Human Gene FMO3 (ENST00000367755.9) from GENCODE V44
  Description: Homo sapiens flavin containing dimethylaniline monoxygenase 3 (FMO3), transcript variant 1, mRNA. (from RefSeq NM_006894)
RefSeq Summary (NM_001002294): 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 different isoforms. 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, Jan 2016].
Gencode Transcript: ENST00000367755.9
Gencode Gene: ENSG00000007933.13
Transcript (Including UTRs)
   Position: hg38 chr1:171,090,905-171,117,819 Size: 26,915 Total Exon Count: 9 Strand: +
Coding Region
   Position: hg38 chr1:171,092,659-171,117,442 Size: 24,784 Coding Exon Count: 8 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesGeneReviewsMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr1:171,090,905-171,117,819)mRNA (may differ from genome)Protein (532 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
BioGPSEnsemblEntrez GeneExonPrimerGencodeGeneCards
HGNCHPRDLynxMalacardsMGIneXtProt
OMIMPubMedReactomeUniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: FMO3_HUMAN
DESCRIPTION: RecName: Full=Dimethylaniline monooxygenase [N-oxide-forming] 3; EC=1.14.13.8; AltName: Full=Dimethylaniline oxidase 3; AltName: Full=FMO II; AltName: Full=FMO form 2; AltName: Full=Hepatic flavin-containing monooxygenase 3; Short=FMO 3; AltName: Full=Trimethylamine monooxygenase; EC=1.14.13.148;
FUNCTION: Involved in the oxidative metabolism of a variety of xenobiotics such as drugs and pesticides. It N-oxygenates primary aliphatic alkylamines as well as secondary and tertiary amines. Plays an important role in the metabolism of trimethylamine (TMA), via the production of TMA N-oxide (TMAO). Is also able to perform S-oxidation when acting on sulfide compounds.
CATALYTIC ACTIVITY: N,N-dimethylaniline + NADPH + O(2) = N,N- dimethylaniline N-oxide + NADP(+) + H(2)O.
CATALYTIC ACTIVITY: N,N,N-trimethylamine + NADPH + O(2) = N,N,N- trimethylamine N-oxide + NADP(+) + H(2)O.
COFACTOR: FAD.
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=21 uM for trimethylamine (at pH 8.5); KM=31 uM for trimethylamine (at pH 7.4 and 37 degrees Celsius); KM=43 uM for benzydamine (at pH 7.4 and 37 degrees Celsius); KM=55.7 uM for ethylenethiourea (at pH 8.5); KM=71.8 uM for methimazole (at pH 8.5); KM=150.1 uM for sulindac (at pH 8.5); KM=248 uM for methyl p-tolyl sulfide (at pH 7.4 and 37 degrees Celsius);
SUBCELLULAR LOCATION: Microsome membrane. Endoplasmic reticulum membrane.
TISSUE SPECIFICITY: Liver.
DISEASE: Defects in FMO3 are the cause of trimethylaminuria (TMAU) [MIM:602079]; also known as fish-odor syndrome. TMAU is an inborn error of metabolism associated with an offensive body odor and caused by deficiency of FMO-mediated N-oxidation of amino- trimethylamine (TMA) derived from foodstuffs. Such individuals excrete relatively large amounts of TMA in their urine, sweat, and breath, and exhibit a fishy body odor characteristic of the malodorous free amine.
SIMILARITY: Belongs to the FMO family.
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/FMO3";
WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/fmo3/";

-  Primer design for this transcript
 

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Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: FMO3
Diseases sorted by gene-association score: trimethylaminuria* (1712), endometriosis of ovary (7), delusional disorder (6)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 92.51 RPKM in Liver
Total median expression: 160.58 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -8.4483-0.102 Picture PostScript Text
3' UTR -65.00377-0.172 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR012143 - DiMe-aniline_mOase
IPR000960 - Flavin_mOase
IPR020946 - Flavin_mOase-like
IPR002255 - Flavin_mOase_3

Pfam Domains:
PF00743 - Flavin-binding monooxygenase-like

ModBase Predicted Comparative 3D Structure on P31513
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0004497 monooxygenase activity
GO:0004499 N,N-dimethylaniline monooxygenase activity
GO:0005515 protein binding
GO:0016491 oxidoreductase activity
GO:0034899 trimethylamine monooxygenase activity
GO:0050660 flavin adenine dinucleotide binding
GO:0050661 NADP binding

Biological Process:
GO:0006805 xenobiotic metabolic process
GO:0055114 oxidation-reduction process

Cellular Component:
GO:0005783 endoplasmic reticulum
GO:0005789 endoplasmic reticulum membrane
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0031090 organelle membrane
GO:0043231 intracellular membrane-bounded organelle


-  Descriptions from all associated GenBank mRNAs
  AK223166 - Homo sapiens mRNA for flavin containing monooxygenase 3 isoform 2 variant, clone: LNG05587.
AK298406 - Homo sapiens cDNA FLJ51030 complete cds, highly similar to Dimethylaniline monooxygenase (N-oxide-forming) 3 (EC 1.14.13.8).
Z47552 - H.sapiens mRNA for flavin-containing monooxygenase 3 (FMO3).
AK298456 - Homo sapiens cDNA FLJ51035 complete cds.
AK310785 - Homo sapiens cDNA, FLJ17827.
AK313197 - Homo sapiens cDNA, FLJ93696, highly similar to Homo sapiens flavin containing monooxygenase 3 (FMO3), mRNA.
AK296105 - Homo sapiens cDNA FLJ60275 complete cds, highly similar to Dimethylaniline monooxygenase (N-oxide-forming) 3 (EC 1.14.13.8).
M83772 - Human flavin-containing monooxygenase form II (FMO2) mRNA, complete cds.
BC032016 - Homo sapiens flavin containing monooxygenase 3, mRNA (cDNA clone MGC:34400 IMAGE:5175615), complete cds.
CU689266 - Synthetic construct Homo sapiens gateway clone IMAGE:100019801 5' read FMO3 mRNA.
KJ896824 - Synthetic construct Homo sapiens clone ccsbBroadEn_06218 FMO3 gene, encodes complete protein.
KR710793 - Synthetic construct Homo sapiens clone CCSBHm_00017218 FMO3 (FMO3) mRNA, encodes complete protein.
KR710794 - Synthetic construct Homo sapiens clone CCSBHm_00017221 FMO3 (FMO3) mRNA, encodes complete protein.
KR710795 - Synthetic construct Homo sapiens clone CCSBHm_00017233 FMO3 (FMO3) mRNA, encodes complete protein.
KR710796 - Synthetic construct Homo sapiens clone CCSBHm_00017243 FMO3 (FMO3) mRNA, encodes complete protein.
KR712212 - Synthetic construct Homo sapiens clone CCSBHm_00900165 FMO3 (FMO3) mRNA, encodes complete protein.
KR712216 - Synthetic construct Homo sapiens clone CCSBHm_00900169 FMO3 (FMO3) mRNA, encodes complete protein.
DQ895643 - Synthetic construct Homo sapiens clone IMAGE:100010103; FLH186250.01L; RZPDo839C0761D flavin containing monooxygenase 3 (FMO3) gene, encodes complete protein.
DQ892429 - Synthetic construct clone IMAGE:100005059; FLH186254.01X; RZPDo839C0771D flavin containing monooxygenase 3 (FMO3) gene, encodes complete protein.
KU178077 - Homo sapiens flavin containing monooxygenase 3 isoform 1 (FMO3) mRNA, partial cds.
KU178078 - Homo sapiens flavin containing monooxygenase 3 isoform 3 (FMO3) mRNA, complete cds, alternatively spliced.
E11406 - cDNA encoding human flavin containing monooxygenase.
JD314563 - Sequence 295587 from Patent EP1572962.
JD502304 - Sequence 483328 from Patent EP1572962.
JD093972 - Sequence 74996 from Patent EP1572962.
JD523936 - Sequence 504960 from Patent EP1572962.
JD521963 - Sequence 502987 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa00982 - Drug metabolism - cytochrome P450

BioCyc Knowledge Library
PWY66-201 - nicotine degradation IV

Reactome (by CSHL, EBI, and GO)

Protein P31513 (Reactome details) participates in the following event(s):

R-HSA-139970 FMO3:FAD N-oxidises TMA to TMAO
R-HSA-217271 FMO oxidises nucleophiles
R-HSA-211945 Phase I - Functionalization of compounds
R-HSA-211859 Biological oxidations
R-HSA-1430728 Metabolism

-  Other Names for This Gene
  Alternate Gene Symbols: B2R816, ENST00000367755.1, ENST00000367755.2, ENST00000367755.3, ENST00000367755.4, ENST00000367755.5, ENST00000367755.6, ENST00000367755.7, ENST00000367755.8, FMO3_HUMAN, NM_006894, P31513, Q14854, Q8N5N5, uc001ghi.1, uc001ghi.2, uc001ghi.3, uc001ghi.4
UCSC ID: ENST00000367755.9
RefSeq Accession: NM_001002294
Protein: P31513 (aka FMO3_HUMAN)
CCDS: CCDS1292.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene FMO3:
trimethylaminuria (Primary Trimethylaminuria)

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.