JADE3

Chr X

jade family PHD finger 3

Also known as: JADE-3, PHF16

The protein functions as a scaffold subunit of HBO1 complexes that acetylate histone H4, playing a direct role in chromatin modification and gene regulation. Mutations cause autosomal dominant intellectual disability with developmental delay and variable additional features. This gene is highly constrained against loss-of-function variants (pLI 0.999, LOEUF 0.124), indicating that even heterozygous disruption can cause disease.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.12
Clinical SummaryJADE3
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
55 unique Pathogenic / Likely Pathogenic· 68 VUS of 130 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.12LOEUF
pLI 1.000
Z-score 4.54
OE 0.00 (0.000.12)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
1.90Z-score
OE missense 0.70 (0.620.78)
218 obs / 312.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.000.12)
00.351.4
Missense OE0.70 (0.620.78)
00.61.4
Synonymous OE0.93
01.21.6
LoF obs/exp: 0 / 24.0Missense obs/exp: 218 / 312.3Syn Z: 0.61
DN
0.3097th %ile
GOF
0.3293th %ile
LOF
0.79top 5%

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

LOFprediction above median · LOEUF 0.12

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

130 submitted variants in ClinVar

Classification Summary

Pathogenic54
Likely Pathogenic1
VUS68
Likely Benign7
54
Pathogenic
1
Likely Pathogenic
68
VUS
7
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
54
0
54
Likely Pathogenic
0
0
1
0
1
VUS
0
62
6
0
68
Likely Benign
0
6
0
1
7
Benign
0
0
0
0
0
Total068611130

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

View in ClinVar →

Protein Context — Lollipop Plot

JADE3 · 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

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC