LOCUS       NM_000478               2536 bp    mRNA    linear   PRI 04-OCT-2024
DEFINITION  Homo sapiens alkaline phosphatase, biomineralization associated
            (ALPL), transcript variant 1, mRNA.
ACCESSION   NM_000478
VERSION     NM_000478.6
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 2536)
  AUTHORS   Ai,D., Yin,Y., Xia,X., Yang,S., Sun,Y., Zhou,J., Qin,H., Xu,X. and
            Song,J.
  TITLE     Validation of a physiological type 2 diabetes model in human
            periodontal ligament stem cells
  JOURNAL   Oral Dis 30 (5), 3363-3375 (2024)
   PUBMED   37794779
REFERENCE   2  (bases 1 to 2536)
  AUTHORS   Martinez-Heredia,L., Munoz-Torres,M., Sanabria-de la Torre,R.,
            Jimenez-Ortas,A., Andujar-Vera,F., Gonzalez-Cejudo,T.,
            Contreras-Bolivar,V., Gonzalez-Salvatierra,S., Gomez-Vida,J.M.,
            Garcia-Fontana,C. and Garcia-Fontana,B.
  TITLE     Systemic effects of hypophosphatasia characterization of two novel
            variants in the ALPL gene
  JOURNAL   Front Endocrinol (Lausanne) 14, 1320516 (2024)
   PUBMED   38234425
  REMARK    GeneRIF: Systemic effects of hypophosphatasia characterization of
            two novel variants in the ALPL gene.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 2536)
  AUTHORS   Calmarza,P., Lapresta,C., Martinez Garcia,M., Ochoa,J., Sienes
            Bailo,P., Acha Perez,J., Beltran Audera,J. and Gonzalez-Roca,E.
  TITLE     Musculoskeletal pain and muscular weakness as the main symptoms of
            adult hypophosphatasia in a Spanish cohort: clinical
            characterization and identification of a new ALPL gene variant
  JOURNAL   J Bone Miner Metab 41 (5), 654-665 (2023)
   PUBMED   37351650
  REMARK    GeneRIF: Musculoskeletal pain and muscular weakness as the main
            symptoms of adult hypophosphatasia in a Spanish cohort: clinical
            characterization and identification of a new ALPL gene variant.
REFERENCE   4  (bases 1 to 2536)
  AUTHORS   Kim,T.H., Park,S.Y., Shin,J.H., Lee,S., Joo,K.B. and Koo,B.S.
  TITLE     Association between changes in serum alkaline phosphatase levels
            and radiographic progression in ankylosing spondylitis
  JOURNAL   Sci Rep 13 (1), 9093 (2023)
   PUBMED   37277451
  REMARK    GeneRIF: Association between changes in serum alkaline phosphatase
            levels and radiographic progression in ankylosing spondylitis.
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 2536)
  AUTHORS   Millan,J.L.
  TITLE     The role of phosphatases in the initiation of skeletal
            mineralization
  JOURNAL   Calcif Tissue Int 93 (4), 299-306 (2013)
   PUBMED   23183786
  REMARK    Review article
REFERENCE   6  (bases 1 to 2536)
  AUTHORS   Nunes,M.E.
  TITLE     Hypophosphatasia
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301329
REFERENCE   7  (bases 1 to 2536)
  AUTHORS   Nishihara,Y., Hayashi,Y., Adachi,T., Koyama,I., Stigbrand,T. and
            Hirano,K.
  TITLE     Chemical nature of intestinal-type alkaline phosphatase in human
            kidney
  JOURNAL   Clin Chem 38 (12), 2539-2542 (1992)
   PUBMED   1458595
REFERENCE   8  (bases 1 to 2536)
  AUTHORS   Henthorn,P.S., Raducha,M., Fedde,K.N., Lafferty,M.A. and Whyte,M.P.
  TITLE     Different missense mutations at the tissue-nonspecific alkaline
            phosphatase gene locus in autosomal recessively inherited forms of
            mild and severe hypophosphatasia
  JOURNAL   Proc Natl Acad Sci U S A 89 (20), 9924-9928 (1992)
   PUBMED   1409720
REFERENCE   9  (bases 1 to 2536)
  AUTHORS   Fedde,K.N. and Whyte,M.P.
  TITLE     Alkaline phosphatase (tissue-nonspecific isoenzyme) is a
            phosphoethanolamine and pyridoxal-5'-phosphate ectophosphatase:
            normal and hypophosphatasia fibroblast study
  JOURNAL   Am J Hum Genet 47 (5), 767-775 (1990)
   PUBMED   2220817
REFERENCE   10 (bases 1 to 2536)
  AUTHORS   Weiss,M.J., Henthorn,P.S., Lafferty,M.A., Slaughter,C., Raducha,M.
            and Harris,H.
  TITLE     Isolation and characterization of a cDNA encoding a human
            liver/bone/kidney-type alkaline phosphatase
  JOURNAL   Proc Natl Acad Sci U S A 83 (19), 7182-7186 (1986)
   PUBMED   3532105
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AL592309.24 and AL359815.26.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 23, 2018 this sequence version replaced NM_000478.5.
            
            Summary: This gene encodes a member of the alkaline phosphatase
            family of proteins. There are at least four distinct but related
            alkaline phosphatases: intestinal, placental, placental-like, and
            liver/bone/kidney (tissue non-specific). The first three are
            located together on chromosome 2, while the tissue non-specific
            form is located on chromosome 1. The product of this gene is a
            membrane bound glycosylated enzyme that is not expressed in any
            particular tissue and is, therefore, referred to as the
            tissue-nonspecific form of the enzyme. Alternative splicing results
            in multiple transcript variants, at least one of which encodes a
            preproprotein that is proteolytically processed to generate the
            mature enzyme. This enzyme may play a role in bone mineralization.
            Mutations in this gene have been linked to hypophosphatasia, a
            disorder that is characterized by hypercalcemia and skeletal
            defects. [provided by RefSeq, Oct 2015].
            
            Transcript Variant: This variant (1) 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 :: BC021289.2, AB209814.1 [ECO:0000332]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000374840.8/ ENSP00000363973.3
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-95                AL592309.24        99733-99827
            96-260              AL592309.24        144288-144452
            261-380             AL592309.24        150936-151055
            381-496             AL592309.24        151407-151522
            497-671             AL592309.24        153420-153594
            672-847             AL592309.24        154351-154526
            848-991             AL592309.24        158414-158557
            992-1061            AL592309.24        160615-160684
            1062-1196           AL592309.24        163975-164109
            1197-1388           AL359815.26        519-710
            1389-1508           AL359815.26        1308-1427
            1509-2536           AL359815.26        2169-3196
FEATURES             Location/Qualifiers
     source          1..2536
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="1"
                     /map="1p36.12"
     gene            1..2536
                     /gene="ALPL"
                     /gene_synonym="AP-TNAP; APTNAP; HOPS; HPPA; HPPC; HPPI;
                     HPPO; TNALP; TNAP; TNS-ALP; TNSALP"
                     /note="alkaline phosphatase, biomineralization associated"
                     /db_xref="GeneID:249"
                     /db_xref="HGNC:HGNC:438"
                     /db_xref="MIM:171760"
     exon            1..95
                     /gene="ALPL"
                     /gene_synonym="AP-TNAP; APTNAP; HOPS; HPPA; HPPC; HPPI;
                     HPPO; TNALP; TNAP; TNS-ALP; TNSALP"
                     /inference="alignment:Splign:2.1.0"
     exon            96..260
                     /gene="ALPL"
                     /gene_synonym="AP-TNAP; APTNAP; HOPS; HPPA; HPPC; HPPI;
                     HPPO; TNALP; TNAP; TNS-ALP; TNSALP"
                     /inference="alignment:Splign:2.1.0"
     CDS             200..1774
                     /gene="ALPL"
                     /gene_synonym="AP-TNAP; APTNAP; HOPS; HPPA; HPPC; HPPI;
                     HPPO; TNALP; TNAP; TNS-ALP; TNSALP"
                     /EC_number="3.1.3.1"
                     /EC_number="3.9.1.1"
                     /note="isoform 1 preproprotein is encoded by transcript
                     variant 1; liver/bone/kidney-type alkaline phosphatase;
                     tissue-nonspecific ALP; alkaline phosphatase
                     liver/bone/kidney isozyme; alkaline phosphatase,
                     liver/bone/kidney; tissue non-specific alkaline
                     phosphatase; phosphoamidase; phosphocreatine phosphatase"
                     /codon_start=1
                     /product="alkaline phosphatase, tissue-nonspecific isozyme
                     isoform 1 preproprotein"
                     /protein_id="NP_000469.3"
                     /db_xref="CCDS:CCDS217.1"
                     /db_xref="GeneID:249"
                     /db_xref="HGNC:HGNC:438"
                     /db_xref="MIM:171760"
                     /translation="MISPFLVLAIGTCLTNSLVPEKEKDPKYWRDQAQETLKYALELQ
                     KLNTNVAKNVIMFLGDGMGVSTVTAARILKGQLHHNPGEETRLEMDKFPFVALSKTYN
                     TNAQVPDSAGTATAYLCGVKANEGTVGVSAATERSRCNTTQGNEVTSILRWAKDAGKS
                     VGIVTTTRVNHATPSAAYAHSADRDWYSDNEMPPEALSQGCKDIAYQLMHNIRDIDVI
                     MGGGRKYMYPKNKTDVEYESDEKARGTRLDGLDLVDTWKSFKPRYKHSHFIWNRTELL
                     TLDPHNVDYLLGLFEPGDMQYELNRNNVTDPSLSEMVVVAIQILRKNPKGFFLLVEGG
                     RIDHGHHEGKAKQALHEAVEMDRAIGQAGSLTSSEDTLTVVTADHSHVFTFGGYTPRG
                     NSIFGLAPMLSDTDKKPFTAILYGNGPGYKVVGGERENVSMVDYAHNNYQAQSAVPLR
                     HETHGGEDVAVFSKGPMAHLLHGVHEQNYVPHVMAYAACIGANLGHCAPASSAGSLAA
                     GPLLLALALYPLSVLF"
     exon            261..380
                     /gene="ALPL"
                     /gene_synonym="AP-TNAP; APTNAP; HOPS; HPPA; HPPC; HPPI;
                     HPPO; TNALP; TNAP; TNS-ALP; TNSALP"
                     /inference="alignment:Splign:2.1.0"
     exon            381..496
                     /gene="ALPL"
                     /gene_synonym="AP-TNAP; APTNAP; HOPS; HPPA; HPPC; HPPI;
                     HPPO; TNALP; TNAP; TNS-ALP; TNSALP"
                     /inference="alignment:Splign:2.1.0"
     exon            497..671
                     /gene="ALPL"
                     /gene_synonym="AP-TNAP; APTNAP; HOPS; HPPA; HPPC; HPPI;
                     HPPO; TNALP; TNAP; TNS-ALP; TNSALP"
                     /inference="alignment:Splign:2.1.0"
     exon            672..847
                     /gene="ALPL"
                     /gene_synonym="AP-TNAP; APTNAP; HOPS; HPPA; HPPC; HPPI;
                     HPPO; TNALP; TNAP; TNS-ALP; TNSALP"
                     /inference="alignment:Splign:2.1.0"
     exon            848..991
                     /gene="ALPL"
                     /gene_synonym="AP-TNAP; APTNAP; HOPS; HPPA; HPPC; HPPI;
                     HPPO; TNALP; TNAP; TNS-ALP; TNSALP"
                     /inference="alignment:Splign:2.1.0"
     exon            992..1061
                     /gene="ALPL"
                     /gene_synonym="AP-TNAP; APTNAP; HOPS; HPPA; HPPC; HPPI;
                     HPPO; TNALP; TNAP; TNS-ALP; TNSALP"
                     /inference="alignment:Splign:2.1.0"
     exon            1062..1196
                     /gene="ALPL"
                     /gene_synonym="AP-TNAP; APTNAP; HOPS; HPPA; HPPC; HPPI;
                     HPPO; TNALP; TNAP; TNS-ALP; TNSALP"
                     /inference="alignment:Splign:2.1.0"
     exon            1197..1388
                     /gene="ALPL"
                     /gene_synonym="AP-TNAP; APTNAP; HOPS; HPPA; HPPC; HPPI;
                     HPPO; TNALP; TNAP; TNS-ALP; TNSALP"
                     /inference="alignment:Splign:2.1.0"
     exon            1389..1508
                     /gene="ALPL"
                     /gene_synonym="AP-TNAP; APTNAP; HOPS; HPPA; HPPC; HPPI;
                     HPPO; TNALP; TNAP; TNS-ALP; TNSALP"
                     /inference="alignment:Splign:2.1.0"
     exon            1509..2536
                     /gene="ALPL"
                     /gene_synonym="AP-TNAP; APTNAP; HOPS; HPPA; HPPC; HPPI;
                     HPPO; TNALP; TNAP; TNS-ALP; TNSALP"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2509..2514
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ALPL"
                     /gene_synonym="AP-TNAP; APTNAP; HOPS; HPPA; HPPC; HPPI;
                     HPPO; TNALP; TNAP; TNS-ALP; TNSALP"
                     /note="hexamer: AATAAA"
     polyA_site      2536
                     /gene="ALPL"
                     /gene_synonym="AP-TNAP; APTNAP; HOPS; HPPA; HPPC; HPPI;
                     HPPO; TNALP; TNAP; TNS-ALP; TNSALP"
                     /note="major polyA site"
ORIGIN      
        1 gccgcgttgc gctcccgcca ctccgcgccc gctatcctgg ctccgtgctc ccacgcgctt
       61 gtgcctggac ggaccctcgc cagtgctctg cgcaggattg gaacatcagt taacatctga
      121 ccactgccag cccaccccct cccacccacg tcgattgcat ctctgggctc cagggataaa
      181 gcaggtcttg gggtgcacca tgatttcacc attcttagta ctggccattg gcacctgcct
      241 tactaactcc ttagtgccag agaaagagaa agaccccaag tactggcgag accaagcgca
      301 agagacactg aaatatgccc tggagcttca gaagctcaac accaacgtgg ctaagaatgt
      361 catcatgttc ctgggagatg ggatgggtgt ctccacagtg acggctgccc gcatcctcaa
      421 gggtcagctc caccacaacc ctggggagga gaccaggctg gagatggaca agttcccctt
      481 cgtggccctc tccaagacgt acaacaccaa tgcccaggtc cctgacagtg ccggcaccgc
      541 caccgcctac ctgtgtgggg tgaaggccaa tgagggcacc gtgggggtaa gcgcagccac
      601 tgagcgttcc cggtgcaaca ccacccaggg gaacgaggtc acctccatcc tgcgctgggc
      661 caaggacgct gggaaatctg tgggcattgt gaccaccacg agagtgaacc atgccacccc
      721 cagcgccgcc tacgcccact cggctgaccg ggactggtac tcagacaacg agatgccccc
      781 tgaggccttg agccagggct gtaaggacat cgcctaccag ctcatgcata acatcaggga
      841 cattgacgtg atcatggggg gtggccggaa atacatgtac cccaagaata aaactgatgt
      901 ggagtatgag agtgacgaga aagccagggg cacgaggctg gacggcctgg acctcgttga
      961 cacctggaag agcttcaaac cgagatacaa gcactcccac ttcatctgga accgcacgga
     1021 actcctgacc cttgaccccc acaatgtgga ctacctattg ggtctcttcg agccagggga
     1081 catgcagtac gagctgaaca ggaacaacgt gacggacccg tcactctccg agatggtggt
     1141 ggtggccatc cagatcctgc ggaagaaccc caaaggcttc ttcttgctgg tggaaggagg
     1201 cagaattgac cacgggcacc atgaaggaaa agccaagcag gccctgcatg aggcggtgga
     1261 gatggaccgg gccatcgggc aggcaggcag cttgacctcc tcggaagaca ctctgaccgt
     1321 ggtcactgcg gaccattccc acgtcttcac atttggtgga tacacccccc gtggcaactc
     1381 tatctttggt ctggccccca tgctgagtga cacagacaag aagcccttca ctgccatcct
     1441 gtatggcaat gggcctggct acaaggtggt gggcggtgaa cgagagaatg tctccatggt
     1501 ggactatgct cacaacaact accaggcgca gtctgctgtg cccctgcgcc acgagaccca
     1561 cggcggggag gacgtggccg tcttctccaa gggccccatg gcgcacctgc tgcacggcgt
     1621 ccacgagcag aactacgtcc cccacgtgat ggcgtatgca gcctgcatcg gggccaacct
     1681 cggccactgt gctcctgcca gctcggcagg cagccttgct gcaggccccc tgctgctcgc
     1741 gctggccctc taccccctga gcgtcctgtt ctgagggccc agggcccggg cacccacaag
     1801 cccgtgacag atgccaactt cccacacggc agcccccccc tcaaggggca gggaggtggg
     1861 ggcctcctca gcctctgcaa ctgcaagaaa ggggacccaa gaaaccaaag tctgccgccc
     1921 acctcgctcc cctctggaat cttccccaag ggccaaaccc acttctggcc tccagccttt
     1981 gctccctccc cgctgccctt tggccaacag ggtagatttc tcttgggcag gcagagagta
     2041 cagactgcag acattctcaa agcctcttat ttttctagcg aacgtatttc tccagaccca
     2101 gaggccctga agcctccgtg gaacattctg gatctgaccc tcccagtctc atctcctgac
     2161 cctcccactc ccatctcctt acctctggaa ccccccaggc cctacaatgc tcatgtccct
     2221 gtccccaggc ccagccctcc ttcaggggag ttgaggtctt tctcctcagg acaaggcctt
     2281 gctcactcac tcactccaag accaccaggg tcccaggaag ccggtgcctg ggtggccatc
     2341 ctacccagcg tggcccaggc cgggaagagc cacctggcag ggctcacact cctgggctct
     2401 gaacacacac gccagctcct ctctgaagcg actctcctgt ttggaacggc aaaaaaaaat
     2461 ttttttttct ctttttggtg gtggttaaaa gggaacacaa aacatttaaa taaaactttc
     2521 caaatatttc cgagga
//
