ALPL Gene

Name	alkaline phosphatase, liver/bone/kidney
Description	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]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The ALPL gene encodes tissue‐nonspecific alkaline phosphatase (TNAP), an enzyme central to extracellular phosphate metabolism with diverse functions in skeletal, metabolic, and even neoplastic processes. Genetic variation in ALPL is strongly associated with circulating alkaline phosphatase levels, with effects that appear to be specific for bone and/or intestine rather than liver function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition to influencing plasma enzyme levels, ALPL variants have been implicated in vitamin B6 catabolism, suggesting that TNAP may modulate vitamin metabolism. Moreover, comparative cytogenetic analyses have identified the ALPL locus as a promising candidate tumor suppressor gene in meningiomas, thereby hinting at a role for ALPL in cellular proliferation and tumor development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the context of mineralization, TNAP is crucial for skeletal development through its ability to hydrolyze inhibitors of calcification—such as extracellular inorganic pyrophosphate—and to modulate the phosphorylation status of key matrix proteins like osteopontin. Loss-of-function mutations in ALPL lead to hypophosphatasia, a condition characterized by impaired bone and tooth mineralization, rickets/osteomalacia, and in severe cases, neonatal seizures, underscoring its essential role in skeletal homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Furthermore, aberrant expression of TNAP has been functionally linked to vascular calcification. In an experimental mouse model, overexpression of human TNAP in vascular smooth muscle cells led to extensive arterial calcification, while pharmacological inhibition of TNAP effectively reduced calcific deposits and associated cardiac hypertrophy. This indicates that ALPL/TNAP not only regulates physiological bone mineralization but may also contribute to pathological calcification in extraosseous tissues."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Xin Yuan, Dawn Waterworth, John R B Perry, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Population-based genome-wide association studies reveal six loci influencing plasma levels of liver enzymes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2008.09.012"}], "href": "https://doi.org/10.1016/j.ajhg.2008.09.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18940312"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18940312"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Toshiko Tanaka, Paul Scheet, Betti Giusti, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-wide association study of vitamin B6, vitamin B12, folate, and homocysteine blood concentrations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2009.02.011"}], "href": "https://doi.org/10.1016/j.ajhg.2009.02.011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19303062"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19303062"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "K D Zang "}, {"type": "b", "children": [{"type": "t", "text": "Meningioma: a cytogenetic model of a complex benign human tumor, including data on 394 karyotyped cases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cytogenet Cell Genet (2001)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1159/000056986"}], "href": "https://doi.org/10.1159/000056986"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11528114"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11528114"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Sara Baumgartner-Sigl, Edda Haberlandt, Steven Mumm, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pyridoxine-responsive seizures as the first symptom of infantile hypophosphatasia caused by two novel missense mutations (c.677T>C, p.M226T; c.1112C>T, p.T371I) of the tissue-nonspecific alkaline phosphatase gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Bone (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bone.2007.01.020"}], "href": "https://doi.org/10.1016/j.bone.2007.01.020"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17395561"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17395561"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Sonoko Narisawa, Manisha C Yadav, José Luis Millán "}, {"type": "b", "children": [{"type": "t", "text": "In vivo overexpression of tissue-nonspecific alkaline phosphatase increases skeletal mineralization and affects the phosphorylation status of osteopontin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Bone Miner Res (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jbmr.1901"}], "href": "https://doi.org/10.1002/jbmr.1901"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23427088"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23427088"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Etienne Mornet "}, {"type": "b", "children": [{"type": "t", "text": "Hypophosphatasia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Best Pract Res Clin Rheumatol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.berh.2007.11.003"}], "href": "https://doi.org/10.1016/j.berh.2007.11.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18328985"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18328985"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Campbell R Sheen, Pia Kuss, Sonoko Narisawa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pathophysiological role of vascular smooth muscle alkaline phosphatase in medial artery calcification."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Bone Miner Res (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jbmr.2420"}], "href": "https://doi.org/10.1002/jbmr.2420"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25428889"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25428889"}]}]}]}
Synonyms	TNALP, HOPS, TNSALP, APTNAP, AP-TNAP, TNAP
Proteins	PPBT_HUMAN
NCBI Gene ID	249
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

ALPL has 11,127 functional associations with biological entities spanning 9 categories (molecular profile, organism, functional term, phrase or reference, disease, phenotype or trait, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 124 datasets.

Click the + buttons to view associations for ALPL from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

ALPL Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of ALPL gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of ALPL gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of ALPL gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of ALPL gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of ALPL gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving ALPL protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of ALPL gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of ALPL gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of ALPL gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of ALPL gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of ALPL gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with ALPL protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with ALPL gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of ALPL gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of ALPL gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of ALPL gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with ALPL gene from the curated ClinVar Gene-Phenotype Associations dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of ALPL gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing ALPL protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing ALPL protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing ALPL protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing ALPL protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with ALPL protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with ALPL protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of ALPL gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with ALPL gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with ALPL gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with ALPL gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with ALPL gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by ALPL gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving ALPL gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving ALPL gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with ALPL gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with ALPL gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with ALPL gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with ALPL gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with ALPL gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with ALPL gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for ALPL protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at ALPL gene from the ENCODE Histone Modification Site Profiles dataset.