ZBTB38

Chr 3

zinc finger and BTB domain containing 38

Also known as: CIBZ, PPP1R171, ZNF921

NCBI Gene: 253461 ENSG00000177311 UniProt: Q8NAP3 OMIM: 612218

The protein encoded by this gene is a zinc finger transcriptional activator that binds methylated DNA. The encoded protein can form homodimers or heterodimers through the zinc finger domains. In mouse, inhibition of this protein has been associated with apoptosis in some cell types. [provided by RefSeq, Jun 2010]

OMIM Research

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

0.22

LOEUF· LoF intol.

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.22LOEUF

pLI 0.999

Z-score 5.02

OE 0.09 (0.04–0.22)

Highly constrained

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

Missense Constraint?

2.31Z-score

OE missense 0.75 (0.69–0.81)

494 obs / 660.9 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.09 (0.04–0.22)

0≤0.351.4

Missense OE?0.75 (0.69–0.81)

0≤0.61.4

Synonymous OE?0.88

0≤1.21.6

LoF obs/exp: 3 / 35.1Missense obs/exp: 494 / 660.9Syn Z: 1.52

Background carrier burden — how many people carry a rare variant somewhere in ZBTB38?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 55

1,153 rare PASS variants

Rare truncating (LoF)

1 in 5,700

61 rare PASS variants

Rare synonymous (reference)

1 in 88

536 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ZBTB38. 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 68	1 in 4,600
South Asian	~43k	1 in 69	≈ 1 in 11,000
Remaining (unassigned)	~30k	1 in 58	none seen
European (Finnish)	~27k	1 in 170	≈ 1 in 6,500
Admixed American	~22k	1 in 46	1 in 3,300
African / African American	~21k	1 in 54	≈ 1 in 17,000
East Asian	~20k	1 in 49	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 180	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 63	≈ 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 ↓