Deep mutational scanning of hOCT1
Deep mutational scanning of human organic cation transporter 1 (SLC22A1), a polyspecific transporter centrally involved in the uptake and excretion of charged endogenous metabolites and xenobiotics. Several polymorphisms are known to modulate metformin and antineoplastic efficacy. A mutational library containing all single-site nonsense mutations and single codon deletions was prepared for hOCT1 in order to measure in an unbiased way the mutational landscape. We measured mutational changes to transport using uptake of a cytotoxic substrate, and abundance using a split-GFP construct (VAMP-Seq). Our results inform clinical pharmacogenetics and fundamental transporter biology.