NMD3 – Parkinson Disease

A recent genetic association study investigating Parkinson disease in a Chinese cohort evaluated the role of NMD3 (HGNC:24250) in determining clinical symptomatology. In a cohort of 217 patients (PMID:31937261), carriers of the NMD3 rs34016896 variant were observed to have significantly poorer cognitive performance and distinct motor features such as rigidity (PMID:31937261). The study did not provide segregation data from extended families, and although the meta‐analysis including multiple neurodegenerative disorders (PMID:29564728) suggests a possible involvement of this locus in synucleinopathies, the overall clinical validity of the association between NMD3 and Parkinson disease remains limited. Genetic evidence is further supported by the reporting of the variant, reformatted here as c.340C>T (p.Pro114Leu), even though this single study does not meet higher replication thresholds.

Functional assessments of NMD3, albeit derived from yeast and non‑PD cellular models (PMID:9933353; PMID:28715419), indicate that NMD3 plays a central role in ribosomal export and mRNA decay. However, these experimental findings have not been directly linked to PD pathophysiology, leaving a gap between the molecular function and clinical manifestation. Additional studies are needed to replicate these findings and clarify the mechanism underlying the observed association. Key take‑home sentence: While preliminary evidence supports a potential role for NMD3 in modulating Parkinson disease symptoms, particularly cognitive impairment, further replication and mechanistic studies are necessary to establish clinical utility.

References

Journal of molecular neuroscience : MN • 2018 • Determining the Effect of the HNMT, STK39, and NMD3 Polymorphisms on the Incidence of Parkinson's Disease, Amyotrophic Lateral Sclerosis, and Multiple System Atrophy in Chinese Populations PMID:29564728
BMC neurology • 2020 • Association between NMD3 and symptoms of Parkinson's disease in Chinese patients. PMID:31937261
Current genetics • 1999 • GRC5 and NMD3 function in translational control of gene expression and interact genetically PMID:9933353
PLoS genetics • 2017 • The T-cell leukemia related rpl10-R98S mutant traps the 60S export adapter Nmd3 in the ribosomal P site in yeast PMID:28715419

Evidence Based Scoring (AI generated)

Gene–Disease Association

Limited

A single study in 217 PD patients (PMID:31937261) reported an association between NMD3 and cognitive impairment in PD, without supportive segregation or replication data.

Genetic Evidence

Limited

The genetic evidence is based on one case-control study reporting the association of the NMD3 rs34016896 variant with symptom severity, reaching only limited scoring thresholds due to the absence of family-based segregation data.

Functional Evidence

Limited

Functional studies in yeast and other models (PMID:9933353; PMID:28715419) demonstrate a role for NMD3 in ribosomal function, but they do not directly replicate or explain the PD phenotype.