FMO3

Protein identityUniProt · HPA

UniProt accession

P31513

Gene

FMO3

Ensembl

ENSG00000007933

Chromosome

1

Canonical length

532 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Potential drug targets, Predicted intracellular proteins, Predicted membrane proteins

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

532 residues, UniProt reviewed canonical sequence.

>P31513|FMO3
     1  MGKKVAIIGA GVSGLASIRS CLEEGLEPTC FEKSNDIGGL WKFSDHAEEG RASIYKSVFS
    61  NSSKEMMCFP DFPFPDDFPN FMHNSKIQEY IIAFAKEKNL LKYIQFKTFV SSVNKHPDFA
   121  TTGQWDVTTE RDGKKESAVF DAVMVCSGHH VYPNLPKESF PGLNHFKGKC FHSRDYKEPG
   181  VFNGKRVLVV GLGNSGCDIA TELSRTAEQV MISSRSGSWV MSRVWDNGYP WDMLLVTRFG
   241  TFLKNNLPTA ISDWLYVKQM NARFKHENYG LMPLNGVLRK EPVFNDELPA SILCGIVSVK
   301  PNVKEFTETS AIFEDGTIFE GIDCVIFATG YSFAYPFLDE SIIKSRNNEI ILFKGVFPPL
   361  LEKSTIAVIG FVQSLGAAIP TVDLQSRWAA QVIKGTCTLP SMEDMMNDIN EKMEKKRKWF
   421  GKSETIQTDY IVYMDELSSF IGAKPNIPWL FLTDPKLAME VYFGPCSPYQ FRLVGPGQWP
   481  GARNAILTQW DRSLKPMQTR VVGRLQKPCF FFHWLKLFAI PILLIAVFLV LT

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against FMO3 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Other membrane

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.24

Highest tissue expression

1,050 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about FMO3.

Disease | AllUniProt

Conditions FMO3 is implicated in, by any mechanism.

• Trimethylaminuria (TMAU) MIM:602079

Disease | GeneticClinVar

96 pathogenic / likely-pathogenic of 311 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Trimethylaminuria
• FMO3-related disorder
• FMO3 activity, decreased
• See cases

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.58

gnomAD pLI

0

gnomAD missense Z

-0.16

DepMap mean gene effect

0.03

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• taurine biosynthetic process

Molecular functions

• flavin adenine dinucleotide binding
• hypotaurine monooxygenase activity
• N,N-dimethylaniline monooxygenase activity
• NADP binding
• trimethylamine monooxygenase activity
• albendazole monooxygenase activity

Cellular components

• endoplasmic reticulum membrane
• intracellular membrane-bounded organelle

Protein domainsUniProt · Pfam · InterPro

• Flavin monooxygenase FMO
• Flavin monooxygenase (FMO) 3
• Flavin monooxygenase-like
• FAD/NAD(P)-binding domain superfamily
• Flavin-containing monooxygenases-like
• Flavin-binding monooxygenase-like

KeywordsUniProt

• Endoplasmic reticulum
• FAD
• Flavoprotein
• Membrane
• Microsome
• Monooxygenase
• NADP
• Oxidoreductase
• Phosphoprotein
• Transmembrane
• Transmembrane helix