ZBTB4

Chr 17

zinc finger and BTB domain containing 4

Also known as: KAISO-L1, ZNF903

NCBI Gene: 57659ENSG00000174282UniProt: Q9P1Z0OMIM: 612308

This gene encodes a transcriptional repressor that binds to methylated CpG dinucleotides and regulates gene expression in a DNA methylation-dependent manner, with additional roles in DNA damage response and postnatal muscle development. The gene is highly constrained against loss-of-function variants (pLI = 1.0, LOEUF = 0.11), but no associated human diseases have been established to date. Given the high constraint scores, pathogenic variants in ZBTB4 would be expected to cause developmental disorders, but clinical phenotypes remain to be defined.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.11
Clinical Summary— ZBTB4
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.11LOEUF
pLI 1.000
Z-score 4.76
OE 0.00 (0.00–0.11)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
1.93Z-score
OE missense 0.78 (0.73–0.84)
498 obs / 634.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.00–0.11)
0≤0.351.4
Missense OE0.78 (0.73–0.84)
0≤0.61.4
Synonymous OE1.03
0≤1.21.6
LoF obs/exp: 0 / 26.3Missense obs/exp: 498 / 634.9Syn Z: -0.34
DN
0.2099th %ile
GOF
0.3292th %ile
LOF
0.88top 5%

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

LOFprediction above median · LOEUF 0.11

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

ClinVar

Protein Context — Lollipop Plot

ZBTB4 · 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 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
MSC-derived exosomes deliver ZBTB4 to mediate transcriptional repression of ITIH3 in astrocytes in spinal cord injury.
Wu H et al.·Brain Res Bull
2024
Demethylase FTO inhibits the occurrence and development of triple-negative breast cancer by blocking m 6A-dependent miR-17-5p maturation-induced ZBTB4 depletion.
Ni J et al.·Acta Biochim Biophys Sin (Shanghai)
2024Open Access
Retraction Notice to: METTL3-mediated m6A modification of ZBTB4 mRNA is involved in the smoking-induced EMT in cancer of the lung.
Cheng C et al.·Mol Ther Nucleic Acids
2023Open Access
Hypoxia derived exosomes promote the proliferation and metastasis of colorectal cancer through the regulation of HIF-1α/miR-4299/ZBTB4.
Wu L et al.·Life Sci
2023
Identification of ZBTB4 as an immunological biomarker that can inhibit the proliferation and invasion of pancreatic cancer.
Yang Z et al.·BMC Cancer
2023Open Access
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