Pre-mRNA-processing factor 17

Pre-mRNA-processing factor 17 (CDC40) is a 579-amino-acid protein essential for pre-mRNA splicing as a component of the activated spliceosome (UniProt: O60508). It also plays an important role in embryonic brain development independent of proline isomerization. The protein is conserved across species and represents a key regulator of post-transcriptional gene expression.

CDC40 is implicated in neurodevelopmental disease; mutations cause pontocerebellar hypoplasia 15 (PCH15), a severe autosomal recessive neurological disorder characterized by progressive microcephaly, intellectual disability, spastic quadriplegia, and seizures (UniProt: O60508). This association underscores the protein's critical role in nervous system development and function.

In Alzheimer's Disease, CDC40 is significantly downregulated in post-mortem AD brain tissue compared to age-matched controls (Chaparral AD proteomics), with a mean log2 fold-change of −0.38 across subcellular fractions. This reduction may reflect altered splicing capacity or spliceosomal dysfunction in the AD brain, potentially contributing to pathological RNA processing patterns observed in neurodegeneration.