ZBTB48
Chr 1zinc finger and BTB domain containing 48
Also known as: HKR3, TZAP, ZNF855, pp9964
The protein directly binds telomeric DNA and regulates telomere length by initiating telomere trimming to prevent accumulation of aberrantly long telomeres, while also functioning as a transcription regulator for genes including the tumor suppressor ARF. Mutations cause autosomal dominant intellectual disability with short stature, behavioral problems, and distinctive facial features. This gene is highly intolerant to loss-of-function mutations, suggesting complete loss of protein function is likely incompatible with normal development.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
The highest-scoring mechanism for this gene is dominant-negative.
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
148 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 | 51 | 0 | 51 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 75 | 6 | 0 | 81 |
Likely Benign | 0 | 2 | 2 | 1 | 5 |
Benign | 0 | 0 | 1 | 0 | 1 |
| Total | 0 | 77 | 61 | 1 | 139 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ZBTB48 · 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