FMO3 (flavin containing dimethylaniline monoxygenase 3)

Gene

• Entrez ID: 2328
• Gene name: Flavin containing dimethylaniline monoxygenase 3
• Gene symbol: FMO3
• Synonyms (NCBI Gene): FMOII, TMAU, dJ127D3.1
• Chromosome: 1
• Chromosome location: 1q24.3
• 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, pes

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs2266780	A>G	Benign, likely-pathogenic, benign-likely-benign, pathogenic	Coding sequence variant, missense variant
rs2266782	G>A	Benign, likely-pathogenic, pathogenic	5 prime UTR variant, coding sequence variant, missense variant
rs3832024	TG>-	Pathogenic	Coding sequence variant, frameshift variant, stop gained, inframe indel
rs61753344	G>A,T	Pathogenic	Missense variant, stop gained, coding sequence variant
rs72549320	G>A	Pathogenic	5 prime UTR variant, genic upstream transcript variant, coding sequence variant, missense variant
rs72549322	A>G	Pathogenic	Missense variant, genic upstream transcript variant, coding sequence variant, intron variant
rs72549323	G>C,T	Pathogenic	Missense variant, genic upstream transcript variant, coding sequence variant, intron variant
rs72549325	G>A,T	Pathogenic, likely-pathogenic	5 prime UTR variant, stop gained, coding sequence variant, missense variant
rs72549326	C>T	Pathogenic	5 prime UTR variant, coding sequence variant, missense variant
rs72549330	G>A,T	Pathogenic	Missense variant, stop gained, coding sequence variant
rs72549331	G>A,T	Pathogenic, likely-pathogenic	Missense variant, coding sequence variant
rs72549334	C>T	Likely-pathogenic	Missense variant, coding sequence variant
rs572292275	C>T	Likely-pathogenic	Missense variant, coding sequence variant
rs769983049	T>C,G	Pathogenic	Missense variant, coding sequence variant
rs886038576	G>A,T	Likely-pathogenic	Splice donor variant, genic upstream transcript variant
rs1057520649	G>T	Pathogenic	Stop gained, coding sequence variant
rs1384237868	C>T	Likely-pathogenic	Stop gained, 5 prime UTR variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT030320	hsa-miR-26b-5p	Microarray	19088304
MIRT2230255	hsa-miR-1278	CLIP-seq
MIRT2230256	hsa-miR-139-5p	CLIP-seq
MIRT2230257	hsa-miR-217	CLIP-seq
MIRT2230258	hsa-miR-3618	CLIP-seq
MIRT2230259	hsa-miR-4418	CLIP-seq
MIRT2230260	hsa-miR-4797-5p	CLIP-seq
MIRT2230261	hsa-miR-509-3-5p	CLIP-seq
MIRT2230262	hsa-miR-509-5p	CLIP-seq
MIRT2230263	hsa-miR-934	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
PBX2	Unknown	17786630
USF1	Unknown	17786630
YY1	Unknown	17786630

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004497	Function	Monooxygenase activity	IEA
GO:0004499	Function	N,N-dimethylaniline monooxygenase activity	IBA
GO:0004499	Function	N,N-dimethylaniline monooxygenase activity	IEA
GO:0005515	Function	Protein binding	IPI	25910212, 31515488, 32296183
GO:0005783	Component	Endoplasmic reticulum	IEA
GO:0005789	Component	Endoplasmic reticulum membrane	IEA
GO:0005789	Component	Endoplasmic reticulum membrane	TAS
GO:0016020	Component	Membrane	IEA
GO:0016491	Function	Oxidoreductase activity	IEA
GO:0016709	Function	Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen	IEA
GO:0034899	Function	Trimethylamine monooxygenase activity	IEA
GO:0042412	Process	Taurine biosynthetic process	IBA
GO:0042412	Process	Taurine biosynthetic process	IDA	32156684
GO:0043231	Component	Intracellular membrane-bounded organelle	TAS	9207220
GO:0047638	Function	Albendazole monooxygenase activity	IEA
GO:0047822	Function	Hypotaurine monooxygenase activity	IDA	32156684
GO:0047822	Function	Hypotaurine monooxygenase activity	IEA
GO:0050660	Function	Flavin adenine dinucleotide binding	IEA
GO:0050661	Function	NADP binding	IEA

Other IDs

• MIM: 136132
• HGNC: 3771
• e!Ensembl: ENSG00000007933

Protein

• UniProt ID: P31513
• Protein name: Flavin-containing monooxygenase 3 (EC 1.14.13.148) (EC 1.14.13.32) (EC 1.14.13.8) (Dimethylaniline monooxygenase [N-oxide-forming] 3) (Dimethylaniline oxidase 3) (FMO II) (FMO form 2) (Hepatic flavin-containing monooxygenase 3) (FMO 3) (Trimethylamine mon
• Protein function: Essential hepatic enzyme that catalyzes the oxygenation of a wide variety of nitrogen- and sulfur-containing compounds including drugs as well as dietary compounds (PubMed:10759686, PubMed:30381441, PubMed:32156684). Plays an important role in t
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00743	FMO-like	2 → 532	Flavin-binding monooxygenase-like	Family

• Tissue specificity: TISSUE SPECIFICITY: Liver.
• Sequence:

  MGKKVAIIGAGVSGLASIRSCLEEGLEPTCFEKSNDIGGLWKFSDHAEEGRASIYKSVFS
  NSSKEMMCFPDFPFPDDFPNFMHNSKIQEYIIAFAKEKNLLKYIQFKTFVSSVNKHPDFA
  TTGQWDVTTERDGKKESAVFDAVMVCSGHHVYPNLPKESFPGLNHFKGKCFHSRDYKEPG
  VFNGKRVLVVGLGNSGCDIATELSRTAEQVMISSRSGSWVMSRVWDNGYPWDMLLVTRFG
  TFLKNNLPTAISDWLYVKQMNARFKHENYGLMPLNGVLRKEPVFNDELPASILCGIVSVK
  PNVKEFTETSAIFEDGTIFEGIDCVIFATGYSFAYPFLDESIIKSRNNEIILFKGVFPPL
  LEKSTIAVIGFVQSLGAAIPTVDLQSRWAAQVIKGTCTLPSMEDMMNDINEKMEKKRKWF
  GKSETIQTDYIVYMDELSSFIGAKPNIPWLFLTDPKLAMEVYFGPCSPYQFRLVGPGQWP
  GARNAILTQWDRSLKPMQTRVVGRLQKPCFFFHWLKLFAIPILLIAVFLVLT

• Sequence length: 532

Pathways

KEGG:

Taurine and hypotaurine metabolism
Drug metabolism - cytochrome P450
Metabolic pathways

Reactome:

FMO oxidises nucleophiles
Defective FMO3 causes Trimethylaminuria (TMAU)

Associated diseases

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
FMO3 activity, decreased	Pathogenic	rs72549325	RCV000017703
FMO3-related disorder	Pathogenic	rs989553837	RCV004756517
See cases	Likely pathogenic; Pathogenic	rs572292275	RCV002252234
Trimethylaminuria	Likely pathogenic; Pathogenic	rs775064534, rs751356173, rs762600525, rs559643079, rs3832024, rs775749562, rs1656200306, rs767079173, rs893223321, rs61757397, rs765373503, rs1185446006, rs1270775688, rs777700920, rs1331483649, rs866756635, rs61753344, rs72549323, rs72549334, rs72549330, rs72549322, rs72549332, rs72549320, rs1331111339, rs1557946006, rs1655736013, rs1057520649, rs1384237868, rs72549325, rs572292275, rs748324481	RCV005003727 RCV005013010 RCV001775501 RCV001783302 RCV000490504 RCV003230932 RCV003388358 RCV005003660 RCV005003662 RCV005003666 RCV005003667 RCV005013048 RCV005003686 RCV004783090 RCV005003687 RCV005013168 RCV000017697 RCV000017699 RCV000017702 RCV000017705 RCV000017706 RCV000017707 RCV000017709 RCV000017710 RCV003988783 RCV004586302 RCV005004152 RCV000681472 RCV000681473 RCV000778196 RCV001096673

Unknown
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
-	no classification for the single variant	rs769983049	-
Chronic lymphocytic leukemia/small lymphocytic lymphoma	Conflicting classifications of pathogenicity	rs11578281	RCV005891519
Colon adenocarcinoma	Conflicting classifications of pathogenicity	rs2066532	RCV005913666
Lymphoma	Conflicting classifications of pathogenicity	rs11578281	RCV005891518
Malignant tumor of esophagus	Conflicting classifications of pathogenicity	rs186763441	RCV005913675
Nonpapillary renal cell carcinoma	Conflicting classifications of pathogenicity	rs11578281	RCV005891517

Associations from Text Mining
Disease Name	Relationship Type	References
Adenoma	Associate	16214918
Adenomatous Polyposis Coli	Associate	16214918
Breast Neoplasms	Associate	29959872
Carcinoma Hepatocellular	Associate	30136421, 35915607
Drug Related Side Effects and Adverse Reactions	Associate	25119182
Essential Hypertension	Associate	32555714
Fibrosis	Associate	34428046
Genetic Diseases Inborn	Associate	16324215
Hypertension	Associate	16324215
Intestinal Polyposis	Associate	16214918
Metabolic Diseases	Associate	17531949
Muscular Atrophy Spinal	Associate	37148485
Neoplasms	Associate	30136421, 34428046
Non alcoholic Fatty Liver Disease	Associate	34428046
Ovarian Diseases	Associate	24390223
Renal Insufficiency Chronic	Associate	27513517
Trimethylaminuria	Associate	16324215, 16858129, 17257434, 17329912, 17531949, 24028545, 25288227, 28196478, 29116146, 29745129, 31533761, 34834137