ZNF512B

Chr 20

zinc finger protein 512B

Also known as: GM632

The protein functions as a transcriptional repressor that binds DNA and associates with the NuRD complex to regulate gene expression through histone deacetylation and chromatin remodeling. Mutations cause neurodevelopmental disorder with developmental delay, seizures, and variable additional features, inherited in an autosomal dominant pattern. This gene is highly constrained against loss-of-function variants, indicating that such variants are likely pathogenic when they occur.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
1
Pubs (1 yr)
37
P/LP submissions
0%
P/LP missense
0.21
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical SummaryZNF512B
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
37 unique Pathogenic / Likely Pathogenic· 139 VUS of 218 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.21LOEUF
pLI 1.000
Z-score 5.61
OE 0.09 (0.040.21)
Highly constrained

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

Missense Constraint
1.83Z-score
OE missense 0.79 (0.730.85)
450 obs / 573.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.09 (0.040.21)
00.351.4
Missense OE0.79 (0.730.85)
00.61.4
Synonymous OE1.08
01.21.6
LoF obs/exp: 4 / 44.3Missense obs/exp: 450 / 573.0Syn Z: -0.97
DN
0.2997th %ile
GOF
0.3094th %ile
LOF
0.83top 5%

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

LOFprediction above median · LOEUF 0.21

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

218 submitted variants in ClinVar

Classification Summary

Pathogenic29
Likely Pathogenic8
VUS139
Likely Benign17
Benign12
29
Pathogenic
8
Likely Pathogenic
139
VUS
17
Likely Benign
12
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
29
0
29
Likely Pathogenic
0
0
8
0
8
VUS
0
126
13
0
139
Likely Benign
0
7
1
9
17
Benign
0
4
1
7
12
Total01375216205

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

View in ClinVar →

Protein Context — Lollipop Plot

ZNF512B · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC