Sook Wah Yee, Christian B Macdonald, Darko Mitrovic, Xujia Zhou, Megan L Koleske, Jia Yang, Dina Buitrago Silva, Patrick Rockefeller Grimes, Donovan D Trinidad, Swati S More, Linda Kachuri, John S Witte, Lucie Delemotte, Kathleen M Giacomini, Willow Coyote-Maestas
Mutations in transporters can impact an individual's response to drugs and cause many diseases. Few variants in transporters have been evaluated for their functional impact. Here, we combine saturation mutagenesis and multi-phenotypic screening to dissect the impact of 11,213 missense single-amino-acid deletions, and synonymous variants across the 554 residues of OCT1, a key liver xenobiotic transporter. By quantifying in parallel expression and substrate uptake, we find that most variants exert their primary effect on protein abundance, a phenotype not commonly measured alongside function...
May 2, 2024: Molecular Cell