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

Gene ID: 249, updated on 17-Jun-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
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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_2023_10 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (21508984..21578410)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (21332916..21402323)
105.20220307 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 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 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 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 dephosphorylation IBA
Inferred from Biological aspect of Ancestor
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_2023_10

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