LOCUS       NM_021830               3616 bp    mRNA    linear   PRI 08-OCT-2024
DEFINITION  Homo sapiens twinkle mtDNA helicase (TWNK), transcript variant 1,
            mRNA.
ACCESSION   NM_021830
VERSION     NM_021830.5
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 3616)
  AUTHORS   Chang,X., Li,G., Fu,H., Guan,M. and Guo,T.
  TITLE     A homozygous mutation of TWNK identified in premature ovarian
            insufficiency warns of late-onset perrault syndrome
  JOURNAL   Eur J Obstet Gynecol Reprod Biol 299, 118-123 (2024)
   PUBMED   38852317
  REMARK    GeneRIF: A homozygous mutation of TWNK identified in premature
            ovarian insufficiency warns of late-onset perrault syndrome.
REFERENCE   2  (bases 1 to 3616)
  AUTHORS   Johnson,L.C., Singh,A. and Patel,S.S.
  TITLE     The N-terminal domain of human mitochondrial helicase Twinkle has
            DNA-binding activity crucial for supporting processive DNA
            synthesis by polymerase gamma
  JOURNAL   J Biol Chem 299 (1), 102797 (2023)
   PUBMED   36528058
  REMARK    GeneRIF: The N-terminal domain of human mitochondrial helicase
            Twinkle has DNA-binding activity crucial for supporting processive
            DNA synthesis by polymerase gamma.
REFERENCE   3  (bases 1 to 3616)
  AUTHORS   Riccio,A.A., Bouvette,J., Perera,L., Longley,M.J., Krahn,J.M.,
            Williams,J.G., Dutcher,R., Borgnia,M.J. and Copeland,W.C.
  TITLE     Structural insight and characterization of human Twinkle helicase
            in mitochondrial disease
  JOURNAL   Proc Natl Acad Sci U S A 119 (32), e2207459119 (2022)
   PUBMED   35914129
  REMARK    GeneRIF: Structural insight and characterization of human Twinkle
            helicase in mitochondrial disease.
REFERENCE   4  (bases 1 to 3616)
  AUTHORS   So,M., Stiban,J., Ciesielski,G.L., Hovde,S.L. and Kaguni,L.S.
  TITLE     Implications of Membrane Binding by the Fe-S Cluster-Containing
            N-Terminal Domain in the Drosophila Mitochondrial Replicative DNA
            Helicase
  JOURNAL   Front Genet 12, 790521 (2021)
   PUBMED   34950192
  REMARK    Publication Status: Online-Only
REFERENCE   5  (bases 1 to 3616)
  AUTHORS   Nikali,K., Isosomppi,J., Lonnqvist,T., Mao,J.I., Suomalainen,A. and
            Peltonen,L.
  TITLE     Toward cloning of a novel ataxia gene: refined assignment and
            physical map of the IOSCA locus (SCA8) on 10q24
  JOURNAL   Genomics 39 (2), 185-191 (1997)
   PUBMED   9027505
REFERENCE   6  (bases 1 to 3616)
  AUTHORS   Nikali,K., Suomalainen,A., Terwilliger,J., Koskinen,T.,
            Weissenbach,J. and Peltonen,L.
  TITLE     Random search for shared chromosomal regions in four affected
            individuals: the assignment of a new hereditary ataxia locus
  JOURNAL   Am J Hum Genet 56 (5), 1088-1095 (1995)
   PUBMED   7726163
REFERENCE   7  (bases 1 to 3616)
  AUTHORS   Suomalainen,A., Kaukonen,J., Amati,P., Timonen,R., Haltia,M.,
            Weissenbach,J., Zeviani,M., Somer,H. and Peltonen,L.
  TITLE     An autosomal locus predisposing to deletions of mitochondrial DNA
  JOURNAL   Nat Genet 9 (2), 146-151 (1995)
   PUBMED   7719341
REFERENCE   8  (bases 1 to 3616)
  AUTHORS   Newman,W.G., Friedman,T.B., Conway,G.S. and Demain,L.A.M.
  TITLE     Perrault Syndrome
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   25254289
REFERENCE   9  (bases 1 to 3616)
  AUTHORS   Lonnqvist,T.
  TITLE     Infantile-Onset Spinocerebellar Ataxia - 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   20301746
REFERENCE   10 (bases 1 to 3616)
  AUTHORS   Perlman,S.
  TITLE     Hereditary Ataxia Overview
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301317
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DB090322.1, AF292004.1,
            AK025485.1 and AL133215.17.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 22, 2018 this sequence version replaced NM_021830.4.
            
            Summary: This gene encodes a hexameric DNA helicase which unwinds
            short stretches of double-stranded DNA in the 5' to 3' direction
            and, along with mitochondrial single-stranded DNA binding protein
            and mtDNA polymerase gamma, is thought to play a key role in mtDNA
            replication. The protein localizes to the mitochondrial matrix and
            mitochondrial nucleoids. Mutations in this gene cause infantile
            onset spinocerebellar ataxia (IOSCA) and progressive external
            ophthalmoplegia (PEO) and are also associated with several
            mitochondrial depletion syndromes. Alternative splicing results in
            multiple transcript variants encoding distinct isoforms.[provided
            by RefSeq, Aug 2009].
            
            Transcript Variant: This variant (1) encodes the longest isoform
            (A; also known as Twinkle).
            
            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 :: SRR1660803.153796.1,
                                           SRR1660807.228176.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            gene product(s) localized to mito. :: reported by MitoCarta
            MANE Ensembl match                 :: ENST00000311916.8/
                                                  ENSP00000309595.2
            RefSeq Select criteria             :: based on conservation,
                                                  expression, longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-483               DB090322.1         7-489
            484-2723            AF292004.1         1-2240
            2724-3614           AK025485.1         1554-2444
            3615-3616           AL133215.17        77226-77227
FEATURES             Location/Qualifiers
     source          1..3616
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="10"
                     /map="10q24.31"
     gene            1..3616
                     /gene="TWNK"
                     /gene_synonym="ATXN8; C10orf2; IOSCA; MTDPS7; PEO; PEO1;
                     PEOA3; PRLTS5; SANDO; SCA8; TWINL"
                     /note="twinkle mtDNA helicase"
                     /db_xref="GeneID:56652"
                     /db_xref="HGNC:HGNC:1160"
                     /db_xref="MIM:606075"
     exon            1..1911
                     /gene="TWNK"
                     /gene_synonym="ATXN8; C10orf2; IOSCA; MTDPS7; PEO; PEO1;
                     PEOA3; PRLTS5; SANDO; SCA8; TWINL"
                     /inference="alignment:Splign:2.1.0"
     CDS             669..2723
                     /gene="TWNK"
                     /gene_synonym="ATXN8; C10orf2; IOSCA; MTDPS7; PEO; PEO1;
                     PEOA3; PRLTS5; SANDO; SCA8; TWINL"
                     /EC_number="5.6.2.3"
                     /note="isoform A is encoded by transcript variant 1;
                     progressive external ophthalmoplegia 1 protein; twinkle
                     protein, mitochondrial; T7-like mitochondrial DNA
                     helicase; T7 gp4-like protein with intramitochondrial
                     nucleoid localization; ataxin 8; T7 helicase-related
                     protein with intramitochondrial nucleoid localization"
                     /codon_start=1
                     /product="twinkle mtDNA helicase isoform A"
                     /protein_id="NP_068602.2"
                     /db_xref="CCDS:CCDS7506.1"
                     /db_xref="GeneID:56652"
                     /db_xref="HGNC:HGNC:1160"
                     /db_xref="MIM:606075"
                     /translation="MWVLLRSGYPLRILLPLRGEWMGRRGLPRNLAPGPPRRRYRKET
                     LQALDMPVLPVTATEIRQYLRGHGIPFQDGHSCLRALSPFAESSQLKGQTGVTTSFSL
                     FIDKTTGHFLCMTSLAEGSWEDFQASVEGRGDGAREGFLLSKAPEFEDSEEVRRIWNR
                     AIPLWELPDQEEVQLADTMFGLTKVTDDTLKRFSVRYLRPARSLVFPWFSPGGSGLRG
                     LKLLEAKCQGDGVSYEETTIPRPSAYHNLFGLPLISRRDAEVVLTSRELDSLALNQST
                     GLPTLTLPRGTTCLPPALLPYLEQFRRIVFWLGDDLRSWEAAKLFARKLNPKRCFLVR
                     PGDQQPRPLEALNGGFNLSRILRTALPAWHKSIVSFRQLREEVLGELSNVEQAAGLRW
                     SRFPDLNRILKGHRKGELTVFTGPTGSGKTTFISEYALDLCSQGVNTLWGSFEISNVR
                     LARVMLTQFAEGRLEDQLDKYDHWADRFEDLPLYFMTFHGQQSIRTVIDTMQHAVYVY
                     DICHVIIDNLQFMMGHEQLSTDRIAAQDYIIGVFRKFATDNNCHVTLVIHPRKEDDDK
                     ELQTASIFGSAKASQEADNVLILQDRKLVTGPGKRYLQVSKNRFDGDVGVFPLEFNKN
                     SLTFSIPPKNKARLKKIKDDTGPVAKKPSSGKKGATTQNSEICSGQAPTPDQPDTSKR
                     SK"
     exon            1912..2152
                     /gene="TWNK"
                     /gene_synonym="ATXN8; C10orf2; IOSCA; MTDPS7; PEO; PEO1;
                     PEOA3; PRLTS5; SANDO; SCA8; TWINL"
                     /inference="alignment:Splign:2.1.0"
     exon            2153..2260
                     /gene="TWNK"
                     /gene_synonym="ATXN8; C10orf2; IOSCA; MTDPS7; PEO; PEO1;
                     PEOA3; PRLTS5; SANDO; SCA8; TWINL"
                     /inference="alignment:Splign:2.1.0"
     exon            2261..2402
                     /gene="TWNK"
                     /gene_synonym="ATXN8; C10orf2; IOSCA; MTDPS7; PEO; PEO1;
                     PEOA3; PRLTS5; SANDO; SCA8; TWINL"
                     /inference="alignment:Splign:2.1.0"
     exon            2403..3616
                     /gene="TWNK"
                     /gene_synonym="ATXN8; C10orf2; IOSCA; MTDPS7; PEO; PEO1;
                     PEOA3; PRLTS5; SANDO; SCA8; TWINL"
                     /inference="alignment:Splign:2.1.0"
     regulatory      3595..3600
                     /regulatory_class="polyA_signal_sequence"
                     /gene="TWNK"
                     /gene_synonym="ATXN8; C10orf2; IOSCA; MTDPS7; PEO; PEO1;
                     PEOA3; PRLTS5; SANDO; SCA8; TWINL"
                     /note="hexamer: ACTAAA"
     polyA_site      3603
                     /gene="TWNK"
                     /gene_synonym="ATXN8; C10orf2; IOSCA; MTDPS7; PEO; PEO1;
                     PEOA3; PRLTS5; SANDO; SCA8; TWINL"
                     /note="major polyA site"
     polyA_site      3616
                     /gene="TWNK"
                     /gene_synonym="ATXN8; C10orf2; IOSCA; MTDPS7; PEO; PEO1;
                     PEOA3; PRLTS5; SANDO; SCA8; TWINL"
                     /note="major polyA site"
ORIGIN      
        1 gcttccgagg tcaaggcgag tagcatgtgc gggagactca cgttgccggc gaagtgggag
       61 agagaaaagt ggtaacctgg ggctgggggc cggcgcggcg gagctcggag tagtagagcg
      121 gagtgaagac acgggggagg atagagactg gcattccttt gggccggggg attggcggga
      181 gtcgtgctgg gtgctctcgc cgtgttgagg tcccagtgag gggaaggaga agcggaagag
      241 ggtctctagt cggggcctag ggcaaaggga ctacaaaaag gatgcagatg actatagaaa
      301 tgaggacgac gaggagatgc tgtggaggag cagtagaggt gagaagatga tgcaaagaaa
      361 ctgtgtcagt gaggaactgt atagagggtc atagaggtga ggtggcggag agaaactaac
      421 taacggacca tagaggtggg ggagccattg tagaaggacg tggacgcgaa agggtcgtgt
      481 agatgggcat atgtgtgaag cagcaacgta gaggggctga agaggagaaa ttcatggaga
      541 gaaagaatgc acctagagtg agctctgcag agtgctgcgt gggatatccc tagagtttgg
      601 tctagtgaag gcacgctaac caggcaccta aggcatttca agtagtgact tcccacattt
      661 ggctaggaat gtgggtcctc ctccgaagtg ggtaccccct ccgtatcttg ttacccctgc
      721 gtggggagtg gatgggtcgg aggggcctgc cccgaaactt ggccccaggc cctcctcgca
      781 gacgttacag gaaggagact ctccaagcct tggatatgcc agtgttgcct gtaactgcaa
      841 ctgaaatccg ccagtatttg cgggggcatg ggatcccctt ccaggatggt cacagttgcc
      901 tgcgggcact gagccccttt gcagagtctt cacagctcaa aggccagact ggtgttacca
      961 cttccttcag cctcttcatt gacaagacca caggccactt tctctgcatg accagcctag
     1021 cagaagggag ctgggaagac ttccaggcca gcgtggaggg gcgaggggat ggggccaggg
     1081 aggggtttct gcttagcaag gcaccagaat ttgaggacag cgaggaggtc cggaggatct
     1141 ggaaccgagc aatacctctc tgggagctgc ctgatcagga ggaggttcag ctggctgata
     1201 caatgtttgg ccttaccaag gttacagatg acacactcaa gcgtttcagt gtgcgatatc
     1261 tgcgacctgc tcgcagtctt gtcttccctt ggttctcccc tgggggctca ggattacgag
     1321 gcctgaagct cctagaggct aaatgccagg gggatggagt gagctacgag gaaaccacta
     1381 ttccccgacc cagcgcctac cacaatctgt ttggattacc actgattagt cgtcgagatg
     1441 ctgaggtggt actgacgagt cgtgagcttg acagcctggc cttgaaccag tccacggggc
     1501 tgcctaccct tactctaccc cgaggaacga cctgcttacc ccctgcctta ctcccttacc
     1561 tggaacagtt ccggcggatt gtattctggt tgggggatga ccttcggtcc tgggaagccg
     1621 ccaagttgtt tgcacgaaaa ctgaacccca aacgatgctt cttggtgcga ccaggagacc
     1681 agcaaccccg tcccctggag gccctgaacg gaggcttcaa tctttctcgt attcttcgta
     1741 ccgccctgcc tgcctggcac aagtccatcg tatctttccg gcagcttcgg gaggaggtgc
     1801 taggagaact gtcaaatgtg gagcaagcag ctggcctccg ctggagccgc tttccagacc
     1861 tcaatcgtat cttgaaggga catcgaaagg gcgagctgac ggtcttcaca gggccaacag
     1921 gcagtggaaa gacgacattc atcagtgagt atgccctgga tttgtgttcc cagggggtga
     1981 acacactgtg gggtagcttc gagatcagca atgtgagact agcccgggtc atgctgacac
     2041 agtttgccga ggggcggctg gaagatcaac tggacaaata tgatcactgg gctgaccgct
     2101 ttgaggacct gcccctctat ttcatgactt tccatggaca gcaaagcatc aggactgtaa
     2161 tagatacaat gcaacatgca gtctacgtct atgacatttg tcatgtgatc atcgacaacc
     2221 tgcagttcat gatgggtcac gagcagctgt ccacagacag gatcgcagct caagactaca
     2281 tcatcggggt ctttcggaag tttgcaacag acaataactg ccatgtgaca ctggtcattc
     2341 acccccggaa agaggatgat gacaaggaac tgcagacagc gtccattttt ggctcagcca
     2401 aagcaagcca ggaagcagac aatgttctga tcctgcagga caggaagctg gtaaccgggc
     2461 cagggaaacg gtatctgcag gtgtccaaga accgctttga tggagatgta ggtgtcttcc
     2521 cgcttgagtt caacaagaac tccctcacct tctccattcc accaaagaac aaggcccggc
     2581 tcaagaagat caaggatgac actggaccag tggccaaaaa gccctcttct ggcaaaaagg
     2641 gggctacgac acagaactct gagatttgct caggccaggc ccccactccc gaccagccag
     2701 acacctccaa gcgttcaaag tgaaggccgt gcagagctgg tcactgaaat gagcctgata
     2761 ggataggctg gagcataaaa ctctgcaagg gctcctctat cctgtggtcc tgagctgtgt
     2821 gcccttctca gtctgagggg cctaacctag agcaggtttc catagtgaga aaattcaatg
     2881 tagcagacta ctgagaaact actgtgttgc tcaggctttg tttgaggtcc tgtatataca
     2941 gcactgaaaa gagagataaa gtccctgcct gcatgcattc tggcggaaga gacaagcaag
     3001 caatgaacaa attagcagaa aacctagttt tagtgaaaaa tgctgtaaag aaaatagaaa
     3061 tgcgatagag tgctggcagg ctagtgtaga taagtggtct gaaaaggtgt ctctgagccg
     3121 agggcatgtg agctggggcc taaacaacta gaaggagaga gccacgtgaa catccggcga
     3181 aggggaccca ggcagagaga aaaggaaatc caagccctga ggtaggaatg agcaggtcag
     3241 attcaaggca gtgaggtcag gccgcatgaa cctggagggg aatcggggac ttcatgcgaa
     3301 actccagcct aggctttcaa agtcaaaggg tgatacagtg ggtaccaagc tcctctgctc
     3361 cccactttgt agagcctagc atgaggtggc atgtactaga attggatcct aggtgcttag
     3421 ccctgcaata tcagggcctc actggtggga gctgcctcgg gctgggttgc ttggtcatag
     3481 agccatagaa ggaagctgtc agcccggagt gcctgccacc tagacactga tgccattgtg
     3541 tgctgcctca agactgctgg agtcaggaca ttttatagag ccttttccag ttttactaaa
     3601 aaatttttcc attgcc
//
