LOCUS       NM_020944               3611 bp    mRNA    linear   PRI 07-OCT-2024
DEFINITION  Homo sapiens glucosylceramidase beta 2 (GBA2), transcript variant
            1, mRNA.
ACCESSION   NM_020944
VERSION     NM_020944.3
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 3611)
  AUTHORS   Kloth,K., Cozma,C., Bester,M., Gerloff,C., Biskup,S. and Zittel,S.
  TITLE     Dystonia as initial presentation of compound heterozygous GBA2
            mutations: Expanding the phenotypic spectrum of SPG46
  JOURNAL   Eur J Med Genet 63 (9), 103992 (2020)
   PUBMED   32590105
  REMARK    GeneRIF: Dystonia as initial presentation of compound heterozygous
            GBA2 mutations: Expanding the phenotypic spectrum of SPG46.
REFERENCE   2  (bases 1 to 3611)
  AUTHORS   Sultana,S., Stewart,J. and van der Spoel,A.C.
  TITLE     Truncated mutants of beta-glucosidase 2 (GBA2) are localized in the
            mitochondrial matrix and cause mitochondrial fragmentation
  JOURNAL   PLoS One 15 (6), e0233856 (2020)
   PUBMED   32492073
  REMARK    GeneRIF: Truncated mutants of beta-glucosidase 2 (GBA2) are
            localized in the mitochondrial matrix and cause mitochondrial
            fragmentation.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 3611)
  AUTHORS   Woeste,M.A., Stern,S., Raju,D.N., Grahn,E., Dittmann,D.,
            Gutbrod,K., Dormann,P., Hansen,J.N., Schonauer,S., Marx,C.E.,
            Hamzeh,H., Korschen,H.G., Aerts,J.M.F.G., Bonigk,W., Endepols,H.,
            Sandhoff,R., Geyer,M., Berger,T.K., Bradke,F. and Wachten,D.
  TITLE     Species-specific differences in nonlysosomal glucosylceramidase
            GBA2 function underlie locomotor dysfunction arising from
            loss-of-function mutations
  JOURNAL   J Biol Chem 294 (11), 3853-3871 (2019)
   PUBMED   30662006
  REMARK    GeneRIF: results shed light on the molecular mechanism underlying
            the pathogenesis of GBA2-related hereditary spastic paraplegia
            (HSP), autosomal-recessive cerebellar ataxia (ARCA) and reveal
            species-specific differences in GBA2 function in vivo
REFERENCE   4  (bases 1 to 3611)
  AUTHORS   Malekkou,A., Samarani,M., Drousiotou,A., Votsi,C., Sonnino,S.,
            Pantzaris,M., Chiricozzi,E., Zamba-Papanicolaou,E., Aureli,M.,
            Loberto,N. and Christodoulou,K.
  TITLE     Biochemical Characterization of the GBA2 c.1780G>C Missense
            Mutation in Lymphoblastoid Cells from Patients with Spastic Ataxia
  JOURNAL   Int J Mol Sci 19 (10), 3099 (2018)
   PUBMED   30308956
  REMARK    GeneRIF: We conclude that the c.1780G>C mutation results in NLGase
            loss of function with abolishment of the enzymatic activity and
            accumulation of GlcCer accompanied by a compensatory increase in
            GCase.
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 3611)
  AUTHORS   Schiumarini,D., Loberto,N., Mancini,G., Bassi,R., Giussani,P.,
            Chiricozzi,E., Samarani,M., Munari,S., Tamanini,A., Cabrini,G.,
            Lippi,G., Dechecchi,M.C., Sonnino,S. and Aureli,M.
  TITLE     Evidence for the Involvement of Lipid Rafts and Plasma Membrane
            Sphingolipid Hydrolases in Pseudomonas aeruginosa Infection of
            Cystic Fibrosis Bronchial Epithelial Cells
  JOURNAL   Mediators Inflamm 2017, 1730245 (2017)
   PUBMED   29333001
  REMARK    GeneRIF: Demonstrate that GBA2 plays a role in the proinflammatory
            state characterizing cystic fibrosis cells. Report for the first
            time that Pseudomonas aeruginosa infection causes a recruitment of
            plasma membrane-associated glycosphingolipid hydrolases into lipid
            rafts of CuFi-1-infected cells.
REFERENCE   6  (bases 1 to 3611)
  AUTHORS   Yildiz,Y., Matern,H., Thompson,B., Allegood,J.C., Warren,R.L.,
            Ramirez,D.M., Hammer,R.E., Hamra,F.K., Matern,S. and Russell,D.W.
  TITLE     Mutation of beta-glucosidase 2 causes glycolipid storage disease
            and impaired male fertility
  JOURNAL   J Clin Invest 116 (11), 2985-2994 (2006)
   PUBMED   17080196
REFERENCE   7  (bases 1 to 3611)
  AUTHORS   Humphray,S.J., Oliver,K., Hunt,A.R., Plumb,R.W., Loveland,J.E.,
            Howe,K.L., Andrews,T.D., Searle,S., Hunt,S.E., Scott,C.E.,
            Jones,M.C., Ainscough,R., Almeida,J.P., Ambrose,K.D., Ashwell,R.I.,
            Babbage,A.K., Babbage,S., Bagguley,C.L., Bailey,J., Banerjee,R.,
            Barker,D.J., Barlow,K.F., Bates,K., Beasley,H., Beasley,O.,
            Bird,C.P., Bray-Allen,S., Brown,A.J., Brown,J.Y., Burford,D.,
            Burrill,W., Burton,J., Carder,C., Carter,N.P., Chapman,J.C.,
            Chen,Y., Clarke,G., Clark,S.Y., Clee,C.M., Clegg,S., Collier,R.E.,
            Corby,N., Crosier,M., Cummings,A.T., Davies,J., Dhami,P., Dunn,M.,
            Dutta,I., Dyer,L.W., Earthrowl,M.E., Faulkner,L., Fleming,C.J.,
            Frankish,A., Frankland,J.A., French,L., Fricker,D.G., Garner,P.,
            Garnett,J., Ghori,J., Gilbert,J.G., Glison,C., Grafham,D.V.,
            Gribble,S., Griffiths,C., Griffiths-Jones,S., Grocock,R., Guy,J.,
            Hall,R.E., Hammond,S., Harley,J.L., Harrison,E.S., Hart,E.A.,
            Heath,P.D., Henderson,C.D., Hopkins,B.L., Howard,P.J., Howden,P.J.,
            Huckle,E., Johnson,C., Johnson,D., Joy,A.A., Kay,M., Keenan,S.,
            Kershaw,J.K., Kimberley,A.M., King,A., Knights,A., Laird,G.K.,
            Langford,C., Lawlor,S., Leongamornlert,D.A., Leversha,M., Lloyd,C.,
            Lloyd,D.M., Lovell,J., Martin,S., Mashreghi-Mohammadi,M.,
            Matthews,L., McLaren,S., McLay,K.E., McMurray,A., Milne,S.,
            Nickerson,T., Nisbett,J., Nordsiek,G., Pearce,A.V., Peck,A.I.,
            Porter,K.M., Pandian,R., Pelan,S., Phillimore,B., Povey,S.,
            Ramsey,Y., Rand,V., Scharfe,M., Sehra,H.K., Shownkeen,R.,
            Sims,S.K., Skuce,C.D., Smith,M., Steward,C.A., Swarbreck,D.,
            Sycamore,N., Tester,J., Thorpe,A., Tracey,A., Tromans,A.,
            Thomas,D.W., Wall,M., Wallis,J.M., West,A.P., Whitehead,S.L.,
            Willey,D.L., Williams,S.A., Wilming,L., Wray,P.W., Young,L.,
            Ashurst,J.L., Coulson,A., Blocker,H., Durbin,R., Sulston,J.E.,
            Hubbard,T., Jackson,M.J., Bentley,D.R., Beck,S., Rogers,J. and
            Dunham,I.
  TITLE     DNA sequence and analysis of human chromosome 9
  JOURNAL   Nature 429 (6990), 369-374 (2004)
   PUBMED   15164053
REFERENCE   8  (bases 1 to 3611)
  AUTHORS   Matern,H., Boermans,H., Lottspeich,F. and Matern,S.
  TITLE     Molecular cloning and expression of human bile acid
            beta-glucosidase
  JOURNAL   J Biol Chem 276 (41), 37929-37933 (2001)
   PUBMED   11489889
REFERENCE   9  (bases 1 to 3611)
  AUTHORS   Matern,H., Heinemann,H., Legler,G. and Matern,S.
  TITLE     Purification and characterization of a microsomal bile acid
            beta-glucosidase from human liver
  JOURNAL   J Biol Chem 272 (17), 11261-11267 (1997)
   PUBMED   9111029
REFERENCE   10 (bases 1 to 3611)
  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 AJ309567.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 23, 2018 this sequence version replaced NM_020944.2.
            
            Summary: This gene encodes a microsomal beta-glucosidase that
            catalyzes the hydrolysis of bile acid 3-O-glucosides as endogenous
            compounds. Studies to determine subcellular localization of this
            protein in the liver indicated that the enzyme was mainly enriched
            in the microsomal fraction where it appeared to be confined to the
            endoplasmic reticulum. This putative transmembrane protein is
            thought to play a role in carbohydrate transport and metabolism.
            [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 :: AJ309567.1, SRR1803615.253153.1
                                           [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000378103.7/ ENSP00000367343.3
            RefSeq Select criteria :: based on conservation, expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-3611              AJ309567.1         1-3611
FEATURES             Location/Qualifiers
     source          1..3611
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="9"
                     /map="9p13.3"
     gene            1..3611
                     /gene="GBA2"
                     /gene_synonym="AD035; NLGase; SPG46"
                     /note="glucosylceramidase beta 2"
                     /db_xref="GeneID:57704"
                     /db_xref="HGNC:HGNC:18986"
                     /db_xref="MIM:609471"
     exon            1..883
                     /gene="GBA2"
                     /gene_synonym="AD035; NLGase; SPG46"
                     /inference="alignment:Splign:2.1.0"
     CDS             525..3308
                     /gene="GBA2"
                     /gene_synonym="AD035; NLGase; SPG46"
                     /EC_number="3.2.1.45"
                     /EC_number="3.2.1.46"
                     /note="isoform 1 is encoded by transcript variant 1;
                     non-lysosomal glucosylceramidase; glucosylceramidase 2;
                     beta-glucocerebrosidase 2; glucosidase, beta (bile acid)
                     2; bile acid beta-glucosidase GBA2;
                     cholesteryl-beta-glucosidase GBA2; bile acid glucosyl
                     transferase GBA2; cholesterol glucosyltransferase GBA2;
                     non-lysosomal glycosylceramidase; non-lysosomal
                     galactosylceramidase; non-lysosomal cholesterol
                     glycosyltransferase"
                     /codon_start=1
                     /product="non-lysosomal glucosylceramidase isoform 1"
                     /protein_id="NP_065995.1"
                     /db_xref="CCDS:CCDS6589.1"
                     /db_xref="GeneID:57704"
                     /db_xref="HGNC:HGNC:18986"
                     /db_xref="MIM:609471"
                     /translation="MGTQDPGNMGTGVPASEQISCAKEDPQVYCPEETGGTKDVQVTD
                     CKSPEDSRPPKETDCCNPEDSGQLMVSYEGKAMGYQVPPFGWRICLAHEFTEKRKPFQ
                     ANNVSLSNMIKHIGMGLRYLQWWYRKTHVEKKTPFIDMINSVPLRQIYGCPLGGIGGG
                     TITRGWRGQFCRWQLNPGMYQHRTVIADQFTVCLRREGQTVYQQVLSLERPSVLRSWN
                     WGLCGYFAFYHALYPRAWTVYQLPGQNVTLTCRQITPILPHDYQDSSLPVGVFVWDVE
                     NEGDEALDVSIMFSMRNGLGGGDDAPGGLWNEPFCLERSGETVRGLLLHHPTLPNPYT
                     MAVAARVTAATTVTHITAFDPDSTGQQVWQDLLQDGQLDSPTGQSTPTQKGVGIAGAV
                     CVSSKLRPRGQCRLEFSLAWDMPRIMFGAKGQVHYRRYTRFFGQDGDAAPALSHYALC
                     RYAEWEERISAWQSPVLDDRSLPAWYKSALFNELYFLADGGTVWLEVLEDSLPEELGR
                     NMCHLRPTLRDYGRFGYLEGQEYRMYNTYDVHFYASFALIMLWPKLELSLQYDMALAT
                     LREDLTRRRYLMSGVMAPVKRRNVIPHDIGDPDDEPWLRVNAYLIHDTADWKDLNLKF
                     VLQVYRDYYLTGDQNFLKDMWPVCLAVMESEMKFDKDHDGLIENGGYADQTYDGWVTT
                     GPSAYCGGLWLAAVAVMVQMAALCGAQDIQDKFSSILSRGQEAYERLLWNGRYYNYDS
                     SSRPQSRSVMSDQCAGQWFLKACGLGEGDTEVFPTQHVVRALQTIFELNVQAFAGGAM
                     GAVNGMQPHGVPDKSSVQSDEVWVGVVYGLAATMIQEGLTWEGFQTAEGCYRTVWERL
                     GLAFQTPEAYCQQRVFRSLAYMRPLSIWAMQLALQQQQHKKASWPKVKQGTGLRTGPM
                     FGPKEAMANLSPE"
     exon            884..975
                     /gene="GBA2"
                     /gene_synonym="AD035; NLGase; SPG46"
                     /inference="alignment:Splign:2.1.0"
     exon            976..1091
                     /gene="GBA2"
                     /gene_synonym="AD035; NLGase; SPG46"
                     /inference="alignment:Splign:2.1.0"
     exon            1092..1310
                     /gene="GBA2"
                     /gene_synonym="AD035; NLGase; SPG46"
                     /inference="alignment:Splign:2.1.0"
     exon            1311..1550
                     /gene="GBA2"
                     /gene_synonym="AD035; NLGase; SPG46"
                     /inference="alignment:Splign:2.1.0"
     exon            1551..1653
                     /gene="GBA2"
                     /gene_synonym="AD035; NLGase; SPG46"
                     /inference="alignment:Splign:2.1.0"
     exon            1654..1807
                     /gene="GBA2"
                     /gene_synonym="AD035; NLGase; SPG46"
                     /inference="alignment:Splign:2.1.0"
     exon            1808..1933
                     /gene="GBA2"
                     /gene_synonym="AD035; NLGase; SPG46"
                     /inference="alignment:Splign:2.1.0"
     exon            1934..2106
                     /gene="GBA2"
                     /gene_synonym="AD035; NLGase; SPG46"
                     /inference="alignment:Splign:2.1.0"
     exon            2107..2211
                     /gene="GBA2"
                     /gene_synonym="AD035; NLGase; SPG46"
                     /inference="alignment:Splign:2.1.0"
     exon            2212..2319
                     /gene="GBA2"
                     /gene_synonym="AD035; NLGase; SPG46"
                     /inference="alignment:Splign:2.1.0"
     exon            2320..2471
                     /gene="GBA2"
                     /gene_synonym="AD035; NLGase; SPG46"
                     /inference="alignment:Splign:2.1.0"
     exon            2472..2578
                     /gene="GBA2"
                     /gene_synonym="AD035; NLGase; SPG46"
                     /inference="alignment:Splign:2.1.0"
     exon            2579..2721
                     /gene="GBA2"
                     /gene_synonym="AD035; NLGase; SPG46"
                     /inference="alignment:Splign:2.1.0"
     exon            2722..2837
                     /gene="GBA2"
                     /gene_synonym="AD035; NLGase; SPG46"
                     /inference="alignment:Splign:2.1.0"
     exon            2838..3029
                     /gene="GBA2"
                     /gene_synonym="AD035; NLGase; SPG46"
                     /inference="alignment:Splign:2.1.0"
     exon            3030..3611
                     /gene="GBA2"
                     /gene_synonym="AD035; NLGase; SPG46"
                     /inference="alignment:Splign:2.1.0"
     regulatory      3591..3596
                     /regulatory_class="polyA_signal_sequence"
                     /gene="GBA2"
                     /gene_synonym="AD035; NLGase; SPG46"
                     /note="hexamer: AATAAA"
     polyA_site      3611
                     /gene="GBA2"
                     /gene_synonym="AD035; NLGase; SPG46"
                     /note="major polyA site"
ORIGIN      
        1 agaccggaaa gggctcgggt catcccggcg cccagggtca ccttcccacg ggctggcacc
       61 tgggcgcggg cgctgccccg gagccggccg gcgggacctg gcgcccaatc ctgggggacc
      121 cggtgccgtg gcccaggggc cgggccgagg tcccgggggc ggtgccttgc gggcccgtcc
      181 cggggcggtg cctggtgggc tggccccgcg gctcctcccc tctctgcggg cccagtcgcc
      241 ctttggccgg gcgagctaat cgtcggctca atgacgacga ggcccgaccc ttcccgtcca
      301 ggacctacag agacaaccga aggagagccc aaggcggctt ctttgctgtc gccgccccca
      361 ctgaagcaag agctccccgg ctccactgaa acaccagctc atttaagctt tccccaacgc
      421 ccggccctcc gggacgatac ctaacaacga ccggcgcccg catctggaat aggctggcga
      481 gatacttagt atccgagggc tcgggacttg gcgccatcga ggtcatgggg acccaggatc
      541 cagggaacat gggaaccggc gtcccagcct cggagcagat aagctgtgcc aaagaggatc
      601 cacaagttta ttgccctgaa gagactggcg gcaccaagga tgtgcaggtt acagactgta
      661 agagtcccga agacagccga cccccaaaag agacggactg ctgcaatccg gaggactctg
      721 ggcagctgat ggtttcctat gagggtaaag ctatgggcta ccaggtgcct ccctttggct
      781 ggcgcatctg tctggctcat gagtttacag agaagaggaa accctttcaa gctaacaacg
      841 tctccctaag caacatgata aagcatatag gcatgggctt gaggtacctg cagtggtggt
      901 accggaagac ccatgtggaa aagaagacac ctttcatcga catgatcaat tctgtacccc
      961 taagacagat ttatggttgt cccttgggtg gcatcggggg aggcactatt acccgtggct
     1021 ggagaggcca gttctgtcgt tggcagctta accctggaat gtatcagcac cggacagtca
     1081 tcgctgacca attcacagtg tgcctgcgtc gggaagggca gactgtgtac cagcaagtcc
     1141 tgtccctgga gcgcccaagt gtcctccgca gctggaactg gggcctgtgt gggtactttg
     1201 ctttctacca tgccctctat ccccgagcct ggactgtcta tcagcttcct ggccagaatg
     1261 tcaccctcac ctgccgtcag atcacaccca tcttgcccca tgactaccag gacagcagcc
     1321 tgcctgtagg agtctttgtg tgggatgtgg aaaatgaagg ggacgaagct ctagatgtgt
     1381 ccatcatgtt ctccatgcgg aatggactgg gtggtggaga cgatgcccca gggggtttgt
     1441 ggaatgagcc cttctgtctg gagcgtagcg gggaaactgt ccgggggctg ctcctgcatc
     1501 atccaaccct tccaaacccc tacacgatgg ctgtggctgc acgagtcacg gcagctacca
     1561 cggtaaccca catcacagcc tttgaccctg acagcacggg gcagcaggtg tggcaggatc
     1621 tacttcagga tggacagctg gactctccca ctggccaaag cacccctacg cagaaaggag
     1681 taggcattgc tggagctgtg tgtgtttcca gcaagttgcg acctcgaggc cagtgccgcc
     1741 tggagttttc actggcttgg gacatgccca ggatcatgtt tggagctaaa ggccaagtcc
     1801 actacaggcg gtatacaagg ttctttggcc aggatggaga tgcagcacct gccctcagcc
     1861 actatgcact gtgccgatac gcagagtggg aagagaggat ctcagcttgg cagagcccgg
     1921 tattggatga cagatcactg cctgcctggt acaaatctgc gctgttcaat gaactatact
     1981 tcctggctga tggaggcaca gtgtggctgg aagttcttga ggactcccta ccagaggagc
     2041 tgggcagaaa catgtgtcac ctccgcccca ccctacggga ctacggtcga tttggctacc
     2101 ttgagggcca ggagtaccgc atgtacaaca catatgatgt ccacttttat gcttcctttg
     2161 ccctcatcat gctctggccc aaacttgagc tcagcctaca gtatgacatg gctctggcca
     2221 ctctcaggga ggacctgaca cggcgacggt acctgatgag tggggtgatg gcacctgtga
     2281 aaaggaggaa cgtcatcccc catgatattg gggacccaga tgatgaacca tggctccgcg
     2341 tcaatgcata tttaatccat gatactgctg attggaagga cctgaacctg aagtttgtgc
     2401 tgcaggttta tcgggactat tacctcacgg gtgatcaaaa cttcctgaag gacatgtggc
     2461 ctgtgtgtct agctgtgatg gaatctgaaa tgaagtttga caaggaccat gatggactca
     2521 ttgaaaatgg aggctatgca gaccagacct atgatggatg ggtgaccaca ggccccagtg
     2581 cttactgtgg agggctgtgg ctggcagctg tggctgtgat ggtccagatg gctgctctgt
     2641 gtggggcaca ggacatccag gataagtttt cttctatcct cagccggggc caagaagcct
     2701 atgagagact gctgtggaat ggccgctatt acaactatga cagcagctct cggcctcagt
     2761 ctcgtagtgt tatgtctgac cagtgtgctg gacagtggtt cctgaaggcc tgtggcctag
     2821 gagaaggaga cactgaggtg tttcctaccc aacatgtggt ccgtgctctc caaactatct
     2881 ttgagctgaa cgtccaggcc tttgcaggag gggccatggg ggctgtgaat gggatgcagc
     2941 cccatggtgt ccctgataaa tccagtgtgc agtctgatga agtctgggtg ggtgtggtct
     3001 acgggctggc agctaccatg atccaagagg gcctgacttg ggagggcttc cagacagctg
     3061 aaggctgcta ccgtaccgtg tgggagcgcc tgggtctggc cttccagacc ccagaggcat
     3121 actgccagca gcgagtgttc cgctcactgg cctacatgcg gccactgagc atatgggcca
     3181 tgcagctagc cctgcaacag cagcagcaca aaaaggcctc ctggccaaaa gtcaaacagg
     3241 gcacaggact aaggacaggg cctatgtttg gaccaaagga agccatggca aacctgagcc
     3301 cagagtgagc cgtctgaact gtgggaggga agtgctaaca gcccagcctc cagcctggcc
     3361 tttcctcctt cccctctgaa cctcctgcaa ccctgagcca tcaggacaat catacccctt
     3421 cccttctctc cacccaattg tgccagtaaa tgggggttga gggtgaccta ggcagcatta
     3481 gaatcactta tttatttctt tcctcacctg ttccctgact gcgtgaaatg ttcagggagg
     3541 tcagttgatt tccccaggta cattcatggt gtgacagaca catgggtaca aataaaagac
     3601 ccagaaagcc a
//
