Investigating the Pleiotropic Role of KIF21B in Schizophrenia and Multiple Sclerosis: A Bioinformatics Analysis

<h4>Objective</h4>Genome-wide association studies have identified shared genetic risk loci between schizophrenia (SCZ) and multiple sclerosis (MS), suggesting overlapping biological mechanisms despite distinct clinical presentations. Here, we aimed to characterize the biological plausibility of <i>KIF21B</i> as a shared genetic risk gene for SCZ and MS, two disorders with overlapping genetic risk loci despite distinct clinical presentations.<h4>Method</h4>We performed bioinformatics analyses of <i>KIF21B</i> using publicly available data from GTEx, STRING, and the GWAS Catalog, including tissue-specific expression profiling, protein interaction network analysis, transcriptome-wide co-expression analysis, and phenome-wide association analysis.<h4>Results</h4><i>KIF21B</i> expression was significantly enriched in both brain and immune tissues compared to other tissue types. Protein interaction network analysis demonstrated that <i>KIF21B</i> functions within microtubule-based transport machinery essential for axonal function. Co-expression analysis identified significant correlation with immune-related genes, including the established MS susceptibility gene <i>ANKRD55</i>, with pathway enrichment for T cell activation and lymphocyte diferentiation. Phenome-wide association analysis confirmed <i>KIF21B</i> pleiotropy across multiple autoimmune and psychiatric conditions.<h4>Conclusions</h4>These findings support <i>KIF21B</i> as a biologically plausible shared risk gene whose dual neural and immune functions may contribute to susceptibility for both neuropsychiatric and autoimmune diseases of the central nervous system.