ZBTB7A

Chr 19AD

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 OMIM: 605878

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Enables several functions, including DNA-binding transcription factor 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 RNA metabolic process. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Macrocephaly, neurodevelopmental delay, lymphoid hyperplasia, and persistent fetal hemoglobinMIM #619769

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Macrocephaly, neurodevelopmental delay, lymphoid hyperplasia, and persistent fetal hemoglobin; no ClinGen or GenCC tier

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.33

LOEUF· LoF intol.

LOF

Mechanism· G2P

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

Background carrier burden — how many people carry a rare variant somewhere in ZBTB7A?

gnomAD v4 · ~730k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 130

673 rare PASS variants

Rare truncating (LoF)

1 in 6,000

39 rare PASS variants

Rare synonymous (reference)

1 in 92

478 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ZBTB7A. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 170	1 in 6,500
South Asian	~43k	1 in 80	1 in 2,400
Remaining (unassigned)	~30k	1 in 90	≈ 1 in 28,000
European (Finnish)	~27k	1 in 160	1 in 2,100
Admixed American	~22k	1 in 140	≈ 1 in 5,100
African / African American	~21k	1 in 130	≈ 1 in 9,200
East Asian	~20k	1 in 140	≈ 1 in 6,900
Ashkenazi Jewish	~13k	1 in 330	none seen
Middle Eastern	~2,884	1 in 110	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 2 coding exons well covered in gnomAD exomes and genomes.? see exons ↓