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. 2023 May 8;8(9):e168688. doi: 10.1172/jci.insight.168688

Figure 1. GM3SD is caused by loss-of-function mutation of ST3GAL5.

Figure 1

(A) Schematic showing de novo gangliosides’ synthesis pathway. ST3GAL5 uses LacCer as a substrate to synthesize GM3, the precursor of all other gangliosides. B4GALNT1 is another key enzyme to catalyze the complex gangliosides’ formation. Loss-of-function mutations in ST3GAL5 and B4GALNT1 cause GM3SD and hereditary spastic paraplegia type 26, respectively. (B) Schematic of the human ST3GAL5 DNA genome and the most abundant mRNA isoform noted in National Center for Biotechnology Information (NM_003896). M1, M2, and M3 represent the 3 initiating start codons for methionine. Stop codon TGA is at exon 10, and Amish mutation (p.862C>T) is located at exon 9. cDNA initiating from M1 (ORF1), M2 (ORF2), M3 (ORF3), and Kozak+M3 (KORF3) is of 1257 bp, 1173 bp, 1089 bp, and 1095 bp, respectively. Black boxes represent exons; black lines represent introns; dashed black lines represent spliced introns. (C) A construct expressing ubiquitous human ST3GAL5 ORF is shown. (D) Representative Western blot images of ST3GAL5 protein expression via different ORF transfections in HeLa cells. The thin black dividing line indicates splicing of noncontiguous lanes of the same blot.