Variants of Flavin-Containing Monooxygenase 3 Found in Subjects in an Updated Database of Genome Resources

Single-nucleotide substitutions of human flavin-containing monooxygenase 3 ( ) identified in the whole-genome sequences of the updated Japanese population reference panel (now containing 38,000 subjects) were investigated. In this study, two stop codon mutations, two frameshifts, and 43 amino-acid-substituted variants were identified. Among these 47 variants, one stop codon mutation, one frameshift, and 24 substituted variants were already recorded in the National Center for Biotechnology Information database. Functionally impaired FMO3 variants are known to be associated with the metabolic disorder trimethylaminuria; consequently, the enzymatic activities of the 43 substituted FMO3 variants were investigated. Twenty-seven recombinant FMO3 variants expressed in bacterial membranes had similar activities toward trimethylamine -oxygenation (∼75%-125%) to that of wild-type FMO3 (98 minutes ). However, six recombinant FMO3 variants (Arg51Gly, Val283Ala, Asp286His, Val382Ala, Arg387His, and Phe451Leu) had moderately decreased (∼50%) activities toward trimethylamine -oxygenation, and 10 recombinant FMO3 variants (Gly11Asp, Gly39Val, Met66Lys, Asn80Lys, Val151Glu, Gly193Arg, Arg387Cys, Thr453Pro, Leu457Trp, and Met497Arg) showed severely decreased FMO3 catalytic activity (