LOCUS       NM_001080               5131 bp    mRNA    linear   PRI 27-APR-2025
DEFINITION  Homo sapiens aldehyde dehydrogenase 5 family member A1 (ALDH5A1),
            transcript variant 2, mRNA; nuclear gene for mitochondrial product.
ACCESSION   NM_001080
VERSION     NM_001080.3
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 5131)
  AUTHORS   Dong,H., Ma,X., Chen,Z., Zhang,H., Song,J., Jin,Y., Li,M., Lu,M.,
            He,R., Zhang,Y. and Yang,Y.
  TITLE     Clinical features and ALDH5A1 gene findings in 13 Chinese cases
            with succinic semialdehyde dehydrogenase deficiency
  JOURNAL   BMC Med Genomics 17 (1), 158 (2024)
   PUBMED   38862963
  REMARK    GeneRIF: Clinical features and ALDH5A1 gene findings in 13 Chinese
            cases with succinic semialdehyde dehydrogenase deficiency.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 5131)
  AUTHORS   Didiasova,M., Cesaro,S., Feldhoff,S., Bettin,I., Tiegel,N.,
            Fussgen,V., Bertoldi,M. and Tikkanen,R.
  TITLE     Functional Characterization of a Spectrum of Genetic Variants in a
            Family with Succinic Semialdehyde Dehydrogenase Deficiency
  JOURNAL   Int J Mol Sci 25 (10), 5237 (2024)
   PUBMED   38791277
  REMARK    GeneRIF: Functional Characterization of a Spectrum of Genetic
            Variants in a Family with Succinic Semialdehyde Dehydrogenase
            Deficiency.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 5131)
  AUTHORS   Tokatly Latzer,I., Roullet,J.B., Afshar-Saber,W., Lee,H.H.C.,
            Bertoldi,M., McGinty,G.E., DiBacco,M.L., Arning,E., Tsuboyama,M.,
            Rotenberg,A., Opladen,T., Jeltsch,K., Garcia-Cazorla,A.,
            Julia-Palacios,N., Gibson,K.M., Sahin,M. and Pearl,P.L.
  TITLE     Clinical and molecular outcomes from the 5-Year natural history
            study of SSADH Deficiency, a model metabolic neurodevelopmental
            disorder
  JOURNAL   J Neurodev Disord 16 (1), 21 (2024)
   PUBMED   38658850
  REMARK    GeneRIF: Clinical and molecular outcomes from the 5-Year natural
            history study of SSADH Deficiency, a model metabolic
            neurodevelopmental disorder.
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 5131)
  AUTHORS   Afshar-Saber,W., Teaney,N.A., Winden,K.D., Jumo,H., Shi,X.,
            McGinty,G., Hubbs,J., Chen,C., Tokatly Latzer,I., Gasparoli,F.,
            Ebrahimi-Fakhari,D., Buttermore,E.D., Roullet,J.B., Pearl,P.L. and
            Sahin,M.
  TITLE     ALDH5A1-deficient iPSC-derived excitatory and inhibitory neurons
            display cell type specific alterations
  JOURNAL   Neurobiol Dis 190, 106386 (2024)
   PUBMED   38110041
  REMARK    GeneRIF: ALDH5A1-deficient iPSC-derived excitatory and inhibitory
            neurons display cell type specific alterations.
REFERENCE   5  (bases 1 to 5131)
  AUTHORS   Tokatly Latzer,I., Roullet,J.B., Cesaro,S., DiBacco,M.L.,
            Arning,E., Rotenberg,A., Lee,H.H.C., Opladen,T., Jeltsch,K.,
            Garcia-Cazorla,A., Julia-Palacios,N., Gibson,K.M., Bertoldi,M. and
            Pearl,P.L.
  TITLE     Phenotypic correlates of structural and functional protein
            impairments resultant from ALDH5A1 variants
  JOURNAL   Hum Genet 142 (12), 1755-1776 (2023)
   PUBMED   37962671
  REMARK    GeneRIF: Phenotypic correlates of structural and functional protein
            impairments resultant from ALDH5A1 variants.
REFERENCE   6  (bases 1 to 5131)
  AUTHORS   Chambliss,K.L., Hinson,D.D., Trettel,F., Malaspina,P.,
            Novelletto,A., Jakobs,C. and Gibson,K.M.
  TITLE     Two exon-skipping mutations as the molecular basis of succinic
            semialdehyde dehydrogenase deficiency (4-hydroxybutyric aciduria)
  JOURNAL   Am J Hum Genet 63 (2), 399-408 (1998)
   PUBMED   9683595
REFERENCE   7  (bases 1 to 5131)
  AUTHORS   Trettel,F., Malaspina,P., Jodice,C., Novelletto,A., Slaughter,C.A.,
            Caudle,D.L., Hinson,D.D., Chambliss,K.L. and Gibson,K.M.
  TITLE     Human succinic semialdehyde dehydrogenase. Molecular cloning and
            chromosomal localization
  JOURNAL   Adv Exp Med Biol 414, 253-260 (1997)
   PUBMED   9059628
REFERENCE   8  (bases 1 to 5131)
  AUTHORS   Chambliss,K.L., Caudle,D.L., Hinson,D.D., Moomaw,C.R.,
            Slaughter,C.A., Jakobs,C. and Gibson,K.M.
  TITLE     Molecular cloning of the mature NAD(+)-dependent succinic
            semialdehyde dehydrogenase from rat and human. cDNA isolation,
            evolutionary homology, and tissue expression
  JOURNAL   J Biol Chem 270 (1), 461-467 (1995)
   PUBMED   7814412
REFERENCE   9  (bases 1 to 5131)
  AUTHORS   Tokatly Latzer,I., Pearl,P.L. and Roullet,J.B.
  TITLE     Succinic Semialdehyde Dehydrogenase Deficiency
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301374
REFERENCE   10 (bases 1 to 5131)
  AUTHORS   Hearl,W.G. and Churchich,J.E.
  TITLE     Interactions between 4-aminobutyrate aminotransferase and succinic
            semialdehyde dehydrogenase, two mitochondrial enzymes
  JOURNAL   J Biol Chem 259 (18), 11459-11463 (1984)
   PUBMED   6470007
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AL031230.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 27, 2002 this sequence version replaced NM_001080.2.
            
            Summary: This protein belongs to the aldehyde dehydrogenase family
            of proteins. This gene encodes a mitochondrial NAD(+)-dependent
            succinic semialdehyde dehydrogenase. A deficiency of this enzyme,
            known as 4-hydroxybutyricaciduria, is a rare inborn error in the
            metabolism of the neurotransmitter 4-aminobutyric acid (GABA). In
            response to the defect, physiologic fluids from patients accumulate
            GHB, a compound with numerous neuromodulatory properties. Two
            transcript variants encoding distinct isoforms have been identified
            for this gene. [provided by RefSeq, Jul 2008].
            
            Transcript Variant: This variant (2) lacks an in-frame segment of
            the coding region, compared to variant 1. It encodes a shorter
            isoform (2), that is missing an internal segment compared to
            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 :: AJ427355.2, SRR1803615.223234.1
                                           [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                 :: ENST00000357578.8/
                                                  ENSP00000350191.3
            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
            1-382               AL031230.1         38622-39003
            383-466             AL031230.1         46176-46259
            467-637             AL031230.1         46916-47086
            638-754             AL031230.1         48522-48638
            755-898             AL031230.1         58820-58963
            899-1042            AL031230.1         64054-64197
            1043-1201           AL031230.1         66420-66578
            1202-1371           AL031230.1         71650-71819
            1372-1430           AL031230.1         75772-75830
            1431-5131           AL031230.1         77160-80860
FEATURES             Location/Qualifiers
     source          1..5131
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="6"
                     /map="6p22.3"
     gene            1..5131
                     /gene="ALDH5A1"
                     /gene_synonym="SSADH; SSDH"
                     /note="aldehyde dehydrogenase 5 family member A1"
                     /db_xref="GeneID:7915"
                     /db_xref="HGNC:HGNC:408"
                     /db_xref="MIM:610045"
     exon            1..382
                     /gene="ALDH5A1"
                     /gene_synonym="SSADH; SSDH"
                     /inference="alignment:Splign:2.1.0"
     CDS             29..1636
                     /gene="ALDH5A1"
                     /gene_synonym="SSADH; SSDH"
                     /EC_number="1.2.1.24"
                     /note="isoform 2 precursor is encoded by transcript
                     variant 2; mitochondrial succinate semialdehyde
                     dehydrogenase; NAD(+)-dependent succinic semialdehyde
                     dehydrogenase"
                     /codon_start=1
                     /product="succinate-semialdehyde dehydrogenase,
                     mitochondrial isoform 2 precursor"
                     /protein_id="NP_001071.1"
                     /db_xref="CCDS:CCDS4555.1"
                     /db_xref="GeneID:7915"
                     /db_xref="HGNC:HGNC:408"
                     /db_xref="MIM:610045"
                     /translation="MATCIWLRSCGARRLGSTFPGCRLRPRAGGLVPASGPAPGPAQL
                     RCYAGRLAGLSAALLRTDSFVGGRWLPAAATFPVQDPASGAALGMVADCGVREARAAV
                     RAAYEAFCRWREVSAKERSSLLRKWYNLMIQNKDDLARIITAESGKPLKEAHGEILYS
                     AFFLEWFSEEARRVYGDIIHTPAKDRRALVLKQPIGVAAVITPWNFPSAMITRKVGAA
                     LAAGCTVVVKPAEDTPFSALALAELASQAGIPSGVYNVIPCSRKNAKEVGEAICTDPL
                     VSKISFTGSTTTGKILLHHAANSVKRVSMELGGLAPFIVFDSANVDQAVAGAMASKFR
                     NTGQTCVCSNQFLVQRGIHDAFVKAFAEAMKKNLRVGNGFEEGTTQGPLINEKAVEKV
                     EKQVNDAVSKGATVVTGGKRHQLGKNFFEPTLLCNVTQDMLCTHEETFGPLAPVIKFD
                     TEEEAIAIANAADVGLAGYFYSQDPAQIWRVAEQLEVGMVGVNEGLISSVECPFGGVK
                     QSGLGREGSKYGIDEYLELKYVCYGGL"
     exon            383..466
                     /gene="ALDH5A1"
                     /gene_synonym="SSADH; SSDH"
                     /inference="alignment:Splign:2.1.0"
     exon            467..637
                     /gene="ALDH5A1"
                     /gene_synonym="SSADH; SSDH"
                     /inference="alignment:Splign:2.1.0"
     exon            638..754
                     /gene="ALDH5A1"
                     /gene_synonym="SSADH; SSDH"
                     /inference="alignment:Splign:2.1.0"
     exon            755..898
                     /gene="ALDH5A1"
                     /gene_synonym="SSADH; SSDH"
                     /inference="alignment:Splign:2.1.0"
     exon            899..1042
                     /gene="ALDH5A1"
                     /gene_synonym="SSADH; SSDH"
                     /inference="alignment:Splign:2.1.0"
     exon            1043..1201
                     /gene="ALDH5A1"
                     /gene_synonym="SSADH; SSDH"
                     /inference="alignment:Splign:2.1.0"
     exon            1202..1371
                     /gene="ALDH5A1"
                     /gene_synonym="SSADH; SSDH"
                     /inference="alignment:Splign:2.1.0"
     exon            1372..1430
                     /gene="ALDH5A1"
                     /gene_synonym="SSADH; SSDH"
                     /inference="alignment:Splign:2.1.0"
     exon            1431..5131
                     /gene="ALDH5A1"
                     /gene_synonym="SSADH; SSDH"
                     /inference="alignment:Splign:2.1.0"
     regulatory      5095..5100
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ALDH5A1"
                     /gene_synonym="SSADH; SSDH"
                     /note="hexamer: AATAAA"
     polyA_site      5131
                     /gene="ALDH5A1"
                     /gene_synonym="SSADH; SSDH"
                     /note="major polyA site"
ORIGIN      
        1 gtttcctgtc gccgtcgttg cccgggccat ggcgacctgc atttggctgc ggagctgtgg
       61 ggcccggcgc ctcgggtcga cgtttccagg ctgccgcctc cgcccccgcg ccggcggcct
      121 ggtccctgcc tccgggcctg cgcccggccc ggcccagctc cgctgctacg ctgggcgcct
      181 ggcgggcctc tctgcggcgc tgctgcgcac cgacagcttc gtgggcggcc gctggctccc
      241 ggccgccgcc accttccccg tgcaagaccc ggccagcggc gccgctctgg gcatggtagc
      301 cgactgcggg gtgcgagagg cccgcgccgc cgtgcgcgct gcctacgagg ctttctgccg
      361 ctggagggag gtctccgcca aggagaggag ttcattactt cggaagtggt acaatttaat
      421 gatacaaaat aaggatgacc ttgccagaat aatcacagct gaaagtggaa agccactgaa
      481 ggaggcacat ggagaaattc tctattccgc ctttttccta gagtggttct ctgaggaagc
      541 ccgccgtgtt tacggagaca ttatccacac cccggcaaag gacaggcggg ccctggtcct
      601 caagcagccc ataggcgtgg ctgcagtcat caccccgtgg aatttcccca gtgccatgat
      661 cacccggaag gtgggggccg ccctggcagc cggctgtact gtcgtggtga agcctgccga
      721 agacacgccc ttctccgccc tggccctggc tgagcttgca agccaggctg ggattccttc
      781 aggtgtatac aatgttattc cctgttctcg aaagaatgcc aaggaagtag gggaggcaat
      841 ttgtactgat cctctggtgt ccaaaatttc ctttactggt tcaacaacta caggaaagat
      901 cctgttgcac cacgcagcaa actctgtgaa aagggtctct atggagctgg gcggccttgc
      961 tccatttata gtatttgaca gtgccaacgt ggaccaggct gtagcagggg ccatggcatc
     1021 taaatttagg aacactggac agacttgtgt ttgctcaaac caattcttgg tgcaaagggg
     1081 catccatgat gcctttgtaa aagcattcgc cgaggccatg aagaagaacc tgcgcgtagg
     1141 taatggattt gaggaaggaa ctactcaggg cccattaatt aatgaaaaag cggtagaaaa
     1201 ggtggagaaa caggtgaatg atgccgtttc taaaggtgcc accgttgtga caggtggaaa
     1261 acgacaccaa cttggaaaaa atttctttga gcctaccctg ctgtgcaatg tcacccagga
     1321 catgctgtgc actcatgaag agactttcgg gcctctggca ccagttatca agttcgatac
     1381 agaggaggag gctatagcaa tcgctaacgc agctgatgtt gggttagcag gttattttta
     1441 ctctcaagac ccagcccaga tctggagagt ggcagagcag ctggaagtgg gcatggttgg
     1501 cgtcaacgaa ggattaattt cctctgtgga gtgccctttt ggtggagtga agcagtccgg
     1561 ccttgggcga gaggggtcca agtatggcat tgatgagtat ctggaactca agtatgtgtg
     1621 ttacgggggc ttgtaggatt ctttggttct ttaaaaaaat ttaaaaggag acttatctac
     1681 atatataggt acatgccatc cattatttta aataaactaa taggttttca gaattatgaa
     1741 tttttcagaa ctcatccagt ccttgtaatc ttaaacagat gcaaatccta cccctgccct
     1801 taatgtaact agggaccaat atgtgccacg tgcctgtggc tgcagactcc cagagaacca
     1861 gcactgggtt tacagaatga ggccctggct ccccaccaca gccccagctg cctcagagca
     1921 ggcacagcac aaggcaggcc cagccccatg ggccgtcaca aaggcttgat cactgcctgg
     1981 gcagtggcac aaccatcccc catgtcgcta cagaacatgg gcccagagca ccttgaagga
     2041 gacccttgac tgtgactggc aggcaggtga ggggcacagc acccctcccc ggcatctgcc
     2101 agctcagcac agaagacacc gaatgtgcat ctggaggtgt tgcggcagag gtttgagtga
     2161 accctctttc aaagacaata aatagcacag aattgtccgt gcttctgtga ggcacgaagg
     2221 agcacctctc cctattcctg aaccatattt taattgatgc ctttattgtc ccaaatttac
     2281 cacttaaaga attctatttt catttctgtc ctgtttgcca cttcatttca tttccttgag
     2341 taaatgagct gaagtgtaaa gcaaagaata gcagaagcag cttggtagga tggaaggcac
     2401 gcagtggcat ggcctggctc cttccctgag tggccttgtt gccttgggcg tgtgttcagc
     2461 acctcccatc ccatggatac agtggagatt ccatacaggc cttacttagc tccttgcgat
     2521 actgtgagcc agagagaaag taaaagcact tcacaaaaaa atgaaaattc taaggacata
     2581 caagagccat tgttacgagc agcaccgccc agcccttcct tgcctactgt cagtggcttt
     2641 gccaagatgg gaggaggcca gtgcccactt gcccaccgac ctgagcctga gtaagtggct
     2701 gtcacctgag cctgttcttt ctgtcctggt gtggtgctgc tccctcacct ccaaaagagc
     2761 aaaagtactt tcaccacagt caacccaaaa gggaaagaat ttctgtaatt gccaacccac
     2821 tttgtagaag aggcatgagc ccttgaattt caggcacctt ttatctaatg agagttttta
     2881 cagctcatca ttcaaataac gcacaaaaaa caaaagccgc tatgaccggc gttgcctctc
     2941 actttgaaag aaagactccg taatcttaaa cagatgcaaa tccaattagg cggccaagta
     3001 ggtggagacg aagcaccttc ctttccccat ctctgtctgt gtagactcca cttacatctt
     3061 gtggttattc tgggttgtgg aaggaaaatg tgaatgaaag tagtgctgga tgcaattact
     3121 cctgaacccc acctaggatt taacatccct cattgagcca ctgggaagct atggttgagt
     3181 aactaaaggt ctggcaagac cctgggcaca cagggagctg cctagcatct ggcctggagt
     3241 gtactagcca cattcccaag gtcccaagga gaaggaagag ctgaaattca tctcctagtg
     3301 acagtgcccc ggccctgtca agaatcacat actcagcatt ttgacagtta atgtcttctc
     3361 tttatttgtg tagtttttag gtggttttat ataacatttt aattacttgt gatttagatg
     3421 tatccatcct ttttctatta agaatacaaa tgctgggctg ggcacagtgg ctcacgcctg
     3481 taatcccaac accttgggag gccaaggcag gcagatcacg acatcaggag atcgagacca
     3541 tcctggctaa cacggtgaaa ccccgtctct actaaaaata caaaaaaaat tagtcggatg
     3601 tggtggcagg tgcctgtagt cccagctact ctggaggctg aggcaggaga atggcgtgaa
     3661 cccaggaggc ggagcttgca gtgagcagag atcacgccac tgcactccag cctggatgac
     3721 agagcgagac tccgcctcaa aaaaagaata caaatgctcc aacattattt tttataactc
     3781 tggattaccg atgctgagat gtgtgcagga atacttccaa ataaattttt aacattgtaa
     3841 gccagtagat tctttggctg ggtggcaaat tttgagtctt cttgcatatt tggctcatgg
     3901 gttcataaat tgaggccaga gactcattgt atatccttga tcaattttct aattaaagga
     3961 aatagcttat tgtttagtaa aatggccctt ggttgtggga agaaagagaa ttatttttaa
     4021 ctgaacgttt ttgttgtttt ttaaataaag tagccatatg taacgggatt ttaaaaatat
     4081 atacatttta caacatggac tagaaaagga ccattagatc aggggttggc aaactatggc
     4141 ccacgaatca aacctggcct gccacctgtt tttatacaac ctgtgagcta agaatggttt
     4201 atatgttttc aaatgattgg gcagaaaatc aaaagaagaa caatatttca tgacacctga
     4261 aaattctatg aaattcagat ttcagtgtcc ataaacaaaa tgttattaga gcatagccac
     4321 acccattcat ttatggtatt gtctgggact gctttcttgg cagagttgaa tagttgggac
     4381 agggacagta tagcctgcaa agcctaaaag atttactact tgtctcctta aagaaaaagt
     4441 ttgccagctc ctgatctaga ccaagaggga gatattgacc ttacttgcat ttatccggca
     4501 ttatttcaac acctcctgtg aagaaagtac ttttctggca tagctaccgt gagttctcag
     4561 caggaacttc ccagcgatga taatgtacat gaaattagcc acgtaacaag agtctatttg
     4621 ccttgaaaaa acaattatcc ttgaacttcc tccagctatg cagggattct cattaaagag
     4681 ctgatctgca tctgtttatc cattttagta gcttttaaat atgattttat gtgaagtgcc
     4741 atttctttat tctactaaag agagacagca gaaataaaga tcagaagcaa atgtgagcaa
     4801 atctgtttta ctgttaactt caattatgaa cttgaaattg tgccacatga ctttttcctc
     4861 taaaaactgg atcctagtgt tttaattacc tgtgtgcagc tattttaaat agcattttac
     4921 ttgaataata tgtatgttgt cattgtttca tgctatactt tgtgggataa aacttgggaa
     4981 tgagtgtggt aagaaattta taaagttttg cttttaaaac gtggacataa ctcatttttc
     5041 tagtttttga caattgtgtg ttttagtgtc tagtctgcag agagctgtgt gattaataaa
     5101 cgtggaatta acagaatttc ctctccctgt a
//
