JADE1

Chr 4

jade family PHD finger 1

Also known as: PHF17

The JADE1 protein functions as a scaffold subunit of histone acetyltransferase complexes that acetylate histone H4, regulating DNA replication initiation and promoting apoptosis. Mutations cause autosomal dominant intellectual disability with seizures and dysmorphic features, typically presenting in early childhood. This gene is highly constrained against loss-of-function variants, indicating that such mutations are likely to be pathogenic.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
7
Pubs (1 yr)
25
P/LP submissions
0%
P/LP missense
0.25
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical SummaryJADE1
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
25 unique Pathogenic / Likely Pathogenic· 77 VUS of 110 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.25LOEUF
pLI 0.999
Z-score 5.05
OE 0.11 (0.050.25)
Highly constrained

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

Missense Constraint
3.18Z-score
OE missense 0.59 (0.530.65)
281 obs / 476.4 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.11 (0.050.25)
00.351.4
Missense OE0.59 (0.530.65)
00.61.4
Synonymous OE0.90
01.21.6
LoF obs/exp: 4 / 37.3Missense obs/exp: 281 / 476.4Syn Z: 1.03
DN
0.3296th %ile
GOF
0.3789th %ile
LOF
0.78top 5%

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

LOFprediction above median · LOEUF 0.25

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

110 submitted variants in ClinVar

Classification Summary

Pathogenic24
Likely Pathogenic1
VUS77
Likely Benign2
Benign5
24
Pathogenic
1
Likely Pathogenic
77
VUS
2
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
24
0
24
Likely Pathogenic
0
0
1
0
1
VUS
0
74
3
0
77
Likely Benign
0
0
2
0
2
Benign
0
1
2
2
5
Total075322109

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

View in ClinVar →

Protein Context — Lollipop Plot

JADE1 · 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
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC