ZBTB12

Chr 6

zinc finger and BTB domain containing 12

Also known as: Bat9, C6orf46, D6S59E, G10, NG35

NCBI Gene: 221527ENSG00000204366UniProt: Q9Y330

Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II; regulation of cytokine production; and regulation of immune system process. Located in nucleoplasm. [provided by Alliance of Genome Resources, Jul 2025]

43
ClinVar variants
7
Pathogenic / LP
0.95
pLI score· haploinsufficient
0
Active trials
Clinical Summary— ZBTB12
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.95). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
7 Pathogenic / Likely Pathogenic· 33 VUS of 43 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
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.
0.32LOEUF
pLI 0.949
Z-score 2.84
OE 0.00 (0.00–0.32)
Highly constrained

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

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.
3.45Z-score
OE missense 0.45 (0.39–0.52)
138 obs / 308.3 exp
Constrained

Highly missense-constrained (top ~0.1%)

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 (0.00–0.32)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.45 (0.39–0.52)
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.0.86
0≤1.21.6
LoF obs/exp: 0 / 9.4Missense obs/exp: 138 / 308.3Syn Z: 1.30

ClinVar Variant Classifications

43 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5
Likely Pathogenic2
VUS33
Likely Benign1
Benign2
5
Pathogenic
2
Likely Pathogenic
33
VUS
1
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
5
0
5
Likely Pathogenic
0
0
2
0
2
VUS
0
29
4
0
33
Likely Benign
0
1
0
0
1
Benign
0
0
0
2
2
Total03011243

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

View in ClinVar →

Protein Context — Lollipop Plot

ZBTB12 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Mitochondrial protein TOMM7 alleviates diabetic kidney disease by regulating mitophagy via intracellular redistribution of phospholipase PLA2G6.
Wang YH et al.·Kidney Int
2026
ZBTB12 is a molecular barrier to dedifferentiation in human pluripotent stem cells.
Han D et al.·Nat Commun
2023
ZBTB12 DNA methylation is associated with coagulation- and inflammation-related blood cell parameters: findings from the Moli-family cohort.
Noro F et al.·Clin Epigenetics
2019Cohort
Serum DLAT Is a Potential Diagnostic Marker in AFP-Negative HCC.
Huang F et al.·Biol Pharm Bull
2024
Astragaloside IV inhibits pathological functions of gastric cancer-associated fibroblasts through regulation of the HOXA6/ZBTB12 axis.
Liu H et al.·Acta Pharm
2023
Epigenome-wide associations between observed maternal sensitivity and offspring DNA methylation: a population-based prospective study in children.
Dall' Aglio L et al.·Psychol Med
2022
ZBTB12 promotes breast cancer progression through transcriptional activation of the DNMT3B/ALDH1A2 axis.
Zhang W et al.·Biochem Biophys Res Commun
2025
Deep analysis of the major histocompatibility complex genetic associations using covariate analysis and haploblocks unravels new mechanisms for the molecular etiology of Elite Control in AIDS.
Rahmouni M et al.·BMC Immunol
2025Functional
The HLA-B*57:01 allele corresponds to a very large MHC haploblock likely explaining its massive effect for HIV-1 elite control.
Rahmouni M et al.·Front Immunol
2023
Association of MHC class-III gene polymorphisms with ER-positive breast cancer in Chinese Han population.
Pan Q et al.·Genet Mol Res
2012
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