ZBTB4

Chr 17

zinc finger and BTB domain containing 4

Also known as: KAISO-L1, ZNF903

NCBI Gene: 57659ENSG00000174282UniProt: Q9P1Z0

Enables several functions, including DNA-binding transcription repressor activity, RNA polymerase II-specific; nucleotide binding activity; and protein homodimerization activity. Involved in DNA damage response and negative regulation of transcription by RNA polymerase II. Located in cytosol and nuclear body. [provided by Alliance of Genome Resources, Jul 2025]

260
ClinVar variants
27
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
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.
📋
ClinVar Variants
27 Pathogenic / Likely Pathogenic· 206 VUS of 260 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.93Z-score
OE missense 0.78 (0.73–0.84)
498 obs / 634.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–0.11)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.78 (0.73–0.84)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.03
0≤1.21.6
LoF obs/exp: 0 / 26.3Missense obs/exp: 498 / 634.9Syn Z: -0.34

ClinVar Variant Classifications

260 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic24
Likely Pathogenic3
VUS206
Likely Benign19
Benign8
24
Pathogenic
3
Likely Pathogenic
206
VUS
19
Likely Benign
8
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
24
0
24
Likely Pathogenic
0
0
3
0
3
VUS
0
199
7
0
206
Likely Benign
0
16
0
3
19
Benign
0
3
0
5
8
Total0218348260

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

View in 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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Identification of ZBTB4 as an immunological biomarker that can inhibit the proliferation and invasion of pancreatic cancer.
Yang Z et al.·BMC Cancer
2023
Variants regulating ZBTB4 are associated with age-at-onset of Alzheimer's disease.
Blue EE et al.·Genes Brain Behav
2018
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
Therapeutic Targeting of Overexpressed MiRNAs in Cancer Progression.
Lee SH et al.·Curr Drug Targets
2022Review
Identification of oncogenic microRNA-17-92/ZBTB4/specificity protein axis in breast cancer.
Kim K et al.·Oncogene
2012
Genetic Determinants of Colonic Diverticulosis-A Systematic Review.
Nehring P et al.·Genes (Basel)
2025Review
The Genomic landscape of short tandem repeats across multiple ancestries.
Vijayaraghavan P et al.·PLoS One
2023
Demethylase FTO inhibits the occurrence and development of triple-negative breast cancer by blocking m (6)A-dependent miR-17-5p maturation-induced ZBTB4 depletion.
Ni J et al.·Acta Biochim Biophys Sin (Shanghai)
2024
U3 snoRNA-mediated degradation of ZBTB7A regulates aerobic glycolysis in isocitrate dehydrogenase 1 wild-type glioblastoma cells.
Dong W et al.·CNS Neurosci Ther
2023
Unifying mechanisms of action of the anticancer activities of triterpenoids and synthetic analogs.
Safe SH et al.·Anticancer Agents Med Chem
2012Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools