ZNF512B

Chr 20

zinc finger protein 512B

Also known as: GM632

NCBI Gene: 57473 ENSG00000196700 UniProt: Q96KM6 OMIM: 617886

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.

OMIM ResearchSummary from RefSeq, UniProt

Enables DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Involved in negative regulation of miRNA transcription. Located in nucleoplasm. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.21

Clinical Summary— ZNF512B

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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.

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ClinVar Variants

126 VUS of 168 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.21LOEUF

pLI 1.000

Z-score 5.61

OE 0.09 (0.04–0.21)

Highly constrained

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

Missense Constraint?

1.83Z-score

OE missense 0.79 (0.73–0.85)

450 obs / 573.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.09 (0.04–0.21)

0≤0.351.4

Missense OE?0.79 (0.73–0.85)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 4 / 44.3Missense obs/exp: 450 / 573.0Syn Z: -0.97

This gene — mechanism propensity

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

168 submitted variants in ClinVar

ClinVar

Classification Summary

VUS126

Likely Benign17

Benign12

126

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	126	0	0	126
Likely Benign	7	1	9	17
Benign	4	1	7	12
Total	137	2	16	155

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

View in ClinVar →

37 pathogenic / likely-pathogenic (of 50) ClinVar copy-number / structural variants overlap ZNF512B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →