biostudies-literatureYuan ZChina Postdoctoral Science FoundationNational Natural Science Foundation of China (National Science Foundation of China)296https://www.ebi.ac.uk/biostudies/studies/S-EPMC12423332biostudies-literatureUnknown10(1)Essential tremor (ET) is a common neurological disease that is characterized by 4-12 Hz kinetic tremors of the upper limbs and high genetic heterogeneity. Although numerous candidate genes and loci have been reported, the etiology of ET remains unclear. A novel ET-related gene was initially identified in a five-generation family via whole-exome sequencing, and other variants were identified in 772 familial ET probands and 640 sporadic individuals via whole-genome sequencing. Among 71 (9.18%) Chinese families and 47 (7.34%) sporadic individuals with ET, we identified 15 types of protein-altering variants in solute carrier family 38 member 6 (SLC38A6), which encodes sodium-coupled neutral amino acid transporter 6 (SNAT6) and is inherited in an autosomal dominant pattern. Over-expression of mSignal transduction and targeted therapyLoss-of-function variations in solute carrier family 38 member 6 are associated with essential tremor.PMC124233322024M762007U20A20355GZB20240453Liu CJLiu JYang KWang CCheng ACui JTang BZhang LMa TJiang MGuo JSun QLuo JZhang YCao YWang TCui HLiu JYShen YSun HXu XGuo AYYang SYuan ZfalseLoss-of-function variations in solute carrier family 38 member 6 are associated with essential tremor.Essential tremor (ET) is a common neurological disease that is characterized by 4-12 Hz kinetic tremors of the upper limbs and high genetic heterogeneity. Although numerous candidate genes and loci have been reported, the etiology of ET remains unclear. A novel ET-related gene was initially identified in a five-generation family via whole-exome sequencing, and other variants were identified in 772 familial ET probands and 640 sporadic individuals via whole-genome sequencing. Among 71 (9.18%) Chinese families and 47 (7.34%) sporadic individuals with ET, we identified 15 types of protein-altering variants in solute carrier family 38 member 6 (SLC38A6), which encodes sodium-coupled neutral amino acid transporter 6 (SNAT6) and is inherited in an autosomal dominant pattern. Over-expression of m2025-01-01T00:00:00Z2025 Sep2026-06-03T02:19:15.759Z2026-04-23T03:09:57.255ZS-EPMC124233324093101610.1038/s41392-025-02380-y