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ZNF646 – Parkinson disease

Recent genetic studies in a Chinese early‑onset Parkinson's disease cohort have included ZNF646 among several ZNF family members investigated for their potential role in disease pathogenesis. In a multi‑patient analysis of 743 unrelated individuals with early‑onset Parkinson's disease (PMID:33723766), rare variants in ZNF646 were detected along with other ZNF genes, although no gene‑specific significant association or familial segregation data was reported. This has limited the overall clinical validity for ZNF646 despite its inclusion in the study.

Complementary functional assessments, including allele‑specific expression analysis performed using post‑mortem brain tissue, identified cis‑regulatory effects for several PD‑associated loci, with ZNF646 being one of the genes demonstrating altered expression patterns (PMID:33436766). While these experimental findings support a potential role in the molecular pathology of Parkinson's disease, the absence of robust genetic segregation and significant variant burden for ZNF646 warrants a cautious interpretation. Key take‑home: Although preliminary data suggest a possible involvement of ZNF646 in Parkinson disease pathogenesis, further replication, deeper segregation analyses, and functional studies are needed before it can be integrated into diagnostic frameworks.

References

  • Molecular neurobiology • 2021 • Genetic Analysis of ZNF Protein Family Members for Early‑Onset Parkinson's Disease in Chinese Population PMID:33723766
  • Scientific reports • 2021 • Allele‑specific expression of Parkinson's disease susceptibility genes in human brain PMID:33436766

Evidence Based Scoring (AI generated)

Gene–Disease Association

Limited

Rare variants in ZNF646 were identified in a large PD cohort (743 unrelated patients PMID:33723766), but the lack of gene‑specific significant associations and familial segregation data limits the strength of this association.

Genetic Evidence

Limited

Although ZNF646 was examined alongside other ZNF genes, no distinct significant variant or segregation evidence was observed for this gene (PMID:33723766).

Functional Evidence

Moderate

Allele‑specific expression studies in brain tissue demonstrated cis‑regulatory effects for ZNF646, providing functional support that is concordant with potential involvement in Parkinson disease (PMID:33436766).