ZNF184 – Parkinson Disease

The association between ZNF184 and Parkinson disease is currently supported by limited evidence. A large multi‑patient study originally aimed to replicate GWAS‐linked loci in Chinese cohorts (PMID:29691093) reported no significant association between the candidate variants, including those in ZNF184, and Parkinson disease. In a separate study focusing on early‑onset Parkinson’s disease from a Chinese cohort, a gene‑based burden analysis across several ZNF family members identified rare variants in ZNF184 among other genes (PMID:33723766), yet did not highlight any specific segregating variants or recurrent mutations in ZNF184. Moreover, there is an absence of confirmed familial segregation evidence as no affected relatives were reported to harbor causative variants in this gene. Functional insights remain indirect for ZNF184, since functional assays in the same study predominantly emphasized other ZNF members such as ZNF746. Additionally, a related functional assessment study examining DNA methylation changes linked to homocysteine did report a trans‑CpG association near ZNF184 (PMID:29084233), but this evidence does not directly support a pathogenic mechanism in Parkinson disease. Overall, the current evidence does not robustly support a causative role for ZNF184 in Parkinson disease.

In summary, while rare variants in ZNF184 have been incidentally observed within large-scale genetic studies of early‑onset Parkinson’s disease, the lack of clear segregation data, specific pathogenic variants, and concordant functional studies results in a limited gene‑disease association classification. The genetic evidence is tempered by the negative replication from an independent cohort, leading to uncertainty regarding its contribution to the clinical phenotype. Functional assessments have provided only indirect support via methylation patterns rather than a definitive effect on protein function or cellular models. No single variant meeting stringent HGVS criteria (e.g., a complete coding change such as “c.123A>T (p.Lys41Asn)”) has been definitively linked to the disease in ZNF184. These mixed findings highlight the need for further studies, including robust segregation analyses and direct functional characterization, to clarify the role of ZNF184 in Parkinson disease. Key take‑home: current clinical utility for diagnostic decision‑making regarding ZNF184 in Parkinson disease remains limited, and further evidence is required before it can be used in commercial or publication settings.

References

• Neurobiology of Aging • 2018 • No association between 5 new GWAS‑linked loci in Parkinson's disease and multiple system atrophy in a Chinese population PMID:29691093
• Molecular Neurobiology • 2021 • Genetic Analysis of ZNF Protein Family Members for Early‑Onset Parkinson's Disease in Chinese Population PMID:33723766
• PLoS One • 2017 • Genetically defined elevated homocysteine levels do not result in widespread changes of DNA methylation in leukocytes PMID:29084233

Evidence Based Scoring (AI generated)