JARID2

Summary

JARID2 (jumonji and AT-rich interaction domain containing 2, HGNC:6196) is a protein-coding gene on chromosome 6p22.3, encoding Protein Jumonji (Q92833). Regulator of histone methyltransferase complexes that plays an essential role in embryonic development, including heart and liver development, neural tube fusion process and hematopoiesis.

This gene encodes a Jumonji- and AT-rich interaction domain (ARID)-domain-containing protein. The encoded protein is a DNA-binding 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. This protein facilitates the recruitment of the PRC2 complex to target genes. Alternate splicing results in multiple transcript variants. Mutations in this gene are associated with chronic myeloid malignancies.

Source: NCBI Gene 3720 — RefSeq curated summary.

At a glance

• Gene–disease (curated): developmental delay with variable intellectual disability and dysmorphic facies (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 11
• Clinical variants (ClinVar): 383 total — 17 pathogenic, 12 likely-pathogenic
• Phenotypes (HPO): 54
• Dosage sensitivity (ClinGen): haploinsufficiency emerging evidence, triplosensitivity no evidence
• Transcription factor: yes — 18 downstream targets (CollecTRI)
• MANE Select transcript: NM_004973

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6196
Approved symbol	JARID2
Name	jumonji and AT-rich interaction domain containing 2
Location	6p22.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000008083
Ensembl biotype	protein_coding
OMIM	601594
Entrez	3720

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 9 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000341776, ENST00000397311, ENST00000474854, ENST00000853926, ENST00000853927, ENST00000930272, ENST00000930273, ENST00000930274, ENST00000930275, ENST00000930276

RefSeq mRNA: 2 — MANE Select: NM_004973 NM_001267040, NM_004973

CCDS: CCDS4533, CCDS58996

Canonical transcript exons

ENST00000341776 — 18 exons

Exon	Start	End
ENSE00000686280	15487307	15487542
ENSE00000686285	15496132	15497170
ENSE00000686289	15500907	15501409
ENSE00000686302	15508340	15508454
ENSE00000686306	15511296	15511401
ENSE00000686308	15512208	15512390
ENSE00000686312	15512915	15513045
ENSE00000686314	15513239	15513422
ENSE00000686317	15517161	15517268
ENSE00001419642	15246069	15246584
ENSE00001855293	15520069	15522042
ENSE00003502958	15507136	15507254
ENSE00003504606	15468542	15468718
ENSE00003512141	15504500	15504592
ENSE00003562440	15374117	15374252
ENSE00003595335	15507346	15507416
ENSE00003642934	15452006	15452175
ENSE00003663656	15410224	15410365

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 99.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 65.6823 / max 1904.3233, expressed in 1818 samples.

FANTOM5 promoters (17 alternative TSS)

Promoter ID	TPM avg	Samples expressed
66043	47.1004	1806
66041	8.7253	1214
66042	2.2548	809
66049	1.8995	712
66062	1.0767	246
66036	0.9458	510
66039	0.7103	319
66048	0.7067	349
66037	0.4663	257
66046	0.4181	131

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.88	gold quality
oocyte	CL:0000023	99.73	gold quality
buccal mucosa cell	CL:0002336	98.68	gold quality
sperm	CL:0000019	98.46	gold quality
male germ cell	CL:0000015	97.14	gold quality
esophagus squamous epithelium	UBERON:0006920	95.60	gold quality
gingival epithelium	UBERON:0001949	95.47	gold quality
trabecular bone tissue	UBERON:0002483	95.07	gold quality
nipple	UBERON:0002030	94.58	gold quality
squamous epithelium	UBERON:0006914	94.34	gold quality
gingiva	UBERON:0001828	94.20	gold quality
amniotic fluid	UBERON:0000173	93.92	gold quality
epithelium of esophagus	UBERON:0001976	93.74	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	93.21	gold quality
tendon of biceps brachii	UBERON:0008188	92.88	gold quality
Brodmann (1909) area 23	UBERON:0013554	92.84	gold quality
epithelium of nasopharynx	UBERON:0001951	92.55	gold quality
oviduct epithelium	UBERON:0004804	92.38	gold quality
inferior olivary complex	UBERON:0002127	92.34	gold quality
tongue squamous epithelium	UBERON:0006919	92.11	gold quality
upper leg skin	UBERON:0004262	92.01	gold quality
nasal cavity epithelium	UBERON:0005384	92.00	gold quality
bone marrow	UBERON:0002371	91.97	gold quality
middle temporal gyrus	UBERON:0002771	91.63	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.87	gold quality
skin of hip	UBERON:0001554	90.82	gold quality
thymus	UBERON:0002370	90.62	gold quality
paraflocculus	UBERON:0005351	90.51	gold quality
mammalian vulva	UBERON:0000997	90.40	gold quality
pharyngeal mucosa	UBERON:0000355	90.36	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	36.00
E-MTAB-6379	no	554.65
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

18 targets.

Target	Regulation
CCND1	Unknown
CDK4
EHMT2	Repression
FLT1
JARID2
KRT9
MYH14	Repression
MYH6	Unknown
MYL1
MYL7	Unknown
MYOG	Repression
NOTCH1
NPPA	Unknown
PER2
PPP1CC
RB1
SETDB1
TERT

Upstream regulators (CollecTRI, top): GATA4, JARID2, NCOR2, NKX2-5

miRNA regulators (miRDB)

180 targeting JARID2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488

Functional genomics

ClinGen dosage: haploinsufficiency 2 (emerging evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• JMJ was evaluated against risk factors for spinal dysraphism and congenital heart defects. Variations within exons and introns of JMJ might be in linkage disequlibrium. (PMID:15057990)
• JARID2 should be viewed as a candidate gene for 6p22.3-linked schizophrenia (PMID:16967465)
• JARID2 appears important in transcriptional regulation of fetal genes and may emerge as a diagnostic marker for left ventricular decompensation in aortic stenosis. (PMID:18805276)
• Based on the findings the authors propose that miR-155 has a prosurvival function that is mediated through the downregulation of targets including JARID2. (PMID:19759154)
• Two SNPs in JARID2 showed association in allelic, genotypic and haplotypic tests with schizophrenia patients from Chang Le area. (PMID:19884986)
• JARID2 is essential for the binding of PcG proteins to target genes and, consistent with this, for the proper differentiation of embryonic stem cells and normal development (PMID:20075857)
• In chronic myeloproliferative neoplasms & myelodysplastic syndromes, there were frequent deletions in a 1.1 Mb region of the short arm of chromosome 6 containing only the JARID2 gene. This del6p was associated with leukemic transformation. (PMID:22190018)
• Patients carrying JARID2 deletion manifested with cognitive impairment, gait disturbance and a characteristic facial appearance, whereas patients with deletion of ATXN1 seemed to be characterized by intellectual disability and behavioural abnormalities (PMID:23294540)
• The interaction of JARID2 at these promoters is dependent on EED. (PMID:23435416)
• The presence of long noncoding RNAs stimulated JARID2-EZH2 interactions in vitro and JARID2-mediated recruitment of PRC2 to chromatin. (PMID:24374312)
• Jarid2 is an important mediator of Xist-induced PRC2 targeting. (PMID:24462204)
• miR-155 regulates the fate of Th17 and Treg cells and miR-155 contributes to Th17 cell function by suppressing the inhibitory effects of Jarid2. (PMID:24856900)
• Decreased miRNA-940 affects the proliferation and migration of the progenitor cells of the secondary heart field by targeting JARID2. (PMID:24889693)
• Data further strengthen the conclusion that JARID2 polymorphisms are associated with NSOC susceptibility. (PMID:25155265)
• TGF-ss-dependent expression changes of EMT-related genes were inhibited by JARID2 knockdown and enhanced by JARID2 overexpression. (PMID:25542019)
• Results suggest a regulation loop where Jarid2 protein methylation fine-tunes polycomb repressive complex 2 (PRC2) activity depending on the chromatin context. (PMID:25620564)
• Jarid2 is an important component of PRC2 that has a central role in coordinating hematopoietic stem and progenitor cell function (PMID:25645357)
• JARID2 inhibits leukemia cell proliferation by regulating CCND1 expression (PMID:25939703)
• JARID2 promotes invasion and metastasis of hepatocellular carcinoma by facilitating epithelial-mesenchymal transition through PTEN/AKT signaling (PMID:27259236)
• Our results suggest that JARID2 rs2237138 shows a protective effect against NSCL +/- P (non-syndromic oral clefts)in the Brazilian population. (PMID:27328068)
• JARID2 plays an important role in glioma development. (PMID:27641964)
• Authors found that knockdown of Jarid2 was able to inhibit the invasive ability and sphere-forming capacity in bladder cancer cells. (PMID:28445934)
• The knockdown of JARID2 inhibited the viability and invasion of trophoblast cells in preeclampsia by suppressing the PI3K/Akt signaling pathway. (PMID:28714012)
• bservations suggested that knockdown of JARID2 inhibited proliferation, migration and invasion in vitro through the inactivation of the PI3K/Akt signaling pathway. Therefore, JARID2 may represent a potential therapeutic target for the treatment of ovarian cancer. (PMID:28765957)
• rs2237126 in JARID2 is not significantly associated with childhood autism spectrum disorder or the severity of the disease in a Chinese Han population. (PMID:29216786)
• In this study, genetic mouse models and patient-derived xenografts demonstrated that JARID2 acts as a tumor suppressor in chronic myeloid disorders. (PMID:30423295)
• show that DeltaN-JARID2 is a cleaved product of full-length JARID2 spanning the C-terminal conserved jumonji domains. JARID2 knockout in keratinocytes results in up-regulation of cell cycle genes and repression of many epidermal differentiation genes (PMID:30573669)
• Promoting role of circ-Jarid2/miR-129-5p/Celf1 axis in cardiac hypertrophy. (PMID:32632266)
• JARID2 haploinsufficiency is associated with a clinically distinct neurodevelopmental syndrome. (PMID:33077894)
• JARID2 and AEBP2 regulate PRC2 in the presence of H2AK119ub1 and other histone modifications. (PMID:33479123)
• LINC00649 Facilitates the Cellular Process of Bladder Cancer Cells via Signaling Axis miR-16-5p/JARID2. (PMID:33789312)
• An RNAi Screening of Clinically Relevant Transcription Factors Regulating Human Adipogenesis and Adipocyte Metabolism. (PMID:33963396)
• microRNA-206 Suppresses Cholangiocarcinoma Cell Growth and Invasion by Targeting Jumonji AT-Rich Interactive Domain 2. (PMID:34240323)
• JARID2 promotes stemness and cisplatin resistance in non-small cell lung cancer via upregulation of Notch1. (PMID:34246759)
• LINC01021 maintains tumorigenicity by enhancing N6-methyladenosine reader IMP2 dependent stabilization of MSX1 and JARID2: implication in colorectal cancer. (PMID:35173309)
• The LINC00852/miR-29a-3p/JARID2 axis regulates the proliferation and invasion of prostate cancer cell. (PMID:36471281)
• JARID2 regulates epithelial mesenchymal transition through the PTEN/AKT signalling pathways in ovarian endometriosis. (PMID:36640627)
• Integrated bioinformatics and experimental validation reveal the role of JARID2 in ovarian cancer. (PMID:37309591)
• JARID2 and EZH2, the eminent epigenetic drivers in human cancer. (PMID:37353042)
• Functional Insight into and Refinement of the Genomic Boundaries of the JARID2-Neurodevelopmental Disorder Episignature. (PMID:37762546)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	jarid2a	ENSDARG00000060925
danio_rerio	jarid2b	ENSDARG00000062268
mus_musculus	Jarid2	ENSMUSG00000038518
rattus_norvegicus	Jarid2	ENSRNOG00000045918
drosophila_melanogaster	Jarid2	FBGN0036004

Paralogs (10): KDM5D (ENSG00000012817), KDM4A (ENSG00000066135), KDM5A (ENSG00000073614), KDM4C (ENSG00000107077), KDM5B (ENSG00000117139), KDM5C (ENSG00000126012), KDM4B (ENSG00000127663), KDM4D (ENSG00000186280), KDM4E (ENSG00000235268), KDM4F (ENSG00000255855)

Protein

Protein identifiers

Protein Jumonji — Q92833 (reviewed: Q92833)

Alternative names: Jumonji/ARID domain-containing protein 2

All UniProt accessions (1): Q92833

UniProt curated annotations — full annotation on UniProt →

Function. Regulator of histone methyltransferase complexes that plays an essential role in embryonic development, including heart and liver development, neural tube fusion process and hematopoiesis. Acts as an accessory subunit for the core PRC2 (Polycomb repressive complex 2) complex, which mediates histone H3K27 (H3K27me3) trimethylation on chromatin. Binds DNA and mediates the recruitment of the PRC2 complex to target genes in embryonic stem cells, thereby playing a key role in stem cell differentiation and normal embryonic development. In cardiac cells, it is required to repress expression of cyclin-D1 (CCND1) by activating methylation of ‘Lys-9’ of histone H3 (H3K9me) by the GLP1/EHMT1 and G9a/EHMT2 histone methyltransferases. Also acts as a transcriptional repressor of ANF via its interaction with GATA4 and NKX2-5. Participates in the negative regulation of cell proliferation signaling. Does not have histone demethylase activity.

Subunit / interactions. Associates with the PRC2 complex, which consists of the core components EED, EZH1 or EZH2, SUZ12, and RBBP4, and various combinations of accessory subunits including AEBP2, JARID2, PHF19, MTF2 and EPOP. Found in a monomeric PRC2.2 (class 2) complex consisting of at least SUZ12, RBBP4, AEBP2 and JARID2. Facilitates nucleosome binding of the PRC2 complex. Interacts with SUZ12 (via C2H2-type zinc finger domain); the interaction is direct; competes with EPOP for SUZ12 binding. Interacts with histone methyltransferases EHMT1/GLP1 and EHMT2/G9a. Interacts with GATA4 (via the N-terminal region). Interacts with NKX2-5 (via the C-terminal region). Interacts with RB1. Interacts with ZNF496. Interacts with ESRRB. Interacts with DDX18; this interaction inhibits the PRC2 complex.

Subcellular location. Nucleus.

Tissue specificity. During embryogenesis, predominantly expressed in neurons and particularly in dorsal root ganglion cells.

Disease relevance. Developmental delay with variable intellectual disability and dysmorphic facies (DIDDF) [MIM:620098] An autosomal dominant disorder characterized by various degrees of developmental delay, mild to moderate intellectual disability, learning difficulties, hypotonia, autistic features, behavior abnormalities, and dysmorphic facial features apparent from infancy or early childhood. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The ARID domain is required to target the PRC2 complex to its target genes. The GSGFP motif is required for the interaction with SUZ12.

Isoforms (3)

UniProt ID	Names	Canonical?
Q92833-1	1	yes
Q92833-2	2
Q92833-3	3

RefSeq proteins (2): NP_001253969, NP_004964* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001606	ARID_dom	Domain
IPR003347	JmjC_dom	Domain
IPR003349	JmjN	Domain
IPR004198	Znf_C5HC2	Domain
IPR036431	ARID_dom_sf	Homologous_superfamily

Pfam: PF01388, PF02373, PF02375, PF02928

UniProt features (51 total): compositionally biased region 13, sequence conflict 9, region of interest 6, helix 5, domain 3, modified residue 3, splice variant 3, short sequence motif 2, sequence variant 2, mutagenesis site 2, chain 1, turn 1, strand 1

Structure

Experimental structures (PDB)

16 structures.

PDB	Method	Resolution (Å)
4X3E	X-RAY DIFFRACTION	2.3
6NQ3	X-RAY DIFFRACTION	2.89
5WAI	X-RAY DIFFRACTION	2.9
5HYN	X-RAY DIFFRACTION	2.95
8VMI	ELECTRON MICROSCOPY	3.1
8VNV	ELECTRON MICROSCOPY	3.1
9C8U	ELECTRON MICROSCOPY	3.1
9DCH	ELECTRON MICROSCOPY	3.4
5LS6	X-RAY DIFFRACTION	3.47
6C24	ELECTRON MICROSCOPY	3.5
6WKR	ELECTRON MICROSCOPY	3.5
8VML	ELECTRON MICROSCOPY	3.5
8VNZ	ELECTRON MICROSCOPY	3.5
6C23	ELECTRON MICROSCOPY	3.9
7KSO	ELECTRON MICROSCOPY	3.9
8TB9	ELECTRON MICROSCOPY	4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92833-F1	62.74	0.33

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (3): 78, 378, 455

Mutagenesis-validated functional residues (2):

Position	Phenotype
149–150	abolishes nucleosome binding activity of a minimal suz12-rbbp4-aebp2-jarid2 prc2 complex.
151–153	abolishes nucleosome binding activity of a minimal suz12-rbbp4-aebp2-jarid2 prc2 complex.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-212300	PRC2 methylates histones and DNA
R-HSA-212165	Epigenetic regulation of gene expression
R-HSA-74160	Gene expression (Transcription)

MSigDB gene sets: 0 (showing top):

GO Biological Process (20): negative regulation of transcription by RNA polymerase II (GO:0000122), liver development (GO:0001889), chromatin remodeling (GO:0006338), central nervous system development (GO:0007417), regulation of gene expression (GO:0010468), spleen development (GO:0048536), thymus development (GO:0048538), stem cell differentiation (GO:0048863), cardiac muscle cell proliferation (GO:0060038), negative regulation of cardiac muscle cell proliferation (GO:0060044), random inactivation of X chromosome (GO:0060816), facultative heterochromatin formation (GO:0140718), protein localization to pericentric heterochromatin (GO:1902682), cellular response to leukemia inhibitory factor (GO:1990830), chromatin organization (GO:0006325), cell population proliferation (GO:0008283), cell differentiation (GO:0030154), regulation of cell population proliferation (GO:0042127), negative regulation of DNA-templated transcription (GO:0045892), system development (GO:0048731)

GO Molecular Function (6): DNA binding (GO:0003677), chromatin binding (GO:0003682), ubiquitin binding (GO:0043130), histone H3K27 methyltransferase activity (GO:0046976), ubiquitin-modified histone reader activity (GO:0061649), protein binding (GO:0005515)

GO Cellular Component (6): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), mitochondrion (GO:0005739), histone methyltransferase complex (GO:0035097), ESC/E(Z) complex (GO:0035098)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Epigenetic regulation of gene expression	1
Gene expression (Transcription)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
gland development	2
hematopoietic or lymphoid organ development	2
binding	2
cellular anatomical structure	2
intracellular membrane-bounded organelle	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
hepaticobiliary system development	1
chromatin organization	1
nervous system development	1
system development	1
gene expression	1
regulation of macromolecule biosynthetic process	1
cell differentiation	1
striated muscle cell proliferation	1
cardiac muscle tissue growth	1
negative regulation of cell population proliferation	1
negative regulation of cardiac muscle tissue growth	1
cardiac muscle cell proliferation	1
regulation of cardiac muscle cell proliferation	1
dosage compensation by inactivation of X chromosome	1
heterochromatin formation	1
protein localization to chromosome, centromeric region	1
protein localization to heterochromatin	1
cellular response to cytokine stimulus	1
response to leukemia inhibitory factor	1
cellular component organization	1
cellular process	1
cellular developmental process	1
cell population proliferation	1
regulation of cellular process	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
multicellular organism development	1
anatomical structure development	1
nucleic acid binding	1
ubiquitin-like protein binding	1
protein-lysine N-methyltransferase activity	1

Protein interactions and networks

STRING

3652 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
JARID2	SUZ12	Q15022	997
JARID2	AEBP2	Q6ZN18	997
JARID2	EZH2	Q15910	995
JARID2	EED	O75530	993
JARID2	MTF2	Q9Y483	990
JARID2	RBBP7	Q16576	983
JARID2	RBBP4	P31149	974
JARID2	EZH1	Q92800	959
JARID2	PHF1	O43189	958
JARID2	PHF19	Q5T6S3	895
JARID2	H3-3A	P06351	842
JARID2	H3C1	P02295	842
JARID2	H3-4	Q16695	842
JARID2	H3C14	Q71DI3	840
JARID2	H3-5	Q6NXT2	840
JARID2	H3-7	Q5TEC6	840

IntAct

35 interactions, top by confidence:

A	B	Type	Score
SUZ12	EED	psi-mi:“MI:0914”(association)	0.910
EZH2	PHF1	psi-mi:“MI:0914”(association)	0.900
RBBP4	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
EZH2	EPOP	psi-mi:“MI:0914”(association)	0.730
AEBP2	EED	psi-mi:“MI:0915”(physical association)	0.650
AEBP2	EED	psi-mi:“MI:0914”(association)	0.650
SUZ12	EPOP	psi-mi:“MI:0914”(association)	0.640
JARID2	EED	psi-mi:“MI:0914”(association)	0.640
EED	EPOP	psi-mi:“MI:0914”(association)	0.530
RBBP4	TNRC18	psi-mi:“MI:0914”(association)	0.530
EZH1	EPOP	psi-mi:“MI:0914”(association)	0.530
Ttll7	TK2	psi-mi:“MI:0914”(association)	0.350
ALB	CNOT1	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
AEBP2	EED	psi-mi:“MI:0914”(association)	0.350
EZH1	RCCD1	psi-mi:“MI:0914”(association)	0.350

BioGRID (107): JARID2 (Affinity Capture-MS), EZH2 (Affinity Capture-MS), SUZ12 (Affinity Capture-MS), EZH1 (Affinity Capture-MS), EED (Affinity Capture-MS), AEBP2 (Affinity Capture-MS), RBBP4 (Affinity Capture-MS), RBBP7 (Affinity Capture-MS), HDAC2 (Affinity Capture-MS), EZH2 (Affinity Capture-Western), SUZ12 (Affinity Capture-Western), EZH1 (Affinity Capture-Western), EED (Affinity Capture-Western), JARID2 (Affinity Capture-Western), JARID2 (Affinity Capture-Western)

ESM2 similar proteins: A0A1L8HBI7, A0A1L8HJK9, A0A1L8HTT5, A6NP61, A8T6P4, C0SPG1, C3VD30, F1N4E5, K7SGN7, O35144, O35253, O70240, O88406, O88566, Q15554, Q1XFL1, Q3ZC82, Q4KLH3, Q5HZN9, Q5JTV8, Q5PQX1, Q5R7A3, Q62315, Q68DK7, Q6P1H6, Q6PDM1, Q6PG95, Q6ZPF3, Q76N89, Q7T3T8, Q7T3T9, Q7T3U0, Q7TNY7, Q7TP65, Q7TSX9, Q80SU3, Q80VM8, Q86XL3, Q8IVF5, Q8K3I4

Diamond homologs: A0A1W2PPD8, A1A5Q5, A1YVX4, B2RXH2, C0SUT9, F4I240, F4I6G4, F4KIX0, O64752, O75164, O94953, P29375, P41229, P41230, P47156, Q10RP4, Q1LVC2, Q23541, Q30DN6, Q336N8, Q38JA7, Q3U2K5, Q3UXZ9, Q53WJ1, Q5F363, Q5F3R2, Q5N712, Q5RD88, Q5XUN4, Q61T02, Q62240, Q62315, Q6B0I6, Q6IQX0, Q80Y84, Q8BW72, Q8GUI6, Q8L7T6, Q8VCD7, Q91VY5

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
PAX7-FOXO1	“up-regulates quantity by expression”	JARID2	“transcriptional regulation”
JARID2	“down-regulates quantity by repression”	MYOG	“transcriptional regulation”
miR-155	“down-regulates quantity by repression”	JARID2	“post transcriptional regulation”
JARID2	“down-regulates activity”	GATA4	binding
JARID2	“down-regulates activity”	NKX2-5	binding
JARID2	“down-regulates quantity by repression”	NPPA	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 20 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Transcriptional Regulation by E2F6	5	86.1×	8e-08
PRC2 methylates histones and DNA	8	71.7×	6e-12
PKMTs methylate histone lysines	6	56.8×	3e-08
Regulation of PTEN gene transcription	5	52.5×	8e-07
Defective pyroptosis	5	46.0×	1e-06
Negative Regulation of CDH1 Gene Transcription	5	35.4×	4e-06
Regulation of PD-L1(CD274) transcription	5	32.0×	6e-06
Activation of anterior HOX genes in hindbrain development during early embryogenesis	5	26.9×	1e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

383 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	17
Likely pathogenic	12
Uncertain significance	237
Likely benign	67
Benign	15

Top pathogenic / likely-pathogenic (29)

Variant ID	HGVS	Classification
1064851	NM_004973.4(JARID2):c.176_177del (p.Val59fs)	Pathogenic
1326871	NM_004973.4(JARID2):c.1506del (p.Thr503fs)	Pathogenic
1384760	NM_004973.4(JARID2):c.2014_2015insT (p.Thr672fs)	Pathogenic
2216682	NM_004973.4(JARID2):c.1272del (p.Arg425fs)	Pathogenic
2387170	NM_004973.4(JARID2):c.416del (p.Pro139fs)	Pathogenic
3062876	GRCh37/hg19 6p22.3(chr6:15302667-15391863)x1	Pathogenic
3062945	GRCh37/hg19 6p22.3(chr6:15372355-15433883)x1	Pathogenic
3112221	NM_004973.4(JARID2):c.2533G>T (p.Glu845Ter)	Pathogenic
3238862	NM_004973.4(JARID2):c.3379C>T (p.Arg1127Ter)	Pathogenic
3375479	NM_004973.4(JARID2):c.2983_2989dup (p.Val997fs)	Pathogenic
3531322	NM_004973.4(JARID2):c.2699_2700del (p.Gly900fs)	Pathogenic
3900339	NM_004973.4(JARID2):c.1186dup (p.Ala396fs)	Pathogenic
4278704	NM_004973.4(JARID2):c.2362C>T (p.Arg788Ter)	Pathogenic
4530608	NM_004973.4(JARID2):c.3007del (p.Gln1003fs)	Pathogenic
4622402	NM_004973.4(JARID2):c.3292C>T (p.Gln1098Ter)	Pathogenic
4759251	NM_004973.4(JARID2):c.1409_1410insCGGCAAGAAGGCCC (p.Pro475fs)	Pathogenic
4849272	NM_004973.4(JARID2):c.2005C>T (p.Gln669Ter)	Pathogenic
1321966	NM_004973.4(JARID2):c.2731+1G>C	Likely pathogenic
1339774	NM_004973.4(JARID2):c.12_13del (p.Arg5fs)	Likely pathogenic
1685354	NM_004973.4(JARID2):c.2731+5G>A	Likely pathogenic
1803984	NM_004973.4(JARID2):c.348G>T (p.Lys116Asn)	Likely pathogenic
1879647	NM_004973.4(JARID2):c.1410_1423del (p.Lys472fs)	Likely pathogenic
2444119	NM_004973.4(JARID2):c.1945+1G>A	Likely pathogenic
3075719	NM_004973.4(JARID2):c.2071C>T (p.Gln691Ter)	Likely pathogenic
3391829	GRCh37/hg19 6p22.3(chr6:15302668-15442633)x1	Likely pathogenic
3903254	NM_004973.4(JARID2):c.2T>C (p.Met1Thr)	Likely pathogenic
3903255	NM_004973.4(JARID2):c.3216del (p.Glu1073fs)	Likely pathogenic
4082028	NM_004973.4(JARID2):c.2374C>T (p.Gln792Ter)	Likely pathogenic
4292150	NM_004973.4(JARID2):c.1930dup (p.Glu644fs)	Likely pathogenic

SpliceAI

4676 predictions. Top by Δscore:

Variant	Effect	Δscore
6:15246585:G:GG	donor_gain	1.0000
6:15374105:AT:A	acceptor_gain	1.0000
6:15374106:T:G	acceptor_gain	1.0000
6:15374106:T:TA	acceptor_gain	1.0000
6:15374114:CAG:C	acceptor_loss	1.0000
6:15374114:CAGGA:C	acceptor_gain	1.0000
6:15374115:A:AG	acceptor_gain	1.0000
6:15374115:AG:A	acceptor_gain	1.0000
6:15374115:AGGAT:A	acceptor_gain	1.0000
6:15374116:G:A	acceptor_loss	1.0000
6:15374116:G:GT	acceptor_gain	1.0000
6:15374116:GG:G	acceptor_gain	1.0000
6:15374116:GGA:G	acceptor_gain	1.0000
6:15374116:GGAT:G	acceptor_gain	1.0000
6:15374116:GGATG:G	acceptor_gain	1.0000
6:15374248:GAATG:G	donor_gain	1.0000
6:15374249:AATGG:A	donor_loss	1.0000
6:15374251:TG:T	donor_gain	1.0000
6:15374252:GG:G	donor_gain	1.0000
6:15374252:GGTGA:G	donor_loss	1.0000
6:15374253:G:GA	donor_loss	1.0000
6:15374253:G:GG	donor_gain	1.0000
6:15374254:TGA:T	donor_loss	1.0000
6:15374255:GAG:G	donor_loss	1.0000
6:15410221:TA:T	acceptor_loss	1.0000
6:15410222:A:AT	acceptor_loss	1.0000
6:15410222:AG:A	acceptor_gain	1.0000
6:15410222:AGG:A	acceptor_gain	1.0000
6:15410223:G:T	acceptor_loss	1.0000
6:15410223:GG:G	acceptor_gain	1.0000

AlphaMissense

8169 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:15246562:G:T	R8M	1.000
6:15246563:G:C	R8S	1.000
6:15246563:G:T	R8S	1.000
6:15374169:T:C	L33P	1.000
6:15374181:T:C	L37P	1.000
6:15452026:G:C	R115T	1.000
6:15452026:G:T	R115M	1.000
6:15452027:G:C	R115S	1.000
6:15452027:G:T	R115S	1.000
6:15452031:T:C	F117L	1.000
6:15452032:T:C	F117S	1.000
6:15452032:T:G	F117C	1.000
6:15452033:T:A	F117L	1.000
6:15452033:T:G	F117L	1.000
6:15452151:T:C	F157L	1.000
6:15452152:T:C	F157S	1.000
6:15452152:T:G	F157C	1.000
6:15452153:T:A	F157L	1.000
6:15452153:T:G	F157L	1.000
6:15452155:T:A	L158H	1.000
6:15452155:T:C	L158P	1.000
6:15452160:T:C	F160L	1.000
6:15452162:T:A	F160L	1.000
6:15452162:T:G	F160L	1.000
6:15452164:T:C	L161P	1.000
6:15452166:T:C	C162R	1.000
6:15452170:T:C	L163P	1.000
6:15497008:T:A	W595R	1.000
6:15497008:T:C	W595R	1.000
6:15497044:T:C	F607L	1.000

dbSNP variants (sampled 300 via entrez): RS1000020201 (6:15487745 A>C,G,T), RS1000033023 (6:15510310 T>C), RS1000035038 (6:15366613 T>C), RS1000063639 (6:15348721 C>G), RS1000063878 (6:15372248 C>G), RS1000068093 (6:15476334 C>T), RS1000084612 (6:15345433 T>C), RS1000095103 (6:15303741 A>T), RS1000095989 (6:15519947 T>C), RS1000113313 (6:15293504 G>C,T), RS1000119088 (6:15418912 T>C), RS1000124699 (6:15414936 G>A), RS1000133546 (6:15470584 T>C), RS1000150030 (6:15267959 T>C), RS1000161644 (6:15307340 A>T)

Disease associations

OMIM: gene MIM:601594 | disease phenotypes: MIM:620098, MIM:209850

GenCC curated gene-disease

Disease	Classification	Inheritance
developmental delay with variable intellectual disability and dysmorphic facies	Strong	Autosomal dominant
syndromic intellectual disability	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
developmental delay with variable intellectual disability and dysmorphic facies	Definitive	AD

Mondo (8): neurodevelopmental disorder (MONDO:0700092), developmental delay with variable intellectual disability and dysmorphic facies (MONDO:0859306), autosomal dominant non-syndromic intellectual disability (MONDO:0015802), intellectual disability (MONDO:0001071), stereotypic movement disorder (MONDO:0002265), autism (MONDO:0005260), microcephaly (MONDO:0001149), syndromic intellectual disability (MONDO:0000508)

Orphanet (2): Autosomal dominant non-syndromic intellectual disability (Orphanet:178469), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

54 total (30 of 54 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000175	Cleft palate
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000278	Retrognathia
HP:0000286	Epicanthus
HP:0000307	Pointed chin
HP:0000316	Hypertelorism
HP:0000319	Smooth philtrum
HP:0000322	Short philtrum
HP:0000325	Triangular face
HP:0000336	Prominent supraorbital ridges
HP:0000337	Broad forehead
HP:0000369	Low-set ears
HP:0000411	Protruding ear
HP:0000414	Bulbous nose
HP:0000431	Wide nasal bridge
HP:0000490	Deeply set eye
HP:0000494	Downslanted palpebral fissures
HP:0000508	Ptosis
HP:0000568	Microphthalmia
HP:0000574	Thick eyebrow
HP:0000582	Upslanted palpebral fissure
HP:0000664	Synophrys
HP:0000709	Psychosis
HP:0000718	Aggressive behavior
HP:0000722	Compulsive behaviors
HP:0000729	Autistic behavior
HP:0000954	Single transverse palmar crease
HP:0000956	Acanthosis nigricans

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST000266_11	Multiple sclerosis (severity)	6.000000e-06
GCST001330_5	Ovarian reserve	3.000000e-07
GCST001826_8	Lymphoma	6.000000e-07
GCST004483_1	Multiple myeloma	1.000000e-08
GCST005830_126	Hand grip strength	8.000000e-10
GCST007576_61	Chronotype	1.000000e-09
GCST008362_108	Birth weight	3.000000e-08
GCST010303_57	Nevus count or cutaneous melanoma	5.000000e-09
GCST012227_228	Hip circumference adjusted for BMI	8.000000e-10
GCST90000025_518	Appendicular lean mass	6.000000e-15
GCST90002388_112	Lymphocyte count	1.000000e-11

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004770	ovarian reserve
EFO:0006941	grip strength measurement
EFO:0008328	chronotype measurement
EFO:0004344	birth weight
EFO:0004632	nevus count
EFO:0008039	BMI-adjusted hip circumference
EFO:0004980	appendicular lean mass
EFO:0004587	lymphocyte count

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D065886	Neurodevelopmental Disorders	F03.625
D019956	Stereotypic Movement Disorder	F03.625.984

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

61 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	4
Valproic Acid	decreases expression, affects cotreatment, increases expression, affects expression	3
Aflatoxin B1	decreases expression, decreases methylation, increases methylation	3
entinostat	increases expression, affects cotreatment	2
Estradiol	affects cotreatment, increases expression	2
Formaldehyde	decreases expression	2
Particulate Matter	affects cotreatment, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
bisphenol A	affects methylation	1
geraniol	increases expression	1
hydroxyhydroquinone	increases expression	1
beta-lapachone	increases expression	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	affects methylation, increases abundance	1
sodium arsenite	decreases expression	1
benzo(e)pyrene	affects methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
aflatoxin B2	decreases methylation	1
S-(1,2-dichlorovinyl)cysteine	decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
scriptaid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
suberoyl bis-hydroxamic acid	increases expression	1
PCI 5002	affects cotreatment, increases expression	1

Cellosaurus cell lines

9 cell lines: 6 cancer cell line, 3 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A3J2	SEES3-1V human JARID2, clone1	Embryonic stem cell	Male
CVCL_A3J3	SEES3-1V human JARID2, clone2	Embryonic stem cell	Male
CVCL_A3J4	SEES3-1V human JARID2, clone3	Embryonic stem cell	Male
CVCL_B8J0	Abcam HCT 116 JARID2 KO	Cancer cell line	Male
CVCL_B9LB	Abcam A-549 JARID2 KO	Cancer cell line	Male
CVCL_D2FY	Abcam MCF-7 JARID2 KO	Cancer cell line	Female
CVCL_ST73	HAP1 JARID2 (-) 1	Cancer cell line	Male
CVCL_ST74	HAP1 JARID2 (-) 2	Cancer cell line	Male
CVCL_ST75	HAP1 JARID2 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

202 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice