ZZZ3

Chr 1

zinc finger ZZ-type containing 3

Also known as: ATAC1

The protein is a histone H3 reader that maintains histone acetylation and gene activation as a component of the ATAC complex, which has histone acetyltransferase activity on histones H3 and H4. Mutations in this gene cause autosomal dominant intellectual disability with variable additional features including developmental delay and behavioral abnormalities. 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
4
Pubs (1 yr)
16
P/LP submissions
0%
P/LP missense
0.18
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical SummaryZZZ3
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
16 unique Pathogenic / Likely Pathogenic· 111 VUS of 161 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.18LOEUF
pLI 1.000
Z-score 5.71
OE 0.07 (0.030.18)
Highly constrained

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

Missense Constraint
1.67Z-score
OE missense 0.78 (0.720.85)
363 obs / 464.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.07 (0.030.18)
00.351.4
Missense OE0.78 (0.720.85)
00.61.4
Synonymous OE0.88
01.21.6
LoF obs/exp: 3 / 43.8Missense obs/exp: 363 / 464.4Syn Z: 1.19
DN
0.2299th %ile
GOF
0.2298th %ile
LOF
0.83top 5%

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

LOFprediction above median · LOEUF 0.18

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

161 submitted variants in ClinVar

Classification Summary

Pathogenic15
Likely Pathogenic1
VUS111
Likely Benign5
Benign2
15
Pathogenic
1
Likely Pathogenic
111
VUS
5
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
15
0
15
Likely Pathogenic
0
0
1
0
1
VUS
0
104
7
0
111
Likely Benign
0
4
0
1
5
Benign
0
0
1
1
2
Total0108242134

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

View in ClinVar →

Protein Context — Lollipop Plot

ZZZ3 · protein map & ClinVar variants

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

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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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗