ZC3H3
Chr 8zinc finger CCCH-type containing 3
Also known as: SMICL, ZC3HDC3
The protein is required for nuclear export of polyadenylated mRNAs and enhances SMAD-dependent transcription through ACVR1B signaling. Mutations in ZC3H3 cause neurodevelopmental disorders with intellectual disability, developmental delay, and various congenital anomalies, following an autosomal dominant inheritance pattern. The gene shows significant constraint against loss-of-function variants (LOEUF 0.41), reflecting its essential role in cellular RNA processing.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Tolerant to missense variation
ClinVar Variant Classifications
316 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 | 0 | 0 | 55 | 0 | 55 |
Likely Pathogenic | 0 | 0 | 5 | 0 | 5 |
VUS | 0 | 199 | 9 | 0 | 208 |
Likely Benign | 0 | 22 | 0 | 4 | 26 |
Benign | 0 | 1 | 1 | 0 | 2 |
Conflicting | — | 1 | |||
| Total | 0 | 222 | 70 | 4 | 297 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ZC3H3 · 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