ZBTB16

Chr 11

zinc finger and BTB domain containing 16

Also known as: PLZF, ZNF145

NCBI Gene: 7704 ENSG00000109906 UniProt: Q05516 OMIM: 176797

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.

OMIM 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]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Leukemia, acute promyelocytic, PL2F/RARA type

UniProtSkeletal defects, genital hypoplasia, and impaired intellectual development

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Leukemia, acute promyelocytic, PL2F/RARA type; no ClinGen or GenCC tier

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.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.19

LOEUF· LoF intol.

LOF

Mechanism· predicted

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

Background carrier burden — how many people carry a rare variant somewhere in ZBTB16?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 160

680 rare PASS variants

Rare truncating (LoF)

1 in 3,200

14 rare PASS variants

Rare synonymous (reference)

1 in 76

394 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ZBTB16. 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 200	1 in 2,500
South Asian	~43k	1 in 75	≈ 1 in 22,000
Remaining (unassigned)	~30k	1 in 140	≈ 1 in 7,500
European (Finnish)	~27k	1 in 360	≈ 1 in 27,000
Admixed American	~22k	1 in 99	none seen
African / African American	~21k	1 in 130	none seen
East Asian	~20k	1 in 110	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 770	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 240	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 6 coding exons well covered in gnomAD exomes and genomes.? see exons ↓