Protein-coding</td>
</tr>
<tr>
<td class="label">OMIM</td>
<td>[601594](https://omim.org/entry/601594)</td>
</tr>
<tr>
<td class="label">UniProt</td>
<td>[Q92833](https://www.uniprot.org/uniprot/Q92833)</td>
</tr>
<tr>
<td class="label">HGNC</td>
<td>[6196](https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:6196)</td>
</tr>
<tr>
<td class="label">Entrez Gene</td>
<td>[3720](https://www.ncbi.nlm.nih.gov/gene/3720)</td>
</tr>
<tr>
<td class="label">Ensembl</td>
<td>[ENSG00000008083](https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000008083)</td>
</tr>
<tr>
<td class="label">Variant</td>
<td>Type</td>
</tr>
<tr>
<td class="label">rs2235258</td>
<td>Intronic</td>
</tr>
<tr>
<td class="label">6p22.3 CNVs</td>
<td>Copy number</td>
</tr>
<tr>
<td class="label">JARID2 promoter CpG methylation</td>
<td>Epigenetic</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/breast-cancer" style="color:#ef9a9a">Breast Cancer</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a>, <a href="/wiki/prostate-cancer" style="color:#ef9a9a">Prostate Cancer</a>, <a href="/wiki/tumor" style="color:#ef9a9a">Tumor</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">17 edges</a></td>
</tr>
</table>
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JARID2
</div>
Overview
Mermaid diagram (expand to render)
JARID2 is a human gene. Variants in JARID2 have been implicated in Alzheimer's Disease, Schizophrenia and Autism, Parkinson's Disease. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration.
JARID2 (Jumonji and AT-Rich Interaction Domain Containing 2), also known as JUMONJI, encodes a catalytically dead Jumonji C (JmjC) domain protein that serves as an essential accessory subunit of Polycomb Repressive Complex 2 (PRC2).<sup>[1]</sup> JARID2 is the founding member of the Jumonji protein family and functions as a critical bridge between PRC1-deposited H2AK119ub1 marks and PRC2, mediating the crosstalk between the two major Polycomb complexes.<sup>[2]</sup> In the nervous system, JARID2 regulates neural tube patterning, cerebellar development, and adult neurogenesis. JARID2 dysfunction has been linked to [Alzheimer's disease](/diseases/alzheimers-disease), schizophrenia, and autism spectrum disorders.
Function and Mechanism
JARID2 is a 1246-amino acid protein containing an N-terminal PRC2-interacting region, a catalytically inactive JmjC domain, an ARID (AT-rich interaction domain) for DNA binding, and a C-terminal zinc finger. Despite possessing a JmjC domain, JARID2 lacks the critical iron-binding residues required for demethylase activity and is catalytically inert.
PRC1-PRC2 Crosstalk
JARID2 contains a ubiquitin-interacting motif (UIM) that specifically recognizes H2AK119ub1 deposited by PRC1 ([RNF2](/genes/rnf2)-[BMI1](/genes/bmi1)). This interaction recruits PRC2 to PRC1-modified chromatin, establishing a hierarchical cascade where PRC1 primes chromatin for subsequent PRC2-mediated H3K27me3 deposition. This PRC1→JARID2→PRC2 pathway is essential for de novo establishment of Polycomb domains at CpG-poor genomic regions.<sup>[2]</sup>
JARID2 Methylation as Allosteric Signal
JARID2 lysine 116 (K116) is methylated by PRC2 itself, and this trimethylated K116 peptide binds the [EED](/genes/eed) aromatic cage similarly to H3K27me3, allosterically activating PRC2. This creates a self-amplifying loop: PRC2 methylates JARID2, which then stimulates PRC2 activity, accelerating H3K27me3 deposition at target loci.<sup>[3]</sup>
JARID2 defines the PRC2.2 subcomplex, where it associates with AEBP2 and the PRC2 core ([EZH2](/genes/ezh2), [EED](/genes/eed), [SUZ12](/genes/suz12)). PRC2.2 has distinct genomic targeting compared to PRC2.1 (which contains PCL proteins), with JARID2 directing PRC2 to active enhancers and poised promoters during lineage commitment.<sup>[4]</sup>
Neural Development
JARID2 is named after the Japanese word "jumonji" (cruciform) because Jarid2-null mice display neural tube defects resulting in a cross-shaped groove on the brain surface. JARID2 regulates neural tube closure, dorsal-ventral patterning, and cerebellar granule cell proliferation.<sup>[5]</sup> In adult neurogenesis, JARID2 maintains the quiescent state of hippocampal neural stem cells by repressing cell cycle activators.
Disease Associations
Alzheimer's Disease
In [Alzheimer's disease](/diseases/alzheimers-disease), JARID2 expression is reduced in [entorhinal cortex](/brain-regions/entorhinal-cortex) and [hippocampus](/brain-regions/hippocampus), disrupting PRC1-PRC2 crosstalk. Loss of JARID2-mediated PRC2 recruitment leads to failure of H3K27me3 maintenance at inflammatory gene loci, contributing to chronic neuroinflammation. JARID2 also regulates [BACE1](/genes/bace1) expression through PRC2-dependent silencing.<sup>[6]</sup>
Schizophrenia and Autism
Genome-wide association studies have identified common variants near JARID2 (6p22.3 locus) associated with schizophrenia risk.<sup>[7]</sup> Rare copy number variations encompassing JARID2 have been identified in autism spectrum disorder cohorts, suggesting haploinsufficiency as a neurodevelopmental risk factor.
Parkinson's Disease
In [Parkinson's disease](/diseases/parkinsons-disease), PRC2.2 complex integrity is compromised in dopaminergic [neurons](/entities/neurons). JARID2's ability to read H2AK119ub1 marks is impaired when PRC1 function is reduced, creating a cascading failure in Polycomb-mediated gene silencing in vulnerable neuronal populations.<sup>[8]</sup>
Neural Tube Defects
Complete loss of JARID2 causes open neural tube defects in mouse models, demonstrating its essential role in neural tube closure. Heterozygous JARID2 mutations have been identified in human neural tube defect cohorts at increased frequency.<sup>[5]</sup>
Expression
JARID2 is highly expressed in the developing brain, with peak levels during embryonic neurogenesis. Key expression domains include the ventricular zone of the cerebral [cortex](/brain-regions/cortex), cerebellar external granule layer, hippocampal dentate gyrus, and neural tube floor plate. In the adult brain, JARID2 maintains moderate expression in cortical neurons, hippocampal pyramidal cells, and Purkinje neurons. JARID2 is also expressed in adult neural stem cell niches (SVZ, dentate gyrus), where it regulates stem cell quiescence.
Common Variants
Therapeutic Implications
- PRC2.2 stabilizers: Small molecules enhancing JARID2-SUZ12 interaction to restore PRC2.2 function in neurodegeneration
- UIM-targeted approaches: Enhancing JARID2's H2AK119ub1 recognition to strengthen PRC1-PRC2 crosstalk
- Allosteric activators: Mimicking JARID2-K116me3 to activate PRC2 through the EED aromatic cage<sup>[9]</sup>
- Gene therapy: AAV-mediated JARID2 delivery to hippocampal and cortical neurons
See Also
- [EED](/genes/eed) — PRC2 core subunit (binds JARID2-K116me3)
- [SUZ12](/genes/suz12) — PRC2 core subunit (JARID2 docking partner)
- [EZH2](/genes/ezh2) — PRC2 catalytic subunit
- [BMI1](/genes/bmi1) — PRC1 core subunit
- [RNF2](/genes/rnf2) — PRC1 catalytic subunit (deposits H2AK119ub1 read by JARID2)
- [KDM6B](/genes/kdm6b) — H3K27me3 demethylase
External Links
- [NCBI Gene: JARID2](https://www.ncbi.nlm.nih.gov/gene/3720)
- [UniProt: Q92833](https://www.uniprot.org/uniprot/Q92833)
- [GeneCards: JARID2](https://www.genecards.org/cgi-bin/carddisp.pl?gene=JARID2)
References
[Li et al., Jarid2 and PRC2, partners in regulating gene expression (2010) (2010)](https://doi.org/10.1101/gad.1886410)
[Cooper et al., JARID2 binds mono-ubiquitylated H2A lysine 119 to mediate crosstalk between Polycomb complexes PRC1 and PRC2 (2016) (2016)](https://doi.org/10.1038/ncomms13661)
[Sanulli et al., Jarid2 methylation via the PRC2 complex regulates H3K27me3 deposition during cell differentiation (2015) (2015)](https://doi.org/10.1016/j.molcel.2015.01.007)
[Healy et al., PRC2.1 and PRC2.2 synergize to coordinate H3K27 trimethylation (2019) (2019)](https://doi.org/10.1016/j.molcel.2019.09.010)
[Takeuchi et al., Gene trap capture of a novel mouse gene, jumonji, required for neural tube formation (1995) (1995)](https://doi.org/10.1101/gad.9.10.1211)
[Nativio et al., Dysregulation of the epigenetic landscape of normal aging in Alzheimer's disease (2018) (2018)](https://doi.org/10.1038/s41593-018-0101-9)
[Pedrosa et al., Association of the JARID2/jumonji gene with schizophrenia (2007) (2007)](https://doi.org/10.1002/ajmg.b.30474)
[von Schimmelmann et al., Polycomb repressive complex 2 silences genes responsible for neurodegeneration (2016) (2016)](https://doi.org/10.1038/nn.4360)
[Kasinath et al., Structures of human PRC2 with its cofactors AEBP2 and JARID2 (2018) (2018)](https://doi.org/10.1126/science.aar5700)
[Pasini et al., JARID2 regulates binding of the Polycomb repressive complex 2 to target genes in ES cells (2010) (2010)](https://doi.org/10.1038/nature08953)Pathway Diagram
The following diagram shows the key molecular relationships involving JARID2 discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)