JARID2

Chr 6AD

jumonji and AT-rich interaction domain containing 2

Also known as: DIDDF, JMJ

NCBI Gene: 3720ENSG00000008083UniProt: Q92833

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. [provided by RefSeq, May 2012]

Primary Disease Associations & Inheritance

Developmental delay with variable intellectual disability and dysmorphic faciesMIM #620098
AD
380
ClinVar variants
53
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— JARID2
🧬
Gene-Disease Validity (ClinGen)
developmental delay with variable intellectual disability and dysmorphic facies · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
53 Pathogenic / Likely Pathogenic· 241 VUS of 380 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.19LOEUF
pLI 1.000
Z-score 6.31
OE 0.09 (0.05–0.19)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.69Z-score
OE missense 0.73 (0.68–0.78)
575 obs / 787.1 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.09 (0.05–0.19)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.73 (0.68–0.78)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.15
0≤1.21.6
LoF obs/exp: 5 / 55.9Missense obs/exp: 575 / 787.1Syn Z: -2.12

ClinVar Variant Classifications

380 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic38
Likely Pathogenic15
VUS241
Likely Benign67
Benign16
Conflicting3
38
Pathogenic
15
Likely Pathogenic
241
VUS
67
Likely Benign
16
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
10
0
28
0
38
Likely Pathogenic
6
2
7
0
15
VUS
2
212
26
1
241
Likely Benign
0
32
6
29
67
Benign
0
4
0
12
16
Conflicting
—3
Total182506742380

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

JARID2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

JARID2-related neurodevelopmental disorder

strong
ADLoss Of FunctionAbsent Gene Product, Altered Gene Product Structure, Decreased Gene Product Level
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Developmental delay with variable intellectual disability and dysmorphic facies

MIM #620098

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
DNA Methylation Signature for JARID2-Neurodevelopmental Syndrome.
Verberne EA et al.·Int J Mol Sci
2022
Homozygous variant in JARID2 causes female infertility characterized by compromised blastulation efficiency.
Sun J et al.·J Ovarian Res
2025
Functional Insight into and Refinement of the Genomic Boundaries of the JARID2-Neurodevelopmental Disorder Episignature.
van der Laan L et al.·Int J Mol Sci
2023Functional
JARID2 haploinsufficiency is associated with a clinically distinct neurodevelopmental syndrome.
Verberne EA et al.·Genet Med
2021
JARID2 promotes stemness and cisplatin resistance in non-small cell lung cancer via upregulation of Notch1.
Wang Q et al.·Int J Biochem Cell Biol
2021
Phenotypic expansion and variable expressivity in individuals with JARID2-related intellectual disability: A case series.
Cadieux-Dion M et al.·Clin Genet
2022Cohort
JARID2, a novel regulatory factor, promotes cell proliferation, migration, and invasion in oral squamous cell carcinoma.
Cheng Y et al.·BMC Cancer
2024
Next-Generation Sequencing and Triple-Negative Breast Cancer: Insights and Applications.
Tierno D et al.·Int J Mol Sci
2023Review
Valproic acid regulates the miR-155/Jarid2 axis by affecting miR-155 promoter methylation in glioma.
Wang R et al.·Acta Biochim Biophys Sin (Shanghai)
2024
JARID2 is a direct target of the PAX3-FOXO1 fusion protein and inhibits myogenic differentiation of rhabdomyosarcoma cells.
Walters ZS et al.·Oncogene
2014
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools