Common exonic missense variants in the C2 domain of the human KIBRA protein modify lipid binding and cognitive performance

摘要: The human KIBRA gene has been linked to cognition through a lead intronic single-nucleotide polymorphism (SNP; rs17070145) that is associated with episodic memory performance and the risk develop Alzheimer's disease. However, it remains unknown how this relates function of protein. Here, we identified two common missense SNPs (rs3822660G/T [M734I], rs3822659T/G [S735A]) in exon 15 affect cognitive performance, be almost complete linkage disequilibrium rs17070145. encode variants C2 domain distinct Ca2+ dependent binding preferences for monophosphorylated phosphatidylinositols likely due differences dynamics folding lipid-binding pocket. Our results further implicate protein higher brain provide direction cellular pathways involved.