LOCUS       NM_001323289           14572 bp    mRNA    linear   PRI 09-FEB-2025
DEFINITION  Homo sapiens cyclin dependent kinase like 5 (CDKL5), transcript
            variant III, mRNA.
ACCESSION   NM_001323289
VERSION     NM_001323289.2
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 14572)
  AUTHORS   Massey,S., Ang,C.S., Davidson,N.M., Quigley,A., Rollo,B.,
            Harris,A.R., Kapsa,R.M.I., Christodoulou,J. and Van Bergen,N.J.
  TITLE     Novel CDKL5 targets identified in human iPSC-derived neurons
  JOURNAL   Cell Mol Life Sci 81 (1), 347 (2024)
   PUBMED   39136782
  REMARK    GeneRIF: Novel CDKL5 targets identified in human iPSC-derived
            neurons.
            Erratum:[Cell Mol Life Sci. 2024 Sep 10;81(1):392. doi:
            10.1007/s00018-024-05421-x.. PMID: 39254686]
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 14572)
  AUTHORS   Wong,K., Davies,G., Leonard,H., Downs,J., Junaid,M. and Amin,S.
  TITLE     Growth patterns in individuals with CDKL5 deficiency disorder
  JOURNAL   Dev Med Child Neurol 66 (4), 469-482 (2024)
   PUBMED   37804112
  REMARK    GeneRIF: Growth patterns in individuals with CDKL5 deficiency
            disorder.
REFERENCE   3  (bases 1 to 14572)
  AUTHORS   Daniels,C., Greene,C., Smith,L., Pestana-Knight,E., Demarest,S.,
            Zhang,B., Benke,T.A., Poduri,A. and Olson,H.E.
  CONSRTM   CDKL5 Study Group
  TITLE     CDKL5 deficiency disorder and other infantile-onset genetic
            epilepsies
  JOURNAL   Dev Med Child Neurol 66 (4), 456-468 (2024)
   PUBMED   37771170
  REMARK    GeneRIF: CDKL5 deficiency disorder and other infantile-onset
            genetic epilepsies.
REFERENCE   4  (bases 1 to 14572)
  AUTHORS   Pestana Knight,E.M. and Olson,H.E.
  TITLE     CDKL5 Deficiency Disorder: Some Lessons Learned 20 Years After the
            First Description
  JOURNAL   Am J Intellect Dev Disabil 129 (2), 101-109 (2024)
   PUBMED   38411242
  REMARK    GeneRIF: CDKL5 Deficiency Disorder: Some Lessons Learned 20 Years
            After the First Description.
REFERENCE   5  (bases 1 to 14572)
  AUTHORS   Sampedro-Castaneda,M., Baltussen,L.L., Lopes,A.T., Qiu,Y.,
            Sirvio,L., Mihaylov,S.R., Claxton,S., Richardson,J.C., Lignani,G.
            and Ultanir,S.K.
  TITLE     Epilepsy-linked kinase CDKL5 phosphorylates voltage-gated calcium
            channel Cav2.3, altering inactivation kinetics and neuronal
            excitability
  JOURNAL   Nat Commun 14 (1), 7830 (2023)
   PUBMED   38081835
  REMARK    GeneRIF: Epilepsy-linked kinase CDKL5 phosphorylates voltage-gated
            calcium channel Cav2.3, altering inactivation kinetics and neuronal
            excitability.
            Publication Status: Online-Only
REFERENCE   6  (bases 1 to 14572)
  AUTHORS   Weaving,L.S., Christodoulou,J., Williamson,S.L., Friend,K.L.,
            McKenzie,O.L., Archer,H., Evans,J., Clarke,A., Pelka,G.J.,
            Tam,P.P., Watson,C., Lahooti,H., Ellaway,C.J., Bennetts,B.,
            Leonard,H. and Gecz,J.
  TITLE     Mutations of CDKL5 cause a severe neurodevelopmental disorder with
            infantile spasms and mental retardation
  JOURNAL   Am J Hum Genet 75 (6), 1079-1093 (2004)
   PUBMED   15492925
  REMARK    GeneRIF: CDKL5 mutations are associated with epilepsy, X-linked
            mental retardation and a clinical phenotype that overlaps Rett
            syndrome.
REFERENCE   7  (bases 1 to 14572)
  AUTHORS   Kalscheuer,V.M., Tao,J., Donnelly,A., Hollway,G., Schwinger,E.,
            Kubart,S., Menzel,C., Hoeltzenbein,M., Tommerup,N., Eyre,H.,
            Harbord,M., Haan,E., Sutherland,G.R., Ropers,H.H. and Gecz,J.
  TITLE     Disruption of the serine/threonine kinase 9 gene causes severe
            X-linked infantile spasms and mental retardation
  JOURNAL   Am J Hum Genet 72 (6), 1401-1411 (2003)
   PUBMED   12736870
REFERENCE   8  (bases 1 to 14572)
  AUTHORS   Montini,E., Andolfi,G., Caruso,A., Buchner,G., Walpole,S.M.,
            Mariani,M., Consalez,G., Trump,D., Ballabio,A. and Franco,B.
  TITLE     Identification and characterization of a novel serine-threonine
            kinase gene from the Xp22 region
  JOURNAL   Genomics 51 (3), 427-433 (1998)
   PUBMED   9721213
REFERENCE   9  (bases 1 to 14572)
  AUTHORS   Krause,S.W., Rehli,M., Kreutz,M., Schwarzfischer,L.,
            Paulauskis,J.D. and Andreesen,R.
  TITLE     Differential screening identifies genetic markers of monocyte to
            macrophage maturation
  JOURNAL   J Leukoc Biol 60 (4), 540-545 (1996)
   PUBMED   8864140
REFERENCE   10 (bases 1 to 14572)
  AUTHORS   Benke,T.A., Demarest,S., Angione,K., Downs,J., Leonard,H.,
            Saldaris,J., Marsh,E.D., Olson,H. and Haviland,I.
  TITLE     CDKL5 Deficiency Disorder
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   38603524
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AL109798.19, HQ171445.1,
            Z92542.2 and AW452901.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On May 16, 2019 this sequence version replaced NM_001323289.1.
            
            Summary: This gene is a member of Ser/Thr protein kinase family and
            encodes a phosphorylated protein with protein kinase activity.
            Mutations in this gene have been associated with X-linked infantile
            spasm syndrome (ISSX), also known as X-linked West syndrome, and
            Rett syndrome (RTT). Alternate transcriptional splice variants have
            been characterized. [provided by RefSeq, Jul 2008].
            
            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 :: SRR14038191.868804.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1968540, SAMEA1968968
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000623535.2/ ENSP00000485244.1
            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
            1-88                AL109798.19        1084-1171
            89-250              AL109798.19        82411-82572
            251-1251            HQ171445.1         1-1001
            1252-1252           Z92542.2           84409-84409
            1253-2553           HQ171445.1         1003-2303
            2554-2554           Z92542.2           100377-100377
            2555-2760           HQ171445.1         2305-2510
            2761-2761           Z92542.2           108868-108868
            2762-3133           HQ171445.1         2512-2883
            3134-9774           Z92542.2           109241-115881
            9775-10008          AW452901.1         17-250              c
            10009-14572         Z92542.2           116116-120679
FEATURES             Location/Qualifiers
     source          1..14572
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="X"
                     /map="Xp22.13"
     gene            1..14572
                     /gene="CDKL5"
                     /gene_synonym="CFAP247; DEE2; EIEE2; ISSX; STK9"
                     /note="cyclin dependent kinase like 5"
                     /db_xref="GeneID:6792"
                     /db_xref="HGNC:HGNC:11411"
                     /db_xref="MIM:300203"
     exon            1..88
                     /gene="CDKL5"
                     /gene_synonym="CFAP247; DEE2; EIEE2; ISSX; STK9"
                     /inference="alignment:Splign:2.1.0"
     exon            89..314
                     /gene="CDKL5"
                     /gene_synonym="CFAP247; DEE2; EIEE2; ISSX; STK9"
                     /inference="alignment:Splign:2.1.0"
     CDS             251..3133
                     /gene="CDKL5"
                     /gene_synonym="CFAP247; DEE2; EIEE2; ISSX; STK9"
                     /EC_number="2.7.11.22"
                     /note="isoform 2 is encoded by transcript variant III;
                     serine/threonine kinase 9; serine/threonine-protein kinase
                     9; cyclin dependent kinase 5 transcript"
                     /codon_start=1
                     /product="cyclin-dependent kinase-like 5 isoform 2"
                     /protein_id="NP_001310218.1"
                     /db_xref="CCDS:CCDS83458.1"
                     /db_xref="GeneID:6792"
                     /db_xref="HGNC:HGNC:11411"
                     /db_xref="MIM:300203"
                     /translation="MKIPNIGNVMNKFEILGVVGEGAYGVVLKCRHKETHEIVAIKKF
                     KDSEENEEVKETTLRELKMLRTLKQENIVELKEAFRRRGKLYLVFEYVEKNMLELLEE
                     MPNGVPPEKVKSYIYQLIKAIHWCHKNDIVHRDIKPENLLISHNDVLKLCDFGFARNL
                     SEGNNANYTEYVATRWYRSPELLLGAPYGKSVDMWSVGCILGELSDGQPLFPGESEID
                     QLFTIQKVLGPLPSEQMKLFYSNPRFHGLRFPAVNHPQSLERRYLGILNSVLLDLMKN
                     LLKLDPADRYLTEQCLNHPTFQTQRLLDRSPSRSAKRKPYHVESSTLSNRNQAGKSTA
                     LQSHHRSNSKDIQNLSVGLPRADEGLPANESFLNGNLAGASLSPLHTKTYQASSQPGS
                     TSKDLTNNNIPHLLSPKEAKSKTEFDFNIDPKPSEGPGTKYLKSNSRSQQNRHSFMES
                     SQSKAGTLQPNEKQSRHSYIDTIPQSSRSPSYRTKAKSHGALSDSKSVSNLSEARAQI
                     AEPSTSRYFPSSCLDLNSPTSPTPTRHSDTRTLLSPSGRNNRNEGTLDSRRTTTRHSK
                     TMEELKLPEHMDSSHSHSLSAPHESFSYGLGYTSPFSSQQRPHRHSMYVTRDKVRAKG
                     LDGSLSIGQGMAARANSLQLLSPQPGEQLPPEMTVARSSVKETSREGTSSFHTRQKSE
                     GGVYHDPHSDDGTAPKENRHLYNDPVPRRVGSFYRVPSPRPDNSFHENNVSTRVSSLP
                     SESSSGTNHSKRQPAFDPWKSPENISHSEQLKEKEKQGFFRSMKKKKKKSQTVPNSDS
                     PDLLTLQKSIHSASTPSSRPKEWRPEKISDLQTQSQPLKSLRKLLHLSSASNHPASSD
                     PRFQPLTAQQTKNSFSEIRIHPLSQASGGSSNIRQEPAPKGRPALQLPGQMDPGWHVS
                     SVTRSATEGPSYSEQLGAKSGPNGHPYNRTNRSRMPNLNDLKETAL"
     exon            315..349
                     /gene="CDKL5"
                     /gene_synonym="CFAP247; DEE2; EIEE2; ISSX; STK9"
                     /inference="alignment:Splign:2.1.0"
     exon            350..395
                     /gene="CDKL5"
                     /gene_synonym="CFAP247; DEE2; EIEE2; ISSX; STK9"
                     /inference="alignment:Splign:2.1.0"
     exon            396..532
                     /gene="CDKL5"
                     /gene_synonym="CFAP247; DEE2; EIEE2; ISSX; STK9"
                     /inference="alignment:Splign:2.1.0"
     exon            533..653
                     /gene="CDKL5"
                     /gene_synonym="CFAP247; DEE2; EIEE2; ISSX; STK9"
                     /inference="alignment:Splign:2.1.0"
     exon            654..713
                     /gene="CDKL5"
                     /gene_synonym="CFAP247; DEE2; EIEE2; ISSX; STK9"
                     /inference="alignment:Splign:2.1.0"
     exon            714..804
                     /gene="CDKL5"
                     /gene_synonym="CFAP247; DEE2; EIEE2; ISSX; STK9"
                     /inference="alignment:Splign:2.1.0"
     exon            805..994
                     /gene="CDKL5"
                     /gene_synonym="CFAP247; DEE2; EIEE2; ISSX; STK9"
                     /inference="alignment:Splign:2.1.0"
     exon            995..1075
                     /gene="CDKL5"
                     /gene_synonym="CFAP247; DEE2; EIEE2; ISSX; STK9"
                     /inference="alignment:Splign:2.1.0"
     exon            1076..1227
                     /gene="CDKL5"
                     /gene_synonym="CFAP247; DEE2; EIEE2; ISSX; STK9"
                     /inference="alignment:Splign:2.1.0"
     exon            1228..2194
                     /gene="CDKL5"
                     /gene_synonym="CFAP247; DEE2; EIEE2; ISSX; STK9"
                     /inference="alignment:Splign:2.1.0"
     exon            2195..2296
                     /gene="CDKL5"
                     /gene_synonym="CFAP247; DEE2; EIEE2; ISSX; STK9"
                     /inference="alignment:Splign:2.1.0"
     exon            2297..2402
                     /gene="CDKL5"
                     /gene_synonym="CFAP247; DEE2; EIEE2; ISSX; STK9"
                     /inference="alignment:Splign:2.1.0"
     exon            2403..2526
                     /gene="CDKL5"
                     /gene_synonym="CFAP247; DEE2; EIEE2; ISSX; STK9"
                     /inference="alignment:Splign:2.1.0"
     exon            2527..2626
                     /gene="CDKL5"
                     /gene_synonym="CFAP247; DEE2; EIEE2; ISSX; STK9"
                     /inference="alignment:Splign:2.1.0"
     exon            2627..2746
                     /gene="CDKL5"
                     /gene_synonym="CFAP247; DEE2; EIEE2; ISSX; STK9"
                     /inference="alignment:Splign:2.1.0"
     exon            2747..14572
                     /gene="CDKL5"
                     /gene_synonym="CFAP247; DEE2; EIEE2; ISSX; STK9"
                     /inference="alignment:Splign:2.1.0"
     regulatory      9746..9751
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CDKL5"
                     /gene_synonym="CFAP247; DEE2; EIEE2; ISSX; STK9"
                     /note="hexamer: AATAAA"
     polyA_site      9770
                     /gene="CDKL5"
                     /gene_synonym="CFAP247; DEE2; EIEE2; ISSX; STK9"
                     /note="major polyA site"
     polyA_site      9795
                     /gene="CDKL5"
                     /gene_synonym="CFAP247; DEE2; EIEE2; ISSX; STK9"
                     /note="major polyA site"
     regulatory      12759..12764
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CDKL5"
                     /gene_synonym="CFAP247; DEE2; EIEE2; ISSX; STK9"
                     /note="hexamer: AATAAA"
     regulatory      12765..12770
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CDKL5"
                     /gene_synonym="CFAP247; DEE2; EIEE2; ISSX; STK9"
                     /note="hexamer: AGTAAA"
     polyA_site      12780
                     /gene="CDKL5"
                     /gene_synonym="CFAP247; DEE2; EIEE2; ISSX; STK9"
     polyA_site      12783
                     /gene="CDKL5"
                     /gene_synonym="CFAP247; DEE2; EIEE2; ISSX; STK9"
     regulatory      14541..14546
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CDKL5"
                     /gene_synonym="CFAP247; DEE2; EIEE2; ISSX; STK9"
                     /note="hexamer: AATAAA"
     polyA_site      14572
                     /gene="CDKL5"
                     /gene_synonym="CFAP247; DEE2; EIEE2; ISSX; STK9"
ORIGIN      
        1 agttgtctct gccgctgggg aaggtaaagc ggcgacggcg tcctcaggag ctgtggggtc
       61 ccctgctaga agtgggggac tcggcggggg agtcatttaa tacttcatga ttagaacaaa
      121 tatgtgaaag ttcccaccaa ccagtgagaa tttcttcctt cagacggttt tggatcttac
      181 tgcacagctt tctgagaagt tcttttggtg ccatgttttg tggcttgcat caaaagagga
      241 gtttgtcttc atgaagattc ctaacattgg taatgtgatg aataaatttg agatccttgg
      301 ggttgtaggt gaaggagcct atggagttgt acttaaatgc agacacaagg aaacacatga
      361 aattgtggcg atcaagaaat tcaaggacag tgaagaaaat gaagaagtca aagaaacgac
      421 tttacgagag cttaaaatgc ttcggactct caagcaggaa aacattgtgg agttgaagga
      481 agcatttcgt cggaggggaa agttgtactt ggtgtttgag tatgttgaaa aaaatatgct
      541 cgaattgctg gaagaaatgc caaatggagt tccacctgag aaagtaaaaa gctacatcta
      601 tcagctaatc aaggctattc actggtgcca taagaatgat attgtccatc gagatataaa
      661 accagaaaat ctcttaatca gccacaatga tgtcctaaaa ctgtgtgact ttggttttgc
      721 tcgtaatctg tcagaaggca ataatgctaa ttacacagag tacgttgcca ccagatggta
      781 tcggtcccca gaactcttac ttggcgctcc ctatggaaag tccgtggaca tgtggtcggt
      841 gggctgtatt cttggggagc ttagcgatgg acagccttta tttcctggag aaagtgaaat
      901 tgaccaactt tttactattc agaaggtgct aggaccactt ccatctgagc agatgaagct
      961 tttctacagt aatcctcgct tccatgggct ccggtttcca gctgttaacc atcctcagtc
     1021 cttggaaaga agataccttg gaattttgaa tagtgttcta cttgacctaa tgaagaattt
     1081 actgaagttg gacccagctg acagatactt gacagaacag tgtttgaatc accctacatt
     1141 tcaaacccag agacttctgg atcgttctcc ttcaaggtca gcaaaaagaa aaccttacca
     1201 tgtggaaagc agcacattgt ctaatagaaa ccaagccggc aaaagtactg ctttgcagtc
     1261 tcaccacaga tctaacagca aggacatcca gaacctgagt gtaggcctgc cccgggctga
     1321 cgaaggtctc cctgccaatg aaagcttcct aaatggaaac cttgctggag ctagtcttag
     1381 tccactgcac accaaaacct accaagcaag cagccagcct gggtctacca gcaaagatct
     1441 caccaacaac aacataccac accttcttag cccaaaagaa gccaagtcaa aaacagagtt
     1501 tgattttaat attgacccaa agccttcaga aggcccaggg acaaagtacc tcaagtcaaa
     1561 cagcagatct cagcagaacc gccactcatt catggaaagc tctcaaagca aagctgggac
     1621 actgcagccc aatgaaaagc agagtcggca tagctatatt gacacaattc cccagtcctc
     1681 taggagtccc tcctacagga ccaaggccaa aagccatggg gcactgagtg actccaagtc
     1741 tgtgagcaac ctttctgaag ccagggccca aattgcggag cccagtacca gtaggtactt
     1801 cccatctagc tgcttagact tgaattctcc caccagccca acccccacca gacacagtga
     1861 cacgagaact ttgctcagcc cttctggaag aaataaccga aatgagggaa cgctggactc
     1921 acgtcgaacc acaaccagac attctaagac gatggaggaa ttgaagctgc cggagcacat
     1981 ggacagtagc cattcccatt cactgtctgc acctcacgaa tctttttctt atggactggg
     2041 ctacaccagc cccttttctt cccagcaacg tcctcatagg cattctatgt atgtgacccg
     2101 tgacaaagtg agagccaagg gcttggatgg aagcttgagc atagggcaag ggatggcagc
     2161 tagagccaac agcctgcaac tcttgtcacc ccagcctgga gaacagctcc ctccagagat
     2221 gactgtggca agatcttcgg tcaaagagac ctccagagaa ggcacctctt ccttccatac
     2281 acgccagaag tctgagggtg gagtgtatca tgacccacac tctgatgatg gcacagcccc
     2341 caaagaaaat agacacctat acaatgatcc tgtgccaagg agagttggta gcttttacag
     2401 agtgccatct ccacgtccag acaattcttt ccatgaaaat aatgtgtcaa ctagagtttc
     2461 ttctctacca tcagagagca gttctggaac caaccactca aaaagacaac cagcattcga
     2521 tccatggaaa agtcctgaaa atattagtca ttcagagcaa ctcaaggaaa aagagaagca
     2581 aggatttttc aggtcaatga aaaagaaaaa gaagaaatct caaacagtac ccaattccga
     2641 cagccctgat cttctgacgt tgcagaaatc cattcattct gctagcactc caagcagcag
     2701 accaaaggag tggcgccccg agaagatctc agatctgcag acccaaagcc agccattaaa
     2761 atcactgcgc aagttgttac atctctcttc ggcctcaaat cacccggctt cctcagatcc
     2821 ccgcttccag cccttaacag ctcaacaaac caaaaattcc ttctcagaaa ttcggattca
     2881 ccccctgagc caggcctctg gcgggagcag caacatccgg caggaacccg caccgaaggg
     2941 caggccagcc ctccagctgc caggtcagat ggatcctggt tggcatgtgt cctctgtgac
     3001 caggagtgcc acagagggcc cttcctactc tgaacagctg ggtgccaaaa gtgggccaaa
     3061 tgggcacccc tataacagaa caaatcgctc acgaatgcca aatctgaatg atttaaaaga
     3121 gacagccttg taatttgtgc tggtaggggg gaggggtgga cagacaagcc agtggggagg
     3181 ggtgggaaag ggtgggctgg gcttggggca tgggccgggc caagtggtga gccaatattt
     3241 tcagctttat gaaggtgtgt gcaatattgc atgtgttggg gccgttgagc tcctcgcggc
     3301 cacaaatgct agtcagggat cttagagcca caggagttcc ttagggatcg ccactcccca
     3361 caggtcttgt gtgagaatag atagagtgtg ccattgagga agaagaaatt cttgccagtt
     3421 tctccccttt acattccagc tttagtgcaa tctctgttga acttgggaat gccaggatgt
     3481 gtcctggcac tgcaagggat aggaaagtcg tgttgaccga tgcccttact acatattttt
     3541 ttctgcctag agtaaatgtg gggtttattg taatccaaga gtatcccttt gaagggttag
     3601 cagatgaact gtatgtctta aattgttttc taaacttcca tatttgatag gatttgtaac
     3661 atttatttat aattaatatt gtactgttaa aatcatatct tttatgttat aatgtaaagt
     3721 tattttgagc tgtttgaaac attgtgaagc agtgggacag ctacagtagt ttctataaaa
     3781 actaaacagt aacatttata tattgcatca ggagtatttt attctatata taatatatat
     3841 atatggtaaa tatctgtttt ataaatatat tcatttaaag aaagtatcgt tatgacacta
     3901 tctgccatat ttttatacat ttgtgatatg aagtgagtat tatacttcta ctaaagggag
     3961 ttgaattgtg gctacacgtg actgtaacag tatgaacctt gctcaacttt gaggccccag
     4021 cagtagcctc tagacatgat ccttggtagc agacgagatg cagcatctct ttccaaacct
     4081 gcaggggaag aaagtcagat aggccagtga gaattccagc aggcctggtt tccgtcctca
     4141 cacacttggc tcctgtttgt gtccagggac gttacttgca cacaggggag aatagattga
     4201 ggcgttactc gtgggtcttt gtagagagaa tgtgctcttc cacttagcat tagtgtagag
     4261 cgtagaccaa agatttgcca gtgaacattc cttgttgtga gatcataaga ggtacctgtc
     4321 tgcagatctt gcaaaccatc tctatgctcc tgaatattgt ccactgtccc ggagactctt
     4381 ggctgatggg gtgtgagata tatgtgtggc atttctattt ctgaatgcct tttttgctat
     4441 tgctctctcc aataccatat ttaaaaggct cctggagcaa ttccagatag ataaaaaatt
     4501 actctatcca tttttttctt cctggggctg tccacttatg acaagatttt catgcacacc
     4561 tgttacgcac acaaccccca tcagaacagg acctatcttc ccctcatctg atctctttca
     4621 gctcccaagt tactcccaag tatcatcaaa ccctttggcc atcaagtgtt atcctcccat
     4681 gcctctgggt catccttgag ggaagtcacc tcagcaccat catctatcag tagtagtaga
     4741 tttttggaat tagtctctga gcaataatac ttttaaaggt ccctcccacc cctcaaagag
     4801 ataacttctc agtatttatt acttgtcctc aaattctgag tgtcagcccc tgcatcaagt
     4861 cagctatgat caaaatgtgc tgttactgtt aaccctcccc cgagattttg agaatcatag
     4921 ctctgatgat tatgaagatt ataaagacta aggtcctagt ttccctgaag cttaaattgt
     4981 gcacatattg catttttata taaatactat aatgtgtatt gattatatag ataggtcatt
     5041 ttaaggtgct ttttatttaa ttttaatgag tgtaataggc actaaaatga aactcgactg
     5101 ggtactatta ctgaaaaaat ttgactcaaa ccaatagttt tgcatgctct ttagttcttt
     5161 ttctgtctta cttctttcac cagttcagta ctgtttgggt agctctgaat tctggctttt
     5221 ccaggcagct gcttgatgat acaaatgagg tggaccatca gcagttttgc ctggacacta
     5281 atgactctaa aagggtgtgt atttaactct tctttttcat actagatctc taccttgtat
     5341 tccccccttg caaaccagaa actacacttt ttttctctgg aaagacttct cactgtgcta
     5401 tgcgcttagg aactgcacgg tcccgttgcc atgctgtggc attcgaggct cgtcacctag
     5461 gggctggttt cccatgttgt catccttgct aacactggga tctcagatgt ttgcagaaca
     5521 tttctattca tgacggttct tcaaagaagg gctagaatat ttgccttcta cctagagcaa
     5581 agtaaaccta attgttgaag agtcaatacg tactttttgt actttcccag atttgagcca
     5641 gaaaatacct acagatatct acaaatgttt tcaaccagtg ttttcgaggt agctctttaa
     5701 tcctcttctc agcttttgtc tgttctgact tttcatccaa taagctgtaa gtgaactaca
     5761 atctgcattt ccagcatgca attctcttcc tgctcacgga gggggatgca aaagttttct
     5821 ctcacaccta atgggccctc tcttagcttt taactgttgt tttcccctgt tgatgaaaaa
     5881 ttactgacat cacaaagatt gccatccatg gtagaaagga cttgatttaa agtcagaaaa
     5941 atttgccttt tctttaggaa ggggaattca tgacatccat gtcctattat cggccgtaac
     6001 ttcctaaaga agaaaaaggg tgaatgaaag cttatgttac ttttatgaaa gtatcactga
     6061 tctcctttgg aaaagaaact ctgcttcact gtttttctac ctttatttct ctgccatcct
     6121 cgtttttcct ctctgaagtt ctaaataccc tttaactgaa ccttgttggt cttgctctaa
     6181 aatttagcct ctttctagag cccaagacca aaagggagtg cttcatgctg aggggctcaa
     6241 gtgagctgac tctacaactg tggttctcaa ctaggggcag atttaccccc aagggtacat
     6301 ttggcaatgt ctggggacat ttggttgtca tagctggggg ggaggtgatg gtatgctact
     6361 ggcatcaagt ggttagaggc cacagatgct actaaacacc ctgccatgca caggacagcc
     6421 ccccaaacaa acagtggtcc agccccaagc actactagtg ctgaggttga gaaaccctgc
     6481 cctacaccat cccaagccca ccagtctgca gagcttggct ctggccttgt tctgtccagg
     6541 ctacagtact gcaggtgtga tttcttcaac atcacattct cttaagagtc ttcaaccact
     6601 atgcctgaat ccttggaatc ctattgttcg tttccattgt cttgggcctg ctaaaaggtg
     6661 catactttgg aaggagacca gagttacttt ataggtgttg gagaacttaa attctaggtt
     6721 agcatcctta gaaaatcttt catagagcca tgaggcttat atttagaagc aagcaacagc
     6781 ctggcagatt ggcatgattt ttaccaactg ctcaaaggca tccgtggctt tcagctgtgt
     6841 ctcccgaaag aaaatgtctt tgttttttat tcaagtcatt taatagctct ttacaaatat
     6901 tagcatatgg cagaccaatt agaagcaaaa aagtccgtat tggtggttgt gatgtggctg
     6961 ttatagaagt atttgtgctg tatgctttgg ttaaatctgt tttaaaacat gctttaagat
     7021 tcaccttacg cagttgtact ttaattctaa gctcagagct atgctgtcag tctctagtca
     7081 cgccatgtat tataaagtat gttgtggttg tagagttagc cagtttagca tgttcctaat
     7141 ctgagaatta gtggactata ctaggaaatg ctatcccatt ttccctttcc agcccctctt
     7201 agttaagatc atagtatcct cacttcttaa actagtcttt agagtaaata aggaaaaaag
     7261 ccatttattt tcttctagcc atgtattatt gagaatgact catagtacaa ctttttttca
     7321 aaggccagag gattactttg caagtgtgta gaaagatctg tctatttctg ttcacctggg
     7381 acctggtggt gactgaactc tttcagcaag ggcaatggct caatgtgatt cggtgctgga
     7441 gctcagctgg gactcagtaa atctgcacgt tctctgctgg tcagaacatg tttcctggag
     7501 agcattgctt ttctatctag aagttcgtta cctcctgcat gatagtggga tattgagatg
     7561 tgggttctaa gatccacaga ctcatacttt tgtgaacttt ggaatgtggt agggtacact
     7621 gaaccaagtc agaaaatagt gaaatatttc cttgcctcct tcagttcatc actaagaaag
     7681 tgtgtaggca gagaaaactt acttatggtt tgaagaacca caattgtttt tgaaagggga
     7741 catagaaaag acagtacaaa ggttgtaagt gtcctgtcgc taattcccag ggccagaatc
     7801 tcacaagaag atcctctcaa agacttaaaa gcctggctta caaaaataac cagaaaccaa
     7861 acttgtaagc agttacaatt tcttcctttt gcttcttgac cagctgagat acagaatatc
     7921 ttgaggtctg gttcagctga tgaaaaattc tgtctcagaa acgatgagta agaaaccata
     7981 caagaaaaag aagtccctca tctatctgca tacacgcaat gtgggagaag tggggtggct
     8041 aggaaactct gggcctgctg cccccttcga ttcttttttt ttttctttgt gaattgaatg
     8101 tacgatacaa atggtaggcc ttcatgtgag ccagttacta catgaatctt catttcccac
     8161 agtggtttgt tcattcatca gcgttaggct tggtcctggc tccacctttc tcctctccgg
     8221 gcactgaccc cacctttccg tgtatttact gtaggctatt aaatatgatc atgacccgcc
     8281 ttgcattttc attcatcacc tgtttatgcc caaatttaaa ggaagtttgt ctcattttgc
     8341 cagaaaaaaa ttgtaatagt cggcacgctg gatttgtagg gccagcaaaa ttgcggcagt
     8401 gaaactagtt tcacttctaa agcccttcat ttcccacaag gttaagctct cgaaacccca
     8461 tttgatcctt ggttcctatt tcgatcctcc tttggaatct gaaaatcggt ctccatgttg
     8521 tatgcagatt agaagttgcc ttgtttgtta ctcttccaac acagggtatc agggagaaag
     8581 aggccttatc tgttcctcca tcccccctgt tttgacagac tgctaagaat tcctcaggac
     8641 ttcctttggt tggggatttt actttcccaa aagtctgatc tgatttcttt caggggtaga
     8701 caagcttgtc ctagtgctct gcttcaggtc ttatcagaag aaacccagga atagaaaagg
     8761 tagatgcctt gacttttgtc cctgttgtgg ggactaaagt gttttttgcc agaattgtca
     8821 aaagctccgg ttcaaactct gtagagtttc atggaaaaac aaaacaaaac aaaaaagatg
     8881 cttatcgtcc cggagaatgt gtaagtaagt tctccagcac ggcttaggtt ttccaaaatg
     8941 gaaagcaaag cttgcagaca acctgttttc tctagagaca cacaatgatt ctggccctca
     9001 gtctgtttcc ctccccttgt ttactctttg gtcaccgatc gagtcaggct agaggggtaa
     9061 tacggtgatt aaaagaagta aattctcact gtaaacttgg attgattaac agaaacaatt
     9121 aaaccaaaca aaatcattgc cccaaatttc tatctccaag aattgctttg tgccattttg
     9181 aattcaggta gttattctgt atatacttag ctaactattc agagcttctt caatctctag
     9241 taagcttgaa ggtggtgtct gggaagacac agggcagggt gacatttaga ctctgttcat
     9301 tcttaaaaat agggataagc cagaatgatg tgacatctag tatgtggtag atgaagaatc
     9361 agtggaaatt cttaattgca cagactttat aatccattat ataaagtgta attccatact
     9421 ttttactgtg gcaagggtgt gatgtgattg ttaatctttt taatttttga atccaaactg
     9481 aatttaaagt gttgaatact taaatcctca caagtgaatt atgaaccatt tgtaaagtgt
     9541 ttctataact ctttgtatca tgtgttggta catcttatca agttttttct ggcatgtaat
     9601 tccattctaa acttatgtaa aatttctatt gttgctgtaa atattacaca aatatctatt
     9661 ccgtgataac cttcattatc agcatgaaat ggttaatttt tactgagcac aatgtatttt
     9721 tgaatggatc ttcccaaatg tctttaataa aatgcagatt ttgcactgac tgatgtgact
     9781 gccaggccgt cccaatcttg agcactgtgg tccttcgtgt ttgaactgcg aacagctcca
     9841 ttttagttcc ttcttgggaa gaaagaatgc attcgaattc aaatgaggga tgatgggcct
     9901 ttgaggttgt aatcagtttg agacagaaat taatgtaaaa ctaggcaaat cctgtaactt
     9961 aatgatgttg atctttgttt tcctatttat aaagcttttt tccccttacg gcattttgaa
    10021 aactttggtt tgttttatac ttgagtgttg tcacctttgc acgtcgctag acactcacgt
    10081 ggtagtttga ggaggatggg aagagaggcc aatcttgtgc taagtgctat ggagaaagca
    10141 aagatgcaca gcttaataag ggttttttga ttctagagga gaggtgggca agcttttcct
    10201 gtaaagggcc agatggtaaa tattgggggc tctgtggccc atcagttccc tgtcaacatt
    10261 actcagctct gcctttgtat tgcagaggct gcatggataa tatgtaaatc agtaagtgtg
    10321 gctgtggtcc cgtaaaactt tacttataga aacaggccat agtttactaa cccgttttag
    10381 gccctcagtt tcatcattta gggtaacacc aaccgagtac atgttcaatc aggagggaaa
    10441 gaacttagct tttgtgataa cttatagatg aaatattccc cagttttctt tctctttcta
    10501 aacaaagggt aggagctgaa agtcagtgct ctccattctt aaaagtcctc tgtcaaccac
    10561 ctcttcactc tatctcctta agtgacatgg aaacttgtgg cctgtgcttt caactataat
    10621 cttaccaaga ctgaatgaaa gtatttggtg cttatacttt ttaatgttca tagcacttac
    10681 tatggccagg cacaatgccc aagtgttttg ctttattatt attattatta ttattattat
    10741 tattattatt attattattt tcacaacaac ccagcgaaac aggtactatt attatcccct
    10801 ttttgtaaat gaggaaacag atttccatac ttgacattaa cctgcccaag gtcacccagt
    10861 ttggaagtgg cagggccagg atttgaagcc gaatatgttc attgtaaagc ccatataccc
    10921 ttaaaagtca ctgcacgtcc acgtatggta atgtggtcac aatcagtatt gtttctcttt
    10981 agtaattcag atttattcaa gtaactccaa ggttcaaatt ttcaaaaaca gtttccaaca
    11041 caggttatat taaaaacttt gcctgaagtt tactctaggt gcagaaataa agacaactta
    11101 gtcaagtgaa ggaaagggta acagacttag aaatggctat ctacactgat ggaataagta
    11161 tactaattag agcaggtaac aagtccccac gatgtataac atattcttct ctaaaagctc
    11221 acaacaattt atgtgccacc ttccatcccc tttcccagca gatggtaatt gatgcaattt
    11281 gagaatagaa cacttcattg aaacaagtca ctggaggtcc tctggggatg cagcttaaaa
    11341 gcccaggatc aggccaggtg tggtggctca cgcctgtaat cccagcactg tgggagactg
    11401 agacgggcag atcacctgaa gtcaggagtt cgagaccagc ctggccaata tagagaaacc
    11461 ccgtctgtac taaaaataca aaaattaggt ctgggcggtg gctcacgccc gtaatcctag
    11521 cactttggga ggccaaggtg ggtggatcac gaggtcagga gttcgagacc agcctggcca
    11581 acatggtgaa accccgtctc tactaaaaat acaaaaattg ggtgtggtgg tacatgcctg
    11641 taatcccagc tgcttaggag gctgaggcag gagaatcact tgaacccaaa aggcagaggt
    11701 tgcagtgagc cgagatcacg ccactgcact ccagcctggc aacagagcga gactctgtct
    11761 caaaaaaaaa aaaaaaaaaa tacaaaaatt agccgggaat ggtggtgaat gtctataatc
    11821 ccagccactc gggaggctga ggcaggagaa tcacttgaac ccaaaaggca gaggttgcag
    11881 tgagccaaga tcgcaccact gcactcccac ctggacgaca gagcgagacg ccatctcaaa
    11941 aataaataaa taaataaatc cctaggatat agagtccgct tgcctgggtg gagtcttggc
    12001 tccatctcct acatctcatg tgacttgaag caaggcactt cactatgcct cagtttcctt
    12061 atctttaaat ggaggtaatc acagtaccta cctcagtgtt gttgtgaaga tttaatgaga
    12121 taataacctg cagagcactt gagagtctca agaaatatga gctcttataa cattattgct
    12181 attgtaaaac attgctatta cttctgtccc aatttggcag tttcaggaaa ttgagaagga
    12241 atgtcactga atctttaatg ccagttacac agagctcagt aggtgtccgc acagcccttt
    12301 agatgcacgt agcctatttg atcttcgtat cagccctgta aggttgggct taagaatgac
    12361 ccagcatgga agtactcttg ggaccacagg ggaagcaaca gtccttgtaa gctgtttgtc
    12421 agtgggcctt agcaaccaag ccccaagtgg acagaaagat ggggttctgt gagcatccat
    12481 tccaagggtc actttagggg tgcaatcttc tgggctctga gaatggattc acagcagcat
    12541 ctctatctgg aaataccttt gctttgtcca agtaacctcc tcccacacag agtacccgaa
    12601 tcagctcaga ttttttttcc ttaatattgg caacacttaa tgctacttct ttgttcgtaa
    12661 catttcattt aattatttaa aaatctgcaa atgttgtgta tattttaccg caatttttaa
    12721 acaaactcca gtgtagaccg tgctctagca tttctaaaaa taaaagtaaa tatgttaaaa
    12781 taaggtaaga gtgagttttt cctacactat gtataatttt taattgaaag tttcccccac
    12841 aaaagaaatg atacttggaa gcatagtttg tgtgtttgac agcaagattc tattaggctt
    12901 cagatttccc tcaataaaag ttttagtttt tatacattct gtcatgaatt gaatgaagta
    12961 aataatatgc tgttgtaagc aaattatctg cagataaatg tcttatgaat cgtatatctt
    13021 actgtttatt aaattctgaa gtattgagca gtttccaatg tgaaatccca gctggcttct
    13081 ttgcaatgat ggacaagtta gttataattc atatggaaat tcaaggaacc cagaatagcc
    13141 aaaacaatcc cgaagagcaa agttggagga ctcacatgcc ccaatttcaa aacttactac
    13201 aaagctacaa taatgaagaa agtgaggtaa tagaatttgg agtccagaaa taaaccctct
    13261 cacatttatg gtcaattgtt ttttgacaag ggtgccaaga tcattcaatg ggggaaagaa
    13321 tagtcttttc agcaaatagt ggtgggacaa ctggatatcc acatgcaaaa gaatgacgtt
    13381 ggactcctat ttcacaccat atacaaaaat taactcaaaa tggaacaaag atctaactgt
    13441 aagaggtaga actataaaac tcatagaaga aaacataggg gtaaatcttc atgaccttgg
    13501 atttggcagt ggtttctcag atatgacacc aaaggcacaa gcaaagagaa aaataaattg
    13561 gacttcatca aatatttaaa attttgtgct taagaggact ctatcgagag ggttaaaaag
    13621 atccacagaa tgggagaaaa tatttgcaaa tcatatccaa taagggaatt agaatataca
    13681 aagaattctt aaactcagta agttgtaagc cgatttaaaa tgggcagagg atctgaaaaa
    13741 cctttatcca aagatgtaca aatggccagt aaacacatga aaagatgctc aacatcatta
    13801 gtcactaggg aaatgcaaat caaaaccaca gttgagatgc aacttcacac attatgggta
    13861 tagtcaaaga tggacagtaa caagtgttgc tgaggatgtg gagaaagtgg aagcctccta
    13921 cattgctggt ggaaatgtaa aatgatgcag ccacttggga taatagttcc tccaaagatt
    13981 aaacaagagt gactgtgtgt cccagcagtt ttactcctaa gtatataccc aagataaatg
    14041 aaaacacaca tccgcacaaa aacttataca caaatgttca tagcagcatt attcataata
    14101 gctaaagagt ggaaacccaa atatccatca atggatgaat ggataaataa caatgtgctc
    14161 ttgacatgat actgaacaat gatgttcagc aataaaaagg agtgacaagt gacatagtga
    14221 tacacatgtt ataacgtgga tgaactttaa aacactatgc taagtgaaag aagccagtca
    14281 cgaaatacca catactatat gatttcattt atgtagaacg tccagaaggc caatctacag
    14341 agacagtcga ttcgtggttg cagagggctt ggggtggccg atgggttggg gagtgttggc
    14401 tgatgggtgc aggatttctc tttggggtga taaactttct aaaattgatc tagtgataat
    14461 ggttgcacaa ctctgaatat accaaaagtc atcaaattgt acactttaaa tggatacaaa
    14521 ttgtatgtga acttaatctc aataaagccg tgacaaaagt ttccaacatg aa
//
