ZBTB43

Chr 9

zinc finger and BTB domain containing 43

Also known as: ZBTB22B, ZNF-X, ZNF297B

NCBI Gene: 23099 ENSG00000169155 UniProt: O43298 OMIM: 618676

This gene encodes a transcription factor that binds DNA and regulates gene expression by RNA polymerase II and III. Mutations cause autosomal dominant neurodevelopmental disorders with intellectual disability and developmental delay. The gene is highly constrained against loss-of-function variants (pLI 0.99, LOEUF 0.23), indicating intolerance to protein-disrupting mutations.

OMIM ResearchSummary from RefSeq, UniProt

Enables RNA polymerase III general transcription initiation factor binding activity and sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in chromatin. [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

0.23

LOEUF· LoF intol.

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.23LOEUF

pLI 0.988

Z-score 3.38

OE 0.00 (0.00–0.23)

Highly constrained

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

Missense Constraint?

2.54Z-score

OE missense 0.57 (0.50–0.65)

161 obs / 280.9 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.23)

0≤0.351.4

Missense OE?0.57 (0.50–0.65)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 0 / 13.3Missense obs/exp: 161 / 280.9Syn Z: 0.42

Background carrier burden — how many people carry a rare variant somewhere in ZBTB43?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 160

406 rare PASS variants

Rare truncating (LoF)

1 in 27,000

12 rare PASS variants

Rare synonymous (reference)

1 in 91

230 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ZBTB43. 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 160	1 in 43,000
South Asian	~43k	1 in 220	none seen
Remaining (unassigned)	~30k	1 in 130	≈ 1 in 29,000
European (Finnish)	~27k	1 in 1,700	1 in 5,300
Admixed American	~22k	1 in 160	none seen
African / African American	~21k	1 in 160	≈ 1 in 5,500
East Asian	~20k	1 in 130	none seen
Ashkenazi Jewish	~13k	1 in 470	none seen
Middle Eastern	~2,884	1 in 130	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 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓