Fig. 1: Determination of the 5’ ends of a GBA gene.

a Summary cartoon of the 5’ ends of all GBA variants. Upper: Exon-intron structures of the reference sequence J03059 and the corresponding translated GCase protein region (gray box) with a catalytic domain (black box). “ATG” in red, the start codon, “TGA” in blue, the stop codon, “N” in pink, glycosylation sites; “E” in green, catalytic residues. Middle (within dotted lines): Alignment of the eight variants (vs) with adjusted exon positions compared to J03059. Variant accession numbers are shown in the data availability section. As shown, variants are categorized into two groups: P1-driven variants (v2, v6, v7, v8, v3, and v4) and P2-driven variants (v1 and v5). Red boxes indicate newly identified exon two. Exon three subdomains are shown in colored boxes (3i, gray; 3ii, green; 3iii, blue; 3iv, pink). Lower: The proposed GBA gene structure. Yellow boxes indicate the P1 and P2 promoter regions. The number above each box indicates the redefined exon number. b GCase protein expression and enzymatic activities of variants v4 and v5. (Left) The GCase protein expression was analyzed using western blot analysis. Representative data is shown. pCI, an empty vector-transfected HEK293 cell lysate; V1, V4, V5, each variant overexpressed HEK293 cell lysate. (Right) GCase activity of each variant transfected HEK293 cells. H, control HEK293 cells (no treatment); V3, variant v3 in pCIneo-transfected cells; others, similar to the right panel. n = 3 biologically independent samples. Data represent the mean ± STDEV.