Defective SLC6A18 does not transport Gly from extracellular region to cytosol

SLC6A18 encodes a neutral amino acid transporter B(0)AT3 which has preference for the amino acid glycine. It is abundantly expressed in the kidney, specifically the S2/3 segments of the kidney proximal tubule. Iminoglycinuria (IG; MIM:242600) or hyperglycinuria (HG; MIM:138500) can arise from defects in SLC36A2, encoding a proton-coupled amino acid transporter 2 (PAT2), a high-affinity cotransporter of glycine and proline. Mutations in SLC6A18 may contribute to both IG and HG. Although SLC6A18 could not be functionally expressed in heterologous systems, surface expression of mutants G79S and G496R in oocytes was abrogated, suggesting loss of functionality (Broer et al. 2008).

SLC6A18 编码一种中性和碱性氨基酸转运蛋白 B(0)AT3，该蛋白对甘氨酸的转运具有偏好性。其在肾脏中表达丰富，尤其是在肾脏近端小管的 S2/3 段。由于 SLC36A2（编码质子偶联氨基酸转运蛋白 2，即 PAT2，甘氨酸和脯氨酸的高亲和力共转运蛋白）基因缺陷，可能导致氨基甘氨酸尿症（IG；MIM:242600）或高甘氨酸尿症（HG；MIM:138500）。SLC6A18 的突变可能同时导致 IG 和 HG。尽管 SLC6A18 在异源系统中无法实现功能表达，但突变体 G79S 和 G496R 在卵母细胞表面的表达被抑制，这表明其功能丧失（Broer 等人，2008 年）。