FIGURE 3.

Overview of the pathogenic Stx1b and Syt1 variants’ effects on synaptic vesicle release. (A) Summary of all reported pathogenic Stx1b (NCBI Accession #: NP_443106.1) variants and the most common clinical phenotype of the patients harboring these variants (Variants are color-coded based on their effects on the protein. Nonsense mutations are presented in red, missense mutations are presented in black, frameshift mutations are presented in blue, and deletions/insertions are presented in orange). (B) Graphical depiction demonstrating the changes in synaptic vesicle release upon genetic deletion of Stx1a and/or Stx1b. (C) Graphical depiction showing that the epileptiform phenotype caused by Stx1b-knockdown in zebrafish cannot be rescued by the V216E variant indicating loss-of-function. (D) Graphical summary of the findings explaining the effects of different Stx1b variants (K45indel, V216E, and G226E) on different modes of neurotransmitter release and their mechanism of action. (E) Summary of all reported pathogenic Syt1 (NCBI Accession #: AAH58917.1) variants and the most common clinical phenotype of the patients harboring these variants (Variants are color-coded based on their effects on the protein. Missense mutations are presented in black, and duplications are presented in orange). (F) Graphical depiction demonstrating the changes in synaptic vesicle release upon genetic deletion of Syt1. (G) Graphical summary of the findings explaining the effects of different Syt1 variants (D4G, D366E, I368T, and M303K) on different modes of neurotransmitter release.