CYP2C18 and knowledge gaps

Pablo Zubiaur & Andrea Gaedigk have an editorial online ahead of print in Pharmacogenomics calling for the inclusion of CYP2C18 in more studies of drug metabolism [PMID: 36331025].

CYP2C18 is in a cluster on chromosome 10 that has CYP2C18, CYP2C19, CYP2C9 and CYP2C8 that spans 500k bases (NCBI gene browser). The authors comment that CYP2C18 is only included in three PharmGKB pathways (there are actually four: clobazam, diclofenac, warfarin and acenocoumarol), while the other genes of the CYP2C locus are in many. CYP2C19 and CYP2C9 have a volume of data annotated in PharmGKB, CYP2C8 is less populated and CYP2C18 has little (see table below). Similarly, CYP2C19, CYP2C9 and CYP2C8 have haplotypes in PharmVar, while CYP2C18 does not. As Zubiaur and Gaedigk discuss, there are comparatively very few PGx peer-reviewed papers about CYP2C18 and PharmGKB depends on these publications for annotations and pathway creation.  We strongly agree with the authors that more studies regarding CYP2C18 would be valuable contributions to the field and look forward to curating them into PharmGKB as they are published.

Like many grant-funded projects, PharmGKB is a small team with limited resources and is unable to manually curate all of PubMed, so sometimes papers are published that we have not yet curated. We encourage PharmGKB users to contact us anytime if they identify important papers for us to curate.  If users find knowledge gaps or have recommendations for additional pathway candidate genes, please send the relevant references to feedback@pharmgkb.org. We also encourage users who are interested in collaborating on a drug pathway to contact us.