LOCUS       NM_001323419            2882 bp    mRNA    linear   PRI 18-NOV-2024
DEFINITION  Homo sapiens aldehyde dehydrogenase 18 family member A1 (ALDH18A1),
            transcript variant 10, mRNA.
ACCESSION   NM_001323419
VERSION     NM_001323419.2
KEYWORDS    RefSeq.
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 2882)
  AUTHORS   Zaman,Q., Iftikhar,A., Rehman,G., Khan,Q., Najumuddin, Jan,A.,
            Khan,J., Anas,M., Laiba, Umair,M., Muthaffar,O.Y.,
            Abdulkareem,A.A., Bibi,F., Naseer,M.I. and Jelani,M.
  TITLE     Two novel homozygous variants of ATP6V0A2 and ALDH18A1 lead to
            autosomal recessive cutis laxa type 2 and 3 in two Pakistani
            families
  JOURNAL   J Gene Med 25 (10), e3522 (2023)
   PUBMED   37119015
  REMARK    GeneRIF: Two novel homozygous variants of ATP6V0A2 and ALDH18A1
            lead to autosomal recessive cutis laxa type 2 and 3 in two
            Pakistani families.
REFERENCE   2  (bases 1 to 2882)
  AUTHORS   Colonna,M.B., Moss,T., Mokashi,S., Srikanth,S., Jones,J.R.,
            Foley,J.R., Skinner,C., Lichty,A., Kocur,A., Wood,T., Stewart,T.M.,
            Casero,R.A. Jr., Flanagan-Steet,H., Edison,A.S., Lyons,M.J. and
            Steet,R.
  TITLE     Functional assessment of homozygous ALDH18A1 variants reveals
            alterations in amino acid and antioxidant metabolism
  JOURNAL   Hum Mol Genet 32 (5), 732-744 (2023)
   PUBMED   36067040
  REMARK    GeneRIF: Functional assessment of homozygous ALDH18A1 variants
            reveals alterations in amino acid and antioxidant metabolism.
REFERENCE   3  (bases 1 to 2882)
  AUTHORS   Morgenstern,M., Peikert,C.D., Lubbert,P., Suppanz,I., Klemm,C.,
            Alka,O., Steiert,C., Naumenko,N., Schendzielorz,A., Melchionda,L.,
            Muhlhauser,W.W.D., Knapp,B., Busch,J.D., Stiller,S.B.,
            Dannenmaier,S., Lindau,C., Licheva,M., Eickhorst,C., Galbusera,R.,
            Zerbes,R.M., Ryan,M.T., Kraft,C., Kozjak-Pavlovic,V., Drepper,F.,
            Dennerlein,S., Oeljeklaus,S., Pfanner,N., Wiedemann,N. and
            Warscheid,B.
  TITLE     Quantitative high-confidence human mitochondrial proteome and its
            dynamics in cellular context
  JOURNAL   Cell Metab 33 (12), 2464-2483 (2021)
   PUBMED   34800366
REFERENCE   4  (bases 1 to 2882)
  AUTHORS   Koh,K., Takaki,R., Ishiura,H., Tsuji,S. and Takiyama,Y.
  TITLE     SPG9A with the new occurrence of an ALDH18A1 mutation in a CMT1A
            family with PMP22 duplication: case report
  JOURNAL   BMC Neurol 21 (1), 64 (2021)
   PUBMED   33573605
  REMARK    GeneRIF: SPG9A with the new occurrence of an ALDH18A1 mutation in a
            CMT1A family with PMP22 duplication: case report.
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 2882)
  AUTHORS   Yang,Z., Zhao,X., Shang,W., Liu,Y., Ji,J.F., Liu,J.P. and Tong,C.
  TITLE     Pyrroline-5-carboxylate synthase senses cellular stress and
            modulates metabolism by regulating mitochondrial respiration
  JOURNAL   Cell Death Differ 28 (1), 303-319 (2021)
   PUBMED   32770108
REFERENCE   6  (bases 1 to 2882)
  AUTHORS   Hu,C.A., Lin,W.W., Obie,C. and Valle,D.
  TITLE     Molecular enzymology of mammalian Delta1-pyrroline-5-carboxylate
            synthase. Alternative splice donor utilization generates isoforms
            with different sensitivity to ornithine inhibition
  JOURNAL   J Biol Chem 274 (10), 6754-6762 (1999)
   PUBMED   10037775
REFERENCE   7  (bases 1 to 2882)
  AUTHORS   Seri,M., Cusano,R., Forabosco,P., Cinti,R., Caroli,F., Picco,P.,
            Bini,R., Morra,V.B., De Michele,G., Lerone,M., Silengo,M., Pela,I.,
            Borrone,C., Romeo,G. and Devoto,M.
  TITLE     Genetic mapping to 10q23.3-q24.2, in a large Italian pedigree, of a
            new syndrome showing bilateral cataracts, gastroesophageal reflux,
            and spastic paraparesis with amyotrophy
  JOURNAL   Am J Hum Genet 64 (2), 586-593 (1999)
   PUBMED   9973297
REFERENCE   8  (bases 1 to 2882)
  AUTHORS   Liu,G., Maunoury,C., Kamoun,P. and Aral,B.
  TITLE     Assignment of the human gene encoding the delta
            1-pyrroline-5-carboxylate synthetase (P5CS) to 10q24.3 by in situ
            hybridization
  JOURNAL   Genomics 37 (1), 145-146 (1996)
   PUBMED   8921385
REFERENCE   9  (bases 1 to 2882)
  AUTHORS   Aral,B., Schlenzig,J.S., Liu,G. and Kamoun,P.
  TITLE     Database cloning human delta 1-pyrroline-5-carboxylate synthetase
            (P5CS) cDNA: a bifunctional enzyme catalyzing the first 2 steps in
            proline biosynthesis
  JOURNAL   C R Acad Sci III 319 (3), 171-178 (1996)
   PUBMED   8761662
REFERENCE   10 (bases 1 to 2882)
  AUTHORS   Hedera,P.
  TITLE     Hereditary Spastic Paraplegia Overview
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301682
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AL356632.12 and AK299557.1.
            
            On May 31, 2019 this sequence version replaced NM_001323419.1.
            
            Summary: This gene is a member of the aldehyde dehydrogenase family
            and encodes a bifunctional ATP- and NADPH-dependent mitochondrial
            enzyme with both gamma-glutamyl kinase and gamma-glutamyl phosphate
            reductase activities. The encoded protein catalyzes the reduction
            of glutamate to delta1-pyrroline-5-carboxylate, a critical step in
            the de novo biosynthesis of proline, ornithine and arginine.
            Mutations in this gene lead to hyperammonemia, hypoornithinemia,
            hypocitrullinemia, hypoargininemia and hypoprolinemia and may be
            associated with neurodegeneration, cataracts and connective tissue
            diseases. Alternatively spliced transcript variants, encoding
            different isoforms, have been described for this gene. [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 :: AK299557.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            gene product(s) localized to mito. :: reported by MitoCarta
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-3                 AL356632.12        90377-90379         c
            4-2123              AK299557.1         1-2120
            2124-2882           AL356632.12        39609-40367         c
FEATURES             Location/Qualifiers
     source          1..2882
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="10"
                     /map="10q24.1"
     gene            1..2882
                     /gene="ALDH18A1"
                     /gene_synonym="ADCL3; ARCL3A; GSAS; P5CS; PYCS; SPG9;
                     SPG9A; SPG9B"
                     /note="aldehyde dehydrogenase 18 family member A1"
                     /db_xref="GeneID:5832"
                     /db_xref="HGNC:HGNC:9722"
                     /db_xref="MIM:138250"
     exon            1..115
                     /gene="ALDH18A1"
                     /gene_synonym="ADCL3; ARCL3A; GSAS; P5CS; PYCS; SPG9;
                     SPG9A; SPG9B"
                     /inference="alignment:Splign:2.1.0"
     exon            116..231
                     /gene="ALDH18A1"
                     /gene_synonym="ADCL3; ARCL3A; GSAS; P5CS; PYCS; SPG9;
                     SPG9A; SPG9B"
                     /inference="alignment:Splign:2.1.0"
     exon            232..390
                     /gene="ALDH18A1"
                     /gene_synonym="ADCL3; ARCL3A; GSAS; P5CS; PYCS; SPG9;
                     SPG9A; SPG9B"
                     /inference="alignment:Splign:2.1.0"
     CDS             310..2061
                     /gene="ALDH18A1"
                     /gene_synonym="ADCL3; ARCL3A; GSAS; P5CS; PYCS; SPG9;
                     SPG9A; SPG9B"
                     /EC_number="1.2.1.41"
                     /EC_number="2.7.2.11"
                     /note="isoform 6 is encoded by transcript variant 10;
                     pyrroline-5-carboxylate synthetase (glutamate
                     gamma-semialdehyde synthetase);
                     delta1-pyrroline-5-carboxlate synthetase;
                     delta-1-pyrroline-5-carboxylate synthetase;
                     delta-1-pyrroline-5-carboxylate synthase; aldehyde
                     dehydrogenase family 18 member A1; spastic paraplegia 9
                     (autosomal dominant); Spastic paraplegia-9 (spastic
                     paraparesis with amyotrophy, cataracts and
                     gastroesophageal reflux)"
                     /codon_start=1
                     /product="delta-1-pyrroline-5-carboxylate synthase isoform
                     6"
                     /protein_id="NP_001310348.1"
                     /db_xref="GeneID:5832"
                     /db_xref="HGNC:HGNC:9722"
                     /db_xref="MIM:138250"
                     /translation="MNIVPIVNTNDAVVPPAEPNSDLQGVNVISVKDNDSLAARLAVE
                     MKTDLLIVLSDVEGLFDSPPGSDDAKLIDIFYPGDQQSVTFGTKSRVGMGGMEAKVKA
                     ALWALQGGTSVVIANGTHPKVSGHVITDIVEGKKVGTFFSEVKPAGPTVEQQGEMARS
                     GGRMLATLEPEQRAEIIHHLADLLTDQRDEILLANKKDLEEAEGRLAAPLLKRLSLST
                     SKLNSLAIGLRQIAASSQDSVGRVLRRTRIAKNLELEQVTVPIGVLLVIFESRPDCLP
                     QVAALAIASGNGLLLKGGKEAAHSNRILHLLTQEALSIHGVKEAVQLVNTREEVEDLC
                     RLDKMIDLIIPRGSSQLVRDIQKAAKGIPVMGHSEGICHMYVDSEASVDKVTRLVRDS
                     KCEYPAACNALETLLIHRDLLRTPLFDQIIDMLRVEQVKIHAGPKFASYLTFSPSEVK
                     SLRTEYGDLELCIEVVDNVQDAIDHIHKYGSSHTDVIVTEDENTAEFFLQHVDSACVF
                     WNASTRFSDGYRFGLGAEVGISTSRIHARGPVGLEGLLTTKWLLRGKDHVVSDFSEHG
                     SLKYLHENLPIPQRNTN"
     exon            391..481
                     /gene="ALDH18A1"
                     /gene_synonym="ADCL3; ARCL3A; GSAS; P5CS; PYCS; SPG9;
                     SPG9A; SPG9B"
                     /inference="alignment:Splign:2.1.0"
     exon            482..606
                     /gene="ALDH18A1"
                     /gene_synonym="ADCL3; ARCL3A; GSAS; P5CS; PYCS; SPG9;
                     SPG9A; SPG9B"
                     /inference="alignment:Splign:2.1.0"
     exon            607..751
                     /gene="ALDH18A1"
                     /gene_synonym="ADCL3; ARCL3A; GSAS; P5CS; PYCS; SPG9;
                     SPG9A; SPG9B"
                     /inference="alignment:Splign:2.1.0"
     exon            752..825
                     /gene="ALDH18A1"
                     /gene_synonym="ADCL3; ARCL3A; GSAS; P5CS; PYCS; SPG9;
                     SPG9A; SPG9B"
                     /inference="alignment:Splign:2.1.0"
     exon            826..919
                     /gene="ALDH18A1"
                     /gene_synonym="ADCL3; ARCL3A; GSAS; P5CS; PYCS; SPG9;
                     SPG9A; SPG9B"
                     /inference="alignment:Splign:2.1.0"
     exon            920..1140
                     /gene="ALDH18A1"
                     /gene_synonym="ADCL3; ARCL3A; GSAS; P5CS; PYCS; SPG9;
                     SPG9A; SPG9B"
                     /inference="alignment:Splign:2.1.0"
     exon            1141..1278
                     /gene="ALDH18A1"
                     /gene_synonym="ADCL3; ARCL3A; GSAS; P5CS; PYCS; SPG9;
                     SPG9A; SPG9B"
                     /inference="alignment:Splign:2.1.0"
     exon            1279..1474
                     /gene="ALDH18A1"
                     /gene_synonym="ADCL3; ARCL3A; GSAS; P5CS; PYCS; SPG9;
                     SPG9A; SPG9B"
                     /inference="alignment:Splign:2.1.0"
     exon            1475..1596
                     /gene="ALDH18A1"
                     /gene_synonym="ADCL3; ARCL3A; GSAS; P5CS; PYCS; SPG9;
                     SPG9A; SPG9B"
                     /inference="alignment:Splign:2.1.0"
     exon            1597..1783
                     /gene="ALDH18A1"
                     /gene_synonym="ADCL3; ARCL3A; GSAS; P5CS; PYCS; SPG9;
                     SPG9A; SPG9B"
                     /inference="alignment:Splign:2.1.0"
     exon            1784..1879
                     /gene="ALDH18A1"
                     /gene_synonym="ADCL3; ARCL3A; GSAS; P5CS; PYCS; SPG9;
                     SPG9A; SPG9B"
                     /inference="alignment:Splign:2.1.0"
     exon            1880..2882
                     /gene="ALDH18A1"
                     /gene_synonym="ADCL3; ARCL3A; GSAS; P5CS; PYCS; SPG9;
                     SPG9A; SPG9B"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2863..2868
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ALDH18A1"
                     /gene_synonym="ADCL3; ARCL3A; GSAS; P5CS; PYCS; SPG9;
                     SPG9A; SPG9B"
                     /note="hexamer: AATAAA"
     polyA_site      2882
                     /gene="ALDH18A1"
                     /gene_synonym="ADCL3; ARCL3A; GSAS; P5CS; PYCS; SPG9;
                     SPG9A; SPG9B"
                     /note="major polyA site"
ORIGIN      
        1 atcgtgcggg acgtggacgg aagaaaaaag agagtgagcg agcgccggaa tcagcccggc
       61 gtggagtgcg gacccgcggt agtgccaggg ggcgaaggcg gcggtggtga ggaagatact
      121 ttggttagtg accacatcgc agcatgttga gtcaagttta ccgctgtggg ttccagccct
      181 tcaaccaaca tcttctgccc tgggtcaagt gtacaaccgt cttcagatct cattttggtg
      241 accaatttgg atttccatga tgagcagaag cgccggaacc tcaatggaac acttcatgaa
      301 ctccttagaa tgaacattgt ccccattgtc aacacaaatg atgctgttgt ccccccagct
      361 gagcccaaca gtgacctgca gggggtaaat gttattagtg ttaaagataa tgatagcctg
      421 gctgcccgac tggctgtgga aatgaaaact gatctcttga ttgttctttc agatgtagaa
      481 ggcctttttg acagcccccc aggttcagat gatgcaaagc ttattgatat attttatccc
      541 ggagatcagc agtctgtgac atttggaacc aagtctagag tgggaatggg tggcatggaa
      601 gccaaggtga aagcagccct ctgggctttg caaggtggca cttctgttgt tattgccaat
      661 ggaacccacc caaaggtgtc tgggcacgtc atcacagaca ttgtggaggg gaagaaagtt
      721 ggtaccttct tttcagaagt aaagcctgca ggccctactg ttgagcagca gggagaaatg
      781 gcgcgatctg gaggaaggat gttggccacc ttggaacctg agcagagagc agaaattatc
      841 catcatctgg ctgatctgtt gacggaccag cgtgatgaga tcctgttagc caacaaaaaa
      901 gacttggagg aggcagaggg gagacttgca gctcctctgc tgaaacgttt aagcctctcc
      961 acatccaaat tgaacagcct ggccatcggt ctgcgacaga tcgcagcctc ctcccaggac
     1021 agcgtgggac gtgttttgcg ccgcacccga atcgccaaaa acttggaact ggaacaagtg
     1081 actgtcccaa ttggagttct gctggtgatc tttgaatctc gtcctgactg tctaccccag
     1141 gtggcagctt tggctatcgc aagtggcaat ggcttgttac tcaaaggagg gaaggaggct
     1201 gcacacagca accggattct ccacctcctg acccaggagg ctctctcaat ccatggagtc
     1261 aaggaggccg tgcaactggt gaataccaga gaagaagttg aagatctttg ccgcctagac
     1321 aaaatgatag atctgatcat tccacgtggc tcttcccagc tggtcagaga catccagaaa
     1381 gctgctaagg ggattccagt gatggggcac agcgaaggga tctgtcacat gtatgtggat
     1441 tccgaggcca gtgttgataa ggtcaccagg ctagtcagag actctaaatg tgaatatcca
     1501 gctgcctgta atgctttgga gactttgtta atccaccggg atctgctcag gacaccatta
     1561 tttgaccaga tcattgatat gctgagagtg gaacaggtaa aaattcatgc aggccccaaa
     1621 tttgcctcct atctgacctt cagcccctcc gaagtgaagt cactccgaac tgagtatggg
     1681 gacctggaat tatgcattga agtagtggac aacgttcagg atgccattga ccacatccac
     1741 aagtatggca gctcccacac ggatgtcatc gtcacagagg acgaaaacac agcggagttc
     1801 ttcctgcagc acgtagacag tgcctgtgtg ttctggaatg ccagcactcg cttttctgat
     1861 ggttaccgct ttggactggg agctgaagtg ggaatcagta catcgagaat ccacgcccgg
     1921 ggaccagtag gacttgaggg actgcttact actaagtggc tgctgcgagg gaaggaccac
     1981 gtggtctcag atttctcaga gcatggaagt ttaaaatatc ttcatgagaa cctccctatt
     2041 cctcagagaa acaccaactg aaaagagcca ggaaaacccg ggaattttcc aaaaggtctt
     2101 cacgttaaac ttgtcttatc tcaggagaga gcccgctctt gtctcccagt tcctggtagg
     2161 gtctgcctgt tggaaagtgt acctggatgc ttctgggctc cgtttggcaa tagcagtctt
     2221 ggctgatgtg cacagtctgg ctcccagctc accctttttt tttaaagtaa gaaaatagtt
     2281 gctaccgata gggactttgc caagtccaat tatcttctag gattgaaagg tgcattttcc
     2341 ccataaaaaa ggcgaggaaa acccatggct gctttgtgtc acctcagtga cttacagtcc
     2401 cccttggcat ttagttggta ctagagccag tcatccttaa caaatctttt cacattttat
     2461 ttctttcaca tgtagtcatc ttcaaaaagg aaagatttgg aattttagaa aaggggcaac
     2521 tcttcttttt agcattctca tcagaaagtc acaaaaatcg atggaatcat ttccactggg
     2581 aagattgacc ttttgtattt atttgtgggg taaattaata agcattccag atgcttgcag
     2641 cttcctgcat ccaggagatg ctgtgttccc cgtgatgcag ctggaaccca agctgcagca
     2701 ggagatgcaa gtttcaggat gttccccact gagctggagg aatatctaca gcagtgatgc
     2761 ttgaaatttt tgtatgaatt attttgtcgt cctacccttt tcctccaaaa caaaaattag
     2821 aggattattt taatactttg gattcttccc ccttttttga gaaataaagt tttttatgaa
     2881 aa
//
