ZZEF1

Chr 17

zinc finger ZZ-type and EF-hand domain containing 1

Also known as: ZZZ4

NCBI Gene: 23140 ENSG00000074755 UniProt: O43149 OMIM: 619459

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.

OMIM ResearchSummary from RefSeq, UniProt

Enables histone binding activity. Predicted to be involved in DNA-templated transcription. Predicted to act upstream of or within several processes, including glutamatergic synaptic transmission; regulation of peptidyl-tyrosine phosphorylation; and visual learning. Predicted to be located in cell surface; postsynapse; and presynaptic active zone. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.29

LOEUF· LoF intol.

LOF

Mechanism· predicted