ZBTB43

Chr 9

zinc finger and BTB domain containing 43

Also known as: ZBTB22B, ZNF-X, ZNF297B

This gene encodes a transcription factor that binds DNA and regulates gene expression by RNA polymerase II and III. Mutations cause autosomal dominant neurodevelopmental disorders with intellectual disability and developmental delay. The gene is highly constrained against loss-of-function variants (pLI 0.99, LOEUF 0.23), indicating intolerance to protein-disrupting mutations.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.23
Clinical SummaryZBTB43
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
36 unique Pathogenic / Likely Pathogenic· 59 VUS of 102 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.23LOEUF
pLI 0.988
Z-score 3.38
OE 0.00 (0.000.23)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.54Z-score
OE missense 0.57 (0.500.65)
161 obs / 280.9 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.00 (0.000.23)
00.351.4
Missense OE0.57 (0.500.65)
00.61.4
Synonymous OE0.95
01.21.6
LoF obs/exp: 0 / 13.3Missense obs/exp: 161 / 280.9Syn Z: 0.42
DN
0.2698th %ile
GOF
0.2298th %ile
LOF
0.82top 5%

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

LOFprediction above median · LOEUF 0.23

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

102 submitted variants in ClinVar

Classification Summary

Pathogenic35
Likely Pathogenic1
VUS59
Likely Benign1
35
Pathogenic
1
Likely Pathogenic
59
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
35
0
35
Likely Pathogenic
0
0
1
0
1
VUS
0
58
1
0
59
Likely Benign
0
1
0
0
1
Benign
0
0
0
0
0
Total05937096

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

View in ClinVar →

Protein Context — Lollipop Plot

ZBTB43 · 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