ZNF526

Chr 19AR

zinc finger protein 526

Also known as: DENNED

NCBI Gene: 116115 ENSG00000167625 UniProt: Q8TF50 OMIM: 614387

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

ARLOEUF 0.471 OMIM phenotype

Clinical Summary— ZNF526

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.52) — some intolerance to loss-of-function variants.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 89 VUS of 99 total submissions

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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

ClinVar Variant Classifications

99 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic1

VUS89

Likely Benign6

Likely Pathogenic

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	1	0	0	0	1
VUS	0	89	0	0	89
Likely Benign	0	4	1	1	6
Benign	0	0	0	0	0
Total	1	93	1	1	96

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

View in ClinVar →

1 pathogenic / likely-pathogenic (of 1) ClinVar copy-number / structural variants overlap ZNF526 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →