Exploring Dysregulated Pathways in STXBP1 Disorder using RNA-Seq Analysis

STXBP1-related disorders, caused by mutations in the STXBP1 gene, are among the most common causes of neurodevelopmental disorders and epilepsy. Despite their prevalence, the molecular mechanisms underlying these disorders remain underexplored. In this study, we used RNA-seq analysis to investigate gene expression changes and dysregulated pathways in STXBP1-related neurodevelopmental epileptic encephalopathy. Using iPSC-derived neurons with STXBP1 knockdown, we performed differential expression and differential pathway activity scoring analyses to identify genes and biological processes affected by STXBP1 deficiency. Our results revealed significant dysregulation of pathways related to synaptic transmission, neurotransmitter release, and intracellular trafficking, consistent with STXBP1's role in presynaptic vesicle fusion. Additionally, we identified downregulated inflammatory signaling pathways, along with disrupted apoptosis and neurodevelopmental pathways, further highlighting the complexity of STXBP1's role in neural development and function. These findings provide novel insights into the molecular basis of STXBP1-related encephalopathy, offering potential targets for therapeutic intervention, particularly through pathway-based drug repurposing strategies.