LOCUS       NM_001002294            2059 bp    mRNA    linear   PRI 09-FEB-2025
DEFINITION  Homo sapiens flavin containing dimethylaniline monoxygenase 3
            (FMO3), transcript variant 2, mRNA.
ACCESSION   NM_001002294
VERSION     NM_001002294.3
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 2059)
  AUTHORS   Shimizu,M., Makiguchi,M., Hishinuma,E., Saito,S., Hiratsuka,M. and
            Yamazaki,H.
  TITLE     Rare but impaired flavin-containing monooxygenase 3 (FMO3) variants
            reported in a recently updated Japanese mega-databank of genome
            resources
  JOURNAL   Drug Metab Pharmacokinet 55, 100539 (2024)
   PUBMED   38280279
  REMARK    GeneRIF: Rare but impaired flavin-containing monooxygenase 3 (FMO3)
            variants reported in a recently updated Japanese mega-databank of
            genome resources.
REFERENCE   2  (bases 1 to 2059)
  AUTHORS   Cleary,Y., Kletzl,H., Grimsey,P., Heinig,K., Ogungbenro,K., Silber
            Baumann,H.E., Frey,N., Aarons,L., Galetin,A. and Gertz,M.
  TITLE     Estimation of FMO3 Ontogeny by Mechanistic Population
            Pharmacokinetic Modelling of Risdiplam and Its Impact on Drug-Drug
            Interactions in Children
  JOURNAL   Clin Pharmacokinet 62 (6), 891-904 (2023)
   PUBMED   37148485
  REMARK    GeneRIF: Estimation of FMO3 Ontogeny by Mechanistic Population
            Pharmacokinetic Modelling of Risdiplam and Its Impact on Drug-Drug
            Interactions in Children.
REFERENCE   3  (bases 1 to 2059)
  AUTHORS   Shimizu,M., Yamamoto,A., Makiguchi,M., Shimamura,E., Yokota,Y.,
            Harano,M. and Yamazaki,H.
  TITLE     A family study of compound variants of flavin-containing
            monooxygenase 3 (FMO3) in Japanese subjects found by urinary
            phenotyping for trimethylaminuria
  JOURNAL   Drug Metab Pharmacokinet 50, 100490 (2023)
   PUBMED   36889044
  REMARK    GeneRIF: A family study of compound variants of flavin-containing
            monooxygenase 3 (FMO3) in Japanese subjects found by urinary
            phenotyping for trimethylaminuria.
REFERENCE   4  (bases 1 to 2059)
  AUTHORS   Moradzad,M., Abdi,M., Sheikh Esmaeili,F., Ghaderi,D., Rahmani,K.,
            Moloudi,M.R. and Vahabzadeh,Z.
  TITLE     Possible correlation between high circulatory levels of
            trimethylamine-N-oxide and 2177G>C polymorphisms of hepatic flavin
            containing monooxygenase 3 in Kurdish Population with non-alcoholic
            fatty liver disease
  JOURNAL   Mol Biol Rep 49 (7), 5927-5937 (2022)
   PUBMED   35348964
  REMARK    GeneRIF: Possible correlation between high circulatory levels of
            trimethylamine-N-oxide and 2177G>C polymorphisms of hepatic flavin
            containing monooxygenase 3 in Kurdish Population with non-alcoholic
            fatty liver disease.
REFERENCE   5  (bases 1 to 2059)
  AUTHORS   Alibrandi,S., Nicita,F., Donato,L., Scimone,C., Rinaldi,C.,
            D'Angelo,R. and Sidoti,A.
  TITLE     Adaptive Modelling of Mutated FMO3 Enzyme Could Unveil Unexplored
            Scenarios Linking Variant Haplotypes to TMAU Phenotypes
  JOURNAL   Molecules 26 (22), 7045 (2021)
   PUBMED   34834137
  REMARK    GeneRIF: Adaptive Modelling of Mutated FMO3 Enzyme Could Unveil
            Unexplored Scenarios Linking Variant Haplotypes to TMAU Phenotypes.
            Publication Status: Online-Only
REFERENCE   6  (bases 1 to 2059)
  AUTHORS   Phillips,I.R. and Shephard,E.A.
  TITLE     Primary Trimethylaminuria
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301282
REFERENCE   7  (bases 1 to 2059)
  AUTHORS   Lomri,N., Gu,Q. and Cashman,J.R.
  TITLE     Molecular cloning of the flavin-containing monooxygenase (form II)
            cDNA from adult human liver
  JOURNAL   Proc Natl Acad Sci U S A 89 (5), 1685-1689 (1992)
   PUBMED   1542660
  REMARK    Erratum:[Proc Natl Acad Sci U S A. 1995 Oct 10;92(21):9910. doi:
            10.1073/pnas.92.21.9910.. PMID: 7568243]
REFERENCE   8  (bases 1 to 2059)
  AUTHORS   Ziegler,D.M.
  TITLE     Flavin-containing monooxygenases: enzymes adapted for
            multisubstrate specificity
  JOURNAL   Trends Pharmacol Sci 11 (8), 321-324 (1990)
   PUBMED   2203193
  REMARK    Review article
REFERENCE   9  (bases 1 to 2059)
  AUTHORS   Higgins,T., Chaykin,S., Hammond,K.B. and Humbert,J.R.
  TITLE     Trimethylamine N-oxide synthesis: a human variant
  JOURNAL   Biochem Med 6 (4), 392-396 (1972)
   PUBMED   5048998
REFERENCE   10 (bases 1 to 2059)
  AUTHORS   Humbert,J.A., Hammond,K.B. and Hathaway,W.E.
  TITLE     Trimethylaminuria: the fish-odour syndrome
  JOURNAL   Lancet 2 (7676), 770-771 (1970)
   PUBMED   4195988
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AK313197.1, BC032016.1 and
            AK223166.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 22, 2018 this sequence version replaced NM_001002294.2.
            
            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 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].
            
            Transcript Variant: This variant (2) encodes the longest isoform
            (a). Variants 1 and 2 both encode the same isoform (a).
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: AK223166.1, SRR1803615.156246.1
                                           [ECO:0000332]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000367755.9/ ENSP00000356729.4
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-1682              AK313197.1         2-1683
            1683-2053           BC032016.1         1646-2016
            2054-2059           AK223166.1         2074-2079
FEATURES             Location/Qualifiers
     source          1..2059
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="1"
                     /map="1q24.3"
     gene            1..2059
                     /gene="FMO3"
                     /gene_synonym="dJ127D3.1; FMOII; TMAU"
                     /note="flavin containing dimethylaniline monoxygenase 3"
                     /db_xref="GeneID:2328"
                     /db_xref="HGNC:HGNC:3771"
                     /db_xref="MIM:136132"
     exon            1..77
                     /gene="FMO3"
                     /gene_synonym="dJ127D3.1; FMOII; TMAU"
                     /inference="alignment:Splign:2.1.0"
     exon            78..215
                     /gene="FMO3"
                     /gene_synonym="dJ127D3.1; FMOII; TMAU"
                     /inference="alignment:Splign:2.1.0"
     CDS             84..1682
                     /gene="FMO3"
                     /gene_synonym="dJ127D3.1; FMOII; TMAU"
                     /EC_number="1.14.13.8"
                     /EC_number="1.14.13.148"
                     /EC_number="1.14.13.32"
                     /note="isoform a is encoded by transcript variant 2;
                     dimethylaniline oxidase 3; dimethylaniline monooxygenase
                     [N-oxide-forming] 3; hepatic flavin-containing
                     monooxygenase-3; FMO form 2; flavin containing
                     monooxygenase 3; trimethylamine monooxygenase"
                     /codon_start=1
                     /product="flavin-containing monooxygenase 3 isoform a"
                     /protein_id="NP_001002294.1"
                     /db_xref="CCDS:CCDS1292.1"
                     /db_xref="GeneID:2328"
                     /db_xref="HGNC:HGNC:3771"
                     /db_xref="MIM:136132"
                     /translation="MGKKVAIIGAGVSGLASIRSCLEEGLEPTCFEKSNDIGGLWKFS
                     DHAEEGRASIYKSVFSNSSKEMMCFPDFPFPDDFPNFMHNSKIQEYIIAFAKEKNLLK
                     YIQFKTFVSSVNKHPDFATTGQWDVTTERDGKKESAVFDAVMVCSGHHVYPNLPKESF
                     PGLNHFKGKCFHSRDYKEPGVFNGKRVLVVGLGNSGCDIATELSRTAEQVMISSRSGS
                     WVMSRVWDNGYPWDMLLVTRFGTFLKNNLPTAISDWLYVKQMNARFKHENYGLMPLNG
                     VLRKEPVFNDELPASILCGIVSVKPNVKEFTETSAIFEDGTIFEGIDCVIFATGYSFA
                     YPFLDESIIKSRNNEIILFKGVFPPLLEKSTIAVIGFVQSLGAAIPTVDLQSRWAAQV
                     IKGTCTLPSMEDMMNDINEKMEKKRKWFGKSETIQTDYIVYMDELSSFIGAKPNIPWL
                     FLTDPKLAMEVYFGPCSPYQFRLVGPGQWPGARNAILTQWDRSLKPMQTRVVGRLQKP
                     CFFFHWLKLFAIPILLIAVFLVLT"
     exon            216..404
                     /gene="FMO3"
                     /gene_synonym="dJ127D3.1; FMOII; TMAU"
                     /inference="alignment:Splign:2.1.0"
     exon            405..567
                     /gene="FMO3"
                     /gene_synonym="dJ127D3.1; FMOII; TMAU"
                     /inference="alignment:Splign:2.1.0"
     exon            568..710
                     /gene="FMO3"
                     /gene_synonym="dJ127D3.1; FMOII; TMAU"
                     /inference="alignment:Splign:2.1.0"
     exon            711..910
                     /gene="FMO3"
                     /gene_synonym="dJ127D3.1; FMOII; TMAU"
                     /inference="alignment:Splign:2.1.0"
     exon            911..1266
                     /gene="FMO3"
                     /gene_synonym="dJ127D3.1; FMOII; TMAU"
                     /inference="alignment:Splign:2.1.0"
     exon            1267..1339
                     /gene="FMO3"
                     /gene_synonym="dJ127D3.1; FMOII; TMAU"
                     /inference="alignment:Splign:2.1.0"
     exon            1340..2059
                     /gene="FMO3"
                     /gene_synonym="dJ127D3.1; FMOII; TMAU"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1750..1755
                     /regulatory_class="polyA_signal_sequence"
                     /gene="FMO3"
                     /gene_synonym="dJ127D3.1; FMOII; TMAU"
                     /note="hexamer: ATTAAA"
     polyA_site      1767
                     /gene="FMO3"
                     /gene_synonym="dJ127D3.1; FMOII; TMAU"
                     /note="major polyA site"
     regulatory      2028..2033
                     /regulatory_class="polyA_signal_sequence"
                     /gene="FMO3"
                     /gene_synonym="dJ127D3.1; FMOII; TMAU"
                     /note="hexamer: AATAAA"
     polyA_site      2059
                     /gene="FMO3"
                     /gene_synonym="dJ127D3.1; FMOII; TMAU"
                     /note="major polyA site"
ORIGIN      
        1 aaactgccca gacggttgga caggacgtag acacacagaa gaaaagaaga caaagaacgg
       61 gtaggaaaat taaaaaggtt accatgggga agaaagtggc catcattgga gctggtgtga
      121 gtggcttggc ctccatcagg agctgtctgg aagaggggct ggagcccacc tgctttgaga
      181 agagcaatga cattgggggc ctgtggaaat tttcagacca tgcagaggag ggcagggcta
      241 gcatttacaa atcagtcttt tccaactctt ccaaagagat gatgtgtttc ccagacttcc
      301 catttcccga tgacttcccc aactttatgc acaacagcaa gatccaggaa tatatcattg
      361 catttgccaa agaaaagaac ctcctgaagt acatacaatt taagacattt gtatccagtg
      421 taaataaaca tcctgatttt gcaactactg gccagtggga tgttaccact gaaagggatg
      481 gtaaaaaaga atcggctgtc tttgatgctg taatggtttg ttccggacat catgtgtatc
      541 ccaacctacc aaaagagtcc tttccaggac taaaccactt taaaggcaaa tgcttccaca
      601 gcagggacta taaagaacca ggtgtattca atggaaagcg tgtcctggtg gttggcctgg
      661 ggaattcggg ctgtgatatt gccacagaac tcagccgcac agcagaacag gtcatgatca
      721 gttccagaag tggctcctgg gtgatgagcc gggtctggga caatggttat ccttgggaca
      781 tgctgctcgt cactcgattt ggaaccttcc tcaagaacaa tttaccgaca gccatctctg
      841 actggttgta cgtgaagcag atgaatgcaa gattcaagca tgaaaactat ggcttgatgc
      901 ctttaaatgg agtcctgagg aaagagcctg tatttaacga tgagctccca gcaagcattc
      961 tgtgtggcat tgtgtccgta aagcctaacg tgaaggaatt cacagagacc tcggccattt
     1021 ttgaggatgg gaccatattt gagggcattg actgtgtaat ctttgcaaca gggtatagtt
     1081 ttgcctaccc cttccttgat gagtctatca tcaaaagcag aaacaatgag atcattttat
     1141 ttaaaggagt atttcctcct ctacttgaga agtcaaccat agcagtgatt ggctttgtcc
     1201 agtcccttgg ggctgccatt cccacagttg acctccagtc ccgctgggca gcacaagtaa
     1261 taaagggaac ttgtactttg ccttctatgg aagacatgat gaatgatatt aatgagaaaa
     1321 tggagaaaaa gcgcaaatgg tttggcaaaa gcgagaccat acagacagat tacattgttt
     1381 atatggatga actctcctcc ttcattgggg caaagcccaa catcccatgg ctgtttctca
     1441 cagatcccaa attggccatg gaagtttatt ttggcccttg tagtccctac cagtttaggc
     1501 tggtgggccc agggcagtgg ccaggagcca gaaatgccat actgacccag tgggaccggt
     1561 cgttgaaacc catgcagaca cgagtggtcg ggagacttca gaagccttgc ttctttttcc
     1621 attggctgaa gctctttgca attcctattc tgttaatcgc tgttttcctt gtgttgacct
     1681 aatcatcatt ttctctagga tttctgaaag ttactgacaa tacccagaca ggggctttgc
     1741 tatttaaaaa ttaaaatttt cacaccacct gcttttctat tcagcatctt ttgcagtact
     1801 ctgtagacat tagtcagtaa tacagtgtta tttctaggct ctgaaatagc cactttaaga
     1861 atcatgtcat gatcttaaga gagcactaat catttctgtt tgagttccac taacacttca
     1921 aaatcagaac tatgttcttt atatctaact taaatcattt cctgaaacat tttgacatga
     1981 ttcctttttc cttttaaaca atgtatgaaa gatgtatttt aaatctaaat aaagagcaaa
     2041 ttaagcagaa taattataa
//
