ZBTB21
Chr 21zinc finger and BTB domain containing 21
Also known as: ZNF295
The ZBTB21 protein acts as a transcription repressor that binds DNA and regulates gene expression by inhibiting RNA polymerase II transcription. Mutations cause autosomal dominant intellectual disability with variable features including developmental delay, seizures, and behavioral abnormalities. This gene is highly constrained against loss-of-function variants, indicating that ZBTB21 haploinsufficiency is likely not tolerated in the general population.
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
250 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 | 75 | 0 | 75 |
Likely Pathogenic | 0 | 0 | 2 | 0 | 2 |
VUS | 0 | 149 | 6 | 0 | 155 |
Likely Benign | 0 | 6 | 1 | 2 | 9 |
Benign | 0 | 0 | 0 | 0 | 0 |
Conflicting | — | 1 | |||
| Total | 0 | 155 | 84 | 2 | 242 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ZBTB21 · 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