ZNF532

Chr 18

zinc finger protein 532

ZNF532 encodes a transcription factor that binds DNA and regulates gene transcription in the nucleus. Mutations cause neurodevelopmental disorders with intellectual disability and developmental delay, following an autosomal dominant inheritance pattern. The gene is highly constrained against loss-of-function variants (pLI 0.99, LOEUF 0.30), indicating that functional copies are essential for normal development.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
2
Pubs (1 yr)
73
P/LP submissions
0%
P/LP missense
0.30
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical SummaryZNF532
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
70 unique Pathogenic / Likely Pathogenic· 141 VUS of 243 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.30LOEUF
pLI 0.989
Z-score 4.98
OE 0.15 (0.080.30)
Highly constrained

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

Missense Constraint
2.68Z-score
OE missense 0.73 (0.680.78)
546 obs / 752.6 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.15 (0.080.30)
00.351.4
Missense OE0.73 (0.680.78)
00.61.4
Synonymous OE1.05
01.21.6
LoF obs/exp: 6 / 40.0Missense obs/exp: 546 / 752.6Syn Z: -0.75
DN
0.2399th %ile
GOF
0.1999th %ile
LOF
0.85top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.30

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

243 submitted variants in ClinVar

Classification Summary

Pathogenic67
Likely Pathogenic3
VUS141
Likely Benign14
Benign2
67
Pathogenic
3
Likely Pathogenic
141
VUS
14
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
67
0
67
Likely Pathogenic
0
0
3
0
3
VUS
2
129
10
0
141
Likely Benign
0
9
0
5
14
Benign
0
1
0
1
2
Total2139806227

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

View in ClinVar →

Protein Context — Lollipop Plot

ZNF532 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC