Trimethylaminuria and a human FMO3 mutation database

Hum Mutat. 2003 Sep;22(3):209-13. doi: 10.1002/humu.10252.


Trimethylaminuria (TMAuria), or fish-odor syndrome, is due to defective flavin-containing monooxygenase 3 (FMO3). In the liver, this protein catalyzes the NADPH-dependent oxidative metabolism of odorous trimethylamine (TMA), derived in the gut from dietary sources, to nonodorous trimethylamine N-oxide (TMA N-oxide). Affected individuals are unable to carry out this reaction and consequently exude a fishy body odor, due to the secretion of TMA in their breath and sweat and its excretion in their urine. This leads to a variety of psychosocial problems, including disruption of schooling, clinical depression, and attempted suicide. Twelve missense, three nonsense, and one gross deletion mutation are known to cause TMAuria. FMO3 is also a drug-metabolizing enzyme and compromised activity is expected to have implications for the efficacy of drug treatment and the possibility of adverse drug reactions both in TMAuric patients and in the general population. To date eight polymorphic variants, not associated with TMAuria, have been reported. A human FMO3 mutation database was created using MuStar, a locus-specific database system for maintaining data about allelic variants and distributing these via the World Wide Web. The database currently contains 24 entries and is accessible on the World Wide Web via the URL Additional entries can be submitted via the curator of the database or via a web-based form.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alleles
  • Animals
  • Databases, Genetic* / trends
  • Genetic Variation
  • Humans
  • Metabolism, Inborn Errors / genetics*
  • Metabolism, Inborn Errors / urine*
  • Methylamines / urine*
  • Mutation*
  • Oxygenases / genetics*
  • Oxygenases / metabolism


  • Methylamines
  • Oxygenases
  • dimethylaniline monooxygenase (N-oxide forming)
  • trimethylamine