LOCUS       NM_021728               3011 bp    mRNA    linear   PRI 11-OCT-2024
DEFINITION  Homo sapiens orthodenticle homeobox 2 (OTX2), transcript variant 1,
            mRNA.
ACCESSION   NM_021728
VERSION     NM_021728.4
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 3011)
  AUTHORS   Ampudia-Mesias,E., Cameron,C.S., Yoo,E., Kelly,M., Anderson,S.M.,
            Manning,R., Abrahante Llorens,J.E., Moertel,C.L., Yim,H.,
            Odde,D.J., Saydam,N. and Saydam,O.
  TITLE     The OTX2 Gene Induces Tumor Growth and Triggers Leptomeningeal
            Metastasis by Regulating the mTORC2 Signaling Pathway in Group 3
            Medulloblastomas
  JOURNAL   Int J Mol Sci 25 (8), 4416 (2024)
   PUBMED   38674001
  REMARK    GeneRIF: The OTX2 Gene Induces Tumor Growth and Triggers
            Leptomeningeal Metastasis by Regulating the mTORC2 Signaling
            Pathway in Group 3 Medulloblastomas.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 3011)
  AUTHORS   Celse,T., Tingaud-Sequeira,A., Dieterich,K., Siegfried,G.,
            Lecaignec,C., Bouneau,L., Fannemel,M., Salaun,G., Laffargue,F.,
            Martinez,G., Satre,V., Vieville,G., Bidart,M., Soussi Zander,C.,
            Turesson,A.C., Splitt,M., Reboul,D., Chiesa,J., Khau Van Kien,P.,
            Godin,M., Gruchy,N., Goel,H., Palmer,E., Demetriou,K., Shalhoub,C.,
            Rooryck,C. and Coutton,C.
  TITLE     OTX2 duplications: a recurrent cause of oculo-auriculo-vertebral
            spectrum
  JOURNAL   J Med Genet 60 (6), 620-626 (2023)
   PUBMED   36368868
  REMARK    GeneRIF: OTX2 duplications: a recurrent cause of
            oculo-auriculo-vertebral spectrum.
REFERENCE   3  (bases 1 to 3011)
  AUTHORS   Cohen-Gulkar,M., David,A., Messika-Gold,N., Eshel,M., Ovadia,S.,
            Zuk-Bar,N., Idelson,M., Cohen-Tayar,Y., Reubinoff,B., Ziv,T.,
            Shamay,M., Elkon,R. and Ashery-Padan,R.
  TITLE     The LHX2-OTX2 transcriptional regulatory module controls retinal
            pigmented epithelium differentiation and underlies genetic risk for
            age-related macular degeneration
  JOURNAL   PLoS Biol 21 (1), e3001924 (2023)
   PUBMED   36649236
  REMARK    GeneRIF: The LHX2-OTX2 transcriptional regulatory module controls
            retinal pigmented epithelium differentiation and underlies genetic
            risk for age-related macular degeneration.
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 3011)
  AUTHORS   Gottardo,N.G.
  TITLE     Genetic alterations of TP53 and OTX2 indicate increased risk of
            relapse in WNT medulloblastomas: 'it's a numbers game'-implications
            for WNT medulloblastoma dose-reduction clinical trials
  JOURNAL   Acta Neuropathol 145 (1), 145-147 (2023)
   PUBMED   36403175
  REMARK    GeneRIF: Genetic alterations of TP53 and OTX2 indicate increased
            risk of relapse in WNT medulloblastomas: 'it's a numbers
            game'-implications for WNT medulloblastoma dose-reduction clinical
            trials.
REFERENCE   5  (bases 1 to 3011)
  AUTHORS   Fong,S.L. and Fong,W.B.
  TITLE     Elements regulating the transcription of human interstitial
            retinoid-binding protein (IRBP) gene in cultured retinoblastoma
            cells
  JOURNAL   Curr Eye Res 18 (4), 283-291 (1999)
   PUBMED   10372988
REFERENCE   6  (bases 1 to 3011)
  AUTHORS   Bobola,N., Briata,P., Ilengo,C., Rosatto,N., Craft,C., Corte,G. and
            Ravazzolo,R.
  TITLE     OTX2 homeodomain protein binds a DNA element necessary for
            interphotoreceptor retinoid binding protein gene expression
  JOURNAL   Mech Dev 82 (1-2), 165-169 (1999)
   PUBMED   10354480
REFERENCE   7  (bases 1 to 3011)
  AUTHORS   Nagao,T., Leuzinger,S., Acampora,D., Simeone,A., Finkelstein,R.,
            Reichert,H. and Furukubo-Tokunaga,K.
  TITLE     Developmental rescue of Drosophila cephalic defects by the human
            Otx genes
  JOURNAL   Proc Natl Acad Sci U S A 95 (7), 3737-3742 (1998)
   PUBMED   9520436
REFERENCE   8  (bases 1 to 3011)
  AUTHORS   Kastury,K., Druck,T., Huebner,K., Barletta,C., Acampora,D.,
            Simeone,A., Faiella,A. and Boncinelli,E.
  TITLE     Chromosome locations of human EMX and OTX genes
  JOURNAL   Genomics 22 (1), 41-45 (1994)
   PUBMED   7959790
REFERENCE   9  (bases 1 to 3011)
  AUTHORS   Kumaran,N., Pennesi,M.E., Yang,P., Trzupek,K.M., Schlechter,C.,
            Moore,A.T., Weleber,R.G. and Michaelides,M.
  TITLE     Leber Congenital Amaurosis / Early-Onset Severe Retinal Dystrophy
            Overview
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   30285347
REFERENCE   10 (bases 1 to 3011)
  AUTHORS   Bardakjian,T., Weiss,A. and Schneider,A.
  TITLE     Microphthalmia/Anophthalmia/Coloboma Spectrum - RETIRED CHAPTER,
            FOR HISTORICAL REFERENCE ONLY
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301552
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AL161757.4, AB593058.1 and
            BC032579.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Jun 2, 2019 this sequence version replaced NM_021728.3.
            
            Summary: This gene encodes a member of the bicoid subfamily of
            homeodomain-containing transcription factors. The encoded protein
            acts as a transcription factor and plays a role in brain,
            craniofacial, and sensory organ development. The encoded protein
            also influences the proliferation and differentiation of
            dopaminergic neuronal progenitor cells during mitosis. Mutations in
            this gene cause syndromic microphthalmia 5 (MCOPS5) and combined
            pituitary hormone deficiency 6 (CPHD6). This gene is also suspected
            of having an oncogenic role in medulloblastoma. Alternative
            splicing results in multiple transcript variants encoding distinct
            isoforms. Pseudogenes of this gene are known to exist on
            chromosomes two and nine. [provided by RefSeq, Jul 2012].
            
            Transcript Variant: This variant (1) encodes the longer isoform
            (a). Variants 1 and 5 encode the same protein (isoform a).
            
            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 :: AB593058.1, SRR1660803.40199.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMN03465402, SAMN03465404
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000672264.2/ ENSP00000500115.1
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-3                 AL161757.4         55098-55100
            4-2207              AB593058.1         1-2204
            2208-2209           BC032579.1         2206-2207
            2210-3011           AL161757.4         64871-65672
FEATURES             Location/Qualifiers
     source          1..3011
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="14"
                     /map="14q22.3"
     gene            1..3011
                     /gene="OTX2"
                     /gene_synonym="CPHD6; MCOPS5"
                     /note="orthodenticle homeobox 2"
                     /db_xref="GeneID:5015"
                     /db_xref="HGNC:HGNC:8522"
                     /db_xref="MIM:600037"
     exon            1..104
                     /gene="OTX2"
                     /gene_synonym="CPHD6; MCOPS5"
                     /inference="alignment:Splign:2.1.0"
     exon            105..168
                     /gene="OTX2"
                     /gene_synonym="CPHD6; MCOPS5"
                     /inference="alignment:Splign:2.1.0"
     exon            169..384
                     /gene="OTX2"
                     /gene_synonym="CPHD6; MCOPS5"
                     /inference="alignment:Splign:2.1.0"
     CDS             288..1181
                     /gene="OTX2"
                     /gene_synonym="CPHD6; MCOPS5"
                     /note="isoform a is encoded by transcript variant 1;
                     homeobox protein OTX2; orthodenticle homolog 2"
                     /codon_start=1
                     /product="homeobox protein OTX2 isoform a"
                     /protein_id="NP_068374.1"
                     /db_xref="CCDS:CCDS9728.1"
                     /db_xref="GeneID:5015"
                     /db_xref="HGNC:HGNC:8522"
                     /db_xref="MIM:600037"
                     /translation="MMSYLKQPPYAVNGLSLTTSGMDLLHPSVGYPGPWASCPAATPR
                     KQRRERTTFTRAQLDVLEALFAKTRYPDIFMREEVALKINLPESRVQVWFKNRRAKCR
                     QQQQQQQNGGQNKVRPAKKKTSPAREVSSESGTSGQFTPPSSTSVPTIASSSAPVSIW
                     SPASISPLSDPLSTSSSCMQRSYPMTYTQASGYSQGYAGSTSYFGGMDCGSYLTPMHH
                     QLPGPGATLSPMGTNAVTSHLNQSPASLSTQGYGASSLGFNSTTDCLDYKDQTASWKL
                     NFNADCLDYKDQTSSWKFQVL"
     exon            385..560
                     /gene="OTX2"
                     /gene_synonym="CPHD6; MCOPS5"
                     /inference="alignment:Splign:2.1.0"
     exon            561..3011
                     /gene="OTX2"
                     /gene_synonym="CPHD6; MCOPS5"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2189..2194
                     /regulatory_class="polyA_signal_sequence"
                     /gene="OTX2"
                     /gene_synonym="CPHD6; MCOPS5"
                     /note="hexamer: ATTAAA"
     polyA_site      2209
                     /gene="OTX2"
                     /gene_synonym="CPHD6; MCOPS5"
                     /note="major polyA site"
     regulatory      2988..2993
                     /regulatory_class="polyA_signal_sequence"
                     /gene="OTX2"
                     /gene_synonym="CPHD6; MCOPS5"
                     /note="hexamer: AATGAA"
     polyA_site      3011
                     /gene="OTX2"
                     /gene_synonym="CPHD6; MCOPS5"
ORIGIN      
        1 agcaaatctc cctgagagcg ggaccggcct cagctccaac acagcctcca ctgtgattaa
       61 aaataaaaat tgctagagca gccctcactc gccacatcta ctttgatagc tggctatttg
      121 gaatttaaag gatatttgac tttttctaac ctcccatgag gctgtaagtt ccactgctcc
      181 aaacccaccc accaaggact ctgaacctgt ccaccccggg cgcatcaaga tcttccagct
      241 gggtaccccc gatttgggcc gactttgcac ctccaaacaa ccttagcatg atgtcttatc
      301 ttaagcaacc gccttacgca gtcaatgggc tgagtctgac cacttcgggt atggacttgc
      361 tgcacccctc cgtgggctac ccggggccct gggcttcttg tcccgcagcc accccccgga
      421 aacagcgccg ggagaggacg acgttcactc gggcgcagct agatgtgctg gaagcactgt
      481 ttgccaagac ccggtaccca gacatcttca tgcgagagga ggtggcactg aaaatcaact
      541 tgcccgagtc gagggtgcag gtatggttta agaatcgaag agctaagtgc cgccaacaac
      601 agcaacaaca gcagaatgga ggtcaaaaca aagtgagacc tgccaaaaag aagacatctc
      661 cagctcggga agtgagttca gagagtggaa caagtggcca attcactccc ccctctagca
      721 cctcagtccc gaccattgcc agcagcagtg ctcctgtgtc tatctggagc ccagcttcca
      781 tctccccact gtcagatccc ttgtccacct cctcttcctg catgcagagg tcctatccca
      841 tgacctatac tcaggcttca ggttatagtc aaggatatgc tggctcaact tcctactttg
      901 ggggcatgga ctgtggatca tatttgaccc ctatgcatca ccagcttccc ggaccagggg
      961 ccacactcag tcccatgggt accaatgcag tcaccagcca tctcaatcag tccccagctt
     1021 ctctttccac ccagggatat ggagcttcaa gcttgggttt taactcaacc actgattgct
     1081 tggattataa ggaccaaact gcctcctgga agcttaactt caatgctgac tgcttggatt
     1141 ataaagatca gacatcctcg tggaaattcc aggttttgtg aagacctgta gaacctcttt
     1201 ttgtgggtga tttttaaata tactgggctg gacattccag ttttagccag gcattggtta
     1261 aaagagttag atgggatgat gctcagactc atctgatcaa agttccgaga ggcatagaag
     1321 gaaaaacgaa gggccttaga ggggcctaca aaccagcaac atgaaatgga caaaccaatc
     1381 tgcttaagat cctgtcatag ttttagatca ttggttatcc tgatttgcaa agtgatcaaa
     1441 agcattctag ccatgtgcaa ccaaacacca ccaaaaataa aatcaaacaa aactaagttg
     1501 tgaaggaagg gagggaaggt catagccttc ttaagcagag gtgttccatt gttttagcca
     1561 atccttggtt gaatcttagg aatgaacagt gtctcaagct cattcacgtt tcatgaccaa
     1621 ctggtagttg gcactgaaaa aacttttcag ggctgtgtga attgtgtgac tgattgtcct
     1681 agatgcacta ctttatttaa aaaataatgt tcataaggag tcaatatgta gtttaagaga
     1741 caatcagtgt gtgtcttata aatggtacat ctgtggtttt taatctgtgc tagacttcaa
     1801 aactgtgatc tcctgttatt gtatgcaacc ttgaactcca cctctgcagg ggttcttctg
     1861 tgattaaata ggttataatt ataagcaaaa ttcagagcaa ctgagtactg atctaaaaag
     1921 attacctttg gctggaggtg agctgcactg aaactttacg acaaaatgtc tctggacaaa
     1981 gagagtcaga gaagagaagc aaaaggacac taattcatct gtaatttact gttggtaagc
     2041 ctagcagtaa agagacattg gtcaattgct ctgaccctga tgaattatta aactgagatc
     2101 attgtcgttt atgcttgcag atgttaaatg gaaaagttat atatgcataa accttttctt
     2161 cctggatttg gcagatatgt ataattatat taaaatggtt ctagcacaac attgggtcca
     2221 gtttaatttt acaccgctat ttatgaataa gaagcctaca ttcagccttt cctccccaaa
     2281 acacgttttt cttaggacag agagtaaatt agcaaactta tttttacttt ttttttttgc
     2341 taatctatgc ataaaataga tatgaatgac agtggtaggt agactttttg tgactttcat
     2401 caggattgct ctgaaattga gtttggagag cctaacaaca agatcttgtt ttccttgctt
     2461 ttccctccct acttcaaacc tgaacgattt cttaggcact ttattagaat gttttaaaat
     2521 atatcaagtt tttaagaggg aggaggagaa ttggagtatc tctgaaaaca tgagaatgac
     2581 aagaatttct tgttactatt ctcttatttg attaagggga tttttttttt ttaacttcca
     2641 aaaactgagg taaacatgag agggagtgta atcagaatct gaaagtaatt caggcagaaa
     2701 tgattcctga acaaaagagt ttcagaaaag ttttaaaacc tataatttca gtagttgaac
     2761 ataaggcacc ctggtcagtt tgtgtgtatg tgtttaagaa agtgccgagg gggaaaaaat
     2821 gggtcccttt tcagttgtac ctgcattttg taaaccagtc accagaaaag acaaatgggc
     2881 caatgatcat ggtgctcctc aggtaaaagc aatatttaat ttcattttaa gctgcttaag
     2941 ctcttacagc tgaccaaaat taagtgactc ttgattgtaa cgttttaaat gaaggttagc
     3001 agttgcaacc a
//
