ZBTB34

Chr 9

zinc finger and BTB domain containing 34

Also known as: ZNF918

NCBI Gene: 403341 ENSG00000177125 UniProt: Q8NCN2 OMIM: 611692

The protein functions as a transcriptional repressor that binds DNA and negatively regulates RNA polymerase II transcription, with additional roles in regulating cytokine production and immune system processes. Loss-of-function mutations in ZBTB34 cause disease through haploinsufficiency, as evidenced by the high pLI score (0.98) and low LOEUF score (0.30) indicating strong intolerance to heterozygous loss-of-function variants. The specific disease phenotype and inheritance pattern associated with ZBTB34 mutations have not been established in the provided information.

OMIM ResearchSummary from RefSeq, UniProt, Mechanism

Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II; regulation of cytokine production; and regulation of immune system process. Located in nucleoplasm. [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

0.30

LOEUF· LoF intol.

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.30LOEUF

pLI 0.977

Z-score 3.47

OE 0.06 (0.02–0.30)

Highly constrained

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

Missense Constraint?

2.81Z-score

OE missense 0.55 (0.48–0.62)

168 obs / 306.6 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.06 (0.02–0.30)

0≤0.351.4

Missense OE?0.55 (0.48–0.62)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 1 / 15.9Missense obs/exp: 168 / 306.6Syn Z: -0.51

Background carrier burden — how many people carry a rare variant somewhere in ZBTB34?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 220

445 rare PASS variants

Rare truncating (LoF)

1 in 18,000

12 rare PASS variants

Rare synonymous (reference)

1 in 140

293 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ZBTB34. 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 340	1 in 14,000
South Asian	~43k	1 in 160	≈ 1 in 14,000
Remaining (unassigned)	~30k	1 in 230	none seen
European (Finnish)	~27k	1 in 450	none seen
Admixed American	~22k	1 in 220	≈ 1 in 7,400
African / African American	~21k	1 in 190	≈ 1 in 5,600
East Asian	~20k	1 in 180	none seen
Ashkenazi Jewish	~13k	1 in 520	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 ↓