In silico analysis identified potential interaction between glutathione and spliceosome in Nager Syndrome

Nager syndrome (NS) is a rare congenital disorder characterized by craniofacial anomalies and preaxial limb defects. Its underlying pathogenic mechanisms remain poorly understood. Recent in vivo and in vitro studies have implicated increased reactive oxygen species (ROS) in NS pathogenesis. In this study, we focused on craniofacial development and employed network pharmacology and bioinformatics to investigate the potential pharmacological targets and mechanisms of glutathione (GSH), an antioxidant, in NS. We identified 139 intersecting targets between GSH and NS. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that GSH may influence RNA splicing pathways essential for craniofacial morphogenesis. Additionally, molecular docking using AutoDock Vina indicated potential hydrogen bonding and hydrophobic interactions between GSH and three spliceosomopathy-associated proteins (elongation Factor Tu GTP binding domain containing 2 (EFTUD2), splicing factor 3B subunit 2 (SF3B2) and eukaryotic translation initiation factor 4A3 (EIF4A3)). This study highlights possible molecular mechanisms by which GSH may ameliorate craniofacial abnormalities in NS and related craniofacial spliceosomonpathies, providing new directions for functional validation and therapeutic development.