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URL of this page: https://medlineplus.gov/genetics/gene/fmo3/

FMO3 gene

flavin containing dimethylaniline monoxygenase 3

Normal Function

The FMO3 gene provides instructions for making an enzyme that is part of a larger enzyme family called flavin-containing dimethylaniline monooxygenases (FMOs). These enzymes break down compounds that contain nitrogen, sulfur, or phosphorus. The FMO3 enzyme, which is made chiefly in the liver, is responsible for breaking down nitrogen-containing compounds derived from the diet. 

One of these compounds is trimethylamine, which is the molecule that gives fish their fishy smell. Trimethylamine is produced as bacteria in the intestine help digest certain proteins obtained from eggs, liver, legumes (such as soybeans and peas), certain kinds of fish, and other foods. The FMO3 enzyme normally converts fishy-smelling trimethylamine into another compound, trimethylamine-N-oxide, which has no odor. Trimethylamine-N-oxide is then excreted from the body in urine.

Researchers believe that the FMO3 enzyme also plays a role in processing some types of drugs. For example, this enzyme is likely needed to break down the anticancer drug tamoxifen, the anti-inflammatory medication benzydamine, the antifungal drug ketoconazole, and certain medications used to treat depression (antidepressants). 

The FMO3 enzyme may also be involved in processing nicotine, an addictive chemical found in tobacco. Normal variations (polymorphisms) in the FMO3 gene may affect the enzyme's ability to break down these substances. Researchers are working to determine whether FMO3 polymorphisms can help explain why people respond differently to certain drugs.

Health Conditions Related to Genetic Changes

Trimethylaminuria

More than 40 variants (also known as mutations) in the FMO3 gene have been identified in people with trimethylaminuria. Some of these variants lead to the production of a small, nonfunctional version of the FMO3 enzyme. Other variants change single building blocks (amino acids) used to build the enzyme, which alters its shape and disrupts its function. Without enough functional FMO3 enzyme, the body is unable to convert trimethylamine into trimethylamine-N-oxide effectively. As a result, trimethylamine builds up in the body and is released in an affected person's sweat, urine, and breath. The excretion of this compound is responsible for the strong body odor characteristic of trimethylaminuria. Studies suggest that diet and stress also play a role in determining the intensity of the fish-like odor.

More About This Health Condition

Other Names for This Gene

  • Dimethylaniline monooxygenase [N-oxide-forming] 3
  • Dimethylaniline oxidase 3
  • FMO3_HUMAN
  • FMOII

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Gene and Variant Databases

References

  • Bain MA, Fornasini G, Evans AM. Trimethylamine: metabolic, pharmacokinetic and safety aspects. Curr Drug Metab. 2005 Jun;6(3):227-40. doi: 10.2174/1389200054021807. Citation on PubMed
  • Dolphin CT, Janmohamed A, Smith RL, Shephard EA, Phillips IR. Missense mutation in flavin-containing mono-oxygenase 3 gene, FMO3, underlies fish-odour syndrome. Nat Genet. 1997 Dec;17(4):491-4. doi: 10.1038/ng1297-491. Citation on PubMed
  • Hernandez D, Addou S, Lee D, Orengo C, Shephard EA, Phillips IR. Trimethylaminuria and a human FMO3 mutation database. Hum Mutat. 2003 Sep;22(3):209-13. doi: 10.1002/humu.10252. Citation on PubMed
  • Koukouritaki SB, Poch MT, Henderson MC, Siddens LK, Krueger SK, VanDyke JE, Williams DE, Pajewski NM, Wang T, Hines RN. Identification and functional analysis of common human flavin-containing monooxygenase 3 genetic variants. J Pharmacol Exp Ther. 2007 Jan;320(1):266-73. doi: 10.1124/jpet.106.112268. Epub 2006 Oct 18. Citation on PubMed
  • Krueger SK, Vandyke JE, Williams DE, Hines RN. The role of flavin-containing monooxygenase (FMO) in the metabolism of tamoxifen and other tertiary amines. Drug Metab Rev. 2006;38(1-2):139-47. doi: 10.1080/03602530600569919. Citation on PubMed
  • Mitchell SC. Trimethylaminuria: susceptibility of heterozygotes. Lancet. 1999 Dec 18-25;354(9196):2164-5. doi: 10.1016/s0140-6736(05)77067-7. No abstract available. Citation on PubMed
  • Phillips IR, Shephard EA. Primary Trimethylaminuria. 2007 Oct 8 [updated 2020 Nov 5]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from http://www.ncbi.nlm.nih.gov/books/NBK1103/ Citation on PubMed
  • Shephard EA, Treacy EP, Phillips IR. Clinical utility gene card for: Trimethylaminuria - update 2014. Eur J Hum Genet. 2015 Sep;23(9). doi: 10.1038/ejhg.2014.226. Epub 2014 Oct 22. No abstract available. Citation on PubMed
  • Zhang J, Tran Q, Lattard V, Cashman JR. Deleterious mutations in the flavin-containing monooxygenase 3 (FMO3) gene causing trimethylaminuria. Pharmacogenetics. 2003 Aug;13(8):495-500. doi: 10.1097/00008571-200308000-00007. Citation on PubMed
  • Zhou J, Shephard EA. Mutation, polymorphism and perspectives for the future of human flavin-containing monooxygenase 3. Mutat Res. 2006 Jun;612(3):165-171. doi: 10.1016/j.mrrev.2005.09.001. Epub 2006 Feb 14. Citation on PubMed
  • Zschocke J, Kohlmueller D, Quak E, Meissner T, Hoffmann GF, Mayatepek E. Mild trimethylaminuria caused by common variants in FMO3 gene. Lancet. 1999 Sep 4;354(9181):834-5. doi: 10.1016/s0140-6736(99)80019-1. Citation on PubMed

The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.