ZBTB5

Chr 9

zinc finger and BTB domain containing 5

This protein functions as a DNA-binding transcription repressor that negatively regulates RNA polymerase II transcription in the nucleus. Mutations in ZBTB5 cause autosomal recessive developmental and epileptic encephalopathy with movement abnormalities, typically presenting in infancy with seizures, developmental delay, and dystonia. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.483), consistent with its role in neurodevelopment.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.48
Clinical SummaryZBTB5
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.62) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
72 unique Pathogenic / Likely Pathogenic· 76 VUS of 150 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.48LOEUF
pLI 0.618
Z-score 3.02
OE 0.19 (0.080.48)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.23Z-score
OE missense 0.82 (0.750.90)
316 obs / 383.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.19 (0.080.48)
00.351.4
Missense OE0.82 (0.750.90)
00.61.4
Synonymous OE1.05
01.21.6
LoF obs/exp: 3 / 16.1Missense obs/exp: 316 / 383.8Syn Z: -0.45
DN
0.4091th %ile
GOF
0.2099th %ile
LOF
0.71top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.48

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

150 submitted variants in ClinVar

Classification Summary

Pathogenic63
Likely Pathogenic9
VUS76
Likely Benign1
63
Pathogenic
9
Likely Pathogenic
76
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
63
0
63
Likely Pathogenic
0
0
9
0
9
VUS
0
72
4
0
76
Likely Benign
0
1
0
0
1
Benign
0
0
0
0
0
Total073760149

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

View in ClinVar →

Protein Context — Lollipop Plot

ZBTB5 · 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

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
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