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    ALPL alkaline phosphatase, biomineralization associated [ Homo sapiens (human) ]

    Gene ID: 249, updated on 3-Dec-2024

    Summary

    Official Symbol
    ALPLprovided by HGNC
    Official Full Name
    alkaline phosphatase, biomineralization associatedprovided by HGNC
    Primary source
    HGNC:HGNC:438
    See related
    Ensembl:ENSG00000162551 MIM:171760; AllianceGenome:HGNC:438
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    HOPS; HPPA; HPPC; HPPI; HPPO; TNAP; TNALP; APTNAP; TNSALP; AP-TNAP; TNS-ALP
    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]
    Expression
    Broad expression in kidney (RPKM 33.8), lung (RPKM 30.4) and 14 other tissues See more
    Orthologs
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See ALPL in Genome Data Viewer
    Location:
    1p36.12
    Exon count:
    14
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (21508984..21578410)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (21332916..21402323)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (21835477..21904903)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene Sharpr-MPRA regulatory region 1847 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 381 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:21766764-21767274 Neighboring gene Sharpr-MPRA regulatory region 4165 Neighboring gene CROCC pseudogene 5 Neighboring gene NBPF member 3 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr1:21791822-21793021 Neighboring gene profilin 1 pseudogene 10 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 382 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:21817787-21818287 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 383 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:21835859-21836429 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:21836430-21836999 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 334 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:21860784-21861513 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:21863949-21864466 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:21864467-21864985 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:21895010-21895594 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:21900641-21901315 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:21901316-21901990 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:21904065-21904588 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:21917321-21917860 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:21917861-21918399 Neighboring gene long intergenic non-protein coding RNA 2596 Neighboring gene ReSE screen-validated silencer GRCh37_chr1:21928741-21928970 Neighboring gene Sharpr-MPRA regulatory region 12165 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:21937517-21938264 Neighboring gene RAP1 GTPase activating protein Neighboring gene ReSE screen-validated silencer GRCh37_chr1:21939576-21939868 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:21945135-21945976 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:21958265-21959233 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:21960338-21961086 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:21961087-21961835 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:21966135-21966964 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:21977615-21978365 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 384 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 385 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 386 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:21992551-21993051 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 387

    Genomic regions, transcripts, and products

    Expression

    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Phenotypes

    EBI GWAS Catalog

    Description
    An atlas of genetic influences on human blood metabolites.
    EBI GWAS Catalog
    Common genetic variants associate with serum phosphorus concentration.
    EBI GWAS Catalog
    Genetic Associations with Plasma B12, B6, and Folate Levels in an Ischemic Stroke Population from the Vitamin Intervention for Stroke Prevention (VISP) Trial.
    EBI GWAS Catalog
    Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma.
    EBI GWAS Catalog
    Genome-wide association study of chemotherapeutic agent-induced severe neutropenia/leucopenia for patients in Biobank Japan.
    EBI GWAS Catalog
    Genome-wide association study of hematological and biochemical traits in a Japanese population.
    EBI GWAS Catalog
    Genome-wide association study of vitamin B6, vitamin B12, folate, and homocysteine blood concentrations.
    EBI GWAS Catalog
    Genome-wide significant predictors of metabolites in the one-carbon metabolism pathway.
    EBI GWAS Catalog
    Human metabolic individuality in biomedical and pharmaceutical research.
    EBI GWAS Catalog
    Investigation of single nucleotide polymorphisms and biological pathways associated with response to TNFα inhibitors in patients with rheumatoid arthritis.
    EBI GWAS Catalog
    Population-based genome-wide association studies reveal six loci influencing plasma levels of liver enzymes.
    EBI GWAS Catalog

    HIV-1 interactions

    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env In human osteoblast (hOB) cell lines, HIV-1 Gag and gp120 downregulate calcium deposition and alkaline phosphatase activity PubMed
    env Cells exposed in vitro to HIV-1 gp120 show a defect in inositol polyphosphate-mediated signal transduction resulting from the downregulation of inositol (1,3,4,5)P4 5-phosphomonoesterase (PME) by gp120 PubMed
    Pr55(Gag) gag In human osteoblast (hOB) cell lines, HIV-1 Gag and gp120 downregulate calcium deposition and alkaline phosphatase activity PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Clone Names

    • FLJ40094, FLJ93059, MGC161443, MGC167935

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ADP phosphatase activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables ATP hydrolysis activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables ATP-dependent H2AZ histone chaperone activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables ATP-dependent H3-H4 histone complex chaperone activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables DNA clamp loader activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables alkaline phosphatase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    enables alkaline phosphatase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables calcium ion binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables chromatin extrusion motor activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables cohesin loader activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables inorganic diphosphate phosphatase activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables phosphoamidase activity ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    enables phosphoethanolamine phosphatase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables pyridoxal phosphatase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables pyrophosphatase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    Process Evidence Code Pubs
    involved_in biomineral tissue development IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in bone mineralization ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in calcium ion homeostasis IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in cellular homeostasis IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in cellular response to organic cyclic compound IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in cementum mineralization IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in chromatin looping IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in chromatin remodeling IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in developmental process involved in reproduction IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in endochondral ossification IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in futile creatine cycle IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in inhibition of non-skeletal tissue mineralization IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in osteoblast differentiation HDA PubMed 
    involved_in phosphate ion homeostasis IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of cold-induced thermogenesis ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in pyridoxal phosphate metabolic process IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in response to antibiotic IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in response to glucocorticoid IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in response to insulin IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in response to lipopolysaccharide IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in response to macrophage colony-stimulating factor IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in response to sodium phosphate IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in response to vitamin B6 IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in response to vitamin D IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    involved_in skeletal system development TAS
    Traceable Author Statement
    more info
    PubMed 
    Component Evidence Code Pubs
    located_in extracellular exosome HDA PubMed 
    located_in extracellular matrix IEA
    Inferred from Electronic Annotation
    more info
     
    located_in extracellular region TAS
    Traceable Author Statement
    more info
     
    located_in membrane HDA PubMed 
    is_active_in mitochondrial intermembrane space ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    is_active_in mitochondrial membrane ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    is_active_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
     
    located_in side of membrane IEA
    Inferred from Electronic Annotation
    more info
     

    General protein information

    Preferred Names
    alkaline phosphatase, tissue-nonspecific isozyme
    Names
    alkaline phosphatase liver/bone/kidney isozyme
    alkaline phosphatase, liver/bone/kidney
    liver/bone/kidney-type alkaline phosphatase
    phosphoamidase
    phosphocreatine phosphatase
    tissue non-specific alkaline phosphatase
    tissue-nonspecific ALP
    NP_000469.3
    NP_001120973.2
    NP_001170991.1
    NP_001356732.1
    NP_001356733.1
    NP_001356734.1
    XP_016856392.1
    XP_054191723.1

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_008940.2 RefSeqGene

      Range
      5441..74428
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000478.6NP_000469.3  alkaline phosphatase, tissue-nonspecific isozyme isoform 1 preproprotein

      See identical proteins and their annotated locations for NP_000469.3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (1).
      Source sequence(s)
      AL359815, AL592309
      Consensus CDS
      CCDS217.1
      UniProtKB/Swiss-Prot
      A1A4E7, B2RMP8, B7Z387, B7Z4Y6, O75090, P05186, Q2TAI7, Q59EJ7, Q5BKZ5, Q5VTG5, Q6NZI8, Q8WU32, Q9UBK0
      UniProtKB/TrEMBL
      B2R6Q2
      Related
      ENSP00000363973.3, ENST00000374840.8
      Conserved Domains (1) summary
      pfam00245
      Location:51490
      Alk_phosphatase; Alkaline phosphatase
    2. NM_001127501.4NP_001120973.2  alkaline phosphatase, tissue-nonspecific isozyme isoform 2

      See identical proteins and their annotated locations for NP_001120973.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream start codon, compared to variant 1. The encoded isoform (2) lacks a predicted signal peptide and is shorter compared to isoform 1.
      Source sequence(s)
      AL359815, AL592309
      Consensus CDS
      CCDS53275.1
      UniProtKB/TrEMBL
      B7Z1D1
      Related
      ENSP00000442672.1, ENST00000540617.5
      Conserved Domains (1) summary
      pfam00245
      Location:1435
      Alk_phosphatase; Alkaline phosphatase
    3. NM_001177520.3NP_001170991.1  alkaline phosphatase, tissue-nonspecific isozyme isoform 3

      See identical proteins and their annotated locations for NP_001170991.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at an alternate start codon, compared to variant 1. This variant also lacks an exon in the 5' coding region, compared to variant 1. The encoded isoform (3) has a distinct N-terminus, lacks a predicted signal peptide, and is shorter compared to isoform 1.
      Source sequence(s)
      AL359815, AL592309
      Consensus CDS
      CCDS53274.1
      UniProtKB/TrEMBL
      B7Z1D1
      Related
      ENSP00000437674.1, ENST00000539907.5
      Conserved Domains (1) summary
      pfam00245
      Location:22413
      Alk_phosphatase; Alkaline phosphatase
    4. NM_001369803.2NP_001356732.1  alkaline phosphatase, tissue-nonspecific isozyme isoform 1 preproprotein

      Status: REVIEWED

      Source sequence(s)
      AL359815, AL592309
      Consensus CDS
      CCDS217.1
      UniProtKB/Swiss-Prot
      A1A4E7, B2RMP8, B7Z387, B7Z4Y6, O75090, P05186, Q2TAI7, Q59EJ7, Q5BKZ5, Q5VTG5, Q6NZI8, Q8WU32, Q9UBK0
      UniProtKB/TrEMBL
      B2R6Q2
      Related
      ENSP00000363965.1, ENST00000374832.5
      Conserved Domains (1) summary
      pfam00245
      Location:51490
      Alk_phosphatase; Alkaline phosphatase
    5. NM_001369804.2NP_001356733.1  alkaline phosphatase, tissue-nonspecific isozyme isoform 1 preproprotein

      Status: REVIEWED

      Source sequence(s)
      AL359815, AL592309
      Consensus CDS
      CCDS217.1
      UniProtKB/Swiss-Prot
      A1A4E7, B2RMP8, B7Z387, B7Z4Y6, O75090, P05186, Q2TAI7, Q59EJ7, Q5BKZ5, Q5VTG5, Q6NZI8, Q8WU32, Q9UBK0
      UniProtKB/TrEMBL
      B2R6Q2
      Conserved Domains (1) summary
      pfam00245
      Location:51490
      Alk_phosphatase; Alkaline phosphatase
    6. NM_001369805.2NP_001356734.1  alkaline phosphatase, tissue-nonspecific isozyme isoform 1 preproprotein

      Status: REVIEWED

      Source sequence(s)
      AL359815, AL592309
      Consensus CDS
      CCDS217.1
      UniProtKB/Swiss-Prot
      A1A4E7, B2RMP8, B7Z387, B7Z4Y6, O75090, P05186, Q2TAI7, Q59EJ7, Q5BKZ5, Q5VTG5, Q6NZI8, Q8WU32, Q9UBK0
      UniProtKB/TrEMBL
      B2R6Q2
      Conserved Domains (1) summary
      pfam00245
      Location:51490
      Alk_phosphatase; Alkaline phosphatase

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000001.11 Reference GRCh38.p14 Primary Assembly

      Range
      21508984..21578410
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017000903.2XP_016856392.1  alkaline phosphatase, tissue-nonspecific isozyme isoform X1

      UniProtKB/TrEMBL
      B7Z1D1

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060925.1 Alternate T2T-CHM13v2.0

      Range
      21332916..21402323
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054335748.1XP_054191723.1  alkaline phosphatase, tissue-nonspecific isozyme isoform X1

      UniProtKB/TrEMBL
      B7Z1D1