The protein encoded by this gene is an alkaline phosphatase, a metalloenzyme that catalyzes the hydrolysis of phosphoric acid monoesters. It belongs to a multigene family composed of four alkaline phosphatase isoenzymes. The enzyme functions as a homodimer and has a catalytic site containing one magnesium and two zinc ions, which are required for its enzymatic function. One of ... See more...

Aliases for ALPP Gene

Aliases for ALPP Gene

  • Alkaline Phosphatase, Placental 2 3 5
  • PLAP 2 3 4
  • Alkaline Phosphatase, Placental Type 3 4
  • Alkaline Phosphatase Regan Isozyme 3 4
  • Placental Alkaline Phosphatase 1 3 4
  • EC 4 50
  • PLAP-1 3 4
  • PALP 2 3
  • Alkaline Phosphatase, Placental (Regan Isozyme) 2
  • Intestinal-Type Alkaline Phosphatase 3
  • Intestinal Alkaline Phosphatase 3
  • Placental Alkaline Phosphatase 2
  • Alkaline Phosphomonoesterase 3
  • Glycerophosphatase 3
  • Regan Isozyme 2
  • ALPI 3
  • ALPP 5
  • ALP 3
  • IAP 3

External Ids for ALPP Gene

Previous GeneCards Identifiers for ALPP Gene

  • GC02P231300
  • GC02P231972
  • GC02P233207
  • GC02P233445
  • GC02P233068
  • GC02P232951
  • GC02P233244
  • GC02P225094

Summaries for ALPP Gene

Entrez Gene Summary for ALPP Gene

  • The protein encoded by this gene is an alkaline phosphatase, a metalloenzyme that catalyzes the hydrolysis of phosphoric acid monoesters. It belongs to a multigene family composed of four alkaline phosphatase isoenzymes. The enzyme functions as a homodimer and has a catalytic site containing one magnesium and two zinc ions, which are required for its enzymatic function. One of the main sources of this enzyme is the liver, and thus, it's one of several indicators of liver injury in different clinical conditions. In pregnant women, this protein is primarily expressed in placental and endometrial tissue, however, strong ectopic expression has been detected in ovarian adenocarcinoma, serous cystadenocarcinoma, and other ovarian cancer cells. [provided by RefSeq, Aug 2020]

GeneCards Summary for ALPP Gene

ALPP (Alkaline Phosphatase, Placental) is a Protein Coding gene. Diseases associated with ALPP include Hypophosphatasia and Obstructive Jaundice. Among its related pathways are Embryonic and Induced Pluripotent Stem Cell Differentiation Pathways and Lineage-specific Markers and Vitamin B6 metabolism. Gene Ontology (GO) annotations related to this gene include magnesium ion binding and alkaline phosphatase activity. An important paralog of this gene is ALPG.

Gene Wiki entry for ALPP Gene

No data available for CIViC Summary , UniProtKB/Swiss-Prot Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for ALPP Gene

Genomics for ALPP Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for ALPP Gene
GeneHancer (GH) Identifier GH Type GH
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH02J232378 Promoter/Enhancer 0.5 EPDnew Ensembl 250.7 -0.2 -198 0.7 ALPP HSALNG0023027 ECEL1P2 ENSG00000224516 DIS3L2
GH02J232503 Enhancer 0.6 FANTOM5 1.9 +124.5 124537 0.4 BRCA1 EGR1 ATF2 CREM ATF1 ATF3 CREB1 ATF7 HSALNG0023041 PRSS56 TIGD1 ECEL1 ALPP ALPI GIGYF2 HSALNG0023042
GH02J232385 Enhancer 0.6 ENCODE 0.4 +8.2 8193 3.2 ZNF513 CTBP1 YY1 NRF1 CTCF DPF2 GLIS1 CREB1 ZNF366 EZH2 ECEL1P2 lnc-ECEL1-3 ECEL1 ALPP ENSG00000224516 ALPG
GH02J232367 Enhancer 0.6 Ensembl 0.4 -10.7 -10723 1.6 ZIC2 CTCF USF2 GLIS1 RAD21 HLF ZNF143 ZBTB17 GLIS2 PHF8 ENSG00000275157 HSALNG0023025 piR-33735-050 ECEL1P2 ALPP DIS3L2
GH02J232300 Enhancer 1.2 Ensembl ENCODE dbSUPER 0.2 -77.4 -77374 1.2 CEBPA FOXA1 HOMEZ ZNF217 THAP11 MBD2 FOXA2 KDM6A CTBP1 MAFF NRBF2P6 MIR1471 COPS7B HSALNG0023022 HSALNG0023023 ALPP DIS3L2
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around ALPP on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for ALPP

Top Transcription factor binding sites by QIAGEN in the ALPP gene promoter:
  • AML1a
  • CUTL1
  • GCNF
  • NF-kappaB
  • NF-kappaB1
  • NF-kappaB2
  • POU2F1
  • POU2F1a
  • SRY
  • TGIF

Genomic Locations for ALPP Gene

Latest Assembly
4,166 bases
Plus strand

Previous Assembly
(GRCh37/hg19 by Entrez Gene)
4,139 bases
Plus strand

(GRCh37/hg19 by Ensembl)
4,356 bases
Plus strand

Genomic View for ALPP Gene

Genes around ALPP on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
ALPP Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for ALPP Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for ALPP Gene

Proteins for ALPP Gene

  • Protein details for ALPP Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Alkaline phosphatase, placental type
    Protein Accession:
    Secondary Accessions:
    • P05188
    • P06861
    • Q53S78
    • Q96DB7

    Protein attributes for ALPP Gene

    535 amino acids
    Molecular mass:
    57954 Da
    Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
    Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
    Quaternary structure:
    • Homodimer.
    • Sequence=AAA51708.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
    • In most mammals there are four different isozymes: placental, germ cell, intestinal and tissue non-specific (liver/bone/kidney).

    Three dimensional structures from OCA and Proteopedia for ALPP Gene

neXtProt entry for ALPP Gene

Selected DME Specific Peptides for ALPP Gene


Post-translational modifications for ALPP Gene

  • Glycosylation at Asn144 and Asn271
  • Modification sites at PhosphoSitePlus

Other Protein References for ALPP Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibodies for research

Domains & Families for ALPP Gene

Gene Families for ALPP Gene

Human Protein Atlas (HPA):
  • Cancer-related genes
  • Enzymes
  • Plasma proteins
  • Predicted intracellular proteins

Protein Domains for ALPP Gene

Suggested Antigen Peptide Sequences for ALPP Gene

GenScript: Design optimal peptide antigens:
  • Placental alkaline phosphatase 1 (PPB1_HUMAN)

Graphical View of Domain Structure for InterPro Entry



  • Belongs to the alkaline phosphatase family.
  • Belongs to the alkaline phosphatase family.
genes like me logo Genes that share domains with ALPP: view

Function for ALPP Gene

Molecular function for ALPP Gene

UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=a phosphate monoester + H2O = an alcohol + phosphate; Xref=Rhea:RHEA:15017, ChEBI:CHEBI:15377, ChEBI:CHEBI:30879, ChEBI:CHEBI:43474, ChEBI:CHEBI:67140; EC=; Evidence={ECO:0000255|PROSITE-ProRule:PRU10042};.
GENATLAS Biochemistry:
phosphatase alkaline,placental (Regan isozyme)

Enzyme Numbers (IUBMB) for ALPP Gene

Phenotypes From GWAS Catalog for ALPP Gene

Gene Ontology (GO) - Molecular Function for ALPP Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000287 magnesium ion binding ISS --
GO:0003824 catalytic activity IEA --
GO:0004035 alkaline phosphatase activity IBA,NAS 3042787
GO:0005515 protein binding IPI 25416956
GO:0008270 zinc ion binding ISS --
genes like me logo Genes that share ontologies with ALPP: view
genes like me logo Genes that share phenotypes with ALPP: view

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for ALPP

No data available for Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for ALPP Gene

Localization for ALPP Gene

Subcellular locations from UniProtKB/Swiss-Prot for ALPP Gene

Cell membrane. Lipid-anchor, GPI-anchor.

Subcellular locations from

Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for ALPP gene
Compartment Confidence
plasma membrane 5
extracellular 2
endoplasmic reticulum 2
cytoskeleton 1
mitochondrion 1
nucleus 1
endosome 1
cytosol 1
lysosome 1
golgi apparatus 1
peroxisome 0

Subcellular locations from the

Human Protein Atlas (HPA)
  • Plasma membrane (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for ALPP Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005886 plasma membrane IBA,IDA --
GO:0009986 cell surface IDA 15907827
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
GO:0031225 anchored component of membrane IEA --
genes like me logo Genes that share ontologies with ALPP: view

Pathways & Interactions for ALPP Gene

genes like me logo Genes that share pathways with ALPP: view

Pathways by source for ALPP Gene

Gene Ontology (GO) - Biological Process for ALPP Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0016311 dephosphorylation IBA 21873635
genes like me logo Genes that share ontologies with ALPP: view

No data available for SIGNOR curated interactions for ALPP Gene

Drugs & Compounds for ALPP Gene

(85) Drugs for ALPP Gene - From: DrugBank, ApexBio, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Magnesium Approved, Experimental, Investigational Pharma 0
Sodium fluorophosphate Approved Pharma Pyruvate/alkaline phosphatase inhibitor 0
Water Approved Pharma 0
4-Nitrophenol Experimental Pharma 0
Dihydroxyacetone Experimental Pharma 0

(60) Additional Compounds for ALPP Gene - From: Novoseek and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
dihydroneopterin triphosphate
  • 2-Amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)dihydropteridine triphosphate
  • 6-(L-Erythro-1,2-dihydroxy-3-triphosphooxypropyl)-7,8-dihydropterin
  • 6-(L-Erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
  • 6-[(1S,2R)-1,2-Dihydroxy-3-triphosphooxypropyl]-7,8-dihydropterin
  • 2-Amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)dihydropteridine triphosphoric acid

(2) ApexBio Compounds for ALPP Gene

Compound Action Cas Number
(-)-p-Bromotetramisole Oxalate 62284-79-1
Sodium Monofluorophosphate Pyruvate/alkaline phosphatase inhibitor 10163-15-2
genes like me logo Genes that share compounds with ALPP: view

Transcripts for ALPP Gene

mRNA/cDNA for ALPP Gene

11 NCBI additional mRNA sequence :
3 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for ALPP

Alternative Splicing Database (ASD) splice patterns (SP) for ALPP Gene

No ASD Table

Relevant External Links for ALPP Gene

GeneLoc Exon Structure for

Expression for ALPP Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for ALPP Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for ALPP Gene

This gene is overexpressed in Lung (x33.1), Cervix - Endocervix (x9.2), and Fallopian Tube (x4.9).

Protein differential expression in normal tissues from HIPED for ALPP Gene

This gene is overexpressed in Cervix (35.1) and Placenta (32.9).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for ALPP Gene

Protein tissue co-expression partners for ALPP Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for ALPP

SOURCE GeneReport for Unigene cluster for ALPP Gene:


mRNA Expression by UniProt/SwissProt for ALPP Gene:

Tissue specificity: Detected in placenta (at protein level).

Evidence on tissue expression from TISSUES for ALPP Gene

  • Intestine(2.4)
  • Liver(2.2)
genes like me logo Genes that share expression patterns with ALPP: view

Primer products for research

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for ALPP Gene

Orthologs for ALPP Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for ALPP Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia ALPP 29 30
  • 97.99 (n)
(Rattus norvegicus)
Mammalia Alpi 29
  • 78.75 (n)
(Mus musculus)
Mammalia Alpi 29 16 30
  • 78.41 (n)
Alppl2 30
  • 73 (a)
Akp3 30
  • 69 (a)
(Bos Taurus)
Mammalia -- 30
  • 76 (a)
-- 30
  • 75 (a)
-- 30
  • 74 (a)
-- 30
  • 74 (a)
(Canis familiaris)
Mammalia -- 30
  • 73 (a)
(Ornithorhynchus anatinus)
Mammalia -- 30
  • 73 (a)
(Monodelphis domestica)
Mammalia -- 30
  • 70 (a)
(Gallus gallus)
Aves -- 30
  • 64 (a)
(Anolis carolinensis)
Reptilia -- 30
  • 60 (a)
(Danio rerio)
Actinopterygii alp3 30
  • 51 (a)
Fruit Fly
(Drosophila melanogaster)
Insecta Aph-4 29 30 31
  • 53.41 (n)
CG1809 30 31
  • 37 (a)
CG5656 30 31
  • 37 (a)
CG5150 30 31
  • 35 (a)
CG10827 30 31
  • 35 (a)
CG8105 30 31
  • 35 (a)
CG3264 30 31
  • 34 (a)
CG10592 30 31
  • 34 (a)
CG8147 30
  • 34 (a)
CG3292 30 31
  • 32 (a)
CG3290 30 31
  • 32 (a)
CG16771 30 31
  • 27 (a)
CG5361 30
  • 22 (a)
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP010596 29
  • 52.05 (n)
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes PHO8 30
  • 21 (a)
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 30
  • 39 (a)
-- 30
  • 39 (a)
-- 30
  • 38 (a)
CSA.180 30
  • 38 (a)
CSA.4362 30
  • 37 (a)
Species where no ortholog for ALPP was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Tropical Clawed Frog (Silurana tropicalis)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for ALPP Gene

Gene Tree for ALPP (if available)
Gene Tree for ALPP (if available)
Evolutionary constrained regions (ECRs) for ALPP: view image
Alliance of Genome Resources:
Additional Orthologs for ALPP

Paralogs for ALPP Gene

Paralogs for ALPP Gene

(3) SIMAP similar genes for ALPP Gene using alignment to 1 proteins:

genes like me logo Genes that share paralogs with ALPP: view

Variants for ALPP Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for ALPP Gene

Placental ALP is highly polymorphic, there are at least three common alleles.

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for ALPP Gene

SNP ID Clinical significance and condition Chr 02 pos Variation AA Info Type
rs1048988 Benign: not provided 232,380,220(+) G/Cp.Arg231Pro
NM_001632.5(ALPP):c.692G>C (p.Arg231Pro)
rs1048989 Likely Benign: not provided 232,380,227(+) A/G
NM_001632.5(ALPP):c.699A>G (p.Gly233=)
NM_001632.3(ALPP):c.74C= (p.Pro25=)
rs1130337 Likely Benign: not provided 232,379,083(+) C/G
NM_001632.5(ALPP):c.189C>G (p.Gly63=)
rs1130345 Benign: not provided 232,379,936(+) C/T
NM_001632.5(ALPP):c.657C>T (p.Asp219=)

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for ALPP Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for ALPP Gene

Variant ID Type Subtype PubMed ID
dgv1218e212 CNV loss 25503493
dgv160n111 CNV duplication 26073780
dgv4182n100 CNV gain 25217958
dgv4183n100 CNV gain+loss 25217958
dgv4184n100 CNV loss 25217958
dgv4185n100 CNV gain 25217958
dgv4186n100 CNV loss 25217958
dgv4187n100 CNV loss 25217958
dgv493n27 CNV loss 19166990
dgv494n27 CNV gain 19166990
dgv632e201 CNV deletion 23290073
dgv7336n54 CNV gain 21841781
dgv7337n54 CNV loss 21841781
dgv7338n54 CNV gain 21841781
dgv765e214 CNV loss 21293372
esv2659833 CNV deletion 23128226
esv2759118 CNV gain 17122850
esv2760660 CNV loss 21179565
esv2763626 CNV gain+loss 21179565
esv34493 CNV gain 17911159
esv3561154 CNV deletion 23714750
esv3575339 CNV gain 25503493
esv3594646 CNV loss 21293372
esv3594649 CNV gain 21293372
esv3893570 CNV gain+loss 25118596
nsv1009043 CNV gain 25217958
nsv1014226 CNV gain 25217958
nsv436293 CNV deletion 17901297
nsv438382 CNV loss 16468122
nsv482057 CNV gain 20164927
nsv518263 CNV loss 19592680
nsv521461 CNV loss 19592680
nsv522450 CNV loss 19592680
nsv584679 CNV gain 21841781
nsv584687 CNV gain+loss 21841781
nsv584692 CNV loss 21841781
nsv821918 CNV gain 20364138

Variation tolerance for ALPP Gene

Residual Variation Intolerance Score: 94.1% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 8.14; 84.67% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for ALPP Gene

Human Gene Mutation Database (HGMD)
SNPedia medical, phenotypic, and genealogical associations of SNPs for
Leiden Open Variation Database (LOVD)

SNP Genotyping and Copy Number Assays for research

Disorders for ALPP Gene

MalaCards: The human disease database

(55) MalaCards diseases for ALPP Gene - From: COP and GCD

Disorder Aliases PubMed IDs
  • childhood hypophosphatasia
obstructive jaundice
  • cholestatic jaundice
  • seminoma, pure
germ cell cancer
  • germ cell neoplasm
- elite association - COSMIC cancer census association via MalaCards
Search ALPP in MalaCards View complete list of genes associated with diseases

Additional Disease Information for ALPP

Human Genome Epidemiology Navigator
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with ALPP: view

No data available for UniProtKB/Swiss-Prot and Genatlas for ALPP Gene

Publications for ALPP Gene

  1. Structural studies of human alkaline phosphatase in complex with strontium: implication for its secondary effect in bones. (PMID: 16815919) Llinas P … Le Du MH (Protein science : a publication of the Protein Society 2006) 3 4 22
  2. Enzyme polymorphisms, smoking, and human reproduction. A study of human placental alkaline phosphatase. (PMID: 14595869) Magrini A … Bottini E (American journal of human biology : the official journal of the Human Biology Council 2003) 3 22 40
  3. Crystal structure of alkaline phosphatase from human placenta at 1.8 A resolution. Implication for a substrate specificity. (PMID: 11124260) Le Du MH … Stura EA (The Journal of biological chemistry 2001) 3 4 22
  4. Products of two common alleles at the locus for human placental alkaline phosphatase differ by seven amino acids. (PMID: 3461452) Henthorn PS … Harris H (Proceedings of the National Academy of Sciences of the United States of America 1986) 2 3 4
  5. Cloning, sequencing, and chromosomal localization of human term placental alkaline phosphatase cDNA. (PMID: 3001717) Kam W … Rutter WJ (Proceedings of the National Academy of Sciences of the United States of America 1985) 2 3 4

Products for ALPP Gene

Sources for ALPP Gene