FMO3 flavin containing monooxygenase 3 [Homo sapiens] - Gene

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Summary

Official Symbol: FMO3provided by HGNC
Official Full Name: flavin containing monooxygenase 3provided by HGNC
Primary source: HGNC:3771
See related: Ensembl:ENSG00000007933; HPRD:00633; MIM:136132; Vega:OTTHUMG00000035505
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: TMAU; FMOII; dJ127D3.1; MGC34400
Summary: Flavin-containing monooxygenases (FMO) are an important class of drug-metabolizing enzymes that catalyze the NADPH-dependent oxygenation of various nitrogen-,sulfur-, and phosphorous-containing xenobiotics such as therapeutic drugs, dietary compounds, pesticides, and other foreign compounds. The human FMO gene family is composed of 5 genes and multiple pseudogenes. FMO members have distinct developmental- and tissue-specific expression patterns. The expression of this FMO3 gene, the major FMO expressed in adult liver, can vary up to 20-fold between individuals. This inter-individual variation in FMO3 expression levels is likely to have significant effects on the rate at which xenobiotics are metabolised and, therefore, is of considerable interest to the pharmaceutical industry. This transmembrane protein localizes to the endoplasmic reticulum of many tissues. Alternative splicing of this gene results in multiple transcript variants encoding the same protein. Mutations in this gene cause the disorder trimethylaminuria (TMAu) which is characterized by the accumulation and excretion of unmetabolized trimethylamine and a distinctive body odor. In healthy individuals, trimethylamine is primarily converted to the non odorous trimethylamine N-oxide.[provided by RefSeq, Aug 2009]

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Genomic context

Location :: 1q24.3

Sequence :: Chromosome: 1; NC_000001.10 (171060018..171086959)

See FMO3 in Epigenomics, MapViewer

Chromosome 1 - NC_000001.10 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

patient heterozygous for 4 FMO3 mutations
Title: What have we here? A man or a fish?
This study is the first to demonstrate a gene-environment interaction in SIDS. The findings suggest that the common polymorphism G472A of FMO3 could act as an additional genetic SIDS risk factor in children whose mothers smoke.
Title: A common FMO3 polymorphism may amplify the effect of nicotine exposure in sudden infant death syndrome (SIDS).
Clinical trial of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
Title: Influence of pharmacogenetic variability on the pharmacokinetics and toxicity of the aurora kinase inhibitor danusertib.
Distribution of functionally relevant FMO3 polymorphisms varies not only between ethnicities but also within
Title: Flavin-containing monooxygenase 3 polymorphisms in 13 ethnic populations from Europe, East Asia and sub-Saharan Africa: frequency and linkage analysis.
The identification in a family from northern Norway of a novel causative mutation of FMO3 gene causing trimethylaminuria, is described.
Title: A novel mutation in the flavin-containing monooxygenase 3 gene (FMO3) of a Norwegian family causes trimethylaminuria.
considerable individual differences in FMO3 levels may exist in Japanese livers. The liver-enriched transcription factor HNF-4 appears to be a determinant of FMO3 expression in livers, as well as the ubiquitous factor NF-Y.
Title: Inter-individual variation in flavin-containing monooxygenase 3 in livers from Japanese: correlation with hepatic transcription factors.
As summarized in this review, FMO3 is apparently unique to the human, yet is the most abundant FMO family member in the adult human liver, whereas FMO1 dominates in most animal models.
Title: Developmental and tissue-specific expression of human flavin-containing monooxygenases 1 and 3.
the combination of V187A/E158K mutations in FMO3, the enzyme activity is severely affected and possibly contributes to the trimethylaminuria observed.
Title: Novel variants of the human flavin-containing monooxygenase 3 (FMO3) gene associated with trimethylaminuria.
Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
Title: Analysis of flavin-containing monooxygenase 3 genotype data in populations administered the anti-schizophrenia agent olanzapine.
Data show that the frequencies of FMO3 mutant alleles varied not only in different ethnic groups, but also in different populations that stemmed from the same ethnic group.
Title: [The frequency distribution of flavin-containing monooxygenase 3 mutant alleles in 28 populations from Yunnan].

Submit: New GeneRIF Correction See all (34)

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Phenotypes

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Trimethylaminuria is characterized by a fishy odor resembling that of rotten or decaying fish that results from excess excretion of trimethylamine in the urine, breath, sweat, and reproductive fluids. No physical symptoms are associated with trimethylaminuria. Affected individuals appear normal and healthy; however, the unpleasant odor often results in social and psychological problems. Symptoms are usually present from birth and may worsen during puberty. In females, symptoms are more severe just before and during menstruation, after taking oral contraceptives, and around the time of menopause.

Diagnosis Testing

Diagnosis of trimethylaminuria is based on either the percent of total trimethylamine (free trimethylamine [TMA] plus the non-odorous metabolite TMA N-oxide) excreted in the urine as unmetabolized free TMA or the concentration of unmetabolized TMA in the urine. FMO3 is the only gene known to be associated with trimethylaminuria. Molecular genetic testing is available clinically.

Genetic Counseling

Trimethylaminuria is inherited in an autosomal recessive manner. The parents of an affected individual are obligate heterozygotes and therefore carry one mutant allele. Heterozygotes (carriers) are asymptomatic. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Prenatal testing is possible for pregnancies at increased risk if the disease-causing mutations in the family have been identified.

References

PMID: 20301282

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General gene information

Markers

D8S2279 (e-PCR)
- UniSTS:473907

RH1468 (e-PCR)
- UniSTS:84804

RH70128 (e-PCR)
- UniSTS:83071

G67587 (e-PCR)
- UniSTS:207002

G67588 (e-PCR)
- UniSTS:207003

G67589 (e-PCR)
- UniSTS:207004

G67583 (e-PCR)
- UniSTS:207005

G67584 (e-PCR)
- UniSTS:207006

G67585 (e-PCR)
- UniSTS:207007

G67586 (e-PCR)
- UniSTS:207008

Genotypes

See FMO3 SNP Geneview Report
See FMO3 SNP Genotype Report
See FMO3 SNP Variation Viewer Report

Related pseudogene(s)

1 found Review record(s) in Gene

Homology

Homologs of the FMO3 gene: The FMO3 gene is conserved in chimpanzee, , dog, cow, mouse, and rat.
Map Viewer (Mouse, Rat)

Pathways from BioSystems

Biological oxidations, organism-specific biosystem (from REACTOME)
Biological oxidations, organism-specific biosystemAll organisms are constantly exposed to foreign chemicals every day. These can be man-made (drugs, industrial chemicals) or natural (alkaloids, toxins from plants and animals). Uptake is usually via ...
Drug metabolism - cytochrome P450, organism-specific biosystem (from KEGG)
Drug metabolism - cytochrome P450, organism-specific biosystem
Drug metabolism - cytochrome P450
Drug metabolism - cytochrome P450, conserved biosystem (from KEGG)
Drug metabolism - cytochrome P450, conserved biosystem
Drug metabolism - cytochrome P450
FMO oxidizes nucleophiles, organism-specific biosystem (from REACTOME)
FMO oxidizes nucleophiles, organism-specific biosystemFlavin-containing monooxygenases (FMOs) are the second family of microsomal oxidative enzymes with broad and overlapping specificity. The major reactions FMOs catalyze are nucleophilic hetero-atom co...
Metabolism, organism-specific biosystem (from REACTOME)
Metabolism, organism-specific biosystemMetabolic processes in human cells generate energy through the oxidation of molecules consumed in the diet and mediate the synthesis of diverse essential molecules not taken in the diet as well as th...
Nicotine metabolism, organism-specific biosystem (from WikiPathways)
Nicotine metabolism, organism-specific biosystemThis pathway shows metabolism of nicotine in human liver including all the candidate genes which may be responsible. Nicotine is extensively metabolized to a number of metabolites in liver. Quantitat...
Phase 1 - Functionalization of compounds, organism-specific biosystem (from REACTOME)
Phase 1 - Functionalization of compounds, organism-specific biosystemPhase 1 of metabolism is concerned with functionalization, that is the introduction or exposure of functional groups on the chemical structure of a compound. This provides a 'handle' for phase 2 conj...
nicotine degradation II, organism-specific biosystem (from BIOCYC)
nicotine degradation II, organism-specific biosystemNicotine is the principal alkaloid in the leaves of commercially used tobacco (Nicotiana tabacum and N. rustica) . Nicotine in tobacco leaves and in plant-derived preparations is mostly in the (S)...
nicotine degradation II, conserved biosystem (from BIOCYC)
nicotine degradation II, conserved biosystemNicotine is the principal alkaloid in the leaves of commercially used tobacco (Nicotiana tabacum and N. rustica) |CITS: [SCHMELTZ77]|. Nicotine in tobacco leaves and in plant-derived preparations i...

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
N,N-dimethylaniline monooxygenase activity	TAS Traceable Author Statement more info
NADP binding	IEA Inferred from Electronic Annotation more info
amino acid binding	IEA Inferred from Electronic Annotation more info
flavin adenine dinucleotide binding	IEA Inferred from Electronic Annotation more info
monooxygenase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
drug metabolic process	IEA Inferred from Electronic Annotation more info
small molecule metabolic process	TAS Traceable Author Statement more info
xenobiotic metabolic process	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
endoplasmic reticulum	IEA Inferred from Electronic Annotation more info
endoplasmic reticulum membrane	TAS Traceable Author Statement more info
integral to membrane	IEA Inferred from Electronic Annotation more info
intrinsic to endoplasmic reticulum membrane	IEA Inferred from Electronic Annotation more info
membrane	IEA Inferred from Electronic Annotation more info
microsome	IEA Inferred from Electronic Annotation more info

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General protein information

Preferred Names: dimethylaniline monooxygenase [N-oxide-forming] 3

Names: dimethylaniline monooxygenase [N-oxide-forming] 3; FMO 3; FMO II; FMO form 2; dimethylaniline oxidase 3; hepatic flavin-containing monooxygenase 3; hepatic flavin-containing monooxygenase-3

NP_001002294.1

EC 1.14.13.8

NP_008825.4

EC 1.14.13.8

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NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_012690.1 RefSeqGene

Range

5001..31942

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001002294.2 → NP_001002294.1 dimethylaniline monooxygenase [N-oxide-forming] 3

Status: REVIEWED

Description

Transcript Variant: This variant (2) represents the longer transcript. Variants 1 and 2 encode the same protein.

Source sequence(s)

AK223166, AK313197, BC032016, BM453951

Consensus CDS

CCDS1292.1

UniProtKB/Swiss-Prot

P31513

UniProtKB/TrEMBL

Q53FW5

Related

ENSP00000356729, OTTHUMP00000033540, ENST00000367755, OTTHUMT00000086219

Conserved Domains (2) summary

pfam00743
Location:2 – 532
Blast Score: 2581

FMO-like; Flavin-binding monooxygenase-like

cl09931
Location:7 – 41
Blast Score: 96

NADB_Rossmann; Rossmann-fold NAD(P)(+)-binding proteins
NM_006894.5 → NP_008825.4 dimethylaniline monooxygenase [N-oxide-forming] 3

Status: REVIEWED

Description

Transcript Variant: This variant (1) differs in the 5' UTR, compared to variant 2. Variants 1 and 2 encode the same protein.

Source sequence(s)

AK223166, AK313197, BC032016, BM453951

Consensus CDS

CCDS1292.1

UniProtKB/Swiss-Prot

P31513

UniProtKB/TrEMBL

Q53FW5

Related

ENSP00000375935, ENST00000392085

Conserved Domains (2) summary

pfam00743
Location:2 – 532
Blast Score: 2581

FMO-like; Flavin-binding monooxygenase-like

cl09931
Location:7 – 41
Blast Score: 96

NADB_Rossmann; Rossmann-fold NAD(P)(+)-binding proteins

RefSeqs of Annotated Genomes: Build 37.3

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000001.10 Reference GRCh37.p5 Primary Assembly

Range

171060018..171086959

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000133.1 Alternate HuRef

Range

142283384..142310544

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AL021026.1	CAA15908.1
genomic	AY895830.1	AAW65372.1
genomic	CH471067.1	EAW90886.1
		EAW90887.1
		EAW90888.1
genomic	U39960.1	None
genomic	U39961.1	AAC51932.1
genomic	U39962.1	AAC51932.1
genomic	U39963.1	AAC51932.1
genomic	U39964.1	AAC51932.1
genomic	U39965.1	AAC51932.1
genomic	U39966.1	AAC51932.1
genomic	U39967.1	AAC51932.1
mRNA	AI478384.1	None
mRNA	AK223166.1	BAD96886.1
mRNA	AK296105.1	BAH12258.1
mRNA	AK298406.1	BAH12779.1
mRNA	AK310785.1	None
mRNA	AK313197.1	BAG36013.1
mRNA	BC032016.1	AAH32016.1
mRNA	BM453951.1	None
mRNA	M83772.1	AAA86284.1
mRNA	Z47552.1	CAA87632.1
other-genetic	DQ892429.2	ABM83355.1
other-genetic	DQ895643.2	ABM86569.1