Additional file 3 of Impaired SorLA maturation and trafficking as a new mechanism for SORL1 missense variants in Alzheimer disease

Additional file 3: Table S1: Summary of analyses performed in HEK293 cells expressing wild-type (WT) or missense variants of SorLA, or in CRISPR/Cas9-edited hiPSC. Nucleotide positions are relative to canonical transcript NM_003105.5. The nucleotide change on cDNA, the corresponding amino acid change on the protein, and the location along the protein (Functional domain) are indicated. The Mis3, Mis2, and Mis0-1 missense variants examined in this study are shown in red, orange and black, respectively. For each variant, the number of carriers among our cohort (or among cohorts described in the litterature when applicable) and the corresponding frequency are indicated, as well as the allele count and the corresponding frequency in the gnomAD v2.1 database (only including individuals of European ancestry, and classified as “non-neuro”). Regarding the functional studies inHEK293 cells and iPSCs, a (Y) indicates an impact of the variants on SorLA protein maturation, transport or function and a (N) indicates no change from the wild-type form of the protein.

附加文件3：表S1：在表达野生型（WT）或错义变异体SorLA的HEK293细胞，或经CRISPR/Cas9编辑的人诱导多能干细胞（hiPSC）中开展的分析汇总。核苷酸位置均以标准转录本NM_003105.5为参照。文中将标注cDNA水平的核苷酸变异、对应蛋白质水平的氨基酸改变，以及该变异在蛋白质上的位置（功能结构域）。本研究涉及的Mis3、Mis2及Mis0-1三种错义变异体，分别以红色、橙色及黑色标记。对于每一种变异，将标注本研究队列中的携带人数（若适用，也包括文献报道队列中的携带人数）及其对应频率；同时标注gnomAD v2.1数据库中的等位基因计数及对应频率（该数据库仅纳入欧洲血统且被归类为"non-neuro"的个体）。关于在HEK293细胞及诱导多能干细胞（iPSC）中开展的功能研究，标记(Y)表示该变异对SorLA蛋白的成熟、转运或功能存在影响，标记(N)表示该变异与野生型蛋白无差异。