Through bioinformatic analysis, we predicted that rs823128, rs1572931, and rs823156 as noncoding variants of NUCKS1, RAB29, and SLC41A1, respectively, might affect PD risk by altering the transcription factor-binding capability of the genes.
Here, we demonstrate that the substitution p.A350V potentially associated with PD is a gain-of-function mutation that enhances a core function of SLC41A1, namely Na⁺-dependent Mg²⁺ efflux by 69±10% under our experimental conditions (10-minute incubation in high-Na⁺ (145 mM) and completely Mg²⁺-free medium).
Subjects Five single-nucleotide polymorphisms (SNPs) located between RAB7L1 and SLC41A1 were analyzed in 720 patients with PD and 642 controls, all of Ashkenazi Jewish origin.