ZNF732
Chr 4zinc finger protein 732
The encoded protein is a KRAB-containing zinc finger transcriptional repressor that functions by recruiting cofactors to induce heterochromatin formation and silence gene expression. Mutations in ZNF732 cause autosomal dominant developmental and epileptic encephalopathy with onset in infancy, characterized by severe intellectual disability, seizures, and distinctive facial features. The gene shows relatively low constraint to loss-of-function variation, suggesting the pathogenic variants may act through alternative mechanisms.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
273 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 | 133 | 0 | 133 |
Likely Pathogenic | 0 | 0 | 4 | 0 | 4 |
VUS | 0 | 94 | 24 | 0 | 118 |
Likely Benign | 0 | 6 | 7 | 2 | 15 |
Benign | 0 | 0 | 0 | 0 | 0 |
Conflicting | — | 1 | |||
| Total | 0 | 100 | 168 | 2 | 271 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ZNF732 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
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 →No open access results found
External Resources
Links to major genomics databases and tools