LOCUS       NM_000329               2605 bp    mRNA    linear   PRI 09-FEB-2025
DEFINITION  Homo sapiens retinoid isomerohydrolase RPE65 (RPE65), transcript
            variant 1, mRNA.
ACCESSION   NM_000329
VERSION     NM_000329.3
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 2605)
  AUTHORS   Parameswarappa,D.C., Bagga,D.K., Upadhyaya,A., Balasubramanian,J.,
            Pochaboina,V., Muthineni,V., Jalali,S. and Kannabiran,C.
  TITLE     RPE65 mutations in Leber congenital amaurosis, early-onset severe
            retinal dystrophy, and retinitis pigmentosa from a tertiary eye
            care center in India
  JOURNAL   Ophthalmic Genet 45 (3), 303-312 (2024)
   PUBMED   38323530
  REMARK    GeneRIF: RPE65 mutations in Leber congenital amaurosis, early-onset
            severe retinal dystrophy, and retinitis pigmentosa from a tertiary
            eye care center in India.
REFERENCE   2  (bases 1 to 2605)
  AUTHORS   Stingl,K., Priglinger,C. and Herrmann,P.
  TITLE     RPE65-Associated Retinal Dystrophies: Phenotypes and Treatment
            Effects with Voretigene Neparvovec
  JOURNAL   Klin Monbl Augenheilkd 241 (3), 259-265 (2024)
   PUBMED   38508214
  REMARK    GeneRIF: RPE65-Associated Retinal Dystrophies: Phenotypes and
            Treatment Effects with Voretigene Neparvovec.
            Review article
            Erratum:[Klin Monbl Augenheilkd. 2024 Mar;241(3):e1. doi:
            10.1055/a-2419-3037.. PMID: 39353611]
REFERENCE   3  (bases 1 to 2605)
  AUTHORS   Wu,J., Sun,Z., Zhang,D.W., Liu,H.L., Li,T., Zhang,S. and Wu,J.
  TITLE     Development of a novel prediction model based on protein structure
            for identifying RPE65-associated inherited retinal disease (IRDs)
            of missense variants
  JOURNAL   PeerJ 11, e15702 (2023)
   PUBMED   37547722
  REMARK    GeneRIF: Development of a novel prediction model based on protein
            structure for identifying RPE65-associated inherited retinal
            disease (IRDs) of missense variants.
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 2605)
  AUTHORS   Nicoletti,A., Wong,D.J., Kawase,K., Gibson,L.H., Yang-Feng,T.L.,
            Richards,J.E. and Thompson,D.A.
  TITLE     Molecular characterization of the human gene encoding an abundant
            61 kDa protein specific to the retinal pigment epithelium
  JOURNAL   Hum Mol Genet 4 (4), 641-649 (1995)
   PUBMED   7633413
REFERENCE   5  (bases 1 to 2605)
  AUTHORS   Hamel,C.P., Jenkins,N.A., Gilbert,D.J., Copeland,N.G. and
            Redmond,T.M.
  TITLE     The gene for the retinal pigment epithelium-specific protein RPE65
            is localized to human 1p31 and mouse 3
  JOURNAL   Genomics 20 (3), 509-512 (1994)
   PUBMED   8034329
REFERENCE   6  (bases 1 to 2605)
  AUTHORS   Chao,D.L., Burr,A. and Pennesi,M.
  TITLE     RPE65-Related Leber Congenital Amaurosis / Early-Onset Severe
            Retinal Dystrophy
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   31725251
REFERENCE   7  (bases 1 to 2605)
  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   8  (bases 1 to 2605)
  AUTHORS   Fahim,A.T., Daiger,S.P. and Weleber,R.G.
  TITLE     Nonsyndromic Retinitis Pigmentosa Overview
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301590
REFERENCE   9  (bases 1 to 2605)
  AUTHORS   Weleber,R.G., Francis,P.J., Trzupek,K.M. and Beattie,C.
  TITLE     Leber Congenital Amaurosis - 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   20301475
REFERENCE   10 (bases 1 to 2605)
  AUTHORS   Bavik,C.O., Busch,C. and Eriksson,U.
  TITLE     Characterization of a plasma retinol-binding protein membrane
            receptor expressed in the retinal pigment epithelium
  JOURNAL   J Biol Chem 267 (32), 23035-23042 (1992)
   PUBMED   1331074
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from U18991.1 and AL139413.11.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 23, 2018 this sequence version replaced NM_000329.2.
            
            Summary: The protein encoded by this gene is a component of the
            vitamin A visual cycle of the retina which supplies the 11-cis
            retinal chromophore of the photoreceptors opsin visual pigments. It
            is a member of the carotenoid cleavage oxygenase superfamily. All
            members of this superfamily are non-heme iron oxygenases with a
            seven-bladed propeller fold and oxidatively cleave carotenoid
            carbon:carbon double bonds. However, the protein encoded by this
            gene has acquired a divergent function that involves the concerted
            O-alkyl ester cleavage of its all-trans retinyl ester substrate and
            all-trans to 11-cis double bond isomerization of the retinyl
            moiety. As such, it performs the essential enzymatic isomerization
            step in the synthesis of 11-cis retinal. Mutations in this gene are
            associated with early-onset severe blinding disorders such as Leber
            congenital. [provided by RefSeq, Oct 2017].
            
            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 :: BC075036.2, U18991.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA2145743, SAMEA2155984
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000262340.6/ ENSP00000262340.5
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-2261              U18991.1           6-2266
            2262-2603           AL139413.11        57251-57592         c
            2604-2605           AL139413.11        57249-57250         c
FEATURES             Location/Qualifiers
     source          1..2605
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="1"
                     /map="1p31.3"
     gene            1..2605
                     /gene="RPE65"
                     /gene_synonym="BCO3; LCA2; mRPE65; p63; rd12; RP20;
                     sRPE65"
                     /note="retinoid isomerohydrolase RPE65"
                     /db_xref="GeneID:6121"
                     /db_xref="HGNC:HGNC:10294"
                     /db_xref="MIM:180069"
     exon            1..60
                     /gene="RPE65"
                     /gene_synonym="BCO3; LCA2; mRPE65; p63; rd12; RP20;
                     sRPE65"
                     /inference="alignment:Splign:2.1.0"
     CDS             50..1651
                     /gene="RPE65"
                     /gene_synonym="BCO3; LCA2; mRPE65; p63; rd12; RP20;
                     sRPE65"
                     /EC_number="3.1.1.64"
                     /EC_number="5.3.3.22"
                     /note="isoform 1 is encoded by transcript variant 1;
                     RBP-binding membrane protein; lutein isomerase; RPE65,
                     retinoid isomerohydrolase; retinitis pigmentosa 20
                     (autosomal recessive); retinol isomerase;
                     all-trans-retinyl-palmitate hydrolase; retinal pigment
                     epithelium-specific 65 kDa protein; BCO family, member 3;
                     retinal pigment epithelium-specific protein 65kDa; retinal
                     pigment epithelium specific protein 65; meso-zeaxanthin
                     isomerase"
                     /codon_start=1
                     /product="retinoid isomerohydrolase isoform 1"
                     /protein_id="NP_000320.1"
                     /db_xref="CCDS:CCDS643.1"
                     /db_xref="GeneID:6121"
                     /db_xref="HGNC:HGNC:10294"
                     /db_xref="MIM:180069"
                     /translation="MSIQVEHPAGGYKKLFETVEELSSPLTAHVTGRIPLWLTGSLLR
                     CGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRRFIRTDAYVRAMTEKRIVITE
                     FGTCAFPDPCKNIFSRFFSYFRGVEVTDNALVNVYPVGEDYYACTETNFITKINPETL
                     ETIKQVDLCNYVSVNGATAHPHIENDGTVYNIGNCFGKNFSIAYNIVKIPPLQADKED
                     PISKSEIVVQFPCSDRFKPSYVHSFGLTPNYIVFVETPVKINLFKFLSSWSLWGANYM
                     DCFESNETMGVWLHIADKKRKKYLNNKYRTSPFNLFHHINTYEDNGFLIVDLCCWKGF
                     EFVYNYLYLANLRENWEEVKKNARKAPQPEVRRYVLPLNIDKADTGKNLVTLPNTTAT
                     AILCSDETIWLEPEVLFSGPRQAFEFPQINYQKYCGKPYTYAYGLGLNHFVPDRLCKL
                     NVKTKETWVWQEPDSYPSEPIFVSHPDALEEDDGVVLSVVVSPGAGQKPAYLLILNAK
                     DLSEVARAEVEINIPVTFHGLFKKS"
     exon            61..143
                     /gene="RPE65"
                     /gene_synonym="BCO3; LCA2; mRPE65; p63; rd12; RP20;
                     sRPE65"
                     /inference="alignment:Splign:2.1.0"
     exon            144..294
                     /gene="RPE65"
                     /gene_synonym="BCO3; LCA2; mRPE65; p63; rd12; RP20;
                     sRPE65"
                     /inference="alignment:Splign:2.1.0"
     exon            295..402
                     /gene="RPE65"
                     /gene_synonym="BCO3; LCA2; mRPE65; p63; rd12; RP20;
                     sRPE65"
                     /inference="alignment:Splign:2.1.0"
     exon            403..544
                     /gene="RPE65"
                     /gene_synonym="BCO3; LCA2; mRPE65; p63; rd12; RP20;
                     sRPE65"
                     /inference="alignment:Splign:2.1.0"
     exon            545..692
                     /gene="RPE65"
                     /gene_synonym="BCO3; LCA2; mRPE65; p63; rd12; RP20;
                     sRPE65"
                     /inference="alignment:Splign:2.1.0"
     exon            693..774
                     /gene="RPE65"
                     /gene_synonym="BCO3; LCA2; mRPE65; p63; rd12; RP20;
                     sRPE65"
                     /inference="alignment:Splign:2.1.0"
     exon            775..907
                     /gene="RPE65"
                     /gene_synonym="BCO3; LCA2; mRPE65; p63; rd12; RP20;
                     sRPE65"
                     /inference="alignment:Splign:2.1.0"
     exon            908..1047
                     /gene="RPE65"
                     /gene_synonym="BCO3; LCA2; mRPE65; p63; rd12; RP20;
                     sRPE65"
                     /inference="alignment:Splign:2.1.0"
     exon            1048..1177
                     /gene="RPE65"
                     /gene_synonym="BCO3; LCA2; mRPE65; p63; rd12; RP20;
                     sRPE65"
                     /inference="alignment:Splign:2.1.0"
     exon            1178..1292
                     /gene="RPE65"
                     /gene_synonym="BCO3; LCA2; mRPE65; p63; rd12; RP20;
                     sRPE65"
                     /inference="alignment:Splign:2.1.0"
     exon            1293..1387
                     /gene="RPE65"
                     /gene_synonym="BCO3; LCA2; mRPE65; p63; rd12; RP20;
                     sRPE65"
                     /inference="alignment:Splign:2.1.0"
     exon            1388..1499
                     /gene="RPE65"
                     /gene_synonym="BCO3; LCA2; mRPE65; p63; rd12; RP20;
                     sRPE65"
                     /inference="alignment:Splign:2.1.0"
     exon            1500..2605
                     /gene="RPE65"
                     /gene_synonym="BCO3; LCA2; mRPE65; p63; rd12; RP20;
                     sRPE65"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2585..2590
                     /regulatory_class="polyA_signal_sequence"
                     /gene="RPE65"
                     /gene_synonym="BCO3; LCA2; mRPE65; p63; rd12; RP20;
                     sRPE65"
                     /note="hexamer: AATAAA"
     polyA_site      2605
                     /gene="RPE65"
                     /gene_synonym="BCO3; LCA2; mRPE65; p63; rd12; RP20;
                     sRPE65"
                     /note="major polyA site"
ORIGIN      
        1 cttcattctg cagttggtgc cagaactctg gatcctgaac tggaagaaaa tgtctatcca
       61 ggttgagcat cctgctggtg gttacaagaa actgtttgaa actgtggagg aactgtcctc
      121 gccgctcaca gctcatgtaa caggcaggat ccccctctgg ctcaccggca gtctccttcg
      181 atgtgggcca ggactctttg aagttggatc tgagccattt taccacctgt ttgatgggca
      241 agccctcctg cacaagtttg actttaaaga aggacatgtc acataccaca gaaggttcat
      301 ccgcactgat gcttacgtac gggcaatgac tgagaaaagg atcgtcataa cagaatttgg
      361 cacctgtgct ttcccagatc cctgcaagaa tatattttcc aggttttttt cttactttcg
      421 aggagtagag gttactgaca atgcccttgt taatgtctac ccagtggggg aagattacta
      481 cgcttgcaca gagaccaact ttattacaaa gattaatcca gagaccttgg agacaattaa
      541 gcaggttgat ctttgcaact atgtctctgt caatggggcc actgctcacc cccacattga
      601 aaatgatgga accgtttaca atattggtaa ttgctttgga aaaaattttt caattgccta
      661 caacattgta aagatcccac cactgcaagc agacaaggaa gatccaataa gcaagtcaga
      721 gatcgttgta caattcccct gcagtgaccg attcaagcca tcttacgttc atagttttgg
      781 tctgactccc aactatatcg tttttgtgga gacaccagtc aaaattaacc tgttcaagtt
      841 cctttcttca tggagtcttt ggggagccaa ctacatggat tgttttgagt ccaatgaaac
      901 catgggggtt tggcttcata ttgctgacaa aaaaaggaaa aagtacctca ataataaata
      961 cagaacttct cctttcaacc tcttccatca catcaacacc tatgaagaca atgggtttct
     1021 gattgtggat ctctgctgct ggaaaggatt tgagtttgtt tataattact tatatttagc
     1081 caatttacgt gagaactggg aagaggtgaa aaaaaatgcc agaaaggctc cccaacctga
     1141 agttaggaga tatgtacttc ctttgaatat tgacaaggct gacacaggca agaatttagt
     1201 cacgctcccc aatacaactg ccactgcaat tctgtgcagt gacgagacta tctggctgga
     1261 gcctgaagtt ctcttttcag ggcctcgtca agcatttgag tttcctcaaa tcaattacca
     1321 gaagtattgt gggaaacctt acacatatgc gtatggactt ggcttgaatc actttgttcc
     1381 agataggctc tgtaagctga atgtcaaaac taaagaaact tgggtttggc aagagcctga
     1441 ttcataccca tcagaaccca tctttgtttc tcacccagat gccttggaag aagatgatgg
     1501 tgtagttctg agtgtggtgg tgagcccagg agcaggacaa aagcctgctt atctcctgat
     1561 tctgaatgcc aaggacttaa gtgaagttgc ccgggctgaa gtggagatta acatccctgt
     1621 cacctttcat ggactgttca aaaaatcttg agcatactcc agcaagatat gtttttggta
     1681 gcaaaactga gaaaatcagc ttcaggtctg caatcaaatt ctgttcaatt ttagcctgct
     1741 atatgtcatg gttttaactt gcagatgcgc acaattttgc aatgttttac agaaagcact
     1801 gagttgagca agcaattcct ttatttaaaa aaaaaagtac gtatttagat aatcatactt
     1861 cctctgtgag acaggccata actgaaaaac tcttaaatat ttagcaatca aataggaaat
     1921 gaatgtggac ttactaaatg gcttttaatt cctattataa gagcatattt taggtaccta
     1981 tctgctccaa ttatattttt aacatttaaa aaccaaagtc ctctacactt gatttatatt
     2041 atatgtggct ttgctgagtc aaggaagtat catgcaataa ggcttaatta ctaaatgtca
     2101 aaccaaactt tttctcaaac cagggactat catctaagat taattacagt aattattttg
     2161 cgtatacgta actgctcaaa gattatgaat cttatgaatg ttaacctttc cgtttattac
     2221 aagcaagtac tattatttct gattttataa taagaaaatc tgtgtttaat caactgaggc
     2281 ctctcaacca aataacatct cagagattaa gttatatatt aaaagcttat gtaacataaa
     2341 agcaagtaca tatagtagtg actatattta aaaaaacagc ataaaatgct taaaaatgta
     2401 atatttacta aaatcagatt atgggataat gttgcaggat tatactttat tgcatctttt
     2461 ttgtttaatt gtatttaagc attgtgcaat cacttgggaa aaatattaaa ttattaacat
     2521 tgaggtatta atacatttta agccttttgt ttttaaattt cttttcttcc agagattgtt
     2581 taaaaataaa tattgacaaa aataa
//
