ZBTB26

Chr 9

zinc finger and BTB domain containing 26

Also known as: ZNF481, bioref

NCBI Gene: 57684ENSG00000171448UniProt: Q9HCK0OMIM: 620164

The protein functions as a transcriptional regulator that binds to specific DNA sequences and negatively regulates RNA polymerase II transcription, with predicted roles in cytokine production and immune system regulation. Currently, no established Mendelian diseases have been definitively linked to ZBTB26 mutations. The gene shows moderate tolerance to loss-of-function variants based on constraint metrics, suggesting that if pathogenic mutations exist, they may cause disease through other mechanisms.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.64
Clinical Summary— ZBTB26
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.28) despite low pLI — interpret in context.
📋
ClinVar Variants
29 unique Pathogenic / Likely Pathogenic· 34 VUS of 64 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.64LOEUF
pLI 0.138
Z-score 2.52
OE 0.28 (0.14–0.64)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
2.48Z-score
OE missense 0.54 (0.46–0.63)
123 obs / 228.6 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.28 (0.14–0.64)
0≤0.351.4
Missense OE0.54 (0.46–0.63)
0≤0.61.4
Synonymous OE0.95
0≤1.21.6
LoF obs/exp: 4 / 14.3Missense obs/exp: 123 / 228.6Syn Z: 0.36
DN
0.6162th %ile
GOF
0.5072th %ile
LOF
0.49top 25%

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

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

64 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic28
Likely Pathogenic1
VUS34
28
Pathogenic
1
Likely Pathogenic
34
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
28
0
28
Likely Pathogenic
0
0
1
0
1
VUS
0
31
3
0
34
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total03132063

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ZBTB26 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients