JARID2

Chr 6AD

jumonji and AT-rich interaction domain containing 2

Also known as: DIDDF, JMJ

NCBI Gene: 3720ENSG00000008083UniProt: Q92833OMIM: 601594

The JARID2 protein functions as a DNA-binding transcriptional repressor that recruits the Polycomb repressive complex 2 (PRC2) to target genes, playing essential roles in embryonic development including heart and liver development, neural tube fusion, and hematopoiesis. Mutations cause autosomal dominant developmental delay with variable intellectual disability and dysmorphic facies. This gene is highly constrained against loss-of-function variants (pLI 1.0, LOEUF 0.19), indicating that most loss-of-function mutations are likely pathogenic.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.191 OMIM phenotype
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
8 unique Pathogenic / Likely Pathogenic· 48 VUS of 100 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
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
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
LoF OE0.09 (0.05–0.19)
0≤0.351.4
Missense OE0.73 (0.68–0.78)
0≤0.61.4
Synonymous OE1.15
0≤1.21.6
LoF obs/exp: 5 / 55.9Missense obs/exp: 575 / 787.1Syn Z: -2.12
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongJARID2-related neurodevelopmental disorderLOFAD
DN
0.19100th %ile
GOF
0.1999th %ile
LOF
0.84top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 88% of P/LP variants are LoF · LOEUF 0.19

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

100 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6
Likely Pathogenic2
VUS48
Likely Benign17
6
Pathogenic
2
Likely Pathogenic
48
VUS
17
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
0
1
0
6
Likely Pathogenic
2
0
0
0
2
VUS
0
45
3
0
48
Likely Benign
0
8
0
9
17
Benign
0
0
0
0
0
Total7534973

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients