ZNF526

Chr 19

zinc finger protein 526

Also known as: DENNED

NCBI Gene: 116115 ENSG00000167625 UniProt: Q8TF50

ZNF526 encodes a probable transcription factor that binds DNA and zinc ions in the nucleus. Mutations cause Dentici-Novelli neurodevelopmental syndrome with autosomal recessive inheritance. The gene is highly constrained against loss-of-function variants (LOEUF 0.47), indicating that complete loss of function is likely pathogenic.

ResearchSummary from RefSeq, OMIM, UniProt

Predicted to enable DNA binding activity and zinc ion binding activity. Predicted to be involved in DNA-templated transcription. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Jun 2026]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtDentici-Novelli neurodevelopmental syndrome

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

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.47

LOEUF

—

Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.47LOEUF

pLI 0.523

Z-score 3.24

OE 0.21 (0.10–0.47)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.45Z-score

OE missense 0.94 (0.86–1.02)

395 obs / 421.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.21 (0.10–0.47)

0≤0.351.4

Missense OE?0.94 (0.86–1.02)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 4 / 19.4Missense obs/exp: 395 / 421.2Syn Z: 0.50

Background carrier burden — how many people carry a rare variant somewhere in ZNF526?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 71

888 rare PASS variants

Rare truncating (LoF)

1 in 1,800

129 rare PASS variants

Rare synonymous (reference)

1 in 130

378 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ZNF526. 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 87	1 in 1,800
South Asian	~43k	1 in 54	1 in 2,600
Remaining (unassigned)	~30k	1 in 54	1 in 1,600
European (Finnish)	~27k	1 in 160	1 in 2,700
Admixed American	~22k	1 in 65	1 in 760
African / African American	~21k	1 in 58	≈ 1 in 9,300
East Asian	~20k	1 in 73	1 in 900
Ashkenazi Jewish	~13k	1 in 180	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 44	≈ 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 ↓