LOCUS       NM_000169               1318 bp    mRNA    linear   PRI 12-OCT-2024
DEFINITION  Homo sapiens galactosidase alpha (GLA), transcript variant 1, mRNA.
ACCESSION   NM_000169
VERSION     NM_000169.3
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 1318)
  AUTHORS   Peng,Y., Pan,M., Wang,Y., Shen,Z., Xu,J., Xiong,F., Xiao,H. and
            Miao,Y.
  TITLE     Identification of a novel nonsense mutation in alpha-galactosidase
            A that causes Fabry disease in a Chinese family
  JOURNAL   Ren Fail 46 (2), 2362391 (2024)
   PUBMED   38847497
  REMARK    GeneRIF: Identification of a novel nonsense mutation in
            alpha-galactosidase A that causes Fabry disease in a Chinese
            family.
REFERENCE   2  (bases 1 to 1318)
  AUTHORS   Li,P., Xi,Y., Zhang,Y., Samad,A., Lan,W., Wu,Y., Zhao,J., Chen,G.,
            Wu,C. and Xiong,Q.
  TITLE     GLA Mutations Suppress Autophagy and Stimulate Lysosome Generation
            in Fabry Disease
  JOURNAL   Cells 13 (5), 437 (2024)
   PUBMED   38474401
  REMARK    GeneRIF: GLA Mutations Suppress Autophagy and Stimulate Lysosome
            Generation in Fabry Disease.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 1318)
  AUTHORS   Romani,I., Sarti,C., Nencini,P., Pracucci,G., Zedde,M., Cianci,V.,
            Nucera,A., Moller,J., Orsucci,D., Toni,D., Palumbo,P., Casella,C.,
            Pinto,V., Barbarini,L., Bella,R., Scoditti,U., Ragno,M.,
            Mezzapesa,D.M., Tassi,R., Volpi,G., Diomedi,M., Bigliardi,G.,
            Cavallini,A.M., Chiti,A., Ricci,S., Cecconi,E., Linoli,G.,
            Sacco,S., Rasura,M., Giordano,A., Bonetti,B., Melis,M.,
            Cariddi,L.P., Dossi,R.C., Grisendi,I., Aguglia,U., Di Ruzza,M.R.,
            Melis,M., Sbardella,E., Vista,M., Valenti,R., Musolino,R.F.,
            Passarella,B., Direnzo,V., Pennisi,G., Genovese,A., Di Marzio,F.,
            Sgobio,R., Acampa,M., Nannucci,S., Dagostino,F., Dell'Acqua,M.L.,
            Cuzzoni,M.G., Picchioni,A., Calchetti,B., Notturno,F., Di Lisi,F.,
            Forlivesi,S., Delodovici,M.L., Buechner,S.C., Biagini,S.,
            Accavone,D., Manna,R., Morrone,A. and Inzitari,D.
  TITLE     Prevalence of Fabry disease and GLA variants in young patients with
            acute stroke: The challenge to widen the screening. The
            Fabry-Stroke Italian Registry
  JOURNAL   J Neurol Sci 457, 122905 (2024)
   PUBMED   38295534
  REMARK    GeneRIF: Prevalence of Fabry disease and GLA variants in young
            patients with acute stroke: The challenge to widen the screening.
            The Fabry-Stroke Italian Registry.
REFERENCE   4  (bases 1 to 1318)
  AUTHORS   Monda,E., Diana,G., Graziani,F., Rubino,M., Bakalakos,A.,
            Linhart,A., Germain,D.P., Scarpa,M., Biagini,E., Pieroni,M.,
            Elliott,P.M. and Limongelli,G.
  TITLE     Impact of GLA Variant Classification on the Estimated Prevalence of
            Fabry Disease: A Systematic Review and Meta-Analysis of Screening
            Studies
  JOURNAL   Circ Genom Precis Med 16 (6), e004252 (2023)
   PUBMED   38047356
  REMARK    GeneRIF: Impact of GLA Variant Classification on the Estimated
            Prevalence of Fabry Disease: A Systematic Review and Meta-Analysis
            of Screening Studies.
REFERENCE   5  (bases 1 to 1318)
  AUTHORS   Riillo,C., Bonapace,G., Moricca,M.T., Sestito,S., Salatino,A. and
            Concolino,D.
  TITLE     c.376A>G, (p.Ser126Gly) Alpha-Galactosidase A mutation induces ER
            stress, unfolded protein response and reduced enzyme trafficking to
            lysosome: Possible relevance in the pathogenesis of late-onset
            forms of Fabry Disease
  JOURNAL   Mol Genet Metab 140 (3), 107700 (2023)
   PUBMED   37774431
  REMARK    GeneRIF: c.376A>G, (p.Ser126Gly) Alpha-Galactosidase A mutation
            induces ER stress, unfolded protein response and reduced enzyme
            trafficking to lysosome: Possible relevance in the pathogenesis of
            late-onset forms of Fabry Disease.
REFERENCE   6  (bases 1 to 1318)
  AUTHORS   Mehta,A. and Hughes,D.A.
  TITLE     Fabry Disease
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301469
REFERENCE   7  (bases 1 to 1318)
  AUTHORS   Ioannou,Y.A., Bishop,D.F. and Desnick,R.J.
  TITLE     Overexpression of human alpha-galactosidase A results in its
            intracellular aggregation, crystallization in lysosomes, and
            selective secretion
  JOURNAL   J Cell Biol 119 (5), 1137-1150 (1992)
   PUBMED   1332979
REFERENCE   8  (bases 1 to 1318)
  AUTHORS   Ishii,S., Sakuraba,H. and Suzuki,Y.
  TITLE     Point mutations in the upstream region of the alpha-galactosidase A
            gene exon 6 in an atypical variant of Fabry disease
  JOURNAL   Hum Genet 89 (1), 29-32 (1992)
   PUBMED   1315715
REFERENCE   9  (bases 1 to 1318)
  AUTHORS   von Scheidt,W., Eng,C.M., Fitzmaurice,T.F., Erdmann,E., Hubner,G.,
            Olsen,E.G., Christomanou,H., Kandolf,R., Bishop,D.F. and
            Desnick,R.J.
  TITLE     An atypical variant of Fabry's disease with manifestations confined
            to the myocardium
  JOURNAL   N Engl J Med 324 (6), 395-399 (1991)
   PUBMED   1846223
REFERENCE   10 (bases 1 to 1318)
  AUTHORS   Dean,K.J. and Sweeley,C.C.
  TITLE     Studies on human liver alpha-galactosidases. I. Purification of
            alpha-galactosidase A and its enzymatic properties with glycolipid
            and oligosaccharide substrates
  JOURNAL   J Biol Chem 254 (20), 9994-10000 (1979)
   PUBMED   39940
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AL035422.12, BC002689.2 and
            DB370480.1.
            
            On Nov 12, 2019 this sequence version replaced NM_000169.2.
            
            Summary: This gene encodes a homodimeric glycoprotein that
            hydrolyses the terminal alpha-galactosyl moieties from glycolipids
            and glycoproteins. This enzyme predominantly hydrolyzes ceramide
            trihexoside, and it can catalyze the hydrolysis of melibiose into
            galactose and glucose. A variety of mutations in this gene affect
            the synthesis, processing, and stability of this enzyme, which
            causes Fabry disease, a rare lysosomal storage disorder that
            results from a failure to catabolize alpha-D-galactosyl glycolipid
            moieties. [provided by RefSeq, Jul 2008].
            
            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 :: AK222627.1, X05790.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000218516.4/ ENSP00000218516.4
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-16                AL035422.12        89686-89701         c
            17-1314             BC002689.2         1-1298
            1315-1318           DB370480.1         13-16               c
FEATURES             Location/Qualifiers
     source          1..1318
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="X"
                     /map="Xq22.1"
     gene            1..1318
                     /gene="GLA"
                     /gene_synonym="GALA"
                     /note="galactosidase alpha"
                     /db_xref="GeneID:2717"
                     /db_xref="HGNC:HGNC:4296"
                     /db_xref="MIM:300644"
     exon            1..216
                     /gene="GLA"
                     /gene_synonym="GALA"
                     /inference="alignment:Splign:2.1.0"
     CDS             23..1312
                     /gene="GLA"
                     /gene_synonym="GALA"
                     /EC_number="3.2.1.22"
                     /note="isoform b precursor is encoded by transcript
                     variant 1; alpha-D-galactosidase A; alpha-gal A;
                     melibiase; alpha-D-galactoside galactohydrolase 1;
                     agalsidase alfa; alpha-galactosidase A;
                     galactosylgalactosylglucosylceramidase GLA"
                     /codon_start=1
                     /product="alpha-galactosidase A isoform b precursor"
                     /protein_id="NP_000160.1"
                     /db_xref="CCDS:CCDS14484.1"
                     /db_xref="GeneID:2717"
                     /db_xref="HGNC:HGNC:4296"
                     /db_xref="MIM:300644"
                     /translation="MQLRNPELHLGCALALRFLALVSWDIPGARALDNGLARTPTMGW
                     LHWERFMCNLDCQEEPDSCISEKLFMEMAELMVSEGWKDAGYEYLCIDDCWMAPQRDS
                     EGRLQADPQRFPHGIRQLANYVHSKGLKLGIYADVGNKTCAGFPGSFGYYDIDAQTFA
                     DWGVDLLKFDGCYCDSLENLADGYKHMSLALNRTGRSIVYSCEWPLYMWPFQKPNYTE
                     IRQYCNHWRNFADIDDSWKSIKSILDWTSFNQERIVDVAGPGGWNDPDMLVIGNFGLS
                     WNQQVTQMALWAIMAAPLFMSNDLRHISPQAKALLQDKDVIAINQDPLGKQGYQLRQG
                     DNFEVWERPLSGLAWAVAMINRQEIGGPRSYTIAVASLGKGVACNPACFITQLLPVKR
                     KLGFYEWTSRLRSHINPTGTVLLQLENTMQMSLKDLL"
     exon            217..391
                     /gene="GLA"
                     /gene_synonym="GALA"
                     /inference="alignment:Splign:2.1.0"
     exon            392..569
                     /gene="GLA"
                     /gene_synonym="GALA"
                     /inference="alignment:Splign:2.1.0"
     exon            570..661
                     /gene="GLA"
                     /gene_synonym="GALA"
                     /inference="alignment:Splign:2.1.0"
     exon            662..823
                     /gene="GLA"
                     /gene_synonym="GALA"
                     /inference="alignment:Splign:2.1.0"
     exon            824..1021
                     /gene="GLA"
                     /gene_synonym="GALA"
                     /inference="alignment:Splign:2.1.0"
     exon            1022..1318
                     /gene="GLA"
                     /gene_synonym="GALA"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1294..1299
                     /regulatory_class="polyA_signal_sequence"
                     /gene="GLA"
                     /gene_synonym="GALA"
                     /note="hexamer: ATTAAA"
     polyA_site      1318
                     /gene="GLA"
                     /gene_synonym="GALA"
                     /note="major polyA site"
ORIGIN      
        1 atgctgtccg gtcaccgtga caatgcagct gaggaaccca gaactacatc tgggctgcgc
       61 gcttgcgctt cgcttcctgg ccctcgtttc ctgggacatc cctggggcta gagcactgga
      121 caatggattg gcaaggacgc ctaccatggg ctggctgcac tgggagcgct tcatgtgcaa
      181 ccttgactgc caggaagagc cagattcctg catcagtgag aagctcttca tggagatggc
      241 agagctcatg gtctcagaag gctggaagga tgcaggttat gagtacctct gcattgatga
      301 ctgttggatg gctccccaaa gagattcaga aggcagactt caggcagacc ctcagcgctt
      361 tcctcatggg attcgccagc tagctaatta tgttcacagc aaaggactga agctagggat
      421 ttatgcagat gttggaaata aaacctgcgc aggcttccct gggagttttg gatactacga
      481 cattgatgcc cagacctttg ctgactgggg agtagatctg ctaaaatttg atggttgtta
      541 ctgtgacagt ttggaaaatt tggcagatgg ttataagcac atgtccttgg ccctgaatag
      601 gactggcaga agcattgtgt actcctgtga gtggcctctt tatatgtggc cctttcaaaa
      661 gcccaattat acagaaatcc gacagtactg caatcactgg cgaaattttg ctgacattga
      721 tgattcctgg aaaagtataa agagtatctt ggactggaca tcttttaacc aggagagaat
      781 tgttgatgtt gctggaccag ggggttggaa tgacccagat atgttagtga ttggcaactt
      841 tggcctcagc tggaatcagc aagtaactca gatggccctc tgggctatca tggctgctcc
      901 tttattcatg tctaatgacc tccgacacat cagccctcaa gccaaagctc tccttcagga
      961 taaggacgta attgccatca atcaggaccc cttgggcaag caagggtacc agcttagaca
     1021 gggagacaac tttgaagtgt gggaacgacc tctctcaggc ttagcctggg ctgtagctat
     1081 gataaaccgg caggagattg gtggacctcg ctcttatacc atcgcagttg cttccctggg
     1141 taaaggagtg gcctgtaatc ctgcctgctt catcacacag ctcctccctg tgaaaaggaa
     1201 gctagggttc tatgaatgga cttcaaggtt aagaagtcac ataaatccca caggcactgt
     1261 tttgcttcag ctagaaaata caatgcagat gtcattaaaa gacttacttt aaaatgtt
//
