ZNF133
Chr 20zinc finger protein 133
Also known as: ZNF150, pHZ-13, pHZ-66
The protein functions as a transcriptional repressor that binds to specific DNA sequences to negatively regulate RNA polymerase II transcription in the nucleus. Mutations in ZNF133 have been associated with neurodevelopmental disorders including developmental delay and intellectual disability. The gene shows moderate constraint against loss-of-function variants and inheritance patterns vary depending on the specific clinical presentation.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Moderately missense-constrained (top ~2.5%)
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
102 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 | 23 | 0 | 23 |
Likely Pathogenic | 0 | 0 | 0 | 0 | 0 |
VUS | 0 | 66 | 3 | 0 | 69 |
Likely Benign | 0 | 4 | 0 | 0 | 4 |
Benign | 0 | 0 | 0 | 2 | 2 |
| Total | 0 | 70 | 26 | 2 | 98 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ZNF133 · 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 →External Resources
Links to major genomics databases and tools