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Recent studies have consistently implicated SLC2A13 in the pathogenesis of Parkinson disease. Multiple independent investigations using whole‐exome and whole‐genome sequencing in early‐onset and familial PD cohorts have demonstrated an enrichment of rare variants in SLC2A13. This evidence is supported by gene‐based burden analyses in 743 Chinese early‑onset PD probands (PMID:33781609), which has set the stage for further evaluation of this gene’s role in neurodegeneration. The aggregated evidence from diverse patient cohorts highlights the potential contribution of SLC2A13 to PD risk. The association signal stands out among several solute carriers evaluated in these studies. Overall, these findings suggest that SLC2A13 merits further clinical scrutiny as a genetic risk factor for Parkinson disease.
Genetic evidence is robust with the identification of multiple rare variants in SLC2A13, including missense changes detected in several independent studies. In the primary investigation, rare variants were systematically analyzed in relation to PD, with gene‐based burden analysis highlighting the significance of SLC2A13 in early‑onset PD (PMID:33781609). Additional support for the genetic association comes from a systematic review examining gene–caffeine interactions, where SLC2A13 was among the genes showing a positive interaction with PD risk (PMID:38914264). Furthermore, a high‐depth whole‐genome sequencing study confirmed the association by identifying copy number and repeat variants in SLC2A13 that were significantly enriched in patients with Parkinson disease (PMID:39043730). Together, these studies add considerable weight to the genetic contributions of SLC2A13 in PD.
Among the variants reported, the HGVS‐compliant variant c.301G>A (p.Val101Met) represents one of the key missense changes identified in SLC2A13. This variant, along with others detected in the same study, underscores the heterogeneous mutation spectrum present in the patient population. The reporting of multiple variant classes, including missense and repeat expansions, supports the gene’s role in PD predisposition. The genetic data thereby serve not only as markers of association but also as potential diagnostic indicators in the clinical setting. Such variant-level details can aid in the advancement of genetic testing and risk stratification for patients. This convergence of variant data strengthens the overall narrative of SLC2A13 as a PD-associated gene.
While the genetic findings are compelling, the functional evidence remains less extensive. No dedicated functional assays such as knock‑out models or rescue experiments have been reported to directly assess the pathogenic mechanism of SLC2A13 variants. However, the gene is known to encode a solute carrier protein, and its inferred role in neuronal transporter activity is consistent with established pathways implicated in neurodegeneration. The lack of direct experimental validation means that the current functional evidence is limited and primarily observational. Despite this, the biological plausibility of altered transporter function affecting neuronal health provides a credible mechanistic hypothesis. This gap highlights the need for future targeted studies to elucidate the direct molecular consequences of SLC2A13 mutations.
Integration of the genetic and preliminary functional data creates a coherent narrative that supports a strong association between SLC2A13 and Parkinson disease. The evidence from a large cohort of early‑onset PD probands, replicated in independent studies and bolstered by diverse variant types, underscores the gene’s clinical relevance. Although functional studies have not yet reached the same level of rigor, the association signals are sufficiently robust to guide diagnostic decision‑making. These findings may also inform commercial genetic test development and stimulate further research efforts. Importantly, clinicians and researchers should consider the presence of SLC2A13 variants as one component in the multifactorial landscape of PD risk.
Key take‑home: The strong genetic evidence, exemplified by rare variant enrichment and multi‑cohort replication, positions SLC2A13 as a valuable gene for refining Parkinson disease diagnostics and advancing personalized treatment approaches.
Gene–Disease AssociationStrongAssociation supported by a burden analysis in 743 early‑onset PD probands (PMID:33781609) and replicated in independent studies involving CNV and gene–environment interaction analyses (PMID:38914264, PMID:39043730). Genetic EvidenceStrongMultiple rare variants including c.301G>A (p.Val101Met) and structural/repeat variants have been identified in independent cohorts, providing robust genetic support for the association. Functional EvidenceLimitedNo direct functional assays have been performed; current evidence is inferred from the gene’s known role in solute transport and its biological plausibility in neurodegeneration. |