LOCUS       NM_000277               3759 bp    mRNA    linear   PRI 09-OCT-2024
DEFINITION  Homo sapiens phenylalanine hydroxylase (PAH), transcript variant 1,
            mRNA.
ACCESSION   NM_000277
VERSION     NM_000277.3
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 3759)
  AUTHORS   Chai,Y., Ning,H., Xia,J., Wang,Y. and Kong,X.
  TITLE     [Analysis of PAH gene variants and prenatal diagnosis for 43
            Chinese pedigrees affected with Phenylketonuria]
  JOURNAL   Zhonghua Yi Xue Yi Chuan Xue Za Zhi 41 (6), 702-707 (2024)
   PUBMED   38818554
  REMARK    GeneRIF: [Analysis of PAH gene variants and prenatal diagnosis for
            43 Chinese pedigrees affected with Phenylketonuria].
REFERENCE   2  (bases 1 to 3759)
  AUTHORS   Alavanda,C., Ceylan,E.I., Kilavuz,S. and Ciki,K.
  TITLE     Comprehensive analyses of phenylalanine hydroxylase variants and
            phenotypic characteristics of patients in the eastern region of
            Turkiye
  JOURNAL   J Pediatr Endocrinol Metab 37 (6), 543-552 (2024)
   PUBMED   38706300
  REMARK    GeneRIF: Comprehensive analyses of phenylalanine hydroxylase
            variants and phenotypic characteristics of patients in the eastern
            region of Turkiye.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 3759)
  AUTHORS   Tebieva,I.S., Mishakova,P.V., Gabisova,Y.V., Khokhova,A.V.,
            Kaloeva,T.G., Marakhonov,A.V., Shchagina,O.A., Polyakov,A.V.,
            Ginter,E.K., Kutsev,S.I. and Zinchenko,R.A.
  TITLE     Genetic Landscape and Clinical Features of Hyperphenylalaninemia in
            North Ossetia-Alania: High Frequency of P281L and P211T Genetic
            Variants in the PAH Gene
  JOURNAL   Int J Mol Sci 25 (9), 4598 (2024)
   PUBMED   38731816
  REMARK    GeneRIF: Genetic Landscape and Clinical Features of
            Hyperphenylalaninemia in North Ossetia-Alania: High Frequency of
            P281L and P211T Genetic Variants in the PAH Gene.
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 3759)
  AUTHORS   Yang,P., Sun,Y., Wang,X., Ma,D., Wang,Y., Zhang,Z. and Jiang,T.
  TITLE     [Analysis of pathogenicity and genotype-phenotype correlation of
            the c.158G>A variant of phenylalanine hydroxylase gene]
  JOURNAL   Zhonghua Yi Xue Yi Chuan Xue Za Zhi 41 (3), 278-283 (2024)
   PUBMED   38448014
  REMARK    GeneRIF: [Analysis of pathogenicity and genotype-phenotype
            correlation of the c.158G>A variant of phenylalanine hydroxylase
            gene].
REFERENCE   5  (bases 1 to 3759)
  AUTHORS   Regier,D.S. and Greene,C.L.
  TITLE     Phenylalanine Hydroxylase Deficiency
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301677
REFERENCE   6  (bases 1 to 3759)
  AUTHORS   Klein,C., Lohmann,K., Marras,C. and Munchau,A.
  TITLE     Hereditary Dystonia Overview
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301334
REFERENCE   7  (bases 1 to 3759)
  AUTHORS   John,S.W., Scriver,C.R., Laframboise,R. and Rozen,R.
  TITLE     In vitro and in vivo correlations for I65T and M1V mutations at the
            phenylalanine hydroxylase locus
  JOURNAL   Hum Mutat 1 (2), 147-153 (1992)
   PUBMED   1301201
REFERENCE   8  (bases 1 to 3759)
  AUTHORS   Svensson,E., Eisensmith,R.C., Dworniczak,B., von Dobeln,U.,
            Hagenfeldt,L., Horst,J. and Woo,S.L.
  TITLE     Two missense mutations causing mild hyperphenylalaninemia
            associated with DNA haplotype 12
  JOURNAL   Hum Mutat 1 (2), 129-137 (1992)
   PUBMED   1301200
REFERENCE   9  (bases 1 to 3759)
  AUTHORS   John,S.W., Rozen,R., Laframboise,R., Laberge,C. and Scriver,C.R.
  TITLE     Five mutations at the PAH locus account for almost 90% of PKU
            mutations in French-Canadians from eastern Quebec
  JOURNAL   Hum Mutat 1 (1), 72-74 (1992)
   PUBMED   1301193
REFERENCE   10 (bases 1 to 3759)
  AUTHORS   Eisensmith,R.C. and Woo,S.L.
  TITLE     Molecular basis of phenylketonuria and related
            hyperphenylalaninemias: mutations and polymorphisms in the human
            phenylalanine hydroxylase gene
  JOURNAL   Hum Mutat 1 (1), 13-23 (1992)
   PUBMED   1301187
  REMARK    Review article
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from U49897.1, BC026251.1,
            AC069227.24 and BQ268294.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 22, 2018 this sequence version replaced NM_000277.2.
            
            Summary: This gene encodes a member of the biopterin-dependent
            aromatic amino acid hydroxylase protein family. The encoded
            phenylalanine hydroxylase enzyme hydroxylates phenylalanine to
            tyrosine and is the rate-limiting step in phenylalanine catabolism.
            Deficiency of this enzyme activity results in the autosomal
            recessive disorder phenylketonuria. [provided by RefSeq, Aug 2017].
            
            Transcript Variant: This variant (1) represents the longer
            transcript. Both variants 1 and 2 encode the same protein.
            
            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 :: U49897.1, L47726.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1968540 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000553106.6/ ENSP00000448059.1
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-809               U49897.1           359-1167
            810-2114            BC026251.1         849-2153
            2115-3443           AC069227.24        102600-103928
            3444-3759           BQ268294.1         17-332              c
FEATURES             Location/Qualifiers
     source          1..3759
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="12"
                     /map="12q23.2"
     gene            1..3759
                     /gene="PAH"
                     /gene_synonym="PH; PKU; PKU1"
                     /note="phenylalanine hydroxylase"
                     /db_xref="GeneID:5053"
                     /db_xref="HGNC:HGNC:8582"
                     /db_xref="MIM:612349"
     exon            1..174
                     /gene="PAH"
                     /gene_synonym="PH; PKU; PKU1"
                     /inference="alignment:Splign:2.1.0"
     CDS             115..1473
                     /gene="PAH"
                     /gene_synonym="PH; PKU; PKU1"
                     /EC_number="1.14.16.1"
                     /note="phenylalanine 4-monooxygenase; phe-4-monooxygenase"
                     /codon_start=1
                     /product="phenylalanine-4-hydroxylase"
                     /protein_id="NP_000268.1"
                     /db_xref="CCDS:CCDS9092.1"
                     /db_xref="GeneID:5053"
                     /db_xref="HGNC:HGNC:8582"
                     /db_xref="MIM:612349"
                     /translation="MSTAVLENPGLGRKLSDFGQETSYIEDNCNQNGAISLIFSLKEE
                     VGALAKVLRLFEENDVNLTHIESRPSRLKKDEYEFFTHLDKRSLPALTNIIKILRHDI
                     GATVHELSRDKKKDTVPWFPRTIQELDRFANQILSYGAELDADHPGFKDPVYRARRKQ
                     FADIAYNYRHGQPIPRVEYMEEEKKTWGTVFKTLKSLYKTHACYEYNHIFPLLEKYCG
                     FHEDNIPQLEDVSQFLQTCTGFRLRPVAGLLSSRDFLGGLAFRVFHCTQYIRHGSKPM
                     YTPEPDICHELLGHVPLFSDRSFAQFSQEIGLASLGAPDEYIEKLATIYWFTVEFGLC
                     KQGDSIKAYGAGLLSSFGELQYCLSEKPKLLPLELEKTAIQNYTVTEFQPLYYVAESF
                     NDAKEKVRNFAATIPRPFSVRYDPYTQRIEVLDNTQQLKILADSINSEIGILCSALQK
                     IK"
     exon            175..282
                     /gene="PAH"
                     /gene_synonym="PH; PKU; PKU1"
                     /inference="alignment:Splign:2.1.0"
     exon            283..466
                     /gene="PAH"
                     /gene_synonym="PH; PKU; PKU1"
                     /inference="alignment:Splign:2.1.0"
     exon            467..555
                     /gene="PAH"
                     /gene_synonym="PH; PKU; PKU1"
                     /inference="alignment:Splign:2.1.0"
     exon            556..623
                     /gene="PAH"
                     /gene_synonym="PH; PKU; PKU1"
                     /inference="alignment:Splign:2.1.0"
     exon            624..820
                     /gene="PAH"
                     /gene_synonym="PH; PKU; PKU1"
                     /inference="alignment:Splign:2.1.0"
     exon            821..956
                     /gene="PAH"
                     /gene_synonym="PH; PKU; PKU1"
                     /inference="alignment:Splign:2.1.0"
     exon            957..1026
                     /gene="PAH"
                     /gene_synonym="PH; PKU; PKU1"
                     /inference="alignment:Splign:2.1.0"
     exon            1027..1083
                     /gene="PAH"
                     /gene_synonym="PH; PKU; PKU1"
                     /inference="alignment:Splign:2.1.0"
     exon            1084..1179
                     /gene="PAH"
                     /gene_synonym="PH; PKU; PKU1"
                     /inference="alignment:Splign:2.1.0"
     exon            1180..1313
                     /gene="PAH"
                     /gene_synonym="PH; PKU; PKU1"
                     /inference="alignment:Splign:2.1.0"
     exon            1314..1429
                     /gene="PAH"
                     /gene_synonym="PH; PKU; PKU1"
                     /inference="alignment:Splign:2.1.0"
     exon            1430..3759
                     /gene="PAH"
                     /gene_synonym="PH; PKU; PKU1"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2303..2308
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PAH"
                     /gene_synonym="PH; PKU; PKU1"
                     /note="hexamer: AATAAA"
     polyA_site      2327
                     /gene="PAH"
                     /gene_synonym="PH; PKU; PKU1"
                     /note="major polyA site"
     regulatory      3613..3618
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PAH"
                     /gene_synonym="PH; PKU; PKU1"
                     /note="hexamer: AATACA"
     polyA_site      3631
                     /gene="PAH"
                     /gene_synonym="PH; PKU; PKU1"
     regulatory      3734..3739
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PAH"
                     /gene_synonym="PH; PKU; PKU1"
                     /note="hexamer: AATAAA"
     polyA_site      3759
                     /gene="PAH"
                     /gene_synonym="PH; PKU; PKU1"
ORIGIN      
        1 actctcttct cctccctagt gcgaggttaa aaccttcagc cccacgtgct gtttgcaaac
       61 ctgcctgtac ctgaggccct aaaaagccag agacctcact cccggggagc cagcatgtcc
      121 actgcggtcc tggaaaaccc aggcttgggc aggaaactct ctgactttgg acaggaaaca
      181 agctatattg aagacaactg caatcaaaat ggtgccatat cactgatctt ctcactcaaa
      241 gaagaagttg gtgcattggc caaagtattg cgcttatttg aggagaatga tgtaaacctg
      301 acccacattg aatctagacc ttctcgttta aagaaagatg agtatgaatt tttcacccat
      361 ttggataaac gtagcctgcc tgctctgaca aacatcatca agatcttgag gcatgacatt
      421 ggtgccactg tccatgagct ttcacgagat aagaagaaag acacagtgcc ctggttccca
      481 agaaccattc aagagctgga cagatttgcc aatcagattc tcagctatgg agcggaactg
      541 gatgctgacc accctggttt taaagatcct gtgtaccgtg caagacggaa gcagtttgct
      601 gacattgcct acaactaccg ccatgggcag cccatccctc gagtggaata catggaggaa
      661 gaaaagaaaa catggggcac agtgttcaag actctgaagt ccttgtataa aacccatgct
      721 tgctatgagt acaatcacat ttttccactt cttgaaaagt actgtggctt ccatgaagat
      781 aacattcccc agctggaaga cgtttctcag ttcctgcaga cttgcactgg tttccgcctc
      841 cgacctgtgg ctggcctgct ttcctctcgg gatttcttgg gtggcctggc cttccgagtc
      901 ttccactgca cacagtacat cagacatgga tccaagccca tgtatacccc cgaacctgac
      961 atctgccatg agctgttggg acatgtgccc ttgttttcag atcgcagctt tgcccagttt
     1021 tcccaggaaa ttggccttgc ctctctgggt gcacctgatg aatacattga aaagctcgcc
     1081 acaatttact ggtttactgt ggagtttggg ctctgcaaac aaggagactc cataaaggca
     1141 tatggtgctg ggctcctgtc atcctttggt gaattacagt actgcttatc agagaagcca
     1201 aagcttctcc ccctggagct ggagaagaca gccatccaaa attacactgt cacggagttc
     1261 cagcccctct attacgtggc agagagtttt aatgatgcca aggagaaagt aaggaacttt
     1321 gctgccacaa tacctcggcc cttctcagtt cgctacgacc catacaccca aaggattgag
     1381 gtcttggaca atacccagca gcttaagatt ttggctgatt ccattaacag tgaaattgga
     1441 atcctttgca gtgccctcca gaaaataaag taaagccatg gacagaatgt ggtctgtcag
     1501 ctgtgaatct gttgatggag atccaactat ttctttcatc agaaaaagtc cgaaaagcaa
     1561 accttaattt gaaataacag ccttaaatcc tttacaagat ggagaaacaa caaataagtc
     1621 aaaataatct gaaatgacag gatatgagta catactcaag agcataatgg taaatctttt
     1681 ggggtcatct ttgatttaga gatgataatc ccatactctc aattgagtta aatcagtaat
     1741 ctgtcgcatt tcatcaagat taattaaaat ttgggacctg cttcattcaa gcttcatata
     1801 tgctttgcag agaactcata aaggagcata taaggctaaa tgtaaaacac aagactgtca
     1861 ttagaattga attattgggc ttaatataaa tcgtaaccta tgaagtttat tttctatttt
     1921 agttaactat gattccaatt actactttgt tattgtacct aagtaaattt tctttaagtc
     1981 agaagcccat taaaatagtt acaagcattg aacttcttta gtattatatt aatataaaaa
     2041 catttttgta tgttttattg taatcataaa tactgctgta taaggtaata aaactctgca
     2101 cctaatcccc ataacttcca gtatcatttt ccaattaatt atcaagtctg ttttgggaaa
     2161 cactttgagg acatttatga tgcagcagat gttgactaaa ggcttggttg gtagatattc
     2221 aggaaatgtt cactgaataa ataagtaaat acattattga aaagcaaatc tgtataaatg
     2281 tgaaattttt atttgtatta gtaataaaac attagtagtt taaacaattt cactgtttca
     2341 gttatttcct ggaatgaaat attcctctca ctgccttaga aatacattag ctagatagtt
     2401 ttgtaacatg agaaaatggc cagaggctca tatctccaac cctttgcagg ggctccttgt
     2461 gacactcaaa gtcatgcctg gacagtcaac ggactttgac ttttgttgat tgtgtgtttg
     2521 ccatgaaaac atgaatatct gagaagcagt ggggagaaaa aaaacaatat ctttgtagct
     2581 atgatttgaa attctcatac tactttacat tttattttgg aaatagttaa gtcttaaaga
     2641 atttgcatag tgtttctttg agtttagttc tcagaacagc tgtagtatca tcaacagcaa
     2701 attctgggta ccttcccagc tccacccaat ttgaatctct gaagataagg cccagagacc
     2761 tgtattttta agtaccccat ttttttaatt attcatagcc aaattctatc aggtacattc
     2821 agtttgagaa aacctgattt gtggtggtca gtctgccact gccaatgatg tcaatgtgga
     2881 taagctgttt cccttcttta gacctcagtg tcactctaac aatgagggag ttaaacttta
     2941 taaaccaagg tccattgcag ccttgaaata tgattcaagt gttcatatgt gtctttatat
     3001 agctatgcct gatccactga tggggtgtta caatacctgc ttatatatgc cagctgggag
     3061 gaaagaggaa tttactgaat gtgtctgaag tttcattgtt ttgaagttgg aattttatgc
     3121 ctgtatctat gtttatgcct ttgtaaaacc cactgatttt aaaagtgaaa aaggactttt
     3181 ttctctgctt ttactctaaa caccaaacaa tccctgcaaa gggattattc tgatgtttct
     3241 tcatttcaca tgaaaagtta attattgact ctggaactta aatattagat aatatttttg
     3301 acaatattga agagtgagtt ttagtccagt aaagatgttt taatgagctt gaaggtaaag
     3361 tttcggttaa gttatgattt tcacaggaag ttacatactg aatgaaagat aatatttgta
     3421 tttttggtaa tgtgctactc agttcttagc tcttttttat ccagatataa aagcccagtc
     3481 tatagctatg ggatttaata aatttccaat atgtaagtgt ttttatttgt ttaatttcta
     3541 gtaaatgagc aatattttag aaacagtatc agtctttact gacagatgat cttgctgagt
     3601 acaatcaaaa taaatacata aaaaattcta agcatgtggc attgatgttt aataagtttc
     3661 tgaaagtagg aatctgaatt ttaactgtag gtttctaagt tatataattt agttgtgttt
     3721 caaaaaatcc accaataaaa tgtcagcttt ataaaaaca
//
