eng Oriental Scientific Publishing Company Biomedical and Pharmacology Journal 0974-6242 2025-09-30 18 3 2024 2036 10.13005/bpj/3234 67290 article Usha Adiga 1 Sampara Vasishta 2 Amulya Tunuguntla 1 Tulasi Govardhan 3 Kasala Farzia 1 Department of Biochemistry, Apollo Institute of Medical Sciences and Research Chittoor, Andhra Pradesh. ICMR, Department of Biochemistry, Apollo Institute of Medical Sciences and Research Chittoor, Andhra Pradesh. Department of Pathology, Apollo Institute of Medical Sciences and Research Chittoor, Andhra Pradesh. Basal cell carcinoma (BCC) represents the most common human malignancy, with significant genetic underpinnings that remain incompletely understood. This study aimed to analyze genes identified through genome-wide association studies (GWAS) to elucidate functional pathways involved in BCC pathogenesis. We performed extensive bioinformatic analyses of GWAS-derived genes associated with BCC susceptibility, focusing on RHOU and PADI6. Functional enrichment analysis included Gene Ontology (GO) biological processes, cellular components, molecular functions, metabolite associations, microRNA interactions, protein-protein interactions, and pathway analyses using Reactome database. Our analysis revealed significant enrichment of RHOU in GTPase-mediated signaling pathways (p=0.0011), cytoskeleton organization (p=0.0165), and endocytosis (p=0.0280). PADI6 showed strong associations with cortical granules (p=0.0007) and maternal-to-zygotic transition (p=0.0162). Both genes displayed interactions with specific microRNAs, with RHOU notably targeted by miR-199a-5p (p=0.0047) and miR-126-3p (p=0.0086). Protein-protein interaction analysis demonstrated RHOU's connection with focal adhesion kinase PTK2 (p=0.0242) and PAK1 (p=0.0261), suggesting cellular adhesion and migration involvement. Reactome pathway analysis further confirmed RHOU's role in GTPase cycle (p=0.0059) and PADI6 in maternal mRNA degradation (p=0.0068). Our findings suggest that RHOU contributes to BCC pathogenesis by disrupting Rho GTPase signaling, affecting cytoskeletal dynamics and cell migration, while PADI6 may influence epigenetic regulation. These molecular mechanisms provide potential therapeutic targets and biomarkers for BCC management. Further experimental validation is warranted to confirm these computational findings. https://biomedpharmajournal.org/vol18no3/functional-analysis-of-rhou-and-padi6-genes-in-basal-cell-carcinoma-insights-from-genome-wide-association-studies/ Basal cell carcinoma GTPase signaling Gene ontology analysis Genome wide association studies PADI6 RHOU