LOCUS       NM_000520               4785 bp    mRNA    linear   PRI 05-OCT-2024
DEFINITION  Homo sapiens hexosaminidase subunit alpha (HEXA), transcript
            variant 2, mRNA.
ACCESSION   NM_000520
VERSION     NM_000520.6
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 4785)
  AUTHORS   Ibrahim,D.M.A., Ali,O.S.M., Nasr,H., Fateen,E. and AbdelAleem,A.
  TITLE     Biochemical and mutational analyses of HEXA in a cohort of Egyptian
            patients with infantile Tay-Sachs disease. Expansion of the
            mutation spectrum
  JOURNAL   Orphanet J Rare Dis 18 (1), 52 (2023)
   PUBMED   36907859
  REMARK    GeneRIF: Biochemical and mutational analyses of HEXA in a cohort of
            Egyptian patients with infantile Tay-Sachs disease. Expansion of
            the mutation spectrum.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 4785)
  AUTHORS   Abtahi,R., Karimzadeh,P., Rezayi,A., Salehpour,S., Akbarzadeh,D.,
            Tonekaboni,S.H., Emameh,R.Z. and Houshmand,M.
  TITLE     Analysis of the HEXA, HEXB, ARSA, and SMPD1 Genes in 68 Iranian
            Patients
  JOURNAL   J Mol Neurosci 72 (3), 555-564 (2022)
   PUBMED   34554397
  REMARK    GeneRIF: Analysis of the HEXA, HEXB, ARSA, and SMPD1 Genes in 68
            Iranian Patients.
REFERENCE   3  (bases 1 to 4785)
  AUTHORS   Pennybacker,M., Liessem,B., Moczall,H., Tifft,C.J., Sandhoff,K. and
            Proia,R.L.
  TITLE     Identification of domains in human beta-hexosaminidase that
            determine substrate specificity
  JOURNAL   J Biol Chem 271 (29), 17377-17382 (1996)
   PUBMED   8663217
REFERENCE   4  (bases 1 to 4785)
  AUTHORS   Toro,C., Shirvan,L. and Tifft,C.
  TITLE     HEXA Disorders
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301397
REFERENCE   5  (bases 1 to 4785)
  AUTHORS   O'Dowd,B.F., Cumming,D.A., Gravel,R.A. and Mahuran,D.
  TITLE     Oligosaccharide structure and amino acid sequence of the major
            glycopeptides of mature human beta-hexosaminidase
  JOURNAL   Biochemistry 27 (14), 5216-5226 (1988)
   PUBMED   2971395
REFERENCE   6  (bases 1 to 4785)
  AUTHORS   Little,L.E., Lau,M.M., Quon,D.V., Fowler,A.V. and Neufeld,E.F.
  TITLE     Proteolytic processing of the alpha-chain of the lysosomal enzyme,
            beta-hexosaminidase, in normal human fibroblasts
  JOURNAL   J Biol Chem 263 (9), 4288-4292 (1988)
   PUBMED   2964446
REFERENCE   7  (bases 1 to 4785)
  AUTHORS   Proia,R.L. and Soravia,E.
  TITLE     Organization of the gene encoding the human beta-hexosaminidase
            alpha-chain
  JOURNAL   J Biol Chem 262 (12), 5677-5681 (1987)
   PUBMED   2952641
  REMARK    Erratum:[J Biol Chem 1987 Nov 5;262(31):15322]
REFERENCE   8  (bases 1 to 4785)
  AUTHORS   Myerowitz,R., Piekarz,R., Neufeld,E.F., Shows,T.B. and Suzuki,K.
  TITLE     Human beta-hexosaminidase alpha chain: coding sequence and homology
            with the beta chain
  JOURNAL   Proc Natl Acad Sci U S A 82 (23), 7830-7834 (1985)
   PUBMED   2933746
REFERENCE   9  (bases 1 to 4785)
  AUTHORS   Beutler,E., Kuhl,W. and Comings,D.
  TITLE     Hexosaminidase isozyme in type O Gm2 gangliosidosis
            (Sandhoff-Jatzkewitz disease)
  JOURNAL   Am J Hum Genet 27 (5), 628-638 (1975)
   PUBMED   808963
REFERENCE   10 (bases 1 to 4785)
  AUTHORS   Gilbert,F., Kucherlapati,R., Creagan,R.P., Murnane,M.J.,
            Darlington,G.J. and Ruddle,F.H.
  TITLE     Tay-Sachs' and Sandhoff's diseases: the assignment of genes for
            hexosaminidase A and B to individual human chromosomes
  JOURNAL   Proc Natl Acad Sci U S A 72 (1), 263-267 (1975)
   PUBMED   1054503
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DC356933.1, BC018927.2,
            AC009690.17 and BM668409.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Jun 2, 2019 this sequence version replaced NM_000520.5.
            
            Summary: This gene encodes a member of the glycosyl hydrolase 20
            family of proteins. The encoded preproprotein is proteolytically
            processed to generate the alpha subunit of the lysosomal enzyme
            beta-hexosaminidase. This enzyme, together with the cofactor GM2
            activator protein, catalyzes the degradation of the ganglioside
            GM2, and other molecules containing terminal N-acetyl hexosamines.
            Mutations in this gene lead to an accumulation of GM2 ganglioside
            in neurons, the underlying cause of neurodegenerative disorders
            termed the GM2 gangliosidoses, including Tay-Sachs disease
            (GM2-gangliosidosis type I). Alternative splicing results in
            multiple transcript variants, at least one of which encodes a
            preproprotein that is proteolytically processed. [provided by
            RefSeq, Jan 2016].
            
            Transcript Variant: This variant (2) uses an alternate in-frame
            splice site in the 5' coding region compared to variant 1. The
            encoded isoform (2) is shorter than 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 :: M13520.1, CR627386.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000268097.10/ ENSP00000268097.6
            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
            1-398               DC356933.1         166-563
            399-1347            BC018927.2         368-1316
            1348-1348           AC009690.17        130462-130462       c
            1349-1559           BC018927.2         1318-1528
            1560-1560           AC009690.17        129365-129365       c
            1561-1824           BC018927.2         1530-1793
            1825-2146           BM668409.1         147-468             c
            2147-2221           AC009690.17        127399-127473       c
            2222-2274           BM668409.1         19-71               c
            2275-4785           AC009690.17        124835-127345       c
FEATURES             Location/Qualifiers
     source          1..4785
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="15"
                     /map="15q23"
     gene            1..4785
                     /gene="HEXA"
                     /gene_synonym="TSD"
                     /note="hexosaminidase subunit alpha"
                     /db_xref="GeneID:3073"
                     /db_xref="HGNC:HGNC:4878"
                     /db_xref="MIM:606869"
     exon            1..295
                     /gene="HEXA"
                     /gene_synonym="TSD"
                     /inference="alignment:Splign:2.1.0"
     CDS             43..1632
                     /gene="HEXA"
                     /gene_synonym="TSD"
                     /EC_number="3.2.1.52"
                     /note="isoform 2 preproprotein is encoded by transcript
                     variant 2; beta-hexosaminidase subunit alpha;
                     hexosaminidase subunit A; hexosaminidase A (alpha
                     polypeptide); beta-N-acetylhexosaminidase subunit alpha;
                     N-acetyl-beta-glucosaminidase subunit alpha"
                     /codon_start=1
                     /product="beta-hexosaminidase subunit alpha isoform 2
                     preproprotein"
                     /protein_id="NP_000511.2"
                     /db_xref="CCDS:CCDS10243.1"
                     /db_xref="GeneID:3073"
                     /db_xref="HGNC:HGNC:4878"
                     /db_xref="MIM:606869"
                     /translation="MTSSRLWFSLLLAAAFAGRATALWPWPQNFQTSDQRYVLYPNNF
                     QFQYDVSSAAQPGCSVLDEAFQRYRDLLFGSGSWPRPYLTGKRHTLEKNVLVVSVVTP
                     GCNQLPTLESVENYTLTINDDQCLLLSETVWGALRGLETFSQLVWKSAEGTFFINKTE
                     IEDFPRFPHRGLLLDTSRHYLPLSSILDTLDVMAYNKLNVFHWHLVDDPSFPYESFTF
                     PELMRKGSYNPVTHIYTAQDVKEVIEYARLRGIRVLAEFDTPGHTLSWGPGIPGLLTP
                     CYSGSEPSGTFGPVNPSLNNTYEFMSTFFLEVSSVFPDFYLHLGGDEVDFTCWKSNPE
                     IQDFMRKKGFGEDFKQLESFYIQTLLDIVSSYGKGYVVWQEVFDNKVKIQPDTIIQVW
                     REDIPVNYMKELELVTKAGFRALLSAPWYLNRISYGPDWKDFYIVEPLAFEGTPEQKA
                     LVIGGEACMWGEYVDNTNLVPRLWPRAGAVAERLWSNKLTSDLTFAYERLSHFRCELL
                     RRGVQAQPLNVGFCEQEFEQT"
     exon            296..388
                     /gene="HEXA"
                     /gene_synonym="TSD"
                     /inference="alignment:Splign:2.1.0"
     exon            389..454
                     /gene="HEXA"
                     /gene_synonym="TSD"
                     /inference="alignment:Splign:2.1.0"
     exon            455..501
                     /gene="HEXA"
                     /gene_synonym="TSD"
                     /inference="alignment:Splign:2.1.0"
     exon            502..612
                     /gene="HEXA"
                     /gene_synonym="TSD"
                     /inference="alignment:Splign:2.1.0"
     exon            613..714
                     /gene="HEXA"
                     /gene_synonym="TSD"
                     /inference="alignment:Splign:2.1.0"
     exon            715..847
                     /gene="HEXA"
                     /gene_synonym="TSD"
                     /inference="alignment:Splign:2.1.0"
     exon            848..1028
                     /gene="HEXA"
                     /gene_synonym="TSD"
                     /inference="alignment:Splign:2.1.0"
     exon            1029..1115
                     /gene="HEXA"
                     /gene_synonym="TSD"
                     /inference="alignment:Splign:2.1.0"
     exon            1116..1188
                     /gene="HEXA"
                     /gene_synonym="TSD"
                     /inference="alignment:Splign:2.1.0"
     exon            1189..1372
                     /gene="HEXA"
                     /gene_synonym="TSD"
                     /inference="alignment:Splign:2.1.0"
     exon            1373..1463
                     /gene="HEXA"
                     /gene_synonym="TSD"
                     /inference="alignment:Splign:2.1.0"
     exon            1464..1568
                     /gene="HEXA"
                     /gene_synonym="TSD"
                     /inference="alignment:Splign:2.1.0"
     exon            1569..4785
                     /gene="HEXA"
                     /gene_synonym="TSD"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1791..1796
                     /regulatory_class="polyA_signal_sequence"
                     /gene="HEXA"
                     /gene_synonym="TSD"
                     /note="hexamer: AATAAA"
     polyA_site      1824
                     /gene="HEXA"
                     /gene_synonym="TSD"
                     /note="major polyA site"
     regulatory      2251..2256
                     /regulatory_class="polyA_signal_sequence"
                     /gene="HEXA"
                     /gene_synonym="TSD"
                     /note="hexamer: ATTAAA"
     polyA_site      2272
                     /gene="HEXA"
                     /gene_synonym="TSD"
     regulatory      4753..4758
                     /regulatory_class="polyA_signal_sequence"
                     /gene="HEXA"
                     /gene_synonym="TSD"
                     /note="hexamer: AATAAA"
     polyA_site      4785
                     /gene="HEXA"
                     /gene_synonym="TSD"
ORIGIN      
        1 ctcacgtggc cagccccctc cgagagggga gaccagcggg ccatgacaag ctccaggctt
       61 tggttttcgc tgctgctggc ggcagcgttc gcaggacggg cgacggccct ctggccctgg
      121 cctcagaact tccaaacctc cgaccagcgc tacgtccttt acccgaacaa ctttcaattc
      181 cagtacgatg tcagctcggc cgcgcagccc ggctgctcag tcctcgacga ggccttccag
      241 cgctatcgtg acctgctttt cggttccggg tcttggcccc gtccttacct cacagggaaa
      301 cggcatacac tggagaagaa tgtgttggtt gtctctgtag tcacacctgg atgtaaccag
      361 cttcctactt tggagtcagt ggagaattat accctgacca taaatgatga ccagtgttta
      421 ctcctctctg agactgtctg gggagctctc cgaggtctgg agacttttag ccagcttgtt
      481 tggaaatctg ctgagggcac attctttatc aacaagactg agattgagga ctttccccgc
      541 tttcctcacc ggggcttgct gttggataca tctcgccatt acctgccact ctctagcatc
      601 ctggacactc tggatgtcat ggcgtacaat aaattgaacg tgttccactg gcatctggta
      661 gatgatcctt ccttcccata tgagagcttc acttttccag agctcatgag aaaggggtcc
      721 tacaaccctg tcacccacat ctacacagca caggatgtga aggaggtcat tgaatacgca
      781 cggctccggg gtatccgtgt gcttgcagag tttgacactc ctggccacac tttgtcctgg
      841 ggaccaggta tccctggatt actgactcct tgctactctg ggtctgagcc ctctggcacc
      901 tttggaccag tgaatcccag tctcaataat acctatgagt tcatgagcac attcttctta
      961 gaagtcagct ctgtcttccc agatttttat cttcatcttg gaggagatga ggttgatttc
     1021 acctgctgga agtccaaccc agagatccag gactttatga ggaagaaagg cttcggtgag
     1081 gacttcaagc agctggagtc cttctacatc cagacgctgc tggacatcgt ctcttcttat
     1141 ggcaagggct atgtggtgtg gcaggaggtg tttgataata aagtaaagat tcagccagac
     1201 acaatcatac aggtgtggcg agaggatatt ccagtgaact atatgaagga gctggaactg
     1261 gtcaccaagg ccggcttccg ggcccttctc tctgccccct ggtacctgaa ccgtatatcc
     1321 tatggccctg actggaagga tttctacata gtggaacccc tggcatttga aggtacccct
     1381 gagcagaagg ctctggtgat tggtggagag gcttgtatgt ggggagaata tgtggacaac
     1441 acaaacctgg tccccaggct ctggcccaga gcaggggctg ttgccgaaag gctgtggagc
     1501 aacaagttga catctgacct gacatttgcc tatgaacgtt tgtcacactt ccgctgtgaa
     1561 ttgctgaggc gaggtgtcca ggcccaaccc ctcaatgtag gcttctgtga gcaggagttt
     1621 gaacagacct gagccccagg caccgaggag ggtgctggct gtaggtgaat ggtagtggag
     1681 ccaggcttcc actgcatcct ggccagggga cggagcccct tgccttcgtg ccccttgcct
     1741 gcgtgcccct gtgcttggag agaaaggggc cggtgctggc gctcgcattc aataaagagt
     1801 aatgtggcat ttttctataa taaacatgga ttacctgtgt ttaaaaaaaa aagtgtgaat
     1861 ggcgttaggg taagggcaca gccaggctgg agtcagtgtc tgcccctgag gtcttttaag
     1921 ttgagggctg ggaatgaaac ctatagcctt tgtgctgttc tgccttgcct gtgagctatg
     1981 tcactcccct cccactcctg accatattcc agacacctgc cctaatcctc agcctgctca
     2041 cttcacttct gcattatatc tccaaggcgt tggtatatgg aaaaagatgt aggggcttgg
     2101 aggtgttctg gacagtgggg agggctccag acccaacctg gtcacagaag agcctctccc
     2161 ccatgcatac tcatccacct ccctccccta gagctattct cctttgggtt tcttgctgct
     2221 tcaattttat acaaccatta tttaaatatt attaaacaca tattgttctc taggcactgt
     2281 ggtagtgggt ttttttgttg tttttgtttt tgagactgtc tcaaaaactc tgtcgcccag
     2341 gctgacagtg cagtggcaca atcttggctc actgcagcct ctgcctcctg ggttcaagcg
     2401 attctcgtgc atcagcctcc tgagtaactg gaattaatag gcacgtgcca ccatgtccat
     2461 ctaattcata tatatatatt ttttttttct gagacggagt ctcactgtca cacaggctgg
     2521 agtgcagtgg cacgatctcg actcactgca agctccacct cctgggttca cgccattctc
     2581 ctgcctcagc ctccccagta gctgggacta caggcgcccg ccaccacgcc cggctaattt
     2641 tttgtatttt tagtagagat ggggtttctc cgtgttagcc aggatggtct cgatctcctg
     2701 acctcgtgat ccgcccgcct tggcctccca aagtgctggg attacaggcg tgagccaccg
     2761 cgcccggccg aattcatcta tttttagtag agatggggtt tcactatatt ggccaggctg
     2821 gtcttgaact catgacctca gatgttcact tgtcttggcc tcccaaagtg ctgggattag
     2881 aggcgtgagc caccgcacgc gggcctgtgg taaattgttg aatttgaagg actcagaggc
     2941 cctggtcaat tccaaaataa cgtaggcgac ttccatcccc ctcctcccaa ccattttcag
     3001 cccaaagcat cttcgcaggg aatggatggc tgcgcggagg tgggcggtgg ctctggagag
     3061 ggtctttgca ggtgtgattt tctctagaag gaaatgtctc gtcgtggacc cagactgccc
     3121 cctcctggtt tcagatgcag aagtgatact gtaagccaga ggcgggggca gtaatgcatc
     3181 gcagccattt taggtgagga tttccttggc ggttatttgt taagttcttt ggctgggccc
     3241 tgggctgggg taacaatgga caggttccag gcattttttt cagaaagctt ccagtgtagt
     3301 ggatacagaa acttcaggaa ggcagggctg agaaggatct gagtaaaact cggtccttca
     3361 acaccatcct tcagcccctg ggtcatgttc cttcgaggtc ctggtgggag gtagacaagc
     3421 ctagccttgt gctgttcctg taaggacagg gtgggcattt tctaccaaca gaattcttgg
     3481 aattttcaca cagcccagcc tagccaagtc cagggctata gcccagatac acaagttaag
     3541 gtcccagcac tggcacccac cacaggagcc cccttacctc tattacccag aagcttgtag
     3601 gaggggtggt ccgcagacaa ggaccctgca caggtgcgac cctgcttccc tcctggtcat
     3661 aactttcatg ttactattgc ttgggataat gttaagtaaa aatagcagac actgagtttt
     3721 aagtctcaag tggatgaagg cagagatcgt gatacacttg agttaaagca gtagggttct
     3781 gtcattttct attcctgttg taaacatttt ctttaatgtt attattttta ccactaaact
     3841 aacgtggcct ggtcacgact ttcattggta aagtgtgctg ttcctcaccc tccaccgttg
     3901 ctcctttggt ccactgatca taagagcatt tacctgaagg tcgtcagacc tcgaatgcca
     3961 acaggtcaac tgcagtggcc tgcagttacc acccagtctg ttccaatgaa cagaatcgct
     4021 gttgccccaa ctcatctccc ttcacctagg ctgtaaattg aaagtcccac ccctgagcgg
     4081 aacacaggcc atcttgtgtg ctgtgcacca ccagggggtg gggaagtttc cagactgact
     4141 tcctggctcc agtcatccta ggaaaagagt tctccagtcg ctccccaccc ccaccccttc
     4201 ccattccagg agtctattaa ggaggcaaag caggcctaac gggtatcaaa gcaaaggagt
     4261 gaatggagac tgggagagtc ttcaacctct cctctccttg gtaggagctg aggctgcatg
     4321 ccaggtacct tcccttcgag gaatctaata aagctaggtc actggtgttt tcaggtgctt
     4381 ctcaaaggat tgccgtaggg gtaggatatc aggatgtggg agcacaggtg ccaccacagc
     4441 actagtgatg gagagtcatt gcccctagac ttctgggaca gtgagactgt gaggaaagct
     4501 gaaatgatac tgggaaaggg tgaaagaaag gatgtaggtg gaatttattt agtattaatg
     4561 taggtacaca taccttatgg caacattcct agcactctaa attctagatt tgtatagttt
     4621 ctgtcaatat cttttgtaag cttaatcaat acagggcatg acaagtatgt gtcacatact
     4681 tttttttcca cgaagaaaaa aaataagtag gaattgggtg ctttgtttat caaaatttgt
     4741 atttccttta taaataaact ttgaaataaa ggttgaaaat tagta
//
