ZNF526

Chr 19AR

zinc finger protein 526

Also known as: DENNED

NCBI Gene: 116115ENSG00000167625UniProt: Q8TF50

Predicted to enable DNA binding activity and zinc ion binding activity. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

Dentici-Novelli neurodevelopmental syndromeMIM #619877
AR
162
ClinVar variants
18
Pathogenic / LP
0.52
pLI score
0
Active trials
Clinical Summary— ZNF526
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.52) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
18 Pathogenic / Likely Pathogenic· 123 VUS of 162 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.45Z-score
OE missense 0.94 (0.86–1.02)
395 obs / 421.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.21 (0.10–0.47)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.94 (0.86–1.02)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.95
0≤1.21.6
LoF obs/exp: 4 / 19.4Missense obs/exp: 395 / 421.2Syn Z: 0.50

ClinVar Variant Classifications

162 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16
Likely Pathogenic2
VUS123
Likely Benign10
Benign7
Conflicting4
16
Pathogenic
2
Likely Pathogenic
123
VUS
10
Likely Benign
7
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
1
13
0
16
Likely Pathogenic
0
1
1
0
2
VUS
0
116
4
3
123
Likely Benign
0
6
1
3
10
Benign
0
3
2
2
7
Conflicting
—4
Total2127218162

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

View in ClinVar →

Protein Context — Lollipop Plot

ZNF526 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

ZNF526-related intellectual developmental disorder

limited
ARUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Dentici-Novelli neurodevelopmental syndrome

MIM #619877

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools