ZBTB16

Chr 11

zinc finger and BTB domain containing 16

Also known as: PLZF, ZNF145

NCBI Gene: 7704 ENSG00000109906 UniProt: Q05516

This gene encodes a zinc finger transcription factor with nine Kruppel-type zinc finger domains that acts as a transcriptional repressor and probable component of an E3 ubiquitin-protein ligase complex involved in protein degradation. Mutations cause acute promyelocytic leukemia with PL2F/RARA gene rearrangements. The gene is highly constrained against loss-of-function variants (pLI 1.0, LOEUF 0.19), indicating intolerance to disruption.

ResearchSummary from RefSeq, OMIM, UniProt

This gene is a member of the Krueppel C2H2-type zinc-finger protein family and encodes a zinc finger transcription factor that contains nine Kruppel-type zinc finger domains at the carboxyl terminus. This protein is located in the nucleus, is involved in cell cycle progression, and interacts with a histone deacetylase. Specific instances of aberrant gene rearrangement at this locus have been associated with acute promyelocytic leukemia (APL). Alternate transcriptional splice variants have been characterized. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.19

Clinical Summary— ZBTB16

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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

64 VUS of 107 total submissions

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.19LOEUF

pLI 0.999

Z-score 4.41

OE 0.04 (0.01–0.19)

Highly constrained

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

Missense Constraint?

2.47Z-score

OE missense 0.65 (0.59–0.72)

264 obs / 403.7 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.04 (0.01–0.19)

0≤0.351.4

Missense OE?0.65 (0.59–0.72)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 1 / 24.6Missense obs/exp: 264 / 403.7Syn Z: -0.51

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

limitedZBTB16-related skeletal defects, genital hypoplasia, and intellectual developmental disorderOTHERAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.3793th %ile

GOF

0.3788th %ile

LOF

0.75top 10%

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

107 submitted variants in ClinVar

ClinVar

Classification Summary

VUS64

Likely Benign28

Benign4

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	64	0	0	64
Likely Benign	4	2	22	28
Benign	0	0	4	4
Total	68	2	26	96

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

View in ClinVar →

15 pathogenic / likely-pathogenic (of 17) ClinVar copy-number / structural variants overlap ZBTB16 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →