ZIC1
Chr 3ADZic family zinc finger 1
Also known as: BAIDCS, CRS6, ZIC, ZNF201
This gene encodes a zinc finger transcription factor that acts as a transcriptional activator involved in neurogenesis and plays important roles in early CNS organogenesis, dorsal spinal cord development, and cerebellar maturation. Mutations cause craniosynostosis 6 and structural brain anomalies with impaired intellectual development and craniosynostosis, inherited in an autosomal dominant pattern. The gene is highly constrained against loss-of-function variants, indicating that proper protein function is critical for normal development.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Moderately missense-constrained (top ~2.5%)
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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.
Literature Evidence
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
126 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 3 | 1 | 10 | 0 | 14 |
Likely Pathogenic | 1 | 1 | 1 | 0 | 3 |
VUS | 3 | 51 | 5 | 1 | 60 |
Likely Benign | 0 | 4 | 5 | 30 | 39 |
Benign | 0 | 5 | 0 | 2 | 7 |
Conflicting | — | 1 | |||
| Total | 7 | 62 | 21 | 33 | 124 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ZIC1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools