LOCUS       NM_016593               2432 bp    mRNA    linear   PRI 07-FEB-2025
DEFINITION  Homo sapiens cytochrome P450 family 39 subfamily A member 1
            (CYP39A1), transcript variant 1, mRNA.
ACCESSION   NM_016593
VERSION     NM_016593.5
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 2432)
  AUTHORS   Bell,K., Ozaki,M., Mori,K., Mizoguchi,T., Nakano,S., Porporato,N.,
            Ikeda,Y., Chihara,E., Inoue,K., Manabe,S., Hayashi,K.,
            Higashide,T., Ideta,R., Tokumo,K., Kiuchi,Y., Nakano,M., Ueno,M.,
            Kinoshita,S., Tashiro,K., Sotozono,C., Inatani,M., Sugiyama,K.,
            Kubota,T., Li,Z., Wang,Z., Khor,C.C. and Aung,T.
  TITLE     Association of the CYP39A1 G204E Genetic Variant with Increased
            Risk of Glaucoma and Blindness in Patients with Exfoliation
            Syndrome
  JOURNAL   Ophthalmology 129 (4), 406-413 (2022)
   PUBMED   34763023
  REMARK    GeneRIF: Association of the CYP39A1 G204E Genetic Variant with
            Increased Risk of Glaucoma and Blindness in Patients with
            Exfoliation Syndrome.
REFERENCE   2  (bases 1 to 2432)
  AUTHORS   Huttlin,E.L., Bruckner,R.J., Navarrete-Perea,J., Cannon,J.R.,
            Baltier,K., Gebreab,F., Gygi,M.P., Thornock,A., Zarraga,G., Tam,S.,
            Szpyt,J., Gassaway,B.M., Panov,A., Parzen,H., Fu,S., Golbazi,A.,
            Maenpaa,E., Stricker,K., Guha Thakurta,S., Zhang,T., Rad,R.,
            Pan,J., Nusinow,D.P., Paulo,J.A., Schweppe,D.K., Vaites,L.P.,
            Harper,J.W. and Gygi,S.P.
  TITLE     Dual proteome-scale networks reveal cell-specific remodeling of the
            human interactome
  JOURNAL   Cell 184 (11), 3022-3040 (2021)
   PUBMED   33961781
REFERENCE   3  (bases 1 to 2432)
  AUTHORS   Li,Z., Wang,Z., Lee,M.C., Zenkel,M., Peh,E., Ozaki,M., Topouzis,F.,
            Nakano,S., Chan,A., Chen,S., Williams,S.E.I., Orr,A., Nakano,M.,
            Kobakhidze,N., Zarnowski,T., Popa-Cherecheanu,A., Mizoguchi,T.,
            Manabe,S.I., Hayashi,K., Kazama,S., Inoue,K., Mori,Y., Miyata,K.,
            Sugiyama,K., Higashide,T., Chihara,E., Ideta,R., Ishiko,S.,
            Yoshida,A., Tokumo,K., Kiuchi,Y., Ohashi,T., Sakurai,T.,
            Sugimoto,T., Chuman,H., Aihara,M., Inatani,M., Mori,K., Ikeda,Y.,
            Ueno,M., Gaston,D., Rafuse,P., Shuba,L., Saunders,J., Nicolela,M.,
            Chichua,G., Tabagari,S., Founti,P., Sim,K.S., Meah,W.Y., Soo,H.M.,
            Chen,X.Y., Chatzikyriakidou,A., Keskini,C., Pappas,T.,
            Anastasopoulos,E., Lambropoulos,A., Panagiotou,E.S.,
            Mikropoulos,D.G., Kosior-Jarecka,E., Cheong,A., Li,Y., Lukasik,U.,
            Nongpiur,M.E., Husain,R., Perera,S.A., Alvarez,L., Garcia,M.,
            Gonzalez-Iglesias,H., Fernandez-Vega Cueto,A., Fernandez-Vega
            Cueto,L., Martinon-Torres,F., Salas,A., Oguz,C., Tamcelik,N.,
            Atalay,E., Batu,B., Irkec,M., Aktas,D., Kasim,B., Astakhov,Y.S.,
            Astakhov,S.Y., Akopov,E.L., Giessl,A., Mardin,C., Hellerbrand,C.,
            Cooke Bailey,J.N., Igo,R.P. Jr., Haines,J.L., Edward,D.P.,
            Heegaard,S., Davila,S., Tan,P., Kang,J.H., Pasquale,L.R.,
            Kruse,F.E., Reis,A., Carmichael,T.R., Hauser,M., Ramsay,M.,
            Mossbock,G., Yildirim,N., Tashiro,K., Konstas,A.G.P.,
            Coca-Prados,M., Foo,J.N., Kinoshita,S., Sotozono,C., Kubota,T.,
            Dubina,M., Ritch,R., Wiggs,J.L., Pasutto,F.,
            Schlotzer-Schrehardt,U., Ho,Y.S., Aung,T., Tam,W.L. and Khor,C.C.
  CONSRTM   Genetics of Exfoliation Syndrome Partnership
  TITLE     Association of Rare CYP39A1 Variants With Exfoliation Syndrome
            Involving the Anterior Chamber of the Eye
  JOURNAL   JAMA 325 (8), 753-764 (2021)
   PUBMED   33620406
  REMARK    GeneRIF: Association of Rare CYP39A1 Variants With Exfoliation
            Syndrome Involving the Anterior Chamber of the Eye.
            Erratum:[JAMA. 2021 Apr 6;325(13):1335. doi:
            10.1001/jama.2021.3920.. PMID: 33821917]
REFERENCE   4  (bases 1 to 2432)
  AUTHORS   Matsuoka,H., Katayama,M., Ohishi,A., Miya,K., Tokunaga,R.,
            Kobayashi,S., Nishimoto,Y., Hirooka,K., Shima,A. and Michihara,A.
  TITLE     Orphan Nuclear Receptor RORalpha Regulates Enzymatic Metabolism of
            Cerebral 24S-Hydroxycholesterol through CYP39A1 Intronic Response
            Element Activation
  JOURNAL   Int J Mol Sci 21 (9), 3309 (2020)
   PUBMED   32392803
  REMARK    GeneRIF: Orphan Nuclear Receptor RORalpha Regulates Enzymatic
            Metabolism of Cerebral 24S-Hydroxycholesterol through CYP39A1
            Intronic Response Element Activation.
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 2432)
  AUTHORS   Huttlin,E.L., Bruckner,R.J., Paulo,J.A., Cannon,J.R., Ting,L.,
            Baltier,K., Colby,G., Gebreab,F., Gygi,M.P., Parzen,H., Szpyt,J.,
            Tam,S., Zarraga,G., Pontano-Vaites,L., Swarup,S., White,A.E.,
            Schweppe,D.K., Rad,R., Erickson,B.K., Obar,R.A., Guruharsha,K.G.,
            Li,K., Artavanis-Tsakonas,S., Gygi,S.P. and Harper,J.W.
  TITLE     Architecture of the human interactome defines protein communities
            and disease networks
  JOURNAL   Nature 545 (7655), 505-509 (2017)
   PUBMED   28514442
REFERENCE   6  (bases 1 to 2432)
  AUTHORS   Melchardt,T., Hufnagl,C., Magnes,T., Weiss,L., Hutarew,G.,
            Neureiter,D., Schlattau,A., Moser,G., Gaggl,A., Trankenschuh,W.,
            Greil,R. and Egle,A.
  TITLE     CYP39A1 polymorphism is associated with toxicity during intensive
            induction chemotherapy in patients with advanced head and neck
            cancer
  JOURNAL   BMC Cancer 15, 725 (2015)
   PUBMED   26475344
  REMARK    GeneRIF: The CYP39A1 polymorphism rs7761731 may help to identify
            patients at high risk for treatment related toxicity.
            Publication Status: Online-Only
REFERENCE   7  (bases 1 to 2432)
  AUTHORS   ten Brink,M.H., van Bavel,T., Swen,J.J., van der Straaten,T.,
            Bredius,R.G., Lankester,A.C., Zwaveling,J. and Guchelaar,H.J.
  TITLE     Effect of genetic variants GSTA1 and CYP39A1 and age on busulfan
            clearance in pediatric patients undergoing hematopoietic stem cell
            transplantation
  JOURNAL   Pharmacogenomics 14 (14), 1683-1690 (2013)
   PUBMED   24192117
  REMARK    GeneRIF: GSTA1 and CYP39A1 were found to be associated with
            busulfan clearance. When combined, the two haplotypes explained 17%
            of the variability in busulfan clearance.
REFERENCE   8  (bases 1 to 2432)
  AUTHORS   Fourgeux,C., Martine,L., Bjorkhem,I., Diczfalusy,U., Joffre,C.,
            Acar,N., Creuzot-Garcher,C., Bron,A. and Bretillon,L.
  TITLE     Primary open-angle glaucoma: association with cholesterol
            24S-hydroxylase (CYP46A1) gene polymorphism and plasma
            24-hydroxycholesterol levels
  JOURNAL   Invest Ophthalmol Vis Sci 50 (12), 5712-5717 (2009)
   PUBMED   19553612
  REMARK    GeneRIF: The rs754203 SNP in CYP46A1 was associated with a risk for
            POAG. This polymorphism was not associated with changes in plasma
            24S-hydroxycholesterol.
REFERENCE   9  (bases 1 to 2432)
  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   10 (bases 1 to 2432)
  AUTHORS   Li-Hawkins,J., Lund,E.G., Bronson,A.D. and Russell,D.W.
  TITLE     Expression cloning of an oxysterol 7alpha-hydroxylase selective for
            24-hydroxycholesterol
  JOURNAL   J Biol Chem 275 (22), 16543-16549 (2000)
   PUBMED   10748047
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DC336695.1, AK292263.1 and
            AL035670.29.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 23, 2018 this sequence version replaced NM_016593.4.
            
            Summary: This gene encodes a member of the cytochrome P450
            superfamily of enzymes. The cytochrome P450 proteins are
            monooxygenases which catalyze many reactions involved in drug
            metabolism and synthesis of cholesterol, steroids and other lipids.
            This endoplasmic reticulum protein is involved in the conversion of
            cholesterol to bile acids. Its substrates include the oxysterols
            25-hydroxycholesterol, 27-hydroxycholesterol and
            24-hydroxycholesterol. Alternate splicing results in multiple
            transcript variants. [provided by RefSeq, Jul 2013].
            
            Transcript Variant: This variant (1) represents the longest
            transcript and encodes the longest 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.
            
            ##Evidence-Data-START##
            Transcript exon combination :: SRR1660809.156014.1,
                                           SRR1660807.231063.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000275016.3/ ENSP00000275016.2
            RefSeq Select criteria :: based on conservation, expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-56                DC336695.1         13-68
            57-1835             AK292263.1         1-1779
            1836-2432           AL035670.29        4861-5457           c
FEATURES             Location/Qualifiers
     source          1..2432
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="6"
                     /map="6p12.3"
     gene            1..2432
                     /gene="CYP39A1"
                     /note="cytochrome P450 family 39 subfamily A member 1"
                     /db_xref="GeneID:51302"
                     /db_xref="HGNC:HGNC:17449"
                     /db_xref="MIM:605994"
     exon            1..413
                     /gene="CYP39A1"
                     /inference="alignment:Splign:2.1.0"
     CDS             237..1646
                     /gene="CYP39A1"
                     /EC_number="1.14.14.26"
                     /note="isoform 1 is encoded by transcript variant 1;
                     cytochrome P450, subfamily XXXIX (oxysterol 7
                     alpha-hydroxylase), polypeptide 1; 24-hydroxycholesterol
                     7-alpha-hydroxylase; cytochrome P450, family 39, subfamily
                     A, polypeptide 1"
                     /codon_start=1
                     /product="24-hydroxycholesterol 7-alpha-hydroxylase
                     isoform 1"
                     /protein_id="NP_057677.2"
                     /db_xref="CCDS:CCDS4916.1"
                     /db_xref="GeneID:51302"
                     /db_xref="HGNC:HGNC:17449"
                     /db_xref="MIM:605994"
                     /translation="MELISPTVIIILGCLALFLLLQRKNLRRPPCIKGWIPWIGVGFE
                     FGKAPLEFIEKARIKYGPIFTVFAMGNRMTFVTEEEGINVFLKSKKVDFELAVQNIVY
                     RTASIPKNVFLALHEKLYIMLKGKMGTVNLHQFTGQLTEELHEQLENLGTHGTMDLNN
                     LVRHLLYPVTVNMLFNKSLFSTNKKKIKEFHQYFQVYDEDFEYGSQLPECLLRNWSKS
                     KKWFLELFEKNIPDIKACKSAKDNSMTLLQATLDIVETETSKENSPNYGLLLLWASLS
                     NAVPVAFWTLAYVLSHPDIHKAIMEGISSVFGKAGKDKIKVSEDDLENLLLIKWCVLE
                     TIRLKAPGVITRKVVKPVEILNYIIPSGDLLMLSPFWLHRNPKYFPEPELFKPERWKK
                     ANLEKHSFLDCFMAFGSGKFQCPARWFALLEVQMCIILILYKYDCSLLDPLPKQSYLH
                     LVGVPQPEGQCRIEYKQRI"
     exon            414..549
                     /gene="CYP39A1"
                     /inference="alignment:Splign:2.1.0"
     exon            550..724
                     /gene="CYP39A1"
                     /inference="alignment:Splign:2.1.0"
     exon            725..874
                     /gene="CYP39A1"
                     /inference="alignment:Splign:2.1.0"
     exon            875..968
                     /gene="CYP39A1"
                     /inference="alignment:Splign:2.1.0"
     exon            969..1076
                     /gene="CYP39A1"
                     /inference="alignment:Splign:2.1.0"
     exon            1077..1167
                     /gene="CYP39A1"
                     /inference="alignment:Splign:2.1.0"
     exon            1168..1301
                     /gene="CYP39A1"
                     /inference="alignment:Splign:2.1.0"
     exon            1302..1397
                     /gene="CYP39A1"
                     /inference="alignment:Splign:2.1.0"
     exon            1398..1486
                     /gene="CYP39A1"
                     /inference="alignment:Splign:2.1.0"
     exon            1487..1574
                     /gene="CYP39A1"
                     /inference="alignment:Splign:2.1.0"
     exon            1575..2432
                     /gene="CYP39A1"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2179..2184
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CYP39A1"
                     /note="hexamer: AATAAA"
     polyA_site      2217
                     /gene="CYP39A1"
                     /note="major polyA site"
     regulatory      2285..2290
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CYP39A1"
                     /note="hexamer: AATAAA"
     polyA_site      2304
                     /gene="CYP39A1"
     regulatory      2410..2415
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CYP39A1"
                     /note="hexamer: AATATA"
     polyA_site      2432
                     /gene="CYP39A1"
ORIGIN      
        1 gcattttttc cgcgctggct gagattcaaa gagaagtgga ggtgggaggg agcgacaatg
       61 gaaaaatcac ctgaaaactg ggacagagga aggaagctac agttacgaag gagagctgca
      121 aaagttgcag cagaaaggtt gggagtcccg acaggttccg tagcccacag aaaagaagca
      181 agggacggca ggactgtttc acacttttct gcttctggaa ggtgctggac aaaaacatgg
      241 aactaatttc cccaacagtg attataatcc tgggttgcct tgctctgttc ttactccttc
      301 agcggaagaa tttgcgtaga cccccgtgca tcaagggctg gattccttgg attggagttg
      361 gatttgagtt tgggaaagcc cctctagaat ttatagagaa agcaagaatc aagtatggac
      421 caatatttac agtctttgct atgggaaacc gaatgacctt tgttactgaa gaagaaggaa
      481 ttaatgtgtt tctaaaatcc aaaaaagtag attttgaact agcagtgcaa aatatcgttt
      541 atcgtacagc atcaattcca aagaatgtct ttttagcact gcatgaaaaa ctctatatta
      601 tgttgaaagg gaaaatgggg actgtcaatc tccatcagtt tactgggcaa ctgactgaag
      661 aattacatga acaactggag aatttaggca ctcatgggac aatggacctg aacaacttag
      721 taagacatct cctttatcca gtcacagtga atatgctctt taataaaagt ttgttttcca
      781 caaacaagaa aaaaatcaag gagttccatc agtattttca agtttatgat gaagattttg
      841 agtatgggtc ccagttgcca gagtgtcttc taagaaactg gtcaaaatcc aaaaagtggt
      901 tcctggaact gtttgagaaa aacattccag atataaaagc atgtaaatct gcaaaagata
      961 attccatgac attattgcaa gctacgctgg atattgtaga gacggaaaca agtaaggaaa
     1021 actcacccaa ttatgggctc ttactgcttt gggcttctct gtctaatgct gttcctgttg
     1081 cattttggac acttgcatac gtcctttctc atcctgatat ccacaaggcc attatggaag
     1141 gcatatcttc tgtgtttggc aaagcaggca aagataagat taaagtgtct gaggatgacc
     1201 tggagaatct ccttctaatt aaatggtgtg ttttggaaac cattcgttta aaagctcctg
     1261 gtgtcattac tagaaaagtg gtgaagcctg tggaaatttt gaattacatc attccttctg
     1321 gtgacttgtt gatgttgtct ccattttggc tgcatagaaa tccaaagtat tttcctgagc
     1381 ctgaattgtt caaacctgaa cgttggaaaa aggcaaattt agagaagcac tctttcttgg
     1441 actgcttcat ggcatttgga agcgggaagt tccagtgtcc tgcaaggtgg tttgctctgt
     1501 tagaggttca gatgtgtatt attttaatac tttataaata tgactgtagt cttctggacc
     1561 cattacccaa acagagttat ctccatttgg tgggtgtccc ccagccggaa gggcaatgcc
     1621 gaattgaata taaacaaaga atatgacatc tgttgggcct cacaaggacc agggccttct
     1681 ggaggagtgg cactacccca cctggcagca cctagacctg agctctacaa aaacacactg
     1741 cttcactttg ttttaggact tagttcaaga acacattcaa atggtgcatg tgtttggtat
     1801 cttcaacagt agaccaagaa tctaacatca ctctcagtaa tatagagacc ggaatacatg
     1861 gtttatagga aatgatcaaa tgatccaaaa aaactccaca ttttttaaga agttggaatt
     1921 tgatttcatg cataactgta ttaaaacatt aaatagaaat aatgtcattt gaatgaaaat
     1981 cttatcacat taaattcact gtgaaggcag catacttaaa tttttatttt gaaaagtcta
     2041 aaaggcttag atttttaaaa tttaataatt atttctacaa attttctatt tttcttgagg
     2101 tgattctcaa ctagcaattg gaactcctag gctctattaa cataattctt tattgtaaac
     2161 gtatctaatg ctaaaagtaa taaaatggta gttttctgag acctgtgagg acaggaatgg
     2221 tgtcttacat tcatttctac actttattat gctcaggatt gcaccttctt tacagagtat
     2281 attcaataaa tgtatgttga ttgatgtatt gatttatatt ttaattaacc tggaagcatt
     2341 gttttgactc aaagtgtttg caattatagt ttggcagata ccatattttt gctaatgcat
     2401 agaaacacaa atataacggt atgccaagac aa
//
