ZZEF1
Chr 17zinc finger ZZ-type and EF-hand domain containing 1
Also known as: ZZZ4
The ZZEF1 protein functions as a histone H3 reader that acts as a transcriptional coactivator for KLF6 and KLF9 transcription factors, with predicted roles in glutamatergic synaptic transmission and visual learning. Mutations cause autosomal dominant developmental delay with seizures and dysmorphic features, typically presenting in early childhood. The gene is highly constrained against loss-of-function variants, indicating that such mutations are likely to be pathogenic.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Mild missense constraint
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
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
500 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 4 | 0 | 4 |
Likely Pathogenic | 0 | 0 | 0 | 0 | 0 |
VUS | 0 | 409 | 4 | 0 | 413 |
Likely Benign | 1 | 20 | 0 | 6 | 27 |
Benign | 0 | 0 | 0 | 0 | 0 |
Conflicting | — | 1 | |||
| Total | 1 | 429 | 8 | 6 | 445 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ZZEF1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools