LOCUS       NM_004937               4139 bp    mRNA    linear   PRI 05-OCT-2024
DEFINITION  Homo sapiens cystinosin, lysosomal cystine transporter (CTNS),
            transcript variant 2, mRNA.
ACCESSION   NM_004937
VERSION     NM_004937.3
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 4139)
  AUTHORS   Baysal,I., Yabanoglu-Ciftci,S., Nemutlu,E., Eylem,C.C.,
            Gok-Topak,E.D., Ulubayram,K., Kir,S., Gulhan,B., Ucar,G.,
            Ozaltin,F. and Topaloglu,R.
  TITLE     Omic Studies on In Vitro Cystinosis Model: siRNA-Mediated CTNS Gene
            Silencing in HK-2 Cells
  JOURNAL   Lab Invest 104 (1), 100287 (2024)
   PUBMED   37949358
  REMARK    GeneRIF: Omic Studies on In Vitro Cystinosis Model: siRNA-Mediated
            CTNS Gene Silencing in HK-2 Cells.
REFERENCE   2  (bases 1 to 4139)
  AUTHORS   Thiyagarajan,R. and Taub,M.
  TITLE     Studies with Human-Induced Pluripotent Stem Cells Reveal That CTNS
            Mutations Can Alter Renal Proximal Tubule Differentiation
  JOURNAL   Int J Mol Sci 24 (23), 17004 (2023)
   PUBMED   38069326
  REMARK    GeneRIF: Studies with Human-Induced Pluripotent Stem Cells Reveal
            That CTNS Mutations Can Alter Renal Proximal Tubule
            Differentiation.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 4139)
  AUTHORS   Guo,X., Schmiege,P., Assafa,T.E., Wang,R., Xu,Y., Donnelly,L.,
            Fine,M., Ni,X., Jiang,J., Millhauser,G., Feng,L. and Li,X.
  TITLE     Structure and mechanism of human cystine exporter cystinosin
  JOURNAL   Cell 185 (20), 3739-3752 (2022)
   PUBMED   36113465
REFERENCE   4  (bases 1 to 4139)
  AUTHORS   Chkioua,L., Amri,Y., Saheli,C., Mili,W., Mabrouk,S., Chabchoub,I.,
            Boudabous,H., Azzouz,W.B., Turkia,H.B., Ferchichi,S., Tebib,N.,
            Massoud,T., Ghorbel,M. and Laradi,S.
  TITLE     Molecular characterization of CTNS mutations in Tunisian patients
            with ocular cystinosis
  JOURNAL   Diagn Pathol 17 (1), 44 (2022)
   PUBMED   35524314
  REMARK    GeneRIF: Molecular characterization of CTNS mutations in Tunisian
            patients with ocular cystinosis.
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 4139)
  AUTHORS   Gholami Yarahmadi,S., Sarlaki,F. and Morovvati,S.
  TITLE     Cystinosis and two rare mutations in CTNS gene: two case reports
  JOURNAL   J Med Case Rep 16 (1), 181 (2022)
   PUBMED   35513889
  REMARK    GeneRIF: Cystinosis and two rare mutations in CTNS gene: two case
            reports.
            Publication Status: Online-Only
REFERENCE   6  (bases 1 to 4139)
  AUTHORS   Anikster,Y., Lucero,C., Touchman,J.W., Huizing,M., McDowell,G.,
            Shotelersuk,V., Green,E.D. and Gahl,W.A.
  TITLE     Identification and detection of the common 65-kb deletion
            breakpoint in the nephropathic cystinosis gene (CTNS)
  JOURNAL   Mol Genet Metab 66 (2), 111-116 (1999)
   PUBMED   10068513
REFERENCE   7  (bases 1 to 4139)
  AUTHORS   Shotelersuk,V., Larson,D., Anikster,Y., McDowell,G., Lemons,R.,
            Bernardini,I., Guo,J., Thoene,J. and Gahl,W.A.
  TITLE     CTNS mutations in an American-based population of cystinosis
            patients
  JOURNAL   Am J Hum Genet 63 (5), 1352-1362 (1998)
   PUBMED   9792862
REFERENCE   8  (bases 1 to 4139)
  AUTHORS   Town,M., Jean,G., Cherqui,S., Attard,M., Forestier,L.,
            Whitmore,S.A., Callen,D.F., Gribouval,O., Broyer,M., Bates,G.P.,
            van't Hoff,W. and Antignac,C.
  TITLE     A novel gene encoding an integral membrane protein is mutated in
            nephropathic cystinosis
  JOURNAL   Nat Genet 18 (4), 319-324 (1998)
   PUBMED   9537412
REFERENCE   9  (bases 1 to 4139)
  AUTHORS   Nesterova,G. and Gahl,W.A.
  TITLE     Cystinosis
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301574
REFERENCE   10 (bases 1 to 4139)
  AUTHORS   Gahl,W.A., Bashan,N., Tietze,F., Bernardini,I. and Schulman,J.D.
  TITLE     Cystine transport is defective in isolated leukocyte lysosomes from
            patients with cystinosis
  JOURNAL   Science 217 (4566), 1263-1265 (1982)
   PUBMED   7112129
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DB026195.1, BC032850.2,
            BX369529.1, AC027796.9 and AC132942.16.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Jun 2, 2019 this sequence version replaced NM_004937.2.
            
            Summary: This gene encodes a seven-transmembrane domain protein
            that functions to transport cystine out of lysosomes. Its activity
            is driven by the H+ electrochemical gradient of the lysosomal
            membrane. Mutations in this gene cause cystinosis, a lysosomal
            storage disorder. Alternative splicing results in multiple
            transcript variants. [provided by RefSeq, Jul 2009].
            
            Transcript Variant: This variant (2) differs in the 5' UTR, 3' UTR
            and 3' coding region, compared to variant 1, resulting in an
            isoform (2) with a distinct and shorter C-terminus, compared to
            isoform 1.
            
            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 :: SRR1803615.237426.1,
                                           SRR1803611.103341.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000046640.9/ ENSP00000046640.4
            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
            1-274               DB026195.1         293-566
            275-804             BC032850.2         433-962
            805-1385            BX369529.1         43-623
            1386-3937           AC027796.9         1-2552              c
            3938-4139           AC132942.16        27676-27877
FEATURES             Location/Qualifiers
     source          1..4139
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="17"
                     /map="17p13.2"
     gene            1..4139
                     /gene="CTNS"
                     /gene_synonym="CTNS-LSB; PQLC4; SLC66A4"
                     /note="cystinosin, lysosomal cystine transporter"
                     /db_xref="GeneID:1497"
                     /db_xref="HGNC:HGNC:2518"
                     /db_xref="MIM:606272"
     exon            1..72
                     /gene="CTNS"
                     /gene_synonym="CTNS-LSB; PQLC4; SLC66A4"
                     /inference="alignment:Splign:2.1.0"
     exon            73..282
                     /gene="CTNS"
                     /gene_synonym="CTNS-LSB; PQLC4; SLC66A4"
                     /inference="alignment:Splign:2.1.0"
     exon            283..362
                     /gene="CTNS"
                     /gene_synonym="CTNS-LSB; PQLC4; SLC66A4"
                     /inference="alignment:Splign:2.1.0"
     CDS             302..1405
                     /gene="CTNS"
                     /gene_synonym="CTNS-LSB; PQLC4; SLC66A4"
                     /note="isoform 2 precursor is encoded by transcript
                     variant 2; cystinosis nephropathic"
                     /codon_start=1
                     /product="cystinosin isoform 2 precursor"
                     /protein_id="NP_004928.2"
                     /db_xref="CCDS:CCDS11031.1"
                     /db_xref="GeneID:1497"
                     /db_xref="HGNC:HGNC:2518"
                     /db_xref="MIM:606272"
                     /translation="MIRNWLTIFILFPLKLVEKCESSVSLTVPPVVKLENGSSTNVSL
                     TLRPPLNATLVITFEITFRSKNITILELPDEVVVPPGVTNSSFQVTSQNVGQLTVYLH
                     GNHSNQTGPRIRFLVIRSSAISIINQVIGWIYFVAWSISFYPQVIMNWRRKSVIGLSF
                     DFVALNLTGFVAYSVFNIGLLWVPYIKEQFLLKYPNGVNPVNSNDVFFSLHAVVLTLI
                     IIVQCCLYERGGQRVSWPAIGFLVLAWLFAFVTMIVAAVGVTTWLQFLFCFSYIKLAV
                     TLVKYFPQAYMNFYYKSTEGWSIGNVLLDFTGGSFSLLQMFLQSYNNDQWTLIFGDPT
                     KFGLGVFSIVFDVVFFIQHFCLYRKRPGYDQLN"
     exon            363..441
                     /gene="CTNS"
                     /gene_synonym="CTNS-LSB; PQLC4; SLC66A4"
                     /inference="alignment:Splign:2.1.0"
     exon            442..526
                     /gene="CTNS"
                     /gene_synonym="CTNS-LSB; PQLC4; SLC66A4"
                     /inference="alignment:Splign:2.1.0"
     exon            527..630
                     /gene="CTNS"
                     /gene_synonym="CTNS-LSB; PQLC4; SLC66A4"
                     /inference="alignment:Splign:2.1.0"
     exon            631..762
                     /gene="CTNS"
                     /gene_synonym="CTNS-LSB; PQLC4; SLC66A4"
                     /inference="alignment:Splign:2.1.0"
     exon            763..862
                     /gene="CTNS"
                     /gene_synonym="CTNS-LSB; PQLC4; SLC66A4"
                     /inference="alignment:Splign:2.1.0"
     exon            863..982
                     /gene="CTNS"
                     /gene_synonym="CTNS-LSB; PQLC4; SLC66A4"
                     /inference="alignment:Splign:2.1.0"
     exon            983..1153
                     /gene="CTNS"
                     /gene_synonym="CTNS-LSB; PQLC4; SLC66A4"
                     /inference="alignment:Splign:2.1.0"
     exon            1154..1271
                     /gene="CTNS"
                     /gene_synonym="CTNS-LSB; PQLC4; SLC66A4"
                     /inference="alignment:Splign:2.1.0"
     exon            1272..4139
                     /gene="CTNS"
                     /gene_synonym="CTNS-LSB; PQLC4; SLC66A4"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2551..2556
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CTNS"
                     /gene_synonym="CTNS-LSB; PQLC4; SLC66A4"
                     /note="hexamer: ATTAAA"
     polyA_site      2578
                     /gene="CTNS"
                     /gene_synonym="CTNS-LSB; PQLC4; SLC66A4"
                     /note="major polyA site"
     regulatory      4085..4090
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CTNS"
                     /gene_synonym="CTNS-LSB; PQLC4; SLC66A4"
                     /note="hexamer: GATAAA"
     regulatory      4113..4118
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CTNS"
                     /gene_synonym="CTNS-LSB; PQLC4; SLC66A4"
                     /note="hexamer: ATTAAA"
     polyA_site      4122
                     /gene="CTNS"
                     /gene_synonym="CTNS-LSB; PQLC4; SLC66A4"
     polyA_site      4139
                     /gene="CTNS"
                     /gene_synonym="CTNS-LSB; PQLC4; SLC66A4"
ORIGIN      
        1 gcattcctga ccggcacctg gcgaggctca tgcgtcccgt gagggcggtt cctcgagcct
       61 gggggcgctc agattgcttt ggagacgctg agagaacctt tgcgagagcg ccggttgacg
      121 tgcggagtgc ggggctccgg gggactgagc agcacgagac cccatcctcc cctccgggtt
      181 ttcacactgg gcgaagggag gactcctgag ctctgcctct tccagtaaca ttgaggatta
      241 ctgtgttttg tgagagctcg ctaggcgccc taagcaacag agttctgaga aatcgagaaa
      301 catgataagg aattggctga ctatttttat cctttttccc ctgaagctcg tagagaaatg
      361 tgagtcaagc gtcagcctca ctgttcctcc tgtcgtaaag ctggagaacg gcagctcgac
      421 caacgtcagc ctcaccctgc ggccaccatt aaatgcaacc ctggtgatca cttttgaaat
      481 cacatttcgt tccaaaaata ttactatcct tgagctcccc gatgaagttg tggtgcctcc
      541 tggagtgaca aactcctctt ttcaagtgac atctcaaaat gttggacaac ttactgttta
      601 tctacatgga aatcactcca atcagaccgg cccgaggata cgctttcttg tgatccgcag
      661 cagcgccatt agcatcataa accaggtgat tggctggatc tactttgtgg cctggtccat
      721 ctccttctac cctcaggtga tcatgaattg gaggcggaaa agtgtcattg gtctgagctt
      781 cgacttcgtg gctctgaacc tgacgggctt cgtggcctac agtgtattca acatcggcct
      841 cctctgggtg ccctacatca aggagcagtt tctcctcaaa taccccaacg gagtgaaccc
      901 cgtgaacagc aacgacgtct tcttcagcct gcacgcggtt gtcctcacgc tgatcatcat
      961 cgtgcagtgc tgcctgtatg agcgcggtgg ccagcgcgtg tcctggcctg ccatcggctt
     1021 cctggtgctc gcgtggctct tcgcatttgt caccatgatc gtggctgcag tgggagtgac
     1081 cacgtggctg cagtttctct tctgcttctc ctacatcaag ctcgcagtca cgctggtcaa
     1141 gtattttcca caggcctaca tgaactttta ctacaaaagc actgagggct ggagcattgg
     1201 caacgtgctc ctggacttca ccgggggcag cttcagcctc ctgcagatgt tcctccagtc
     1261 ctacaacaac gaccagtgga cgctgatctt cggagaccca accaagtttg gactcggggt
     1321 cttctccatc gtcttcgacg tcgtcttctt catccagcac ttctgtttgt acagaaagag
     1381 accggggtat gaccagctga actagcaccc agggacccag tgtacccagc ctctggcctc
     1441 gtgccctgct ggggaaggcc tcacccagcg aaggccggag aagcggttgg gccctggcac
     1501 acagggctgg ctcagtgtgc ggacagagga gaccactctg ctcctggggc cagaggccat
     1561 tcaatagcct gccttcgtcc gggcccctcc tgggcctccc cggccaggca cgtggcaccg
     1621 tcgccttgac accgccatct cttttcttta aggcttcagg cagcgcgcac aggctctggc
     1681 agccgtctca ggcaggactg ggcaccaagc ttgcagccga aggccttgcc ccaaactacc
     1741 agcgtttctg caagcagctt gaagggctga ccttgcagcc gggtgagcca agggcacttt
     1801 gctgccaccg ctgcattccc agagatcaag cagcccggtg ccgtggccag tgaactcaga
     1861 ggtgctggtg gacgggctag gactttgggg ttaggccatg gggctctttc tctgaaggcc
     1921 actttcctga cgtactctct gtacataact cagcgtccgt gactgcagta acagccagcc
     1981 ctacccagag tatttctgag ccatgagggg cccaccagat tggttctgaa ttggattcat
     2041 gcccagcgca ttagcatagt aactcctttc agattttttg gagggacgtt tggaagtggc
     2101 ttactctctt ctgccctctc tcctacctcc accttctcag attagcccca tctgagcaca
     2161 tccagctgct ccttacccag catctggagt acaggacata gctctctcct gctaccagtc
     2221 tgtgccttag aggtctgtta ggcctgccaa acggcgacca gctcccctgg agcgagggca
     2281 ggccccttcc ctctctttcc ccagacacct acttgagact caccaatttc tggcctgttc
     2341 aggagcctca gataagtatt tgtacttgag accacctcac acaatctgta tgggcccaac
     2401 cctgatctca aacctccttc cctctgccca aagctgtcct tcctatggca ggaggggtgg
     2461 gggtcccagg acgtgcctca tacatgactt gagcttgtca gtccactgag tttccttcta
     2521 cgagatcaac gcgaggggcc tgtatcttga attaaaacct actcgcttcc tttctgcact
     2581 ctgtgtgctc gatacagaag gcaggtgtgc tggccttcag agccaggtgc cctgctcccc
     2641 tcgtgtaagg aagcgcataa ggttgtgaag gtcactgacc cgagagcgct gcgtgctgac
     2701 cccacacttc actggggagc cctcttgggt agcgcgagac gcctacccgc ccagggccag
     2761 gtcagtctcc caggctccgt gtcttcacgg ttaccagggc acgccactca atctggatgt
     2821 gagccggggt ggatgaggtt ctgaagggca caccagcact gggagcgggg gcagtggggg
     2881 tcttattctc cagacgcttc ctctatctag ttgtaacaaa cgtcaaagaa tgtcaggtct
     2941 tgtttctgca gagcagactt tggcctgacg gggtccacag acctgtttca cttgcaacac
     3001 ccagtaaatg tgttactggg tgccctactt taaaaatcag agatttcaaa tgattgactt
     3061 ttccggctga gtgcggtggc tcacgcctgt aatcccagca ctttgggagg ccaaggcaga
     3121 tggatcacct gacatcagga gttcgagacc agcctagcca acattgcaaa accccatctc
     3181 tactaaagat acaaaaatta gctgggcatg gtggcgggca cctgtaatcc cagctacttg
     3241 gttggctgag gcaggagaat tacttgaacc caggaggcgg aggttgcagt gagcgaagat
     3301 cacgccattg cactccagcc tgggcaacaa gaacgaaact ccatctcaaa aaaaaaaaaa
     3361 aattattgac ttttctttaa aatctgattt ggcagtgcta ggtaggtcca ggagtgctaa
     3421 caccttccca gaggtggtac gcaggtagtc aggtgctctc tgactcaccc ccatctggcc
     3481 agatcacggc ccccagcaac acgtggggtt gtgtccctcg ctgggataca cggagtgccc
     3541 ttataggcag ggagtcttat aggcaggggt ctctcccagg cacctctggg tgtccctacg
     3601 gcccctccca ggtgggagct gaggctaggt tgcaaaaagg aggttgggag caagtagggg
     3661 cttcacagta acacccaaga aagcacacgc accccagggt cccaccccag tgctcccaga
     3721 cactcccaca gatgtggttc tggtcaggcg cagtgcagct gctgcggctc caccagcccc
     3781 gggctttcag gcaggtgggc ctgggagtag ttgagctttg tcccagaaca gtgggggatg
     3841 gggccatcat taaaaccaca gctctggccc caatatccca ccgccacccc caccccgata
     3901 tcccagccca tgcctcagca aagccccctg tgaattccag catttttatt gagcgcacca
     3961 catcggggag gggcggcagt ggtttccacg gtaaccaaag taaggcttgt gcacttgctg
     4021 agcttccaga tgcgaattag taaaagctaa attcaaaagt agaatgggca tctccaaaga
     4081 gtacgataaa aacattttgt atcaaacttg tgattaaaaa aatacaaaag ttaaaccca
//
