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

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: mouse all
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Genomic context

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_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues 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

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Systemic effects of hypophosphatasia characterization of two novel variants in the ALPL gene.
Title: Systemic effects of hypophosphatasia characterization of two novel variants in the ALPL gene.
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.
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.
Promotion effect of FGF23 on osteopenia in congenital scoliosis through FGFr3/TNAP/OPN pathway.
Title: Promotion effect of FGF23 on osteopenia in congenital scoliosis through FGFr3/TNAP/OPN pathway.
Association between changes in serum alkaline phosphatase levels and radiographic progression in ankylosing spondylitis.
Title: Association between changes in serum alkaline phosphatase levels and radiographic progression in ankylosing spondylitis.
Early elevated alkaline phosphatase as a surrogate biomarker of ongoing metabolic bone disease of prematurity.
Title: Early elevated alkaline phosphatase as a surrogate biomarker of ongoing metabolic bone disease of prematurity.
Not just a carrier: Clinical presentation and management of patients with heterozygous disease-causing alkaline phosphatase (ALPL) variants identified through expanded carrier screening.
Title: Not just a carrier: Clinical presentation and management of patients with heterozygous disease-causing alkaline phosphatase (ALPL) variants identified through expanded carrier screening.
The effect of ALPL gene polymorphism on the development of urolithiasis in the Turkish population.
Title: The effect of ALPL gene polymorphism on the development of urolithiasis in the Turkish population.
A new perspective on the function of Tissue Non-Specific Alkaline Phosphatase: from bone mineralization to intra-cellular lipid accumulation.
Title: A new perspective on the function of Tissue Non-Specific Alkaline Phosphatase: from bone mineralization to intra-cellular lipid accumulation.
Characterization of Genetic Variants of Uncertain Significance for the ALPL Gene in Patients With Adult Hypophosphatasia.
Title: Characterization of Genetic Variants of Uncertain Significance for the ALPL Gene in Patients With Adult Hypophosphatasia.
ALPL Genotypes in Patients With Atypical Femur Fractures or Other Biochemical and Clinical Signs of Hypophosphatasia.
Title: ALPL Genotypes in Patients With Atypical Femur Fractures or Other Biochemical and Clinical Signs of Hypophosphatasia.

Submit: New GeneRIF Correction See all GeneRIFs (200)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Adult hypophosphatasia MedGen: C0268413 OMIM: 146300 GeneReviews: Hypophosphatasia	not available
Childhood hypophosphatasia MedGen: C0220743 OMIM: 241510 GeneReviews: Hypophosphatasia	not available
Hypophosphatasia MedGen: C0020630 GeneReviews: Hypophosphatasia	not available
Infantile hypophosphatasia MedGen: C0268412 OMIM: 241500 GeneReviews: Hypophosphatasia	not available

EBI GWAS Catalog

Description
An atlas of genetic influences on human blood metabolites. EBI GWAS Catalog EBI GWAS CatalogPubMed
Common genetic variants associate with serum phosphorus concentration. EBI GWAS Catalog EBI GWAS CatalogPubMed
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 EBI GWAS CatalogPubMed
Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of chemotherapeutic agent-induced severe neutropenia/leucopenia for patients in Biobank Japan. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of hematological and biochemical traits in a Japanese population. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of vitamin B6, vitamin B12, folate, and homocysteine blood concentrations. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide significant predictors of metabolites in the one-carbon metabolism pathway. EBI GWAS Catalog EBI GWAS CatalogPubMed
Human metabolic individuality in biomedical and pharmaceutical research. EBI GWAS Catalog EBI GWAS CatalogPubMed
Investigation of single nucleotide polymorphisms and biological pathways associated with response to TNF&#x003b1; inhibitors in patients with rheumatoid arthritis. EBI GWAS Catalog EBI GWAS CatalogPubMed
Population-based genome-wide association studies reveal six loci influencing plasma levels of liver enzymes. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-74342 (e-PCR)
- UniSTS:74264

AL009634 (e-PCR)
- UniSTS:62760

SHGC-74343 (e-PCR)
- UniSTS:53109

GDB:178682 (e-PCR)
- UniSTS:155039

RH93776 (e-PCR)
- UniSTS:93100

GDB:549217 (e-PCR)
- UniSTS:157635

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 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 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 more info	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 more info	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 more info	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

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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

EC 3.1.3.1

EC 3.9.1.1

NP_001120973.2

EC 3.1.3.1

EC 3.9.1.1

NP_001170991.1

EC 3.1.3.1

EC 3.9.1.1

NP_001356732.1

EC 3.1.3.1

EC 3.9.1.1

NP_001356733.1

EC 3.1.3.1

EC 3.9.1.1

NP_001356734.1

EC 3.1.3.1

EC 3.9.1.1

XP_016856392.1

EC 3.1.3.1

EC 3.9.1.1

XP_054191723.1

EC 3.1.3.1

EC 3.9.1.1

NCBI Reference Sequences (RefSeq)

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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

NG_008940.2 RefSeqGene

Range

5441..74428

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000478.6 → NP_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:51 → 490

Alk_phosphatase; Alkaline phosphatase
NM_001127501.4 → NP_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:1 → 435

Alk_phosphatase; Alkaline phosphatase
NM_001177520.3 → NP_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:22 → 413

Alk_phosphatase; Alkaline phosphatase
NM_001369803.2 → NP_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:51 → 490

Alk_phosphatase; Alkaline phosphatase
NM_001369804.2 → NP_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:51 → 490

Alk_phosphatase; Alkaline phosphatase
NM_001369805.2 → NP_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:51 → 490

Alk_phosphatase; Alkaline phosphatase