LOCUS       NM_015107               6357 bp    mRNA    linear   PRI 12-NOV-2024
DEFINITION  Homo sapiens PHD finger protein 8 (PHF8), transcript variant 2,
            mRNA.
ACCESSION   NM_015107
VERSION     NM_015107.3
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 6357)
  AUTHORS   Witucki,L. and Jakubowski,H.
  TITLE     Homocysteine metabolites impair the PHF8/H4K20me1/mTOR/autophagy
            pathway by upregulating the expression of histone demethylase
            PHF8-targeting microRNAs in human vascular endothelial cells and
            mice
  JOURNAL   FASEB J 38 (18), e70072 (2024)
   PUBMED   39323294
  REMARK    GeneRIF: Homocysteine metabolites impair the
            PHF8/H4K20me1/mTOR/autophagy pathway by upregulating the expression
            of histone demethylase PHF8-targeting microRNAs in human vascular
            endothelial cells and mice.
REFERENCE   2  (bases 1 to 6357)
  AUTHORS   Tang,X., He,J. and Hao,Y.
  TITLE     Histone demethylase PHF8 protected against chondrocyte injury and
            alleviated posttraumatic osteoarthritis by epigenetically enhancing
            WWP2 expression
  JOURNAL   Hum Exp Toxicol 43, 9603271241292165 (2024)
   PUBMED   39454680
  REMARK    GeneRIF: Histone demethylase PHF8 protected against chondrocyte
            injury and alleviated posttraumatic osteoarthritis by
            epigenetically enhancing WWP2 expression.
REFERENCE   3  (bases 1 to 6357)
  AUTHORS   Feng,W., Yonezawa,M., Ye,J., Jenuwein,T. and Grummt,I.
  TITLE     PHF8 activates transcription of rRNA genes through H3K4me3 binding
            and H3K9me1/2 demethylation
  JOURNAL   Nat Struct Mol Biol 17 (4), 445-450 (2010)
   PUBMED   20208542
  REMARK    GeneRIF: PHF8 exerts a positive effect on rDNA transcription, with
            transcriptional activation requiring both the JmjC domain and the
            PHD finger. PHF8 demethylates H3K9me1/2, and its catalytic activity
            is stimulated by adjacent H3K4me3
REFERENCE   4  (bases 1 to 6357)
  AUTHORS   Yue,W.W., Hozjan,V., Ge,W., Loenarz,C., Cooper,C.D.,
            Schofield,C.J., Kavanagh,K.L., Oppermann,U. and McDonough,M.A.
  TITLE     Crystal structure of the PHF8 Jumonji domain, an Nepsilon-methyl
            lysine demethylase
  JOURNAL   FEBS Lett 584 (4), 825-830 (2010)
   PUBMED   20067792
  REMARK    GeneRIF: Results rationalize the lack of activity for the
            clinically observed F279S PHF8 variant and they will help to
            identify inhibitors selective for specific N(epsilon)-methyl lysine
            demethylase subfamilies.
REFERENCE   5  (bases 1 to 6357)
  AUTHORS   Yu,L., Wang,Y., Huang,S., Wang,J., Deng,Z., Zhang,Q., Wu,W.,
            Zhang,X., Liu,Z., Gong,W. and Chen,Z.
  TITLE     Structural insights into a novel histone demethylase PHF8
  JOURNAL   Cell Res 20 (2), 166-173 (2010)
   PUBMED   20101266
  REMARK    GeneRIF: Molecular mechanism underlying PHF8-associated
            developmental and neurological diseases.
REFERENCE   6  (bases 1 to 6357)
  AUTHORS   Loenarz,C., Ge,W., Coleman,M.L., Rose,N.R., Cooper,C.D.,
            Klose,R.J., Ratcliffe,P.J. and Schofield,C.J.
  TITLE     PHF8, a gene associated with cleft lip/palate and mental
            retardation, encodes for an Nepsilon-dimethyl lysine demethylase
  JOURNAL   Hum Mol Genet 19 (2), 217-222 (2010)
   PUBMED   19843542
  REMARK    GeneRIF: PHF8 is an Fe(II) and 2-oxoglutarate-dependent
            N(epsilon)-methyl lysine demethylase.
            GeneRIF: PHF8 is a histone lysine demethylase with di-/monomethyl
            state selectivity. Clinical PHF8 mutants disrupt PHF8 activity.
            Oxygen-dependence of PHF8 activity suggests link with increased
            incidence of cleft lip/palate from maternal hypoxia during
            gestation.
REFERENCE   7  (bases 1 to 6357)
  AUTHORS   Qiao,Y., Liu,X., Harvard,C., Hildebrand,M.J., Rajcan-Separovic,E.,
            Holden,J.J. and Lewis,M.E.
  TITLE     Autism-associated familial microdeletion of Xp11.22
  JOURNAL   Clin Genet 74 (2), 134-144 (2008)
   PUBMED   18498374
  REMARK    GeneRIF: deletion of the PHF8 gene is associated with the X-linked
            mental retardation Siderius-Hamel syndrome and the larger size of
            the Xp11.22 deletion including genes FAM120C and WNK3 may be
            involved in the pathogenesis of autism.
            GeneRIF: Observational study of gene-disease association. (HuGE
            Navigator)
REFERENCE   8  (bases 1 to 6357)
  AUTHORS   Koivisto,A.M., Ala-Mello,S., Lemmela,S., Komu,H.A., Rautio,J. and
            Jarvela,I.
  TITLE     Screening of mutations in the PHF8 gene and identification of a
            novel mutation in a Finnish family with XLMR and cleft lip/cleft
            palate
  JOURNAL   Clin Genet 72 (2), 145-149 (2007)
   PUBMED   17661819
  REMARK    GeneRIF: A novel missense mutation c.836C>T of the PHF8 gene was
            identified in a Finnish family with multiple-affected male patients
            with X-linked mental retardation
REFERENCE   9  (bases 1 to 6357)
  AUTHORS   Laumonnier,F., Holbert,S., Ronce,N., Faravelli,F., Lenzner,S.,
            Schwartz,C.E., Lespinasse,J., Van Esch,H., Lacombe,D., Goizet,C.,
            Phan-Dinh Tuy,F., van Bokhoven,H., Fryns,J.P., Chelly,J.,
            Ropers,H.H., Moraine,C., Hamel,B.C. and Briault,S.
  TITLE     Mutations in PHF8 are associated with X linked mental retardation
            and cleft lip/cleft palate
  JOURNAL   J Med Genet 42 (10), 780-786 (2005)
   PUBMED   16199551
  REMARK    GeneRIF: an important function of PHF8 is in midline formation and
            in the development of cognitive abilities, and may have a role in X
            linked mental retardation associated with cleft lip/palate
REFERENCE   10 (bases 1 to 6357)
  AUTHORS   Siderius,L.E., Hamel,B.C., van Bokhoven,H., de Jager,F., van den
            Helm,B., Kremer,H., Heineman-de Boer,J.A., Ropers,H.H. and
            Mariman,E.C.
  TITLE     X-linked mental retardation associated with cleft lip/palate maps
            to Xp11.3-q21.3
  JOURNAL   Am J Med Genet 85 (3), 216-220 (1999)
   PUBMED   10398231
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AL589872.9, BE676640.1,
            BC053861.1 and AL732374.14.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Jun 2, 2019 this sequence version replaced NM_015107.2.
            
            Summary: The protein encoded by this gene is a histone lysine
            demethylase that preferentially acts on histones in the monomethyl
            or dimethyl states. The encoded protein requires Fe(2+) ion,
            2-oxoglutarate, and oxygen for its catalytic activity. The protein
            has an N-terminal PHD finger and a central Jumonji C domain. This
            gene is thought to function as a transcription activator. Defects
            in this gene are a cause of syndromic X-linked Siderius type
            intellectual disability (MRXSSD) and over-expression of this gene
            is associated with several forms of cancer. Multiple transcript
            variants encoding different isoforms have been found for this gene.
            [provided by RefSeq, Jul 2017].
            
            Transcript Variant: This variant (2) differs in the 5' UTR and
            coding sequence compared to variant 1. The resulting isoform (2) is
            shorter at the N-terminus compared to 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 :: BC053861.1, CR933612.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000338154.11/ ENSP00000338868.6
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-299               AL589872.9         183-481             c
            300-595             BE676640.1         1-296
            596-4881            BC053861.1         1-4286
            4882-6350           AL732374.14        122352-123820       c
            6351-6357           BC053861.1         5756-5762
FEATURES             Location/Qualifiers
     source          1..6357
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="X"
                     /map="Xp11.22"
     gene            1..6357
                     /gene="PHF8"
                     /gene_synonym="JHDM1F; KDM7B; MRXSSD; ZNF422"
                     /note="PHD finger protein 8"
                     /db_xref="GeneID:23133"
                     /db_xref="HGNC:HGNC:20672"
                     /db_xref="MIM:300560"
     exon            1..712
                     /gene="PHF8"
                     /gene_synonym="JHDM1F; KDM7B; MRXSSD; ZNF422"
                     /inference="alignment:Splign:2.1.0"
     exon            713..902
                     /gene="PHF8"
                     /gene_synonym="JHDM1F; KDM7B; MRXSSD; ZNF422"
                     /inference="alignment:Splign:2.1.0"
     CDS             805..3879
                     /gene="PHF8"
                     /gene_synonym="JHDM1F; KDM7B; MRXSSD; ZNF422"
                     /EC_number="1.14.11.27"
                     /EC_number="1.14.11.65"
                     /note="isoform 2 is encoded by transcript variant 2;
                     jumonji C domain-containing histone demethylase 1F;
                     histone lysine demethylase PHF8; [histone
                     H3]-dimethyl-L-lysine(9) demethylase PHF8; [histone
                     H3]-dimethyl-L-lysine(36) demethylase PHF8; lysine
                     demethylase 7B; zinc finger protein 422"
                     /codon_start=1
                     /product="histone lysine demethylase PHF8 isoform 2"
                     /protein_id="NP_055922.1"
                     /db_xref="CCDS:CCDS14355.1"
                     /db_xref="GeneID:23133"
                     /db_xref="HGNC:HGNC:20672"
                     /db_xref="MIM:300560"
                     /translation="MASVPVYCLCRLPYDVTRFMIECDMCQDWFHGSCVGVEEEKAAD
                     IDLYHCPNCEVLHGPSIMKKRRGSSKGHDTHKGKPVKTGSPTFVRELRSRTFDSSDEV
                     ILKPTGNQLTVEFLEENSFSVPILVLKKDGLGMTLPSPSFTVRDVEHYVGSDKEIDVI
                     DVTRQADCKMKLGDFVKYYYSGKREKVLNVISLEFSDTRLSNLVETPKIVRKLSWVEN
                     LWPEECVFERPNVQKYCLMSVRDSYTDFHIDFGGTSVWYHVLKGEKIFYLIRPTNANL
                     TLFECWSSSSNQNEMFFGDQVDKCYKCSVKQGQTLFIPTGWIHAVLTPVDCLAFGGNF
                     LHSLNIEMQLKAYEIEKRLSTADLFRFPNFETICWYVGKHILDIFRGLRENRRHPASY
                     LVHGGKALNLAFRAWTRKEALPDHEDEIPETVRTVQLIKDLAREIRLVEDIFQQNVGK
                     TSNIFGLQRIFPAGSIPLTRPAHSTSVSMSRLSLPSKNGSKKKGLKPKELFKKAERKG
                     KESSALGPAGQLSYNLMDTYSHQALKTGSFQKAKFNITGACLNDSDDDSPDLDLDGNE
                     SPLALLMSNGSTKRVKSLSKSRRTKIAKKVDKARLMAEQVMEDEFDLDSDDELQIDER
                     LGKEKATLIIRPKFPRKLPRAKPCSDPNRVREPGEVEFDIEEDYTTDEDMVEGVEGKL
                     GNGSGAGGILDLLKASRQVGGPDYAALTEAPASPSTQEAIQGMLCMANLQSSSSSPAT
                     SSLQAWWTGGQDRSSGSSSSGLGTVSNSPASQRTPGKRPIKRPAYWRTESEEEEENAS
                     LDEQDSLGACFKDAEYIYPSLESDDDDPALKSRPKKKKNSDDAPWSPKARVTPTLPKQ
                     DRPVREGTRVASIETGLAAAAAKLAQQELQKAQKKKYIKKKPLLKEVEQPRPQDSNLS
                     LTVPAPTVAATPQLVTSSSPLPPPEPKQEALSGSLADHEYTARPNAFGMAQANRSTTP
                     MAPGVFLTQRRPSVGSQSNQAGQGKRPKKGLATAKQRLGRILKIHRNGKLLL"
     exon            903..988
                     /gene="PHF8"
                     /gene_synonym="JHDM1F; KDM7B; MRXSSD; ZNF422"
                     /inference="alignment:Splign:2.1.0"
     exon            989..1097
                     /gene="PHF8"
                     /gene_synonym="JHDM1F; KDM7B; MRXSSD; ZNF422"
                     /inference="alignment:Splign:2.1.0"
     exon            1098..1258
                     /gene="PHF8"
                     /gene_synonym="JHDM1F; KDM7B; MRXSSD; ZNF422"
                     /inference="alignment:Splign:2.1.0"
     exon            1259..1400
                     /gene="PHF8"
                     /gene_synonym="JHDM1F; KDM7B; MRXSSD; ZNF422"
                     /inference="alignment:Splign:2.1.0"
     exon            1401..1587
                     /gene="PHF8"
                     /gene_synonym="JHDM1F; KDM7B; MRXSSD; ZNF422"
                     /inference="alignment:Splign:2.1.0"
     exon            1588..1750
                     /gene="PHF8"
                     /gene_synonym="JHDM1F; KDM7B; MRXSSD; ZNF422"
                     /inference="alignment:Splign:2.1.0"
     exon            1751..1838
                     /gene="PHF8"
                     /gene_synonym="JHDM1F; KDM7B; MRXSSD; ZNF422"
                     /inference="alignment:Splign:2.1.0"
     exon            1839..1945
                     /gene="PHF8"
                     /gene_synonym="JHDM1F; KDM7B; MRXSSD; ZNF422"
                     /inference="alignment:Splign:2.1.0"
     exon            1946..2037
                     /gene="PHF8"
                     /gene_synonym="JHDM1F; KDM7B; MRXSSD; ZNF422"
                     /inference="alignment:Splign:2.1.0"
     exon            2038..2127
                     /gene="PHF8"
                     /gene_synonym="JHDM1F; KDM7B; MRXSSD; ZNF422"
                     /inference="alignment:Splign:2.1.0"
     exon            2128..2430
                     /gene="PHF8"
                     /gene_synonym="JHDM1F; KDM7B; MRXSSD; ZNF422"
                     /inference="alignment:Splign:2.1.0"
     exon            2431..2534
                     /gene="PHF8"
                     /gene_synonym="JHDM1F; KDM7B; MRXSSD; ZNF422"
                     /inference="alignment:Splign:2.1.0"
     exon            2535..2713
                     /gene="PHF8"
                     /gene_synonym="JHDM1F; KDM7B; MRXSSD; ZNF422"
                     /inference="alignment:Splign:2.1.0"
     exon            2714..2799
                     /gene="PHF8"
                     /gene_synonym="JHDM1F; KDM7B; MRXSSD; ZNF422"
                     /inference="alignment:Splign:2.1.0"
     exon            2800..2933
                     /gene="PHF8"
                     /gene_synonym="JHDM1F; KDM7B; MRXSSD; ZNF422"
                     /inference="alignment:Splign:2.1.0"
     exon            2934..3247
                     /gene="PHF8"
                     /gene_synonym="JHDM1F; KDM7B; MRXSSD; ZNF422"
                     /inference="alignment:Splign:2.1.0"
     exon            3248..3343
                     /gene="PHF8"
                     /gene_synonym="JHDM1F; KDM7B; MRXSSD; ZNF422"
                     /inference="alignment:Splign:2.1.0"
     exon            3344..3453
                     /gene="PHF8"
                     /gene_synonym="JHDM1F; KDM7B; MRXSSD; ZNF422"
                     /inference="alignment:Splign:2.1.0"
     exon            3454..3790
                     /gene="PHF8"
                     /gene_synonym="JHDM1F; KDM7B; MRXSSD; ZNF422"
                     /inference="alignment:Splign:2.1.0"
     exon            3791..6357
                     /gene="PHF8"
                     /gene_synonym="JHDM1F; KDM7B; MRXSSD; ZNF422"
                     /inference="alignment:Splign:2.1.0"
     regulatory      6334..6339
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PHF8"
                     /gene_synonym="JHDM1F; KDM7B; MRXSSD; ZNF422"
                     /note="hexamer: GATAAA"
     polyA_site      6357
                     /gene="PHF8"
                     /gene_synonym="JHDM1F; KDM7B; MRXSSD; ZNF422"
                     /note="major polyA site"
ORIGIN      
        1 ctcgcgagtc cagccctcat aagatggcgg tcgccttggt tgtctgggta gcgccgccac
       61 tctcaacatg gtagctgttt atcccgtatt tctcctcccc tctccgcctc aacttcctca
      121 ttgttttgaa taaactttat tgactactcc gaattgccta ccaccgccac tgggcttctc
      181 ccagcgactt ttcgggccgt gtgcctcgga cgtggcggcc ggttcatctc tttccccgtt
      241 ggtttgctcg cgagtatctc ctgccggccc agcgacgacg ccacttgccc gttcgccggg
      301 cggccgccag actaggccca agccgcggtc tccagtaggc ccgaacggcc gggccgaggg
      361 gaatgttgtg gaggaggctg ctctgaagca ccgttgagcg gctggcgccg cgcgacccag
      421 cggggggctc gaggggaagg cgagcgaggt tcccggcggt acggggacta tcccagaatt
      481 cgacgcgcgt cgccgtaggg gccggaacta ccggacgagc ctccgctgag gcgcttcgca
      541 gtcccggagc tagcccggct gccggcgtgt cgctggggct gagctccgcg ggcgtggagt
      601 ccttgcagcc caaagcatga ggaggtccct gtaggattct ggactgaaga cgttcttgtc
      661 aggtttgggg cgtgaggagg ttcctgtcag ttggggaagc gttaagattc ctctatcgtc
      721 cagagaggac gcgtgctgcc gcctcccgcc cctcttgaca cgacgaacct ggccggccgc
      781 agaacgctcc agggccgagc gaagatggcc tcggtgccgg tgtattgcct ctgccggctg
      841 ccttacgatg tgacccgctt catgatcgag tgtgacatgt gccaggactg gtttcatggc
      901 agttgtgttg gtgttgaaga ggagaaggct gctgacattg acctctacca ctgccccaac
      961 tgtgaagtct tgcatgggcc ctccattatg aaaaaacgcc gtggatcttc aaaggggcat
     1021 gatacacaca aggggaaacc agtgaagacc gggagcccta cgttcgtcag agagctccgg
     1081 agtaggactt ttgacagctc agatgaagtg attctgaagc ccactggaaa tcaactgacc
     1141 gtggaattcc tggaagaaaa tagcttcagt gtgcccatcc tggtcctgaa gaaggatggg
     1201 ttgggcatga cgctgccctc gccatcattc actgtgaggg atgttgaaca ctatgttggt
     1261 tctgacaaag agattgatgt gattgatgtg acccgccagg ctgactgcaa gatgaagctt
     1321 ggtgattttg tgaaatacta ttacagcggg aagagggaga aagtcctcaa tgtcattagt
     1381 ttggaattct ctgataccag actttctaac cttgtggaga caccgaagat tgttcgaaag
     1441 ctgtcatggg tcgaaaactt gtggccagag gaatgtgtct ttgagagacc caatgtacag
     1501 aagtactgcc tcatgagtgt gcgagatagc tatacagact ttcacattga ctttggtggc
     1561 acctctgtct ggtaccatgt actcaagggt gaaaagatct tctacctgat ccgcccaaca
     1621 aatgccaatc tgactctctt tgagtgctgg agcagttcct ctaatcagaa tgagatgttc
     1681 tttggggacc aggtggacaa gtgctacaag tgttccgtga agcaaggaca gacacttttc
     1741 attcccacag ggtggatcca tgctgtgctg acgcctgtgg actgccttgc ctttggaggg
     1801 aacttcttac acagccttaa catcgagatg cagctcaaag cctatgagat tgagaagcgg
     1861 ctgagcacag cagacctctt cagattcccc aactttgaga ccatctgttg gtatgtggga
     1921 aagcacatcc tggacatctt tcgcggtttg cgagagaaca ggagacaccc tgcctcctac
     1981 ctggtccatg gtggcaaagc cttgaacttg gcctttagag cctggacaag gaaagaagct
     2041 ctgccagacc atgaggatga gatcccggag acagtgcgaa ccgtacagct cattaaagat
     2101 ctggccaggg agatccgcct ggtggaagac atcttccaac agaacgttgg gaagacgagc
     2161 aatatctttg ggctgcagag gatcttccca gccggctcca ttcccctaac caggccagcc
     2221 cattccactt cagtgtccat gtccaggctg tcactgccct ccaaaaatgg ttcaaagaag
     2281 aaaggcctga agcccaagga actcttcaag aaggcagagc gaaagggcaa ggagagttca
     2341 gccttggggc ctgctggcca gttgagctat aatctcatgg acacatacag tcatcaggca
     2401 ctgaagacag gctctttcca gaaagcaaag ttcaacatca ctggtgcctg cttgaatgac
     2461 tcagatgacg actcaccaga cttggacctt gatggaaatg agagcccatt ggccctattg
     2521 atgtctaacg gcagtacgaa aagggtgaag agtttatcca aatctcggcg aaccaagata
     2581 gcaaagaagg tagacaaggc taggctgatg gcagaacagg tgatggaaga cgaatttgac
     2641 ttggattcag atgatgagct gcagattgac gagagattgg gaaaggagaa ggcgaccctg
     2701 ataataagac caaaatttcc ccggaaattg ccccgtgcga agccttgctc tgaccccaac
     2761 cgagttcgtg aaccaggaga agttgagttt gacattgagg aggactatac aacagatgag
     2821 gacatggtgg aaggggttga aggcaagctt gggaatggta gtggcgctgg tggcattctt
     2881 gatctgctca aggccagcag gcaggtgggg ggacctgact atgctgccct caccgaggcc
     2941 ccagcttctc ccagcactca ggaggccatc cagggcatgc tgtgcatggc caacctgcag
     3001 tcctcatcgt cctcaccggc tacctctagc ctgcaggcct ggtggactgg gggacaggat
     3061 cgaagcagtg ggagctccag cagtgggctg ggcacagtgt ctaacagtcc tgcttcccag
     3121 cgcaccccag ggaagcggcc catcaagcgg ccagcatact ggagaaccga gagcgaggag
     3181 gaggaggaga acgccagtct ggatgaacag gacagcttgg gagcgtgctt caaggatgca
     3241 gagtatatct atccttcact ggagtctgat gatgatgacc ctgctttgaa atctcgaccc
     3301 aagaaaaaga agaattcaga tgatgctcca tggagtccta aagcccgcgt gaccccaact
     3361 ctgccgaagc aggaccgtcc tgtgcgtgag gggacccggg tagcctctat tgagacaggt
     3421 ttggctgcag cagctgcaaa gctggcccag caggagctac agaaggccca aaagaagaaa
     3481 tatatcaaga agaagccttt gctgaaggag gtagaacagc ctcgccctca agactccaat
     3541 ctcagtctga cagtaccagc ccccactgtg gctgccacac cacaacttgt cacctcctcc
     3601 tcacccctgc ctcctcctga gcctaaacaa gaggccctgt caggaagtct cgctgaccat
     3661 gagtacaccg ctcgtcccaa tgcctttggc atggcccagg caaaccgcag caccacacct
     3721 atggcccccg gtgtcttctt gacccagcgg cgcccttcag ttggctccca gagcaatcag
     3781 gcaggacaag gaaagcgtcc caaaaagggc ctggccacag caaagcagag actcggccgt
     3841 atcctgaaaa tccacagaaa tggcaaacta cttctgtgag ccctcctgtg tcccacccct
     3901 caccccttta cccccattgc cttctccatt gtcaactctt ggggcactcc tggatcctat
     3961 ctgccctgga caaggtgctg aggtgcattg tcctgctttc ttgggactta ccaaaggcac
     4021 ggacccctcc accgactcct tctagttccc ttccccactt tcactagagc atcctgcctg
     4081 ccttctccac tgaggagcag gtaaatggga gaggtttcca gctgactaga accctctttt
     4141 ctactcgtcc aaaccactcc cgtcacctgc cttgtctgtt ctttattctt catcccccgc
     4201 tagagctgga aggcaggatg aggagaggta tgaaggagcc tgagccatga agtgggaagc
     4261 ccagtgcttg acactttctg caactctagc cctatatcca gaagcctgcc cacctccacc
     4321 cattctgttt gccccatttc cccagtccag tggacatgcc ccacctccag acttgctcat
     4381 gggagaaggc tgtggtctct gccccctctt gccaaatgct tcatggaaat gaagaggaag
     4441 gcctagagcc tccttcctgc cccactgtgg gccatttcca gaagtggcct agaaatgcca
     4501 acttcactta cctttcaaaa gaaaggtgat tcctatcact tgtcaaggta gggagaggtc
     4561 agatgcccaa gcctttgacc acggttttgt agcctgttgg aggaagctac ttttagctgg
     4621 ctacacatga ggccacttgt tttagggtga gctccaggga tttgcctgga ttttgaaatc
     4681 atgtagaaca ttatccacgt ggctgtggct gtggctgtgg ctgggccctg gcaggtggaa
     4741 aaccatctcc cagaaacctg aaagcacctg ccaatgacgc agataaccct ggccctacag
     4801 cctgcttgct ccgcctatac cacagagcac agcctggaca ttatggaggg tgtggcggga
     4861 cggcccacac ctgggtcctc catcgggaac ttttcatgct tctttctcca cctgaggtct
     4921 tggtctgaag aagacctcag gactcacatc ttcactcctg ggcctttgca cttccagacg
     4981 acaggtcatc gttcaagcag aatgcagaca ggccattcac gagcccaagt tgaagagaag
     5041 agacgcccat ccgtgaagga gcagaccatc catccgatcc tccccttccc ctgtccttcc
     5101 ttcgtggatt gtctccattg tccagacagt gcccccacct cccaccgcct tgcctcactg
     5161 gcaatctgga ctcgatggag aacatccccc cacctccatt tggcactacc caagtggagt
     5221 gtacccttgc cctttccacc tgtaccaccc actccaacct caccccagct tgcccaatgc
     5281 ttctggggaa tttaatagct accatgcagg ccacagggaa tttgtgaggc ttcttttgtc
     5341 atctttgtat ctccagtttg tctttctttt ctccatagcc ctgcctctac tttccttcct
     5401 tggaatcagg ggttccttta gcccatttgc tttctctacc ttggggaccc caggggccaa
     5461 gcagttctcc atctagtcac accaaaggca aaaagcctgg ctacctcccc cctagcacgt
     5521 gagtccctac tcccctcccc tctgtttctg cccagctttg cttattttgg ggatttcaag
     5581 gcagcagagg gtagtgaggg gagagcagga gaagcctctg tcctgtatag gcaactgcct
     5641 gactatgcgg tgactgctgt aaccaagatc aggtccccag cccttttgtc cattaacacc
     5701 ccttcttgat ctttcaaagg cagctaattg ctagcaaatc cccccgattc cggccttttc
     5761 cctctatttc tttgttagaa gttttctgtg gagctgaaac ccagcctctg tttgactggg
     5821 tttcatttag cttagttggg ttcttagagc cccctgtttg ttgttttgtg ttgtttccaa
     5881 tgaaaagcaa gtttaccctc agagttatgc ttttccaaag aggctgatgt ctttgttttt
     5941 gtttttttta atgtttcagg ttctaagtga agtgagttgg ggaggggttg ggagtgttag
     6001 taatcaaggt ttagaacacc atgagatagt tacccctgat ctccagtccc tagctggggg
     6061 ctggacaggg ggaagggaga gaggatttct attcaccttt aatatatttt tacaaaaaaa
     6121 gcaaacaatt taaaaacaag cccaccgctt ctgtacatgt ctaaatatat ttttagaagt
     6181 gggtaggatt gtgaatttct gatgcagggc ctttttataa ataggttagg gtagcatcat
     6241 tcagacttct ctgttgtttt tgtccctgtc tttttcttat gttgtgttac taatgtaatt
     6301 tatatttttt ttagatcctc cctttcctat agagataaaa gtgatttatc ttggcaa
//
