ZBTB7A

Chr 19

zinc finger and BTB domain containing 7A

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

NCBI Gene: 51341 ENSG00000178951 UniProt: O95365

The ZBTB7A protein is a transcription factor that represses genes involved in cell proliferation, differentiation, and the switch from fetal to adult hemoglobin expression during red blood cell development. Mutations cause autosomal dominant macrocephaly, neurodevelopmental delay, lymphoid hyperplasia, and persistent fetal hemoglobin. This gene is highly constrained against loss-of-function variants, with primary involvement of the nervous system, immune system, and hematopoietic system.

ResearchSummary from RefSeq, OMIM, UniProt

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]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.33

Clinical Summary— ZBTB7A

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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.

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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 OE?0.07 (0.02–0.33)

0≤0.351.4

Missense OE?0.43 (0.38–0.49)

0≤0.61.4

Synonymous OE?0.83

0≤1.21.6

LoF obs/exp: 1 / 14.4Missense obs/exp: 175 / 403.5Syn Z: 1.89

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

moderateZBTB7A-related developmental disorder with macrocephaly, obstructive sleep apnea, and persistent fetal hemoglobinLOFAD

This gene — mechanism propensity

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 the1

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

References