Keeping pace with CYP2D6 haplotype discovery: innovative methods to assign function

Pharmacogenomics. 2022 Mar;23(4):255-262. doi: 10.2217/pgs-2021-0149. Epub 2022 Jan 27.


The discovery of haplotypes with unknown or uncertain function in the CYP2D6 pharmacogene is outpacing the capabilities of traditional in vitro and in vivo approaches to characterize their function. This challenge will undoubtedly grow as pharmacogenomic research becomes more inclusive of globally diverse populations. As accurate phenotypic assignment is paramount to the utility of pharmacogenomics, high-throughput technologies are needed for this complex pharmacogene. We describe the evolving landscape of innovative approaches to assign function to CYP2D6 haplotypes and possibilities for adopting these technologies into cohesive processes. Promising approaches include ADME-optimized prediction frameworks, machine learning algorithms, deep mutational scanning and phenoconversion predictions. Implementing these approaches will lead to improved personalization of treatment for patients.

Keywords: CYP2D6; drug metabolism; genotype; pharmacogenetics; pharmacogenomics; phenotype.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Cytochrome P-450 CYP2D6* / genetics
  • Genotype
  • Haplotypes / genetics
  • Humans
  • Pharmacogenetics* / methods
  • Phenotype


  • Cytochrome P-450 CYP2D6