ZC3H3

Chr 8

zinc finger CCCH-type containing 3

Also known as: SMICL, ZC3HDC3

NCBI Gene: 23144 ENSG00000014164 UniProt: Q8IXZ2

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.

ResearchSummary from RefSeq, UniProt

Predicted to enable DNA binding activity; R-SMAD binding activity; and zinc ion binding activity. Predicted to be involved in mRNA transport. Predicted to act upstream of or within mRNA 3'-end processing and positive regulation of activin receptor signaling pathway. Located in nucleus. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.41

LOEUF

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Mechanism

Some data sources returned errors (1)

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