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…

LOFmechanismLOEUF 0.22

Clinical Summary— ZBTB38

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

110 VUS of 128 total submissions

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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

This gene — mechanism propensity

0.2897th %ile

GOF

0.2198th %ile

LOF

0.81top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.22

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

128 submitted variants in ClinVar

ClinVar

Classification Summary

VUS110

Likely Benign10

Benign4

110

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	110	0	110
Likely Benign	8	2	10
Benign	2	2	4
Total	120	4	124

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

22 pathogenic / likely-pathogenic (of 24) ClinVar copy-number / structural variants overlap ZBTB38 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →