ZBTB3

Chr 11

zinc finger and BTB domain containing 3

NCBI Gene: 79842 ENSG00000185670 UniProt: Q9H5J0 OMIM: 621294

ZBTB3 encodes a DNA-binding transcription factor that regulates gene expression through RNA polymerase II in the nucleus. The gene shows low constraint to loss-of-function variants (pLI 0.02, LOEUF 0.68), and no definitive disease associations have been established in humans to date.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.68

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.68LOEUF

pLI 0.019

Z-score 2.55

OE 0.34 (0.19–0.68)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.08Z-score

OE missense 0.83 (0.75–0.92)

274 obs / 329.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.34 (0.19–0.68)

0≤0.351.4

Missense OE?0.83 (0.75–0.92)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 6 / 17.5Missense obs/exp: 274 / 329.4Syn Z: 0.41

Background carrier burden — how many people carry a rare variant somewhere in ZBTB3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 100

728 rare PASS variants

Rare truncating (LoF)

1 in 3,000

81 rare PASS variants

Rare synonymous (reference)

1 in 170

319 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ZBTB3. 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 2,600
South Asian	~43k	1 in 110	1 in 1,600
Remaining (unassigned)	~30k	1 in 94	1 in 4,300
European (Finnish)	~27k	1 in 300	≈ 1 in 6,400
Admixed American	~22k	1 in 110	1 in 2,500
African / African American	~21k	1 in 83	≈ 1 in 21,000
East Asian	~20k	1 in 130	1 in 2,200
Ashkenazi Jewish	~13k	1 in 590	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 110	≈ 1 in 1,400

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 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓