This gene is a member of the ecto-nucleotide pyrophosphatase/phosphodiesterase (ENPP) family. The encoded protein is a type II transmembrane glycoprotein comprising two identical disulfide-bonded subunits. This protein has broad specificity and cleaves a variety of substrates, including phosphodiester bonds of nucleotides and nucleotide sugars and pyrophosphate bonds of nucleot... See more...

Aliases for ENPP1 Gene

Aliases for ENPP1 Gene

  • Ectonucleotide Pyrophosphatase/Phosphodiesterase 1 2 3 5
  • Ectonucleotide Pyrophosphatase/Phosphodiesterase Family Member 1 3 4
  • Phosphodiesterase I/Nucleotide Pyrophosphatase 1 3 4
  • Plasma-Cell Membrane Glycoprotein PC-1 3 4
  • E-NPP 1 3 4
  • PDNP1 3 4
  • M6S1 3 4
  • NPPS 3 4
  • PC-1 2 3
  • PCA1 2 3
  • Membrane Component, Chromosome 6, Surface Marker 1 3
  • Membrane Component Chromosome 6 Surface Marker 1 4
  • Plasma-Cell Membrane Glycoprotein 1 3
  • Alkaline Phosphodiesterase 1 3
  • Ly-41 Antigen 3
  • ARHR2 3
  • COLED 3
  • ENPP1 5
  • NPP1 3
  • PC1 4

External Ids for ENPP1 Gene

Previous HGNC Symbols for ENPP1 Gene

  • NPPS
  • M6S1
  • PDNP1

Previous GeneCards Identifiers for ENPP1 Gene

  • GC06P131752
  • GC06P131976
  • GC06P132109
  • GC06P132170
  • GC06P129704
  • GC06P132129

Summaries for ENPP1 Gene

Entrez Gene Summary for ENPP1 Gene

  • This gene is a member of the ecto-nucleotide pyrophosphatase/phosphodiesterase (ENPP) family. The encoded protein is a type II transmembrane glycoprotein comprising two identical disulfide-bonded subunits. This protein has broad specificity and cleaves a variety of substrates, including phosphodiester bonds of nucleotides and nucleotide sugars and pyrophosphate bonds of nucleotides and nucleotide sugars. This protein may function to hydrolyze nucleoside 5' triphosphates to their corresponding monophosphates and may also hydrolyze diadenosine polyphosphates. Mutations in this gene have been associated with 'idiopathic' infantile arterial calcification, ossification of the posterior longitudinal ligament of the spine (OPLL), and insulin resistance. [provided by RefSeq, Jul 2008]

GeneCards Summary for ENPP1 Gene

ENPP1 (Ectonucleotide Pyrophosphatase/Phosphodiesterase 1) is a Protein Coding gene. Diseases associated with ENPP1 include Cole Disease and Hypophosphatemic Rickets, Autosomal Recessive, 2. Among its related pathways are Pantothenate and CoA biosynthesis and Metabolism of water-soluble vitamins and cofactors. Gene Ontology (GO) annotations related to this gene include nucleic acid binding and protein homodimerization activity. An important paralog of this gene is ENPP3.

UniProtKB/Swiss-Prot Summary for ENPP1 Gene

  • Nucleotide pyrophosphatase that generates diphosphate (PPi) and functions in bone mineralization and soft tissue calcification by regulating pyrophosphate levels (By similarity). PPi inhibits bone mineralization and soft tissue calcification by binding to nascent hydroxyapatite crystals, thereby preventing further growth of these crystals (PubMed:11004006). Preferentially hydrolyzes ATP, but can also hydrolyze other nucleoside 5' triphosphates such as GTP, CTP, TTP and UTP to their corresponding monophosphates with release of pyrophosphate and diadenosine polyphosphates, and also 3',5'-cAMP to AMP (PubMed:27467858, PubMed:8001561, PubMed:25344812). May also be involved in the regulation of the availability of nucleotide sugars in the endoplasmic reticulum and Golgi, and the regulation of purinergic signaling (PubMed:27467858, PubMed:8001561). Inhibits ectopic joint calcification and maintains articular chondrocytes by repressing hedgehog signaling; it is however unclear whether hedgehog inhibition is direct or indirect (By similarity). Appears to modulate insulin sensitivity and function (PubMed:10615944). Also involved in melanogenesis (PubMed:28964717). Also able to hydrolyze 2'-3'-cGAMP (cyclic GMP-AMP), a second messenger that activates TMEM173/STING and triggers type-I interferon production (PubMed:25344812). 2'-3'-cGAMP degradation takes place in the lumen or extracellular space, and not in the cytosol where it is produced; the role of 2'-3'-cGAMP hydrolysis is therefore unclear (PubMed:25344812). Not able to hydrolyze the 2'-3'-cGAMP linkage isomer 3'-3'-cGAMP (PubMed:25344812).

Gene Wiki entry for ENPP1 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for ENPP1 Gene

Genomics for ENPP1 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for ENPP1 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH06J131807 Promoter/Enhancer 1.9 EPDnew Ensembl ENCODE CraniofacialAtlas 600.7 +0.4 385 2.8 HNRNPL GATAD2A CTCF PRDM10 REST ZNF629 TFE3 ZNF692 TARDBP PRDM1 ENPP1 MED23 ENSG00000237115 lnc-CTAGE9-2 RF00017-5778 CCN2
GH06J132510 Promoter/Enhancer 2.4 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 9.9 +704.3 704270 5.4 SP1 HNRNPL ATF7 TEAD4 PRDM10 ZNF629 REST ZNF512 IKZF1 ZNF692 STX7 lnc-MOXD1-2 SNORA33 MED23 RPS12 SNORD100 SNORD101 ENSG00000237115 ENPP1 VNN2
GH06J131627 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE CraniofacialAtlas 10.5 -180.1 -180115 2.6 ZNF221 BRCA1 SP1 HNRNPL CREB1 GATAD2A CTCF PRDM10 REST ZNF629 MED23 ENPP3 lnc-OR2A4-1 ARG1 CTAGE9 ENSG00000237115 ENPP1 lnc-OR2A4-3
GH06J131892 Enhancer 1.1 Ensembl ENCODE 8.5 +86.3 86299 3.7 HNRNPL GATAD2A ATF7 TFE3 SOX13 NFKBIZ RCOR2 FOXA1 RBFOX2 RXRB ENPP1 ENSG00000236673 CCN2 LOC100421775
GH06J131753 Enhancer 1.2 Ensembl ENCODE dbSUPER 5.4 -52.7 -52715 3 GATAD2A ATF7 TFE3 SOX13 IKZF1 NFKBIZ RCOR2 FOXA1 RXRB GABPA MED23 ENPP1 MF281437-043 RF00017-5778 CTAGE9
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around ENPP1 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for ENPP1

Top Transcription factor binding sites by QIAGEN in the ENPP1 gene promoter:
  • CUTL1
  • E2F
  • E2F-1
  • E2F-2
  • E2F-3a
  • E2F-4
  • E2F-5
  • FOXF2
  • Pax-2
  • Pax-2a

Genomic Locations for ENPP1 Gene

Genomic Locations for ENPP1 Gene
chr6:131,808,016-131,895,155
(GRCh38/hg38)
Size:
87,140 bases
Orientation:
Plus strand
chr6:132,129,156-132,216,295
(GRCh37/hg19)
Size:
87,140 bases
Orientation:
Plus strand

Genomic View for ENPP1 Gene

Genes around ENPP1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
ENPP1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for ENPP1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for ENPP1 Gene

Proteins for ENPP1 Gene

  • Protein details for ENPP1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P22413-ENPP1_HUMAN
    Recommended name:
    Ectonucleotide pyrophosphatase/phosphodiesterase family member 1
    Protein Accession:
    P22413
    Secondary Accessions:
    • Q5T9R6
    • Q9NPZ3
    • Q9P1P6
    • Q9UP61
    • Q9Y6K3

    Protein attributes for ENPP1 Gene

    Size:
    925 amino acids
    Molecular mass:
    104924 Da
    Cofactor:
    Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
    Quaternary structure:
    • [Ectonucleotide pyrophosphatase/phosphodiesterase family member 1]: Homodimer (PubMed:28964717). Interacts with INSR; leading to inhibit INSR autophosphorylation and subsequent activation of INSR kinase activity (PubMed:10615944).
    • [Ectonucleotide pyrophosphatase/phosphodiesterase family member 1, secreted form]: Monomeric (By similarity).
    SequenceCaution:
    • Sequence=AAA63237.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=AAH59375.2; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=BAA02054.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for ENPP1 Gene

neXtProt entry for ENPP1 Gene

Post-translational modifications for ENPP1 Gene

  • Autophosphorylated as part of the catalytic cycle of phosphodiesterase/pyrophosphatase activity.
  • N-glycosylated.
  • The secreted form is produced through cleavage at Lys-103 by intracellular processing.
  • Glycosylation at Asn179, Asn285, Asn341, Asn477, Asn585, Asn643, Asn700, Asn731, and Asn748
  • Modification sites at PhosphoSitePlus
  • Glycosylation from GlyConnect
    • ENPP1_HUMAN (1196)

Other Protein References for ENPP1 Gene

No data available for DME Specific Peptides for ENPP1 Gene

Domains & Families for ENPP1 Gene

Gene Families for ENPP1 Gene

HGNC:
Human Protein Atlas (HPA):
  • CD markers
  • Disease related genes
  • Enzymes
  • Potential drug targets
  • Predicted membrane proteins
  • Predicted secreted proteins

Protein Domains for ENPP1 Gene

Suggested Antigen Peptide Sequences for ENPP1 Gene

GenScript: Design optimal peptide antigens:
  • Plasma-cell membrane glycoprotein PC-1 (ENPP1_HUMAN)
  • Phosphodiesterase I/nucleotide pyrophosphatase 1 (Q9NS95_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P22413

UniProtKB/Swiss-Prot:

ENPP1_HUMAN :
  • The di-leucine motif is required for basolateral targeting in epithelial cells, and for targeting to matrix vesicles derived from mineralizing cells.
  • Belongs to the nucleotide pyrophosphatase/phosphodiesterase family.
Domain:
  • The di-leucine motif is required for basolateral targeting in epithelial cells, and for targeting to matrix vesicles derived from mineralizing cells.
Family:
  • Belongs to the nucleotide pyrophosphatase/phosphodiesterase family.
genes like me logo Genes that share domains with ENPP1: view

Function for ENPP1 Gene

Molecular function for ENPP1 Gene

UniProtKB/Swiss-Prot Function:
Nucleotide pyrophosphatase that generates diphosphate (PPi) and functions in bone mineralization and soft tissue calcification by regulating pyrophosphate levels (By similarity). PPi inhibits bone mineralization and soft tissue calcification by binding to nascent hydroxyapatite crystals, thereby preventing further growth of these crystals (PubMed:11004006). Preferentially hydrolyzes ATP, but can also hydrolyze other nucleoside 5' triphosphates such as GTP, CTP, TTP and UTP to their corresponding monophosphates with release of pyrophosphate and diadenosine polyphosphates, and also 3',5'-cAMP to AMP (PubMed:27467858, PubMed:8001561, PubMed:25344812). May also be involved in the regulation of the availability of nucleotide sugars in the endoplasmic reticulum and Golgi, and the regulation of purinergic signaling (PubMed:27467858, PubMed:8001561). Inhibits ectopic joint calcification and maintains articular chondrocytes by repressing hedgehog signaling; it is however unclear whether hedgehog inhibition is direct or indirect (By similarity). Appears to modulate insulin sensitivity and function (PubMed:10615944). Also involved in melanogenesis (PubMed:28964717). Also able to hydrolyze 2'-3'-cGAMP (cyclic GMP-AMP), a second messenger that activates TMEM173/STING and triggers type-I interferon production (PubMed:25344812). 2'-3'-cGAMP degradation takes place in the lumen or extracellular space, and not in the cytosol where it is produced; the role of 2'-3'-cGAMP hydrolysis is therefore unclear (PubMed:25344812). Not able to hydrolyze the 2'-3'-cGAMP linkage isomer 3'-3'-cGAMP (PubMed:25344812).
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=Hydrolytically removes 5'-nucleotides successively from the 3'-hydroxy termini of 3'-hydroxy-terminated oligonucleotides.; EC=3.1.4.1; Evidence={ECO:0000269|PubMed:8001561};.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-phosphate + diphosphate + H(+); Xref=Rhea:RHEA:23996, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019, ChEBI:CHEBI:58043, ChEBI:CHEBI:61557; EC=3.6.1.9; Evidence={ECO:0000269|PubMed:25344812, ECO:0000269|PubMed:8001561};.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + H2O = a 2'-deoxyribonucleoside 5'-phosphate + diphosphate + H(+); Xref=Rhea:RHEA:44644, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560, ChEBI:CHEBI:65317; EC=3.6.1.9; Evidence={ECO:0000269|PubMed:8001561};.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=2',3'-cGAMP + 2 H2O = AMP + GMP + 2 H(+); Xref=Rhea:RHEA:58808, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:58115, ChEBI:CHEBI:143093, ChEBI:CHEBI:456215; Evidence={ECO:0000269|PubMed:25344812};.
UniProtKB/Swiss-Prot BiophysicochemicalProperties:
Kinetic parameters: KM=15 uM for 2'-3'-cGAMP {ECO:0000269|PubMed:25344812}; KM=20 uM for ATP {ECO:0000269|PubMed:25344812}; Note=Kcat is 4 sec(-1) with 2'-3'-cGAMP (PubMed:25344812). Kcat is 12 sec(-1) with ATP (PubMed:25344812). {ECO:0000269|PubMed:25344812};
UniProtKB/Swiss-Prot EnzymeRegulation:
At low concentrations of ATP, a phosphorylated intermediate is formed which inhibits further hydrolysis.

Phenotypes From GWAS Catalog for ENPP1 Gene

Gene Ontology (GO) - Molecular Function for ENPP1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003676 nucleic acid binding IEA --
GO:0003824 catalytic activity IEA --
GO:0004527 exonuclease activity IDA 22285541
GO:0004528 phosphodiesterase I activity IBA,ISS --
GO:0004551 nucleotide diphosphatase activity IBA,IDA 12746903
genes like me logo Genes that share ontologies with ENPP1: view
genes like me logo Genes that share phenotypes with ENPP1: view

Human Phenotype Ontology for ENPP1 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for ENPP1 Gene

MGI Knock Outs for ENPP1:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for ENPP1

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for ENPP1 Gene

Localization for ENPP1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for ENPP1 Gene

[Ectonucleotide pyrophosphatase/phosphodiesterase family member 1]: Cell membrane. Single-pass type II membrane protein. Basolateral cell membrane. Single-pass type II membrane protein. Note=Targeted to the basolateral membrane in polarized epithelial cells and in hepatocytes, and to matrix vesicles in osteoblasts (PubMed:11598187). In bile duct cells and cancer cells, located to the apical cytoplasmic side (PubMed:11598187). {ECO:0000269 PubMed:11598187}.
[Ectonucleotide pyrophosphatase/phosphodiesterase family member 1, secreted form]: Secreted. Note=Secreted following proteolytic cleavage. {ECO:0000250 UniProtKB:P06802}.

Subcellular locations from

COMPARTMENTS
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 ENPP1 gene
Compartment Confidence
plasma membrane 5
extracellular 5
lysosome 4
cytosol 3
cytoskeleton 2
mitochondrion 2
nucleus 2
endoplasmic reticulum 2
peroxisome 1
endosome 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for ENPP1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IEA --
GO:0005615 extracellular space IDA 11159191
GO:0005623 cell IEA --
GO:0005765 lysosomal membrane HDA 17897319
GO:0005886 plasma membrane TAS --
genes like me logo Genes that share ontologies with ENPP1: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for ENPP1 Gene

Pathways & Interactions for ENPP1 Gene

genes like me logo Genes that share pathways with ENPP1: view

Pathways by source for ENPP1 Gene

Interacting Proteins for ENPP1 Gene

SIGNOR curated interactions for ENPP1 Gene

Inactivates:
Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for ENPP1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006091 generation of precursor metabolites and energy IDA 12746903
GO:0006771 riboflavin metabolic process TAS --
GO:0006796 phosphate-containing compound metabolic process IDA 10513816
GO:0006897 endocytosis IEA --
GO:0006955 immune response IEA --
genes like me logo Genes that share ontologies with ENPP1: view

Drugs & Compounds for ENPP1 Gene

(29) Drugs for ENPP1 Gene - From: DrugBank, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Crotalus adamanteus antivenin Approved, Experimental Pharma Enzyme, ligand 0
Polyethylene glycol 400 Approved Pharma Target, other 0
Amifostine Approved, Investigational Pharma 82
FAD Approved Pharma 0
Flavin Mononucleotide Approved, Investigational Pharma 12

(19) Additional Compounds for ENPP1 Gene - From: Novoseek and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Alpha-D-Glucose
  • alpha-D-GLC
  • alpha-Dextrose
  • a-D-GLC
  • α-D-GLC
  • a-D-Glucose
492-62-6
beta-nicotinamide D-ribonucleotide
Dephospho-CoA
  • 3'-dephospho-CoA
  • 3'-dephospho-coenzyme A
  • 3'-O-dephosphono-CoA
  • 3'-O-dephosphono-coenzyme A
  • dephospho-coenzyme A
3633-59-8
Glucose 1-phosphate
  • 1-O-phosphono-D-Glucopyranose
  • Cori ester
  • D-Glucose 1-phosphate
  • GLC-1-P
  • Glucose 1-phosphoric acid
2255-14-3, 59-56-3
Nicotinamide ribotide
  • 3-(Aminocarbonyl)-1-(5-O-phosphonato-beta-D-ribofuranosyl)pyridinium
  • 3-(Aminocarbonyl)-1-(5-O-phosphono-beta-D-ribofuranosyl)pyridinium, inner salt
  • beta-Nicotinamide D-ribonucleotide
  • beta-Nicotinamide mononucleotide
  • beta-Nicotinamide ribonucleotide
1094-61-7
genes like me logo Genes that share compounds with ENPP1: view

Transcripts for ENPP1 Gene

mRNA/cDNA for ENPP1 Gene

1 REFSEQ mRNAs :
6 NCBI additional mRNA sequence :
8 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for ENPP1

Alternative Splicing Database (ASD) splice patterns (SP) for ENPP1 Gene

ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9a · 9b ^ 10 ^ 11a · 11b ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17 ^ 18a · 18b ^ 19 ^ 20 ^ 21 ^ 22 ^ 23 ^
SP1: -
SP2: -

ExUns: 24 ^ 25
SP1:
SP2:

Relevant External Links for ENPP1 Gene

GeneLoc Exon Structure for
ENPP1

Expression for ENPP1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for ENPP1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for ENPP1 Gene

This gene is overexpressed in Liver (x6.3) and Uterus (x5.2).

Protein differential expression in normal tissues from HIPED for ENPP1 Gene

This gene is overexpressed in Placenta (25.4), Breast (6.3), and Uterus (6.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for ENPP1 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for ENPP1

SOURCE GeneReport for Unigene cluster for ENPP1 Gene:

Hs.527295

mRNA Expression by UniProt/SwissProt for ENPP1 Gene:

P22413-ENPP1_HUMAN
Tissue specificity: Expressed in plasma cells and also in a number of non-lymphoid tissues, including the distal convoluted tubule of the kidney, chondrocytes and epididymis (PubMed:9344668). Expressed in melanocytes but not in keratinocytes (PubMed:28964717).

Evidence on tissue expression from TISSUES for ENPP1 Gene

  • Blood(5)
  • Liver(4.7)
  • Skin(4.5)
  • Kidney(2.7)
  • Nervous system(2.6)
  • Thyroid gland(2.5)
  • Bone(2.4)
  • Heart(2.4)
  • Pancreas(2.4)
  • Muscle(2.2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for ENPP1 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • immune
  • integumentary
  • nervous
  • respiratory
  • skeletal muscle
  • skeleton
  • urinary
Regions:
Head and neck:
  • brain
  • cranial nerve
  • ear
  • eye
  • head
  • jaw
  • mandible
  • maxilla
  • meninges
  • mouth
  • neck
  • skull
  • tooth
Thorax:
  • chest wall
  • clavicle
  • diaphragm
  • heart
  • heart valve
  • lung
  • rib
  • rib cage
  • scapula
  • sternum
Abdomen:
  • intestine
  • kidney
  • large intestine
  • small intestine
  • stomach
Pelvis:
  • pelvis
  • ureter
  • urinary bladder
Limb:
  • ankle
  • arm
  • digit
  • elbow
  • femur
  • fibula
  • finger
  • foot
  • forearm
  • hand
  • hip
  • humerus
  • knee
  • lower limb
  • nail
  • radius
  • shin
  • shoulder
  • thigh
  • tibia
  • toe
  • ulna
  • upper limb
  • wrist
General:
  • blood
  • blood vessel
  • coagulation system
  • hair
  • peripheral nervous system
  • red blood cell
  • skin
  • spinal column
  • spinal cord
  • vertebrae
  • white blood cell
genes like me logo Genes that share expression patterns with ENPP1: view

No data available for Protein tissue co-expression partners for ENPP1 Gene

Orthologs for ENPP1 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for ENPP1 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia ENPP1 30 31
  • 99.57 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia ENPP1 30 31
  • 88.73 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia ENPP1 30 31
  • 88.49 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Enpp1 30 17 31
  • 81.15 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Enpp1 30
  • 80.43 (n)
Oppossum
(Monodelphis domestica)
Mammalia ENPP1 31
  • 77 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia ENPP1 31
  • 50 (a)
OneToOne
Chicken
(Gallus gallus)
Aves ENPP1 30 31
  • 70.9 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia ENPP1 31
  • 63 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia enpp1 30
  • 64.53 (n)
Zebrafish
(Danio rerio)
Actinopterygii enpp1 30 31
  • 59.85 (n)
OneToOne
Worm
(Caenorhabditis elegans)
Secernentea CELE_C27A7.1 30
  • 46.27 (n)
C27A7.1 32
  • 28 (a)
C27A7.3 31 32
  • 26 (a)
ManyToMany
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes NPP2 31
  • 23 (a)
ManyToMany
NPP1 31
  • 21 (a)
ManyToMany
Thale Cress
(Arabidopsis thaliana)
eudicotyledons AT4G29680 30
  • 50.54 (n)
Rice
(Oryza sativa)
Liliopsida Os01g0196600 30
  • 50.54 (n)
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 37 (a)
ManyToMany
Species where no ortholog for ENPP1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • 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)
  • Fruit Fly (Drosophila melanogaster)
  • 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 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)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for ENPP1 Gene

ENSEMBL:
Gene Tree for ENPP1 (if available)
TreeFam:
Gene Tree for ENPP1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for ENPP1: view image

Paralogs for ENPP1 Gene

Paralogs for ENPP1 Gene

(8) SIMAP similar genes for ENPP1 Gene using alignment to 2 proteins:

  • ENPP1_HUMAN
  • E9PE72_HUMAN
genes like me logo Genes that share paralogs with ENPP1: view

Variants for ENPP1 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for ENPP1 Gene

SNP ID Clinical significance and condition Chr 06 pos Variation AA Info Type
692042 Pathogenic: Coronary sclerosis, medial, of infancy 131,864,548(+) G/A NONSENSE
708715 Likely Benign: not provided 131,851,275(+) G/T INTRON_VARIANT
713097 Likely Benign: not provided 131,864,947(+) A/G INTRON_VARIANT
717550 Likely Benign: not provided 131,858,702(+) G/A SYNONYMOUS_VARIANT
722482 Conflicting Interpretations: Arterial calcification, generalized, of infancy, 1; Hypophosphatemic rickets, autosomal recessive, 2; not provided 131,851,233(+) C/T SYNONYMOUS_VARIANT

Additional dbSNP identifiers (rs#s) for ENPP1 Gene

Structural Variations from Database of Genomic Variants (DGV) for ENPP1 Gene

Variant ID Type Subtype PubMed ID
dgv88n68 CNV loss 17160897
esv3610819 CNV gain 21293372
nsv1117667 CNV deletion 24896259
nsv475881 CNV novel sequence insertion 20440878
nsv475954 CNV novel sequence insertion 20440878
nsv5479 CNV deletion 18451855
nsv7968 CNV loss 18304495

Variation tolerance for ENPP1 Gene

Residual Variation Intolerance Score: 21.3% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 8.57; 86.11% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for ENPP1 Gene

Human Gene Mutation Database (HGMD)
ENPP1
SNPedia medical, phenotypic, and genealogical associations of SNPs for
ENPP1

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for ENPP1 Gene

Disorders for ENPP1 Gene

MalaCards: The human disease database

(49) MalaCards diseases for ENPP1 Gene - From: UniProtKB/Swiss-Prot, OMIM, ClinVar, GTR, Orphanet, DISEASES, Novoseek, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search ENPP1 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

ENPP1_HUMAN
  • Ossification of the posterior longitudinal ligament of the spine (OPLL) [MIM:602475]: A calcification of the posterior longitudinal ligament of the spinal column, usually at the level of the cervical spine. Patients with OPLL frequently present with a severe myelopathy that can lead to tetraparesis. {ECO:0000269 PubMed:10453738}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Arterial calcification of infancy, generalized, 1 (GACI1) [MIM:208000]: A severe autosomal recessive disorder characterized by calcification of the internal elastic lamina of muscular arteries and stenosis due to myointimal proliferation. The disorder is often fatal within the first 6 months of life because of myocardial ischemia resulting in refractory heart failure. {ECO:0000269 PubMed:12881724, ECO:0000269 PubMed:15605415, ECO:0000269 PubMed:15940697, ECO:0000269 PubMed:20016754, ECO:0000269 PubMed:22209248, ECO:0000269 PubMed:23430823, ECO:0000269 PubMed:27467858}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Diabetes mellitus, non-insulin-dependent (NIDDM) [MIM:125853]: A multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to the body's own insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. {ECO:0000269 PubMed:16186408, ECO:0000269 PubMed:29958952}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
  • Hypophosphatemic rickets, autosomal recessive, 2 (ARHR2) [MIM:613312]: A hereditary form of hypophosphatemic rickets, a disorder of proximal renal tubule function that causes phosphate loss, hypophosphatemia and skeletal deformities, including rickets and osteomalacia unresponsive to vitamin D. Symptoms are bone pain, fractures and growth abnormalities. {ECO:0000269 PubMed:20137772, ECO:0000269 PubMed:20137773, ECO:0000269 PubMed:25741938}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Cole disease (COLED) [MIM:615522]: A rare autosomal dominant genodermatosis characterized by punctate keratoderma associated with irregularly shaped hypopigmented macules, which are typically found over the arms and legs but not the trunk or acral regions. Skin biopsies of palmoplantar lesions show hyperorthokeratosis, hypergranulosis, and acanthosis. Hypopigmented areas of skin, however, reveal a reduction in melanin content in keratinocytes but not in melanocytes, as well as hyperkeratosis and a normal number of melanocytes. Ultrastructurally, melanocytes show a disproportionately large number of melanosomes in the cytoplasm and dendrites, whereas keratinocytes show a paucity of these organelles, suggestive of impaired melanosome transfer. Some patients also exhibit calcinosis cutis or calcific tendinopathy. {ECO:0000269 PubMed:24075184, ECO:0000269 PubMed:26617416, ECO:0000269 PubMed:28964717}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for ENPP1

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with ENPP1: view

No data available for Genatlas for ENPP1 Gene

Publications for ENPP1 Gene

  1. Association of the human NPPS gene with ossification of the posterior longitudinal ligament of the spine (OPLL). (PMID: 10453738) Nakamura I … Nakamura Y (Human genetics 1999) 3 4 23 41
  2. Autosomal-recessive hypophosphatemic rickets is associated with an inactivation mutation in the ENPP1 gene. (PMID: 20137772) Levy-Litan V … Parvari R (American journal of human genetics 2010) 3 4 23
  3. Loss-of-function ENPP1 mutations cause both generalized arterial calcification of infancy and autosomal-recessive hypophosphatemic rickets. (PMID: 20137773) Lorenz-Depiereux B … Strom TM (American journal of human genetics 2010) 3 4 23
  4. [ENPP1 K121Q polymorphism and ischemic heart disease in diabetic patients]. (PMID: 20428609) Moehlecke M … Canani LH (Arquivos brasileiros de cardiologia 2010) 3 23 41
  5. The ENPP1 K121Q polymorphism determines individual susceptibility to the insulin-sensitising effect of lifestyle intervention. (PMID: 20091022) Müssig K … Staiger H (Diabetologia 2010) 3 23 41

Products for ENPP1 Gene

Sources for ENPP1 Gene