LOCUS       NM_000543               2410 bp    mRNA    linear   PRI 08-OCT-2024
DEFINITION  Homo sapiens sphingomyelin phosphodiesterase 1 (SMPD1), transcript
            variant 1, mRNA.
ACCESSION   NM_000543
VERSION     NM_000543.5
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 2410)
  AUTHORS   Scrima,S., Lambrughi,M., Tiberti,M., Fadda,E. and Papaleo,E.
  TITLE     ASM variants in the spotlight: A structure-based atlas for
            unraveling pathogenic mechanisms in lysosomal acid sphingomyelinase
  JOURNAL   Biochim Biophys Acta Mol Basis Dis 1870 (7), 167260 (2024)
   PUBMED   38782304
  REMARK    GeneRIF: ASM variants in the spotlight: A structure-based atlas for
            unraveling pathogenic mechanisms in lysosomal acid
            sphingomyelinase.
REFERENCE   2  (bases 1 to 2410)
  AUTHORS   Choi,B.J., Park,M.H., Jin,H.K. and Bae,J.S.
  TITLE     Acid sphingomyelinase as a pathological and therapeutic target in
            neurological disorders: focus on Alzheimer's disease
  JOURNAL   Exp Mol Med 56 (2), 301-310 (2024)
   PUBMED   38337058
  REMARK    GeneRIF: Acid sphingomyelinase as a pathological and therapeutic
            target in neurological disorders: focus on Alzheimer's disease.
            Review article
REFERENCE   3  (bases 1 to 2410)
  AUTHORS   Loeck,M., Placci,M. and Muro,S.
  TITLE     Effect of acid sphingomyelinase deficiency in type A Niemann-Pick
            disease on the transport of therapeutic nanocarriers across the
            blood-brain barrier
  JOURNAL   Drug Deliv Transl Res 13 (12), 3077-3093 (2023)
   PUBMED   37341882
  REMARK    GeneRIF: Effect of acid sphingomyelinase deficiency in type A
            Niemann-Pick disease on the transport of therapeutic nanocarriers
            across the blood-brain barrier.
REFERENCE   4  (bases 1 to 2410)
  AUTHORS   Wasserstein,M.P. and Schuchman,E.H.
  TITLE     Acid Sphingomyelinase Deficiency
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301544
REFERENCE   5  (bases 1 to 2410)
  AUTHORS   Newrzella,D. and Stoffel,W.
  TITLE     Molecular cloning of the acid sphingomyelinase of the mouse and the
            organization and complete nucleotide sequence of the gene
  JOURNAL   Biol Chem Hoppe Seyler 373 (12), 1233-1238 (1992)
   PUBMED   1292508
REFERENCE   6  (bases 1 to 2410)
  AUTHORS   Takahashi,T., Desnick,R.J., Takada,G. and Schuchman,E.H.
  TITLE     Identification of a missense mutation (S436R) in the acid
            sphingomyelinase gene from a Japanese patient with type B
            Niemann-Pick disease
  JOURNAL   Hum Mutat 1 (1), 70-71 (1992)
   PUBMED   1301192
REFERENCE   7  (bases 1 to 2410)
  AUTHORS   Schuchman,E.H., Suchi,M., Takahashi,T., Sandhoff,K. and
            Desnick,R.J.
  TITLE     Human acid sphingomyelinase. Isolation, nucleotide sequence and
            expression of the full-length and alternatively spliced cDNAs
  JOURNAL   J Biol Chem 266 (13), 8531-8539 (1991)
   PUBMED   1840600
REFERENCE   8  (bases 1 to 2410)
  AUTHORS   Levran,O., Desnick,R.J. and Schuchman,E.H.
  TITLE     Niemann-Pick disease: a frequent missense mutation in the acid
            sphingomyelinase gene of Ashkenazi Jewish type A and B patients
  JOURNAL   Proc Natl Acad Sci U S A 88 (9), 3748-3752 (1991)
   PUBMED   2023926
REFERENCE   9  (bases 1 to 2410)
  AUTHORS   da Veiga Pereira,L., Desnick,R.J., Adler,D.A., Disteche,C.M. and
            Schuchman,E.H.
  TITLE     Regional assignment of the human acid sphingomyelinase gene (SMPD1)
            by PCR analysis of somatic cell hybrids and in situ hybridization
            to 11p15.1----p15.4
  JOURNAL   Genomics 9 (2), 229-234 (1991)
   PUBMED   2004772
REFERENCE   10 (bases 1 to 2410)
  AUTHORS   Quintern,L.E., Schuchman,E.H., Levran,O., Suchi,M., Ferlinz,K.,
            Reinke,H., Sandhoff,K. and Desnick,R.J.
  TITLE     Isolation of cDNA clones encoding human acid sphingomyelinase:
            occurrence of alternatively processed transcripts
  JOURNAL   EMBO J 8 (9), 2469-2473 (1989)
   PUBMED   2555181
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AB209775.1, M59916.1 and
            AA746054.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 23, 2018 this sequence version replaced NM_000543.4.
            
            Summary: The protein encoded by this gene is a lysosomal acid
            sphingomyelinase that converts sphingomyelin to ceramide. The
            encoded protein also has phospholipase C activity. Defects in this
            gene are a cause of Niemann-Pick disease type A (NPA) and
            Niemann-Pick disease type B (NPB). Multiple transcript variants
            encoding different isoforms have been identified. [provided by
            RefSeq, Jul 2010].
            
            Transcript Variant: This variant (1) represents the longest
            transcript and encodes the longest 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 :: SRR3476690.126536.1, AB209775.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000342245.9/ ENSP00000340409.4
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-231               AB209775.1         44-274
            232-232             M59916.1           207-207
            233-2409            AB209775.1         276-2452
            2410-2410           AA746054.1         15-15               c
FEATURES             Location/Qualifiers
     source          1..2410
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="11"
                     /map="11p15.4"
     gene            1..2410
                     /gene="SMPD1"
                     /gene_synonym="ASM; ASMASE; NPD"
                     /note="sphingomyelin phosphodiesterase 1"
                     /db_xref="GeneID:6609"
                     /db_xref="HGNC:HGNC:11120"
                     /db_xref="MIM:607608"
     exon            1..443
                     /gene="SMPD1"
                     /gene_synonym="ASM; ASMASE; NPD"
                     /inference="alignment:Splign:2.1.0"
     CDS             126..2021
                     /gene="SMPD1"
                     /gene_synonym="ASM; ASMASE; NPD"
                     /EC_number="3.1.4.12"
                     /EC_number="3.1.4.3"
                     /note="isoform 1 precursor is encoded by transcript
                     variant 1; acid sphingomyelinase; sphingomyelin
                     phosphodiesterase 1, acid lysosomal; Niemann-Pick type
                     A/B"
                     /codon_start=1
                     /product="sphingomyelin phosphodiesterase isoform 1
                     precursor"
                     /protein_id="NP_000534.3"
                     /db_xref="CCDS:CCDS44531.1"
                     /db_xref="GeneID:6609"
                     /db_xref="HGNC:HGNC:11120"
                     /db_xref="MIM:607608"
                     /translation="MPRYGASLRQSCPRSGREQGQDGTAGAPGLLWMGLVLALALALA
                     LALALSDSRVLWAPAEAHPLSPQGHPARLHRIVPRLRDVFGWGNLTCPICKGLFTAIN
                     LGLKKEPNVARVGSVAIKLCNLLKIAPPAVCQSIVHLFEDDMVEVWRRSVLSPSEACG
                     LLLGSTCGHWDIFSSWNISLPTVPKPPPKPPSPPAPGAPVSRILFLTDLHWDHDYLEG
                     TDPDCADPLCCRRGSGLPPASRPGAGYWGEYSKCDLPLRTLESLLSGLGPAGPFDMVY
                     WTGDIPAHDVWHQTRQDQLRALTTVTALVRKFLGPVPVYPAVGNHESTPVNSFPPPFI
                     EGNHSSRWLYEAMAKAWEPWLPAEALRTLRIGGFYALSPYPGLRLISLNMNFCSRENF
                     WLLINSTDPAGQLQWLVGELQAAEDRGDKVHIIGHIPPGHCLKSWSWNYYRIVARYEN
                     TLAAQFFGHTHVDEFEVFYDEETLSRPLAVAFLAPSATTYIGLNPGYRVYQIDGNYSG
                     SSHVVLDHETYILNLTQANIPGAIPHWQLLYRARETYGLPNTLPTAWHNLVYRMRGDM
                     QLFQTFWFLYHKGHPPSEPCGTPCRLATLCAQLSARADSPALCRHLMPDGSLPEAQSL
                     WPRPLFC"
     exon            444..1216
                     /gene="SMPD1"
                     /gene_synonym="ASM; ASMASE; NPD"
                     /inference="alignment:Splign:2.1.0"
     exon            1217..1388
                     /gene="SMPD1"
                     /gene_synonym="ASM; ASMASE; NPD"
                     /inference="alignment:Splign:2.1.0"
     exon            1389..1465
                     /gene="SMPD1"
                     /gene_synonym="ASM; ASMASE; NPD"
                     /inference="alignment:Splign:2.1.0"
     exon            1466..1611
                     /gene="SMPD1"
                     /gene_synonym="ASM; ASMASE; NPD"
                     /inference="alignment:Splign:2.1.0"
     exon            1612..2410
                     /gene="SMPD1"
                     /gene_synonym="ASM; ASMASE; NPD"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2385..2390
                     /regulatory_class="polyA_signal_sequence"
                     /gene="SMPD1"
                     /gene_synonym="ASM; ASMASE; NPD"
                     /note="hexamer: AATAAA"
     polyA_site      2410
                     /gene="SMPD1"
                     /gene_synonym="ASM; ASMASE; NPD"
                     /note="major polyA site"
ORIGIN      
        1 agtcagccga ctacagagaa gggtaatcgg gtgtccccgg cgccgcccgg ggccctgagg
       61 gctggctagg gtccaggccg ggggggacgg gacagacgaa ccagccccgt gtaggaagcg
      121 cgacaatgcc ccgctacgga gcgtcactcc gccagagctg ccccaggtcc ggccgggagc
      181 agggacaaga cgggaccgcc ggagcccccg gactcctttg gatgggcctg gtgctggcgc
      241 tggcgctggc gctggcgctg gcgctggctc tgtctgactc tcgggttctc tgggctccgg
      301 cagaggctca ccctctttct ccccaaggcc atcctgccag gttacatcgc atagtgcccc
      361 ggctccgaga tgtctttggg tgggggaacc tcacctgccc aatctgcaaa ggtctattca
      421 ccgccatcaa cctcgggctg aagaaggaac ccaatgtggc tcgcgtgggc tccgtggcca
      481 tcaagctgtg caatctgctg aagatagcac cacctgccgt gtgccaatcc attgtccacc
      541 tctttgagga tgacatggtg gaggtgtgga gacgctcagt gctgagccca tctgaggcct
      601 gtggcctgct cctgggctcc acctgtgggc actgggacat tttctcatct tggaacatct
      661 ctttgcctac tgtgccgaag ccgcccccca aaccccctag ccccccagcc ccaggtgccc
      721 ctgtcagccg catcctcttc ctcactgacc tgcactggga tcatgactac ctggagggca
      781 cggaccctga ctgtgcagac ccactgtgct gccgccgggg ttctggcctg ccgcccgcat
      841 cccggccagg tgccggatac tggggcgaat acagcaagtg tgacctgccc ctgaggaccc
      901 tggagagcct gttgagtggg ctgggcccag ccggcccttt tgatatggtg tactggacag
      961 gagacatccc cgcacatgat gtctggcacc agactcgtca ggaccaactg cgggccctga
     1021 ccaccgtcac agcacttgtg aggaagttcc tggggccagt gccagtgtac cctgctgtgg
     1081 gtaaccatga aagcacacct gtcaatagct tccctccccc cttcattgag ggcaaccact
     1141 cctcccgctg gctctatgaa gcgatggcca aggcttggga gccctggctg cctgccgaag
     1201 ccctgcgcac cctcagaatt ggggggttct atgctctttc cccatacccc ggtctccgcc
     1261 tcatctctct caatatgaat ttttgttccc gtgagaactt ctggctcttg atcaactcca
     1321 cggatcccgc aggacagctc cagtggctgg tgggggagct tcaggctgct gaggatcgag
     1381 gagacaaagt gcatataatt ggccacattc ccccagggca ctgtctgaag agctggagct
     1441 ggaattatta ccgaattgta gccaggtatg agaacaccct ggctgctcag ttctttggcc
     1501 acactcatgt ggatgaattt gaggtcttct atgatgaaga gactctgagc cggccgctgg
     1561 ctgtagcctt cctggcaccc agtgcaacta cctacatcgg ccttaatcct ggttaccgtg
     1621 tgtaccaaat agatggaaac tactccggga gctctcacgt ggtcctggac catgagacct
     1681 acatcctgaa tctgacccag gcaaacatac cgggagccat accgcactgg cagcttctct
     1741 acagggctcg agaaacctat gggctgccca acacactgcc taccgcctgg cacaacctgg
     1801 tatatcgcat gcggggcgac atgcaacttt tccagacctt ctggtttctc taccataagg
     1861 gccacccacc ctcggagccc tgtggcacgc cctgccgtct ggctactctt tgtgcccagc
     1921 tctctgcccg tgctgacagc cctgctctgt gccgccacct gatgccagat gggagcctcc
     1981 cagaggccca gagcctgtgg ccaaggccac tgttttgcta gggccccagg gcccacattt
     2041 gggaaagttc ttgatgtagg aaagggtgaa aaagcccaaa tgctgctgtg gttcaaccag
     2101 gcaagatcat ccggtgaaag aaccagtccc tgggccccaa ggatgccggg gaaacaggac
     2161 cttctccttt cctggagctg gtttagctgg atatgggagg gggtttggct gcctgtgccc
     2221 aggagctaga ctgccttgag gctgctgtcc tttcacagcc atggagtaga ggcctaagtt
     2281 gacactgccc tgggcagaca agacaggagc tgtcgcccca ggcctgtgct gcccagccag
     2341 gaaccctgta ctgctgctgc gacctgatgc tgccagtctg ttaaaataaa gataagagac
     2401 ttggactcca
//
