Deep mutational scanning of P2RY8: surface expression, migration, proliferation

P2RY8 is a G-protein-coupled receptor expressed on several lymphocyte subsets, including germinal center B cells, and is frequently mutated in diffuse large B cell lymphoma and Burkitt lymphoma. Our understanding of how missense variants affect its function is limited. We performed near-saturation deep mutational scanning of P2RY8, assaying the effect of each variant on surface expression, migration, and proliferation. We identified positions essential for expression, positions essential for function independent of expression, and variants with differential effects on migration and proliferation. These data were also used to improve variant effect prediction algorithm accuracy and to assign phenotypes to human germline and somatic variants.