LOCUS       NM_017460               2781 bp    mRNA    linear   PRI 01-OCT-2024
DEFINITION  Homo sapiens cytochrome P450 family 3 subfamily A member 4
            (CYP3A4), transcript variant 1, mRNA.
ACCESSION   NM_017460 NM_000776
VERSION     NM_017460.6
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 2781)
  AUTHORS   Musyoka,K., Chan,C.W., Gutierrez Rico,E.M., Omondi,P., Kijogi,C.,
            Okai,T., Kongere,J., Ngara,M., Kagaya,W., Kanoi,B.N., Hiratsuka,M.,
            Kido,Y., Gitaka,J. and Kaneko,A.
  TITLE     Genetic variation present in the CYP3A4 gene in Ni-Vanuatu and
            Kenyan populations in malaria endemicity
  JOURNAL   Drug Metab Pharmacokinet 57, 101029 (2024)
   PUBMED   39079373
  REMARK    GeneRIF: Genetic variation present in the CYP3A4 gene in Ni-Vanuatu
            and Kenyan populations in malaria endemicity.
REFERENCE   2  (bases 1 to 2781)
  AUTHORS   Zhao,T., Li,H.J., Zhang,H.L., Feng,J.R., Yu,J., Sun,K.F., Feng,J.,
            Sun,Y. and Yu,L.H.
  TITLE     Effects of CYP3A4 genetic polymorphisms on the pharmacokinetics and
            efficacy of perampanel in Chinese pediatric patients with epilepsy
  JOURNAL   Seizure 120, 142-149 (2024)
   PUBMED   38996572
  REMARK    GeneRIF: Effects of CYP3A4 genetic polymorphisms on the
            pharmacokinetics and efficacy of perampanel in Chinese pediatric
            patients with epilepsy.
REFERENCE   3  (bases 1 to 2781)
  AUTHORS   Wei,W., Tang,L.W.T., Verma,R.K., Fan,H. and Chan,E.C.Y.
  TITLE     Probe Substrate Dependencies in CYP3A4 Allosteric Inhibition: A
            Novel Molecular Mechanism Involving F-F' Loop Perturbations
  JOURNAL   J Chem Inf Model 64 (6), 2058-2067 (2024)
   PUBMED   38457234
  REMARK    GeneRIF: Probe Substrate Dependencies in CYP3A4 Allosteric
            Inhibition: A Novel Molecular Mechanism Involving F-F' Loop
            Perturbations.
REFERENCE   4  (bases 1 to 2781)
  AUTHORS   Islam,S., Jayaram,D.T., Biswas,P. and Stuehr,D.J.
  TITLE     Functional maturation of cytochromes P450 3A4 and 2D6 relies on
            GAPDH- and Hsp90-Dependent heme allocation
  JOURNAL   J Biol Chem 300 (2), 105633 (2024)
   PUBMED   38199567
  REMARK    GeneRIF: Functional maturation of cytochromes P450 3A4 and 2D6
            relies on GAPDH- and Hsp90-Dependent heme allocation.
REFERENCE   5  (bases 1 to 2781)
  AUTHORS   Lee,S.W., Chen,P.T., Liu,C.W., Li,Y.H. and Wu,L.S.
  TITLE     Polymorphism of CYP3A4*18 is associated with anti-tuberculosis
            drug-induced hepatotoxicity
  JOURNAL   Pharmacogenomics 25 (5-6), 241-247 (2024)
   PUBMED   38884784
  REMARK    GeneRIF: Polymorphism of CYP3A4*18 is associated with
            anti-tuberculosis drug-induced hepatotoxicity.
REFERENCE   6  (bases 1 to 2781)
  AUTHORS   Nelson,D.R., Zeldin,D.C., Hoffman,S.M., Maltais,L.J., Wain,H.M. and
            Nebert,D.W.
  TITLE     Comparison of cytochrome P450 (CYP) genes from the mouse and human
            genomes, including nomenclature recommendations for genes,
            pseudogenes and alternative-splice variants
  JOURNAL   Pharmacogenetics 14 (1), 1-18 (2004)
   PUBMED   15128046
  REMARK    Review article
REFERENCE   7  (bases 1 to 2781)
  AUTHORS   Inoue,K., Inazawa,J., Nakagawa,H., Shimada,T., Yamazaki,H.,
            Guengerich,F.P. and Abe,T.
  TITLE     Assignment of the human cytochrome P-450 nifedipine oxidase gene
            (CYP3A4) to chromosome 7 at band q22.1 by fluorescence in situ
            hybridization
  JOURNAL   Jpn J Hum Genet 37 (2), 133-138 (1992)
   PUBMED   1391968
REFERENCE   8  (bases 1 to 2781)
  AUTHORS   Bork,R.W., Muto,T., Beaune,P.H., Srivastava,P.K., Lloyd,R.S. and
            Guengerich,F.P.
  TITLE     Characterization of mRNA species related to human liver cytochrome
            P-450 nifedipine oxidase and the regulation of catalytic activity
  JOURNAL   J Biol Chem 264 (2), 910-919 (1989)
   PUBMED   2463251
REFERENCE   9  (bases 1 to 2781)
  AUTHORS   Shimada,T. and Guengerich,F.P.
  TITLE     Evidence for cytochrome P-450NF, the nifedipine oxidase, being the
            principal enzyme involved in the bioactivation of aflatoxins in
            human liver
  JOURNAL   Proc Natl Acad Sci U S A 86 (2), 462-465 (1989)
   PUBMED   2492107
REFERENCE   10 (bases 1 to 2781)
  AUTHORS   Komori,M., Hashizume,T., Ohi,H., Miura,T., Kitada,M., Nagashima,K.
            and Kamataki,T.
  TITLE     Cytochrome P-450 in human liver microsomes: high-performance liquid
            chromatographic isolation of three forms and their characterization
  JOURNAL   J Biochem 104 (6), 912-916 (1988)
   PUBMED   3243766
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC069294.5 and AK312967.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 23, 2018 this sequence version replaced NM_017460.5.
            
            Summary: This gene encodes a member of the cytochrome P450
            superfamily of enzymes. The cytochrome P450 proteins are
            monooxygenases that catalyze many reactions involved in drug
            metabolism and synthesis of cholesterol, steroids and other lipids.
            This protein localizes to the endoplasmic reticulum and its
            expression is induced by glucocorticoids and some pharmacological
            agents. This enzyme is involved in the metabolism of approximately
            half the drugs in use today, including acetaminophen, codeine,
            cyclosporin A, diazepam, erythromycin, and chloroquine. The enzyme
            also metabolizes some steroids and carcinogens. This gene is part
            of a cluster of cytochrome P450 genes on chromosome 7q21.1.
            Previously another CYP3A gene, CYP3A3, was thought to exist;
            however, it is now thought that this sequence represents a
            transcript variant of CYP3A4. Alternatively spliced transcript
            variants encoding different isoforms have been identified.
            [provided by RefSeq, Aug 2020].
            
            Transcript Variant: This variant (1) represents the longer
            transcript and encodes the longer isoform (1).
            
            Sequence Note: This RefSeq record was created from transcript and
            genomic sequence data to make the sequence consistent with the
            reference genome assembly. The genomic coordinates used for the
            transcript record were based on transcript alignments.
            
            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 :: SRR5189664.85929.1,
                                           SRR5189664.163908.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA2153733 [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000651514.1/ ENSP00000498939.1
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-3                 AC069294.5         35203-35205
            4-1615              AK312967.1         1-1612
            1616-2781           AC069294.5         61255-62420
FEATURES             Location/Qualifiers
     source          1..2781
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="7"
                     /map="7q22.1"
     gene            1..2781
                     /gene="CYP3A4"
                     /gene_synonym="CP33; CP34; CYP3A; CYP3A3; CYPIIIA3;
                     CYPIIIA4; HLP; NF-25; P450C3; P450PCN1; VDDR3"
                     /note="cytochrome P450 family 3 subfamily A member 4"
                     /db_xref="GeneID:1576"
                     /db_xref="HGNC:HGNC:2637"
                     /db_xref="MIM:124010"
     exon            1..174
                     /gene="CYP3A4"
                     /gene_synonym="CP33; CP34; CYP3A; CYP3A3; CYPIIIA3;
                     CYPIIIA4; HLP; NF-25; P450C3; P450PCN1; VDDR3"
                     /inference="alignment:Splign:2.1.0"
     CDS             104..1615
                     /gene="CYP3A4"
                     /gene_synonym="CP33; CP34; CYP3A; CYP3A3; CYPIIIA3;
                     CYPIIIA4; HLP; NF-25; P450C3; P450PCN1; VDDR3"
                     /EC_number="1.14.14.1"
                     /EC_number="1.14.14.55"
                     /EC_number="1.14.14.56"
                     /EC_number="1.14.14.73"
                     /note="isoform 1 is encoded by transcript variant 1;
                     P450-III, steroid inducible; glucocorticoid-inducible
                     P450; nifedipine oxidase; cytochrome P450, subfamily IIIA
                     (niphedipine oxidase), polypeptide 4; cytochrome P450 3A3;
                     cytochrome P450 3A4; cytochrome P450, subfamily IIIA
                     (niphedipine oxidase), polypeptide 3; cytochrome P450 HLp;
                     cytochrome P450-PCN1; cytochrome P450 NF-25; albendazole
                     sulfoxidase; quinine 3-monooxygenase;
                     taurochenodeoxycholate 6-alpha-hydroxylase; 1,8-cineole
                     2-exo-monooxygenase; cholesterol 25-hydroxylase;
                     cytochrome P450, family 3, subfamily A, polypeptide 4;
                     1,4-cineole 2-exo-monooxygenase; albendazole monooxygenase
                     (sulfoxide-forming)"
                     /codon_start=1
                     /product="cytochrome P450 3A4 isoform 1"
                     /protein_id="NP_059488.2"
                     /db_xref="CCDS:CCDS5674.1"
                     /db_xref="GeneID:1576"
                     /db_xref="HGNC:HGNC:2637"
                     /db_xref="MIM:124010"
                     /translation="MALIPDLAMETWLLLAVSLVLLYLYGTHSHGLFKKLGIPGPTPL
                     PFLGNILSYHKGFCMFDMECHKKYGKVWGFYDGQQPVLAITDPDMIKTVLVKECYSVF
                     TNRRPFGPVGFMKSAISIAEDEEWKRLRSLLSPTFTSGKLKEMVPIIAQYGDVLVRNL
                     RREAETGKPVTLKDVFGAYSMDVITSTSFGVNIDSLNNPQDPFVENTKKLLRFDFLDP
                     FFLSITVFPFLIPILEVLNICVFPREVTNFLRKSVKRMKESRLEDTQKHRVDFLQLMI
                     DSQNSKETESHKALSDLELVAQSIIFIFAGYETTSSVLSFIMYELATHPDVQQKLQEE
                     IDAVLPNKAPPTYDTVLQMEYLDMVVNETLRLFPIAMRLERVCKKDVEINGMFIPKGV
                     VVMIPSYALHRDPKYWTEPEKFLPERFSKKNKDNIDPYIYTPFGSGPRNCIGMRFALM
                     NMKLALIRVLQNFSFKPCKETQIPLKLSLGGLLQPEKPVVLKVESRDGTVSGA"
     exon            175..268
                     /gene="CYP3A4"
                     /gene_synonym="CP33; CP34; CYP3A; CYP3A3; CYPIIIA3;
                     CYPIIIA4; HLP; NF-25; P450C3; P450PCN1; VDDR3"
                     /inference="alignment:Splign:2.1.0"
     exon            269..321
                     /gene="CYP3A4"
                     /gene_synonym="CP33; CP34; CYP3A; CYP3A3; CYPIIIA3;
                     CYPIIIA4; HLP; NF-25; P450C3; P450PCN1; VDDR3"
                     /inference="alignment:Splign:2.1.0"
     exon            322..421
                     /gene="CYP3A4"
                     /gene_synonym="CP33; CP34; CYP3A; CYP3A3; CYPIIIA3;
                     CYPIIIA4; HLP; NF-25; P450C3; P450PCN1; VDDR3"
                     /inference="alignment:Splign:2.1.0"
     exon            422..535
                     /gene="CYP3A4"
                     /gene_synonym="CP33; CP34; CYP3A; CYP3A3; CYPIIIA3;
                     CYPIIIA4; HLP; NF-25; P450C3; P450PCN1; VDDR3"
                     /inference="alignment:Splign:2.1.0"
     exon            536..624
                     /gene="CYP3A4"
                     /gene_synonym="CP33; CP34; CYP3A; CYP3A3; CYPIIIA3;
                     CYPIIIA4; HLP; NF-25; P450C3; P450PCN1; VDDR3"
                     /inference="alignment:Splign:2.1.0"
     exon            625..773
                     /gene="CYP3A4"
                     /gene_synonym="CP33; CP34; CYP3A; CYP3A3; CYPIIIA3;
                     CYPIIIA4; HLP; NF-25; P450C3; P450PCN1; VDDR3"
                     /inference="alignment:Splign:2.1.0"
     exon            774..901
                     /gene="CYP3A4"
                     /gene_synonym="CP33; CP34; CYP3A; CYP3A3; CYPIIIA3;
                     CYPIIIA4; HLP; NF-25; P450C3; P450PCN1; VDDR3"
                     /inference="alignment:Splign:2.1.0"
     exon            902..968
                     /gene="CYP3A4"
                     /gene_synonym="CP33; CP34; CYP3A; CYP3A3; CYPIIIA3;
                     CYPIIIA4; HLP; NF-25; P450C3; P450PCN1; VDDR3"
                     /inference="alignment:Splign:2.1.0"
     exon            969..1129
                     /gene="CYP3A4"
                     /gene_synonym="CP33; CP34; CYP3A; CYP3A3; CYPIIIA3;
                     CYPIIIA4; HLP; NF-25; P450C3; P450PCN1; VDDR3"
                     /inference="alignment:Splign:2.1.0"
     exon            1130..1356
                     /gene="CYP3A4"
                     /gene_synonym="CP33; CP34; CYP3A; CYP3A3; CYPIIIA3;
                     CYPIIIA4; HLP; NF-25; P450C3; P450PCN1; VDDR3"
                     /inference="alignment:Splign:2.1.0"
     exon            1357..1519
                     /gene="CYP3A4"
                     /gene_synonym="CP33; CP34; CYP3A; CYP3A3; CYPIIIA3;
                     CYPIIIA4; HLP; NF-25; P450C3; P450PCN1; VDDR3"
                     /inference="alignment:Splign:2.1.0"
     exon            1520..2781
                     /gene="CYP3A4"
                     /gene_synonym="CP33; CP34; CYP3A; CYP3A3; CYPIIIA3;
                     CYPIIIA4; HLP; NF-25; P450C3; P450PCN1; VDDR3"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2049..2054
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CYP3A4"
                     /gene_synonym="CP33; CP34; CYP3A; CYP3A3; CYPIIIA3;
                     CYPIIIA4; HLP; NF-25; P450C3; P450PCN1; VDDR3"
                     /note="hexamer: AATAAA"
     polyA_site      2072
                     /gene="CYP3A4"
                     /gene_synonym="CP33; CP34; CYP3A; CYP3A3; CYPIIIA3;
                     CYPIIIA4; HLP; NF-25; P450C3; P450PCN1; VDDR3"
                     /note="major polyA site"
     regulatory      2746..2751
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CYP3A4"
                     /gene_synonym="CP33; CP34; CYP3A; CYP3A3; CYPIIIA3;
                     CYPIIIA4; HLP; NF-25; P450C3; P450PCN1; VDDR3"
                     /note="hexamer: AATAAA"
     polyA_site      2781
                     /gene="CYP3A4"
                     /gene_synonym="CP33; CP34; CYP3A; CYP3A3; CYPIIIA3;
                     CYPIIIA4; HLP; NF-25; P450C3; P450PCN1; VDDR3"
ORIGIN      
        1 actgctgtgc agggcaggaa agctccatgc acatagccca gcaaagagca acacagagct
       61 gaaaggaaga ctcagaggag agagataagt aaggaaagta gtgatggctc tcatcccaga
      121 cttggccatg gaaacctggc ttctcctggc tgtcagcctg gtgctcctct atctatatgg
      181 aacccattca catggacttt ttaagaagct tggaattcca gggcccacac ctctgccttt
      241 tttgggaaat attttgtcct accataaggg cttttgtatg tttgacatgg aatgtcataa
      301 aaagtatgga aaagtgtggg gcttttatga tggtcaacag cctgtgctgg ctatcacaga
      361 tcctgacatg atcaaaacag tgctagtgaa agaatgttat tctgtcttca caaaccggag
      421 gccttttggt ccagtgggat ttatgaaaag tgccatctct atagctgagg atgaagaatg
      481 gaagagatta cgatcattgc tgtctccaac cttcaccagt ggaaaactca aggagatggt
      541 ccctatcatt gcccagtatg gagatgtgtt ggtgagaaat ctgaggcggg aagcagagac
      601 aggcaagcct gtcaccttga aagacgtctt tggggcctac agcatggatg tgatcactag
      661 cacatcattt ggagtgaaca tcgactctct caacaatcca caagacccct ttgtggaaaa
      721 caccaagaag cttttaagat ttgatttttt ggatccattc tttctctcaa taacagtctt
      781 tccattcctc atcccaattc ttgaagtatt aaatatctgt gtgtttccaa gagaagttac
      841 aaatttttta agaaaatctg taaaaaggat gaaagaaagt cgcctcgaag atacacaaaa
      901 gcaccgagtg gatttccttc agctgatgat tgactctcag aattcaaaag aaactgagtc
      961 ccacaaagct ctgtccgatc tggagctcgt ggcccaatca attatcttta tttttgctgg
     1021 ctatgaaacc acgagcagtg ttctctcctt cattatgtat gaactggcca ctcaccctga
     1081 tgtccagcag aaactgcagg aggaaattga tgcagtttta cccaataagg caccacccac
     1141 ctatgatact gtgctacaga tggagtatct tgacatggtg gtgaatgaaa cgctcagatt
     1201 attcccaatt gctatgagac ttgagagggt ctgcaaaaaa gatgttgaga tcaatgggat
     1261 gttcattccc aaaggggtgg tggtgatgat tccaagctat gctcttcacc gtgacccaaa
     1321 gtactggaca gagcctgaga agttcctccc tgaaagattc agcaagaaga acaaggacaa
     1381 catagatcct tacatataca caccctttgg aagtggaccc agaaactgca ttggcatgag
     1441 gtttgctctc atgaacatga aacttgctct aatcagagtc cttcagaact tctccttcaa
     1501 accttgtaaa gaaacacaga tccccctgaa attaagctta ggaggacttc ttcaaccaga
     1561 aaaacccgtt gttctaaagg ttgagtcaag ggatggcacc gtaagtggag cctgaatttt
     1621 cctaaggact tctgctttgc tcttcaagaa atctgtgcct gagaacacca gagacctcaa
     1681 attactttgt gaatagaact ctgaaatgaa gatgggcttc atccaatgga ctgcataaat
     1741 aaccggggat tctgtacatg cattgagctc tctcattgtc tgtgtagagt gttatacttg
     1801 ggaatataaa ggaggtgacc aaatcagtgt gaggaggtag atttggctcc tctgcttctc
     1861 acgggactat ttccaccacc cccagttagc accattaact cctcctgagc tctgataaga
     1921 gaatcaacat ttctcaataa tttcctccac aaattattaa tgaaaataag aattattttg
     1981 atggctctaa caatgacatt tatatcacat gttttctctg gagtattcta taagttttat
     2041 gttaaatcaa taaagaccac tttacaaaag tattatcaga tgctttcctg cacattaagg
     2101 agaaatctat agaactgaat gagaaccaac aagtaaatat ttttggtcat tgtaatcact
     2161 gttggcgtgg ggcctttgtc agaactagaa tttgattatt aacataggtg aaagttaatc
     2221 cactgtgact ttgcccattg tttagaaaga atattcatag tttaattatg ccttttttga
     2281 tcaggcacag tggctcacgc ctgtaatcct agcagtttgg gaggctgagc cgggtggatc
     2341 gcctgaggtc aggagttcaa gacaagcctg gcctacatgg ttgaaacccc atctctacta
     2401 aaaatacaca aattagctag gcatggtgga ctcgcctgta atctcactac acaggaggct
     2461 gaggcaggag aatcacttga acctgggagg cggatgttga agtgagctga gattgcacca
     2521 ctgcactcca gtctgggtga gagtgagact cagtcttaaa aaaatatgcc tttttgaagc
     2581 acgtacattt tgtaacaaag aactgaagct cttattatat tattagtttt gatttaatgt
     2641 tttcagccca tctcctttca tatttctggg agacagaaaa catgtttccc tacacctctt
     2701 gcattccatc ctcaacaccc aactgtctcg atgcaatgaa cacttaataa aaaacagtcg
     2761 attggtcaat tgattgagca a
//
