My PhD project “From genes to functions: understanding the impact of novel variants on the pathogenesis of hereditary kidney and liver conditions” is part of the solid organ transplantation area of research. The aim of this project is to functionally validate the variants identified through NGS technologies and classified as variants of unknown significance, which make the genetic diagnosis difficult to confirm. The project will be focused particularly on our cohort of patients affected by Polycystic Kidney Disease (PKD), among which 40,8% present C3 variants. Our main goal is to establish a proper cellular model to functionally validate in an high-throughput way the most interesting variants, starting from the mutational hotspots: indeed, it would be noteworthy to understand why variants in PKD1 mostly rely on specific segment of the gene compared to the others and whether they could differently impact on the onset of the disease. Moreover, our cohort is also composed of pediatric patients and the possibility of reproducing their variants in an in vitro model could shed light on the possible mechanisms responsible for an earlier onset of the disease, paving the way to a better understanding of the altered renal condition.