LOCUS       NM_002860               3352 bp    mRNA    linear   PRI 18-NOV-2024
DEFINITION  Homo sapiens aldehyde dehydrogenase 18 family member A1 (ALDH18A1),
            transcript variant 1, mRNA.
ACCESSION   NM_002860
VERSION     NM_002860.4
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 3352)
  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 3352)
  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 3352)
  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 3352)
  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 3352)
  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 3352)
  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 3352)
  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 3352)
  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 3352)
  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 3352)
  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 CD642171.1, U76542.1, X94453.1,
            BU170321.1 and AW467503.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 23, 2018 this sequence version replaced NM_002860.3.
            
            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].
            
            Transcript Variant: This variant (1), also known as P5CSL, encodes
            the longest isoform (1). Variants 1, 4, and 5 all encode the same
            isoform (1).
            
            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 :: BC106054.1, SRR1803611.6395.1
                                           [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
            MANE Ensembl match                 :: ENST00000371224.7/
                                                  ENSP00000360268.2
            RefSeq Select criteria             :: based on conservation,
                                                  expression, longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-86                CD642171.1         139-224
            87-316              U76542.1           1-230
            317-518             X94453.1           312-513
            519-2685            U76542.1           433-2599
            2686-3288           BU170321.1         22-624
            3289-3348           U76542.1           3203-3262
            3349-3352           AW467503.1         20-23               c
FEATURES             Location/Qualifiers
     source          1..3352
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="10"
                     /map="10q24.1"
     gene            1..3352
                     /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"
     CDS             144..2531
                     /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 1 is encoded by transcript variant 1;
                     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
                     1"
                     /protein_id="NP_002851.2"
                     /db_xref="CCDS:CCDS7443.1"
                     /db_xref="GeneID:5832"
                     /db_xref="HGNC:HGNC:9722"
                     /db_xref="MIM:138250"
                     /translation="MLSQVYRCGFQPFNQHLLPWVKCTTVFRSHCIQPSVIRHVRSWS
                     NIPFITVPLSRTHGKSFAHRSELKHAKRIVVKLGSAVVTRGDECGLALGRLASIVEQV
                     SVLQNQGREMMLVTSGAVAFGKQRLRHEILLSQSVRQALHSGQNQLKEMAIPVLEARA
                     CAAAGQSGLMALYEAMFTQYSICAAQILVTNLDFHDEQKRRNLNGTLHELLRMNIVPI
                     VNTNDAVVPPAEPNSDLQGVNVISVKDNDSLAARLAVEMKTDLLIVLSDVEGLFDSPP
                     GSDDAKLIDIFYPGDQQSVTFGTKSRVGMGGMEAKVKAALWALQGGTSVVIANGTHPK
                     VSGHVITDIVEGKKVGTFFSEVKPAGPTVEQQGEMARSGGRMLATLEPEQRAEIIHHL
                     ADLLTDQRDEILLANKKDLEEAEGRLAAPLLKRLSLSTSKLNSLAIGLRQIAASSQDS
                     VGRVLRRTRIAKNLELEQVTVPIGVLLVIFESRPDCLPQVAALAIASGNGLLLKGGKE
                     AAHSNRILHLLTQEALSIHGVKEAVQLVNTREEVEDLCRLDKMIDLIIPRGSSQLVRD
                     IQKAAKGIPVMGHSEGICHMYVDSEASVDKVTRLVRDSKCEYPAACNALETLLIHRDL
                     LRTPLFDQIIDMLRVEQVKIHAGPKFASYLTFSPSEVKSLRTEYGDLELCIEVVDNVQ
                     DAIDHIHKYGSSHTDVIVTEDENTAEFFLQHVDSACVFWNASTRFSDGYRFGLGAEVG
                     ISTSRIHARGPVGLEGLLTTKWLLRGKDHVVSDFSEHGSLKYLHENLPIPQRNTN"
     exon            232..446
                     /gene="ALDH18A1"
                     /gene_synonym="ADCL3; ARCL3A; GSAS; P5CS; PYCS; SPG9;
                     SPG9A; SPG9B"
                     /inference="alignment:Splign:2.1.0"
     exon            447..596
                     /gene="ALDH18A1"
                     /gene_synonym="ADCL3; ARCL3A; GSAS; P5CS; PYCS; SPG9;
                     SPG9A; SPG9B"
                     /inference="alignment:Splign:2.1.0"
     exon            597..701
                     /gene="ALDH18A1"
                     /gene_synonym="ADCL3; ARCL3A; GSAS; P5CS; PYCS; SPG9;
                     SPG9A; SPG9B"
                     /inference="alignment:Splign:2.1.0"
     exon            702..860
                     /gene="ALDH18A1"
                     /gene_synonym="ADCL3; ARCL3A; GSAS; P5CS; PYCS; SPG9;
                     SPG9A; SPG9B"
                     /inference="alignment:Splign:2.1.0"
     exon            861..951
                     /gene="ALDH18A1"
                     /gene_synonym="ADCL3; ARCL3A; GSAS; P5CS; PYCS; SPG9;
                     SPG9A; SPG9B"
                     /inference="alignment:Splign:2.1.0"
     exon            952..1076
                     /gene="ALDH18A1"
                     /gene_synonym="ADCL3; ARCL3A; GSAS; P5CS; PYCS; SPG9;
                     SPG9A; SPG9B"
                     /inference="alignment:Splign:2.1.0"
     exon            1077..1221
                     /gene="ALDH18A1"
                     /gene_synonym="ADCL3; ARCL3A; GSAS; P5CS; PYCS; SPG9;
                     SPG9A; SPG9B"
                     /inference="alignment:Splign:2.1.0"
     exon            1222..1295
                     /gene="ALDH18A1"
                     /gene_synonym="ADCL3; ARCL3A; GSAS; P5CS; PYCS; SPG9;
                     SPG9A; SPG9B"
                     /inference="alignment:Splign:2.1.0"
     exon            1296..1389
                     /gene="ALDH18A1"
                     /gene_synonym="ADCL3; ARCL3A; GSAS; P5CS; PYCS; SPG9;
                     SPG9A; SPG9B"
                     /inference="alignment:Splign:2.1.0"
     exon            1390..1610
                     /gene="ALDH18A1"
                     /gene_synonym="ADCL3; ARCL3A; GSAS; P5CS; PYCS; SPG9;
                     SPG9A; SPG9B"
                     /inference="alignment:Splign:2.1.0"
     exon            1611..1748
                     /gene="ALDH18A1"
                     /gene_synonym="ADCL3; ARCL3A; GSAS; P5CS; PYCS; SPG9;
                     SPG9A; SPG9B"
                     /inference="alignment:Splign:2.1.0"
     exon            1749..1944
                     /gene="ALDH18A1"
                     /gene_synonym="ADCL3; ARCL3A; GSAS; P5CS; PYCS; SPG9;
                     SPG9A; SPG9B"
                     /inference="alignment:Splign:2.1.0"
     exon            1945..2066
                     /gene="ALDH18A1"
                     /gene_synonym="ADCL3; ARCL3A; GSAS; P5CS; PYCS; SPG9;
                     SPG9A; SPG9B"
                     /inference="alignment:Splign:2.1.0"
     exon            2067..2253
                     /gene="ALDH18A1"
                     /gene_synonym="ADCL3; ARCL3A; GSAS; P5CS; PYCS; SPG9;
                     SPG9A; SPG9B"
                     /inference="alignment:Splign:2.1.0"
     exon            2254..2349
                     /gene="ALDH18A1"
                     /gene_synonym="ADCL3; ARCL3A; GSAS; P5CS; PYCS; SPG9;
                     SPG9A; SPG9B"
                     /inference="alignment:Splign:2.1.0"
     exon            2350..3352
                     /gene="ALDH18A1"
                     /gene_synonym="ADCL3; ARCL3A; GSAS; P5CS; PYCS; SPG9;
                     SPG9A; SPG9B"
                     /inference="alignment:Splign:2.1.0"
     regulatory      3333..3338
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ALDH18A1"
                     /gene_synonym="ADCL3; ARCL3A; GSAS; P5CS; PYCS; SPG9;
                     SPG9A; SPG9B"
                     /note="hexamer: AATAAA"
     polyA_site      3352
                     /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 cattgtatcc
      241 agccttcagt catcagacat gttcgttctt ggagcaacat cccgtttatc actgtacccc
      301 tcagtcgtac acatggcaag tccttcgccc accgcagtga gctgaagcat gccaagagaa
      361 tcgtggtgaa gctcggcagt gccgtggtga cccgagggga tgaatgtggc ctggccctgg
      421 ggcgcttggc atctattgtt gagcaggtat cagtgctgca gaatcagggc agagagatga
      481 tgctggtgac cagtggagcc gtagcctttg gcaaacaacg cttgcgccat gagatccttc
      541 tgtctcagag cgtgcggcag gccctccact cggggcagaa ccagctgaaa gaaatggcaa
      601 ttccagtctt agaggcacga gcctgtgcag ctgccggaca gagtgggctg atggccttgt
      661 atgaggctat gtttacccag tacagcatct gtgctgccca gattttggtg accaatttgg
      721 atttccatga tgagcagaag cgccggaacc tcaatggaac acttcatgaa ctccttagaa
      781 tgaacattgt ccccattgtc aacacaaatg atgctgttgt ccccccagct gagcccaaca
      841 gtgacctgca gggggtaaat gttattagtg ttaaagataa tgatagcctg gctgcccgac
      901 tggctgtgga aatgaaaact gatctcttga ttgttctttc agatgtagaa ggcctttttg
      961 acagcccccc aggttcagat gatgcaaagc ttattgatat attttatccc ggagatcagc
     1021 agtctgtgac atttggaacc aagtctagag tgggaatggg tggcatggaa gccaaggtga
     1081 aagcagccct ctgggctttg caaggtggca cttctgttgt tattgccaat ggaacccacc
     1141 caaaggtgtc tgggcacgtc atcacagaca ttgtggaggg gaagaaagtt ggtaccttct
     1201 tttcagaagt aaagcctgca ggccctactg ttgagcagca gggagaaatg gcgcgatctg
     1261 gaggaaggat gttggccacc ttggaacctg agcagagagc agaaattatc catcatctgg
     1321 ctgatctgtt gacggaccag cgtgatgaga tcctgttagc caacaaaaaa gacttggagg
     1381 aggcagaggg gagacttgca gctcctctgc tgaaacgttt aagcctctcc acatccaaat
     1441 tgaacagcct ggccatcggt ctgcgacaga tcgcagcctc ctcccaggac agcgtgggac
     1501 gtgttttgcg ccgcacccga atcgccaaaa acttggaact ggaacaagtg actgtcccaa
     1561 ttggagttct gctggtgatc tttgaatctc gtcctgactg tctaccccag gtggcagctt
     1621 tggctatcgc aagtggcaat ggcttgttac tcaaaggagg gaaggaggct gcacacagca
     1681 accggattct ccacctcctg acccaggagg ctctctcaat ccatggagtc aaggaggccg
     1741 tgcaactggt gaataccaga gaagaagttg aagatctttg ccgcctagac aaaatgatag
     1801 atctgatcat tccacgtggc tcttcccagc tggtcagaga catccagaaa gctgctaagg
     1861 ggattccagt gatggggcac agcgaaggga tctgtcacat gtatgtggat tccgaggcca
     1921 gtgttgataa ggtcaccagg ctagtcagag actctaaatg tgaatatcca gctgcctgta
     1981 atgctttgga gactttgtta atccaccggg atctgctcag gacaccatta tttgaccaga
     2041 tcattgatat gctgagagtg gaacaggtaa aaattcatgc aggccccaaa tttgcctcct
     2101 atctgacctt cagcccctcc gaagtgaagt cactccgaac tgagtatggg gacctggaat
     2161 tatgcattga agtagtggac aacgttcagg atgccattga ccacatccac aagtatggca
     2221 gctcccacac ggatgtcatc gtcacagagg acgaaaacac agcggagttc ttcctgcagc
     2281 acgtagacag tgcctgtgtg ttctggaatg ccagcactcg cttttctgat ggttaccgct
     2341 ttggactggg agctgaagtg ggaatcagta catcgagaat ccacgcccgg ggaccagtag
     2401 gacttgaggg actgcttact actaagtggc tgctgcgagg gaaggaccac gtggtctcag
     2461 atttctcaga gcatggaagt ttaaaatatc ttcatgagaa cctccctatt cctcagagaa
     2521 acaccaactg aaaagagcca ggaaaacccg ggaattttcc aaaaggtctt cacgttaaac
     2581 ttgtcttatc tcaggagaga gcccgctctt gtctcccagt tcctggtagg gtctgcctgt
     2641 tggaaagtgt acctggatgc ttctgggctc cgtttggcaa tagcagtctt ggctgatgtg
     2701 cacagtctgg ctcccagctc accctttttt tttaaagtaa gaaaatagtt gctaccgata
     2761 gggactttgc caagtccaat tatcttctag gattgaaagg tgcattttcc ccataaaaaa
     2821 ggcgaggaaa acccatggct gctttgtgtc acctcagtga cttacagtcc cccttggcat
     2881 ttagttggta ctagagccag tcatccttaa caaatctttt cacattttat ttctttcaca
     2941 tgtagtcatc ttcaaaaagg aaagatttgg aattttagaa aaggggcaac tcttcttttt
     3001 agcattctca tcagaaagtc acaaaaatcg atggaatcat ttccactggg aagattgacc
     3061 ttttgtattt atttgtgggg taaattaata agcattccag atgcttgcag cttcctgcat
     3121 ccaggagatg ctgtgttccc cgtgatgcag ctggaaccca agctgcagca ggagatgcaa
     3181 gtttcaggat gttccccact gagctggagg aatatctaca gcagtgatgc ttgaaatttt
     3241 tgtatgaatt attttgtcgt cctacccttt tcctccaaaa caaaaattag aggattattt
     3301 taatactttg gattcttccc ccttttttga gaaataaagt tttttatgaa aa
//
