LOCUS       NM_000320               1507 bp    mRNA    linear   PRI 19-SEP-2024
DEFINITION  Homo sapiens quinoid dihydropteridine reductase (QDPR), transcript
            variant 1, mRNA.
ACCESSION   NM_000320
VERSION     NM_000320.3
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 1507)
  AUTHORS   Girish,A., Sutar,S., Murthy,T.P.K., Premanand,S.A., Garg,V.,
            Patil,L., Shreyas,S., Shukla,R., Yadav,A.K. and Singh,T.R.
  TITLE     Comprehensive bioinformatics analysis of structural and functional
            consequences of deleterious missense mutations in the human QDPR
            gene
  JOURNAL   J Biomol Struct Dyn 42 (11), 5485-5501 (2024)
   PUBMED   37382215
  REMARK    GeneRIF: Comprehensive bioinformatics analysis of structural and
            functional consequences of deleterious missense mutations in the
            human QDPR gene.
REFERENCE   2  (bases 1 to 1507)
  AUTHORS   Liu,J., He,X., Deng,S., Zhao,S., Zhang,S., Chen,Z., Xue,C.,
            Zeng,L., Zhao,H., Zhou,Y., Bai,R., Xu,Z., Liu,S., Zhou,Q., Li,M.,
            Zhang,J., Huang,X., Chen,R., Wang,L., Lin,D. and Zheng,J.
  TITLE     QDPR deficiency drives immune suppression in pancreatic cancer
  JOURNAL   Cell Metab 36 (5), 984-999 (2024)
   PUBMED   38642552
  REMARK    GeneRIF: QDPR deficiency drives immune suppression in pancreatic
            cancer.
REFERENCE   3  (bases 1 to 1507)
  AUTHORS   Morgenstern,M., Peikert,C.D., Lubbert,P., Suppanz,I., Klemm,C.,
            Alka,O., Steiert,C., Naumenko,N., Schendzielorz,A., Melchionda,L.,
            Muhlhauser,W.W.D., Knapp,B., Busch,J.D., Stiller,S.B.,
            Dannenmaier,S., Lindau,C., Licheva,M., Eickhorst,C., Galbusera,R.,
            Zerbes,R.M., Ryan,M.T., Kraft,C., Kozjak-Pavlovic,V., Drepper,F.,
            Dennerlein,S., Oeljeklaus,S., Pfanner,N., Wiedemann,N. and
            Warscheid,B.
  TITLE     Quantitative high-confidence human mitochondrial proteome and its
            dynamics in cellular context
  JOURNAL   Cell Metab 33 (12), 2464-2483 (2021)
   PUBMED   34800366
REFERENCE   4  (bases 1 to 1507)
  AUTHORS   Chandrashekaran,S., Karthikeyan,S., Balakrishnan,A., Nair,S.,
            Satheesh Kumar,M.K., Vattathara,J.J. and Menon,K.N.
  TITLE     Expression and Purification of Quinine Dihydro Pteridine Reductase
            from astrocytes and its significance in the astrocyte pathology
  JOURNAL   Int J Biol Macromol 110, 567-572 (2018)
   PUBMED   29355631
  REMARK    GeneRIF: show for the first time statistically significant up
            regulation of iNOS in QDPR overexpressing astrocytes. Increased
            expression of iNOS associated with astrocyte pathology seen in many
            neurodegenerative disorders may have implications in autoimmune
            neurodegenerative disorders.
REFERENCE   5  (bases 1 to 1507)
  AUTHORS   Si,Q., Sun,S. and Gu,Y.
  TITLE     A278C mutation of dihydropteridine reductase decreases autophagy
            via mTOR signaling
  JOURNAL   Acta Biochim Biophys Sin (Shanghai) 49 (8), 706-712 (2017)
   PUBMED   28633336
  REMARK    GeneRIF: Mutation of dihydropteridine reductase (QDPR) inhibited
            the regulation of TOR serine-threonine kinases (mTOR), suggesting
            that QDPR is a positive regulator of autophagy via suppressing mTOR
            signaling.
REFERENCE   6  (bases 1 to 1507)
  AUTHORS   Howells,D.W., Forrest,S.M., Dahl,H.H. and Cotton,R.G.
  TITLE     Insertion of an extra codon for threonine is a cause of
            dihydropteridine reductase deficiency
  JOURNAL   Am J Hum Genet 47 (2), 279-285 (1990)
   PUBMED   2116088
REFERENCE   7  (bases 1 to 1507)
  AUTHORS   Sumi,S., Ishikawa,T., Ito,Y., Oishi,H., Asai,K. and Wada,Y.
  TITLE     Probable assignment of the dihydropteridine reductase gene to
            4p15.31
  JOURNAL   Tohoku J Exp Med 160 (1), 93-94 (1990)
   PUBMED   2330583
REFERENCE   8  (bases 1 to 1507)
  AUTHORS   Lockyer,J., Cook,R.G., Milstien,S., Kaufman,S., Woo,S.L. and
            Ledley,F.D.
  TITLE     Structure and expression of human dihydropteridine reductase
  JOURNAL   Proc Natl Acad Sci U S A 84 (10), 3329-3333 (1987)
   PUBMED   3033643
REFERENCE   9  (bases 1 to 1507)
  AUTHORS   Dahl,H.H., Hutchison,W., McAdam,W., Wake,S., Morgan,F.J. and
            Cotton,R.G.
  TITLE     Human dihydropteridine reductase: characterisation of a cDNA clone
            and its use in analysis of patients with dihydropteridine reductase
            deficiency
  JOURNAL   Nucleic Acids Res 15 (5), 1921-1932 (1987)
   PUBMED   3031582
REFERENCE   10 (bases 1 to 1507)
  AUTHORS   Kaufman,S., Holtzman,N.A., Milstien,S., Butler,L.J. and Krumholz,A.
  TITLE     Phenylketonuria due to a deficiency of dihydropteridine reductase
  JOURNAL   N Engl J Med 293 (16), 785-790 (1975)
   PUBMED   1160969
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from BM762805.1, BC000576.2,
            AC093600.3 and AW104747.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 23, 2018 this sequence version replaced NM_000320.2.
            
            Summary: This gene encodes the enzyme dihydropteridine reductase,
            which catalyzes the NADH-mediated reduction of quinonoid
            dihydrobiopterin.  This enzyme is an essential component of the
            pterin-dependent aromatic amino acid hydroxylating systems.
            Mutations in this gene resulting in QDPR deficiency include
            aberrant splicing, amino acid substitutions, insertions, or
            premature terminations.  Dihydropteridine reductase deficiency
            presents as atypical phenylketonuria due to insufficient production
            of biopterin, a cofactor for phenylalanine hydroxylase. [provided
            by RefSeq, Jul 2008].
            
            Transcript Variant: This variant (1) represents the longest
            transcript and encodes the longer isoform (1).
            
            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 :: SRR3476690.736743.1,
                                           SRR3476690.840895.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA2146411 [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000281243.10/ ENSP00000281243.5
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-12                BM762805.1         145-156
            13-990              BC000576.2         1-978
            991-1504            AC093600.3         121331-121844       c
            1505-1507           AW104747.1         10-12               c
FEATURES             Location/Qualifiers
     source          1..1507
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="4"
                     /map="4p15.32"
     gene            1..1507
                     /gene="QDPR"
                     /gene_synonym="DHPR; HDHPR; PKU2; SDR33C1"
                     /note="quinoid dihydropteridine reductase"
                     /db_xref="GeneID:5860"
                     /db_xref="HGNC:HGNC:9752"
                     /db_xref="MIM:612676"
     exon            1..141
                     /gene="QDPR"
                     /gene_synonym="DHPR; HDHPR; PKU2; SDR33C1"
                     /inference="alignment:Splign:2.1.0"
     CDS             37..771
                     /gene="QDPR"
                     /gene_synonym="DHPR; HDHPR; PKU2; SDR33C1"
                     /EC_number="1.5.1.34"
                     /note="isoform 1 is encoded by transcript variant 1;
                     6,7-dihydropteridine reductase; testis secretory
                     sperm-binding protein Li 236P; short chain
                     dehydrogenase/reductase family 33C member 1"
                     /codon_start=1
                     /product="dihydropteridine reductase isoform 1"
                     /protein_id="NP_000311.2"
                     /db_xref="CCDS:CCDS3421.1"
                     /db_xref="GeneID:5860"
                     /db_xref="HGNC:HGNC:9752"
                     /db_xref="MIM:612676"
                     /translation="MAAAAAAGEARRVLVYGGRGALGSRCVQAFRARNWWVASVDVVE
                     NEEASASIIVKMTDSFTEQADQVTAEVGKLLGEEKVDAILCVAGGWAGGNAKSKSLFK
                     NCDLMWKQSIWTSTISSHLATKHLKEGGLLTLAGAKAALDGTPGMIGYGMAKGAVHQL
                     CQSLAGKNSGMPPGAAAIAVLPVTLDTPMNRKSMPEADFSSWTPLEFLVETFHDWITG
                     KNRPSSGSLIQVVTTEGRTELTPAYF"
     exon            142..234
                     /gene="QDPR"
                     /gene_synonym="DHPR; HDHPR; PKU2; SDR33C1"
                     /inference="alignment:Splign:2.1.0"
     exon            235..331
                     /gene="QDPR"
                     /gene_synonym="DHPR; HDHPR; PKU2; SDR33C1"
                     /inference="alignment:Splign:2.1.0"
     exon            332..472
                     /gene="QDPR"
                     /gene_synonym="DHPR; HDHPR; PKU2; SDR33C1"
                     /inference="alignment:Splign:2.1.0"
     exon            473..581
                     /gene="QDPR"
                     /gene_synonym="DHPR; HDHPR; PKU2; SDR33C1"
                     /inference="alignment:Splign:2.1.0"
     exon            582..665
                     /gene="QDPR"
                     /gene_synonym="DHPR; HDHPR; PKU2; SDR33C1"
                     /inference="alignment:Splign:2.1.0"
     exon            666..1507
                     /gene="QDPR"
                     /gene_synonym="DHPR; HDHPR; PKU2; SDR33C1"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1347..1352
                     /regulatory_class="polyA_signal_sequence"
                     /gene="QDPR"
                     /gene_synonym="DHPR; HDHPR; PKU2; SDR33C1"
                     /note="hexamer: AATAAA"
     polyA_site      1377
                     /gene="QDPR"
                     /gene_synonym="DHPR; HDHPR; PKU2; SDR33C1"
                     /note="major polyA site"
     regulatory      1486..1491
                     /regulatory_class="polyA_signal_sequence"
                     /gene="QDPR"
                     /gene_synonym="DHPR; HDHPR; PKU2; SDR33C1"
                     /note="hexamer: AATAAA"
     polyA_site      1507
                     /gene="QDPR"
                     /gene_synonym="DHPR; HDHPR; PKU2; SDR33C1"
                     /note="major polyA site"
ORIGIN      
        1 attcggagct gcgggagccg ggctggcagg agcaggatgg cggcggcggc ggctgcaggc
       61 gaggcgcgcc gggtgctggt gtacggcggc aggggcgctc tgggttctcg atgcgtgcag
      121 gcttttcggg cccgcaactg gtgggttgcc agcgttgatg tggtggagaa tgaagaggcc
      181 agcgctagca tcattgttaa aatgacagac tcgttcactg agcaggctga ccaggtgact
      241 gctgaggttg gaaagctctt gggtgaagag aaggtggatg caattctttg cgttgctgga
      301 ggatgggccg ggggcaatgc caaatccaag tctctcttta agaactgtga cctgatgtgg
      361 aagcagagca tatggacatc gaccatctcc agccatctgg ctaccaagca tctcaaggaa
      421 ggaggcctcc tgaccttggc tggcgcaaag gctgccctgg atgggactcc tggtatgatc
      481 gggtacggca tggccaaggg tgctgttcac cagctctgcc agagcctggc tgggaagaac
      541 agcggcatgc cgcccggggc agccgccatc gctgtgctcc cggttaccct ggataccccg
      601 atgaacagga aatcaatgcc tgaggctgac ttcagctcct ggacaccctt agaattccta
      661 gttgaaactt tccatgactg gatcacaggg aaaaaccgac cgagctcagg aagcctaatc
      721 caggtggtaa ccacagaagg aaggacggaa ctcaccccag catattttta ggcctcatct
      781 cagtgcctat gaggggcctg ccagaaaagt cactaacctg tctcagtgtg gccttgtcca
      841 gccttgtgtt ttctgtaacc cctgtttgtg gtacgagata atgagtccta tttttctctc
      901 acataatatg catttgctct cctaggacag tgtaatacat ttatgtgaag taaagacatg
      961 cgagactggt ggcctgcaaa tagcatccgt tgatctgtgt taactgcata gggagggctc
     1021 tgcatagcac ctgctatagc ggtgtcatgt tggatcgctt ttgtgactgt tcatctgtcc
     1081 ttgacagtgg ctgtcatctt gactactttg ttgatttgtt ggtattgggg acattttaaa
     1141 ggctgagtta tttttgaatg tcatgtttat gtcatagacg tagttttcgc atccttgaat
     1201 taaactgcct taactccttt tgtggtataa gcaaaactac atggactctg tcctggtatc
     1261 cttttcctgt gtggttgccc cgtgtcctct ggcctagggt taagtgtgca agataactac
     1321 tcgtgagtat tcagaatgtt gttcctaata aatgcacttg ttgtctgtct tctttaatca
     1381 aatcacatct tatatacagc agtcagagat gagtatacta gaatcatgga ttgctggagg
     1441 tcttttaatc tgatgttctc agaagggggt ggatttaaat cctgaaataa atatttcaac
     1501 acaagaa
//
