ZNF768 encodes a transcription factor that binds to specific DNA sequences called mammalian-wide interspersed repeats (MIRs) in gene promoter regions and is required for cellular homeostasis. Mutations cause autosomal recessive neurodevelopmental disorder with microcephaly, epilepsy, and brain malformations. The gene is highly constrained against loss-of-function variants (LOEUF 0.498), consistent with the severe developmental phenotypes observed when both copies are disrupted.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.50
Clinical SummaryZNF768
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.22) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.50LOEUF
pLI 0.424
Z-score 3.11
OE 0.22 (0.110.50)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.72Z-score
OE missense 0.59 (0.530.67)
212 obs / 356.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.22 (0.110.50)
00.351.4
Missense OE0.59 (0.530.67)
00.61.4
Synonymous OE1.12
01.21.6
LoF obs/exp: 4 / 18.4Missense obs/exp: 212 / 356.4Syn Z: -1.15
DN
0.6744th %ile
GOF
0.6052th %ile
LOF
0.55top 25%

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ZNF768 · 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.

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