ZBTB20
Chr 3ADzinc finger and BTB domain containing 20
Also known as: DPZF, HOF, ODA-8S, PRIMS, ZNF288
This transcriptional repressor contains an N-terminal BTB/POZ domain and C-terminal zinc finger domain, functioning in neurogenesis, glucose homeostasis, and postnatal growth. Heterozygous loss-of-function mutations cause Primrose syndrome, an autosomal dominant disorder characterized by intellectual disability, distinctive facial features, and metabolic abnormalities. The high constraint scores (pLI 0.97, LOEUF 0.32) indicate this gene is highly intolerant to loss-of-function variants.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Highly missense-constrained (top ~0.1%)
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function 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.
Literature Evidence
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
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
ZBTB20 · 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
External Resources
Links to major genomics databases and tools