| SCAPER | |
|---|---|
| Full Name | S-Phase Cyclin-Associated Protein Homolog |
| Symbol | SCAPER |
| Chromosome | 15q24.2 |
| NCBI Gene ID | 55856 |
| OMIM ID | 611493 |
| Ensembl ID | ENSG00000141741 |
| UniProt ID | [Q9BYX4](https://www.uniprot.org/uniprot/Q9BYX4) |
| Protein Length | 1,328 amino acids |
| Associated Diseases | [Parkinson's Disease](/diseases/parkinsons-disease), Retinitis Pigmentosa |
SCAPER (S-Phase Cyclin-Associated Protein Homolog) is a protein coding gene located on chromosome 15q24.2. The gene encodes a 1,328 amino acid protein containing multiple WD40 repeat domains that mediate protein-protein interactions. SCAPER is primarily involved in cell cycle regulation during S-phase, where it serves as a regulatory partner for cyclin-dependent kinases (CDKs), and participates in DNA damage response pathways. Genome-wide association studies (GWAS) have identified SCAPER as a susceptibility locus for Parkinson's Disease, suggesting a role in dopaminergic neuron survival. Loss-of-function mutations in SCAPER cause autosomal recessive retinitis pigmentosa, indicating its essential function in maintaining cellular homeostasis in highly specialized neurons [@nalls2019][@zanette2019].
SCAPER belongs to the uncharacterized protein family UPF05456 and contains multiple WD40 repeat domains at its C-terminus. These domains form a beta-propeller structure that serves as a scaffold for protein-protein interactions. The protein localizes to both the nucleus and cytoplasm, consistent with its roles in cell cycle regulation and DNA damage response [@ohi2005].
SCAPER functions as a regulatory partner during S-phase of the cell cycle:
SCAPER participates in cellular responses to DNA damage:
SCAPER variants have been associated with Parkinson's Disease risk in large-scale GWAS meta-analyses. The gene is expressed in dopaminergic neurons of the substantia nigra pars compacta, the neuronal population most vulnerable in PD. The association between SCAPER and PD risk suggests several potential mechanisms [@nalls2019]:
| Mechanism | Description | Evidence |
|---|---|---|
| Cell cycle re-entry | Aberrant re-activation of cell cycle machinery in post-mitotic neurons leads to apoptosis | [@chan2018] |
| DNA damage accumulation | Impaired DNA repair pathways lead to genomic instability and neuronal death | [@chang2019] |
| Transcriptional dysregulation | Altered gene expression programs critical for neuronal survival | GWAS signal colocalization |
| Mitochondrial dysfunction | SCAPER variants may affect mitochondrial quality control pathways | Indirect evidence |
Homozygous or compound heterozygous loss-of-function mutations in SCAPER cause autosomal recessive retinitis pigmentosa (RP), characterized by progressive photoreceptor cell death leading to night blindness, tunnel vision, and eventual complete blindness. This indicates SCAPER's essential role in maintaining cellular homeostasis in retinal cells [@zanette2019].
SCAPER is expressed in various tissues with notable expression in:
Single-cell RNA-seq data from the substantia nigra shows SCAPER expression in dopaminergic neurons, supporting its relevance to Parkinson's Disease pathogenesis.
Currently, SCAPER is not a primary drug target, but understanding its role in neuronal survival provides insights for therapeutic development:
Key areas for future investigation include: