ZBTB7A

Chr 19AD

zinc finger and BTB domain containing 7A

Also known as: FBI-1, FBI1, LRF, MNDLFH, TIP21, ZBTB7, ZNF857A, pokemon

NCBI Gene: 51341ENSG00000178951UniProt: O95365

Enables several functions, including SMAD binding activity; nuclear androgen receptor binding activity; and transcription corepressor binding activity. Involved in several processes, including erythrocyte maturation; negative regulation of signal transduction; and regulation of nucleobase-containing compound metabolic process. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

Macrocephaly, neurodevelopmental delay, lymphoid hyperplasia, and persistent fetal hemoglobinMIM #619769
AD
0
Active trials
0
Pathogenic / LP
0
ClinVar variants
30
Pubs (1 yr)
4.0
Missense Z· constrained
0.33
LOEUF· LoF intolerant
Clinical Summary— ZBTB7A
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.96). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
0.33LOEUF
pLI 0.959
Z-score 3.27
OE 0.07 (0.02–0.33)
Highly constrained

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

Missense Constraint
4.04Z-score
OE missense 0.43 (0.38–0.49)
175 obs / 403.5 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.07 (0.02–0.33)
0≤0.351.4
Missense OE0.43 (0.38–0.49)
0≤0.61.4
Synonymous OE0.83
0≤1.21.6
LoF obs/exp: 1 / 14.4Missense obs/exp: 175 / 403.5Syn Z: 1.89
LOFDN
DN
0.2798th %ile
GOF
0.2994th %ile
LOF
0.83top 5%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOFprediction above median · LOEUF 0.33
DN1 literature citation

Literature Evidence

DNWe identified a de novo likely pathogenic heterozygous missense variant of ZBTB7A (NM_015898.3:c.1152C>G, p.(Cys384Trp)) in a Japanese boy with macrocephaly, intellectual disability, and sleep apnea. This variant affects the conserved cysteine residue forming the coordinate bond with Zn2+ ion at thePMID:31645653

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

ZBTB7A · protein map & ClinVar variants

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

Gene2Phenotype Curations

ZBTB7A-related developmental disorder

limited
ADUndeterminedAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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