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ENPP1 Gene

protein-coding   GIFtS: 70
GCID: GC06P132129

Ectonucleotide Pyrophosphatase/Phosphodiesterase 1


(Previous symbols: NPPS, M6S1, PDNP1)
  See ENPP1-related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Ectonucleotide Pyrophosphatase/Phosphodiesterase 11 2     PCA12 5
M6S11 2 3 5     NPP12
NPPS1 2 3 5     PC-12
PDNP11 2 3 5     Alkaline Phosphodiesterase 12
Membrane Component Chromosome 6 Surface Marker 12 3     Ectonucleotide Pyrophosphatase/Phosphodiesterase Family Member 12
Phosphodiesterase I/Nucleotide Pyrophosphatase 12 3     Ly-41 Antigen2
Plasma-Cell Membrane Glycoprotein PC-12 3     Membrane Component, Chromosome 6, Surface Marker 12
E-NPP 12 3     Plasma-Cell Membrane Glycoprotein 12
ARHR22 5     PC13
COLED2 5     

External Ids:    HGNC: 33561   Entrez Gene: 51672   Ensembl: ENSG000001975947   OMIM: 1733355   UniProtKB: P224133   

Export aliases for ENPP1 gene to outside databases

Previous GC identifers: GC06P131752 GC06P131976 GC06P132109 GC06P132170 GC06P129704


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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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 ossification of the posterior longitudinal ligament of the spine, and arterial calcification, generalized, of infancy, 1. GO annotations related to this gene include scavenger receptor activity and protein homodimerization activity. An important paralog of this gene is ENPP6.

UniProtKB/Swiss-Prot: ENPP1_HUMAN, P22413
Function: By generating PPi, plays a role in regulating pyrophosphate levels, and functions in bone mineralization
and soft tissue calcification. PPi inhibits mineralization by binding to nascent hydroxyapatite (HA) crystals,
thereby preventing further growth of these crystals. 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. 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. Appears to modulate insulin sensitivity

Gene Wiki entry for ENPP1 (Ectonucleotide pyrophosphatase/phosphodiesterase 1) Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:
NC_000006.11  NT_025741.16  NC_018917.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the ENPP1 gene promoter:
         E2F-3a   E2F-4   E2F-5   FOXF2   Pax-2   Pax-2a   CUTL1   E2F-2   E2F-1   E2F   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidENPP1 promoter sequence
   Search Chromatin IP Primers for ENPP1

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat ENPP1


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 6q22-q23   Ensembl cytogenetic band:  6q23.2   HGNC cytogenetic band: 6q22-q23

ENPP1 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
ENPP1 gene location

GeneLoc information about chromosome 6         GeneLoc Exon Structure

GeneLoc location for GC06P132129:  view genomic region     (about GC identifiers)

Start:
132,129,156 bp from pter      End:
132,216,295 bp from pter
Size:
87,140 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., and/or eBioscience,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., and/or eBioscience, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: ENPP1_HUMAN, P22413 (See protein sequence)
Recommended Name: Ectonucleotide pyrophosphatase/phosphodiesterase family member 1  
Size: 925 amino acids; 104924 Da
Cofactor: Binds 2 zinc ions per subunit (By similarity)
Subunit: The secreted form is monomeric (By similarity). Homodimer. Interacts with INSR
Caution: It is uncertain whether Met-1 or Met-53 is the initiator
Sequence caution: Sequence=AAA63237.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
Sequence=AAH59375.2; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=BAA02054.1;
Type=Erroneous initiation; Note=Translation N-terminally extended;
1 PDB 3D structure from and Proteopedia for ENPP1:
2YS0 (3D)    
Secondary accessions: Q5T9R6 Q9NPZ3 Q9P1P6 Q9UP61 Q9Y6K3

Explore the universe of human proteins at neXtProt for ENPP1: NX_P22413

Explore proteomics data for ENPP1 at MOPED

Post-translational modifications: 

  • Autophosphorylated as part of the catalytic cycle of phosphodiesterase/pyrophosphatase activity1
  • N-glycosylated1
  • A secreted form is produced through cleavage at Lys-103 by intracellular processing (By similarity)1
  • Glycosylation2 at Asn179, Asn285, Asn341, Asn477, Asn585, Asn643, Asn700, Asn731, Asn748
  • Modification sites at PhosphoSitePlus

  • See ENPP1 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_006199.2  
    ENSEMBL proteins: 
     ENSP00000354238   ENSP00000422424  
    Reactome Protein details: P22413

    ENPP1 Human Recombinant Protein Products:

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    OriGene Protein Over-expression Lysate for ENPP1
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    Novus Biologicals ENPP1 Proteins
    Novus Biologicals ENPP1 Lysates
    Browse Sino Biological Recombinant Proteins
    Browse Sino Biological Cell Lysates
    ProSpec Recombinant Protein for ENPP1
    Cloud-Clone Corp. Proteins for ENPP1

     
    Search eBioscience for Proteins for ENPP1 

    ENPP1 Antibody Products:

    Browse EMD Millipore's Extensive Line of Mono- and Polyclonal Antibodies
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    Abcam antibodies for ENPP1
    Cloud-Clone Corp. Antibodies for ENPP1
    ThermoFisher Antibodies for ENPP1
    LSBio Antibodies in human, mouse, rat for ENPP1

    ENPP1 Assay Products:

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    Browse Enzo Life Sciences for kits & assays
    Cloud-Clone Corp. ELISAs for ENPP1
    Cloud-Clone Corp. CLIAs for ENPP1
    Search eBioscience for ELISAs for ENPP1 


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    Selected InterPro protein domains (see all 8):
     IPR002591 Phosphodiest/P_Trfase
     IPR001604 DNA/RNA_non-sp_Endonuclease
     IPR017849 Alkaline_Pase-like_a/b/a
     IPR024873 E-NPP
     IPR020821 Extracellular_endonuc_su_A

    Graphical View of Domain Structure for InterPro Entry P22413

    ProtoNet protein and cluster: P22413

    2 Blocks protein domains:
    IPB001212 Somatomedin B
    IPB002591 Type I phosphodiesterase/nucleotide pyrophosphatase


    UniProtKB/Swiss-Prot: ENPP1_HUMAN, P22413
    Domain: The di-leucine motif is required for basolateral targeting in epithelial cells, and for targeting to
    matrix vesicles derived from mineralizing cells (By similarity)
    Similarity: Belongs to the nucleotide pyrophosphatase/phosphodiesterase family
    Similarity: Contains 2 SMB (somatomedin-B) domains


    Find genes that share domains with ENPP1           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: ENPP1_HUMAN, P22413
    Function: By generating PPi, plays a role in regulating pyrophosphate levels, and functions in bone mineralization
    and soft tissue calcification. PPi inhibits mineralization by binding to nascent hydroxyapatite (HA) crystals,
    thereby preventing further growth of these crystals. 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. 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. Appears to modulate insulin sensitivity
    Catalytic activity: Hydrolytically removes 5'-nucleotides successively from the 3'-hydroxy termini of
    3'-hydroxy-terminated oligonucleotides
    Catalytic activity: A dinucleotide + H(2)O = 2 mononucleotides
    Enzyme regulation: At low concentrations of ATP, a phosphorylated intermediate is formed which inhibits further
    hydrolysis

         Gene Ontology (GO): Selected molecular function terms (see all 17):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0003676nucleic acid binding IEA--
    GO:0003824catalytic activity ----
    GO:0004528phosphodiesterase I activity ISS--
    GO:0004551nucleotide diphosphatase activity TAS--
    GO:0005044scavenger receptor activity IEA--
         
    Find genes that share ontologies with ENPP1           About GenesLikeMe


    Phenotypes:
         1 GenomeRNAi human phenotype for ENPP1:
     Decreased Salmonella enterica  

         Selected MGI mutant phenotypes (inferred from 4 alleles(MGI details for Enpp1) (see all 16):
     adipose tissue  behavior/neurological  cardiovascular system  growth/size/body  hearing/vestibular/ear 
     homeostasis/metabolism  immune system  integument  liver/biliary system  mortality/aging 
     muscle  nervous system  other  renal/urinary system  skeleton 

    Find genes that share phenotypes with ENPP1           About GenesLikeMe

    Animal Models:
         MGI mouse knock-out Enpp1tm1Gdg for ENPP1

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for ENPP1
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for ENPP1

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for ENPP1
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for ENPP1

    miRNA
    Products:
        
    Block miRNA regulation of human, mouse, rat ENPP1 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate ENPP1 (see all 45):
    hsa-miR-607 hsa-miR-513a-5p hsa-miR-3653 hsa-miR-105 hsa-miR-9 hsa-miR-3658 hsa-miR-520g hsa-miR-181b
    SwitchGear 3'UTR luciferase reporter plasmidENPP1 3' UTR sequence
    Inhib. RNA
    Products:
        
    OriGene RNAi products in human, mouse, rat for ENPP1
    Predesigned siRNA for gene silencing in human, mouse, rat ENPP1

    Gene Editing
    Products:
    DNA2.0 Custom Protein Engineering Service for ENPP1

    Clone
    Products:
         
    OriGene clones in human, mouse for ENPP1 (see all 9)
    OriGene ORF clones in mouse, rat for ENPP1
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector: ENPP1 (NM_006208)
    Browse Sino Biological Human cDNA Clones
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for ENPP1
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat ENPP1

    Cell Line
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    Browse ESI BIO Cell Lines and PureStem Progenitors for ENPP1 
    In Situ Assay
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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for ENPP1


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    ENPP1_HUMAN, P22413: Cell membrane; Single-pass type II membrane protein. Basolateral cell membrane; Single-pass
    type II membrane protein. Secreted (By similarity). Note=The proteolytically processed form is secreted (By
    similarity). Targeted to the basolateral membrane in polarized epithelial cells and in hepatocytes, and to matrix
    vesicles in osteoblasts. In bile duct cells and cancer cells, located to the apical cytoplasmic side
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    plasma membrane5
    extracellular4
    cytosol2
    mitochondrion1
    nucleus1
    peroxisome1

    Gene Ontology (GO): Selected cellular component terms (see all 7):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005615extracellular space IDA11159191
    GO:0005765lysosomal membrane IDA17897319
    GO:0005886plasma membrane TAS--
    GO:0005887integral component of plasma membrane ISS--
    GO:0009986cell surface IDA10513816

    Find genes that share ontologies with ENPP1           About GenesLikeMe


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for ENPP1 About   (see all 11)  
    See pathways by source

    SuperPathSelected contained pathways About (see all per SuperPath)
    1Nicotinate and nicotinamide metabolism
    Nicotinate and nicotinamide metabolism0.43
    NAD metabolism0.43
    2Metabolism
    Metabolism0.38
    Metabolic pathways0.38
    3Defective BTD causes biotidinase deficiency
    Defective BTD causes biotidinase deficiency1.00
    Metabolism of vitamins and cofactors1.00
    Defective AMN causes hereditary megaloblastic anemia 11.00
    Defective MMACHC causes methylmalonic aciduria and homocystinuria type cblC1.00
    Defective MMAA causes methylmalonic aciduria type cblA1.00
    Defective MUT causes methylmalonic aciduria mut type1.00
    Defective CD320 causes methylmalonic aciduria1.00
    Defects in cobalamin (B12) metabolism1.00
    4Glucuronidation
    Starch and sucrose metabolism0.41
    5Purine metabolism (KEGG)
    Purine metabolism0.38


    Find genes that share SuperPaths with ENPP1           About GenesLikeMe

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways


    1 Cell Signaling Technology (CST) Pathway for ENPP1
        Glucose / Energy Metabolism

    1 GeneGo (Thomson Reuters) Pathway for ENPP1
        NAD metabolism

    2 BioSystems Pathways for ENPP1
        Insulin Signaling
    Endochondral Ossification

    1 Reactome Pathway for ENPP1
        Vitamin B2 (riboflavin) metabolism


    Selected Kegg Pathways  (Kegg details for ENPP1) (see all 6):
        Purine metabolism
    Starch and sucrose metabolism
    Riboflavin metabolism
    Nicotinate and nicotinamide metabolism
    Pantothenate and CoA biosynthesis

        Pathway & Disease-focused RT2 Profiler PCR Array including ENPP1: 
              Diabetes in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for ENPP1

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for ENPP1 (P224131, 2, 3 ENSP000003542384) via UniProtKB, MINT, STRING, and/or I2D (see all 45)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    INSRP062131, 3, ENSP000003038304EBI-3197846,EBI-475899 I2D: score=2 STRING: ENSP00000303830
    SQSTM1Q135013I2D: score=3 
    ACPPENSP000003230364STRING: ENSP00000323036
    BST1ENSP000002650164STRING: ENSP00000265016
    CD38ENSP000002262794STRING: ENSP00000226279
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    Gene Ontology (GO): Selected biological process terms (see all 26):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0006091generation of precursor metabolites and energy IDA12746903
    GO:0006200ATP catabolic process ISS--
    GO:0006766vitamin metabolic process TAS--
    GO:0006767water-soluble vitamin metabolic process TAS--
    GO:0006771riboflavin metabolic process TAS--

    Find genes that share ontologies with ENPP1           About GenesLikeMe



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for ENPP1

    Selected HMDB Compounds for ENPP1 (see all 20)    About this table
    CompoundSynonyms CAS #PubMed Ids
    Adenosine 3',5'-diphosphate3,5-Diphosphoadenosine (see all 10)1053-73-2--
    Adenosine monophosphate5'-AMP (see all 28)61-19-8--
    Alpha-D-GlucoseHexopyranose (see all 11)492-62-6--
    Cyclic AMPCyclic AMP (see all 19)60-92-4--
    Dephospho-CoA3'-O-dephosphono-Coenzyme A (see all 7)3633-59-8--
    FAD1H-Purin-6-amine flavin dinucleotide (see all 21)146-14-5--
    Flavin MononucleotideFMN (see all 19)146-17-8--
    Glucose 1-phosphateCori ester (see all 22)59-56-3--
    Guanosine triphosphate5'-GTP (see all 10)86-01-1--
    NAD3-Carbamoyl-1-D-ribofuranosylpyridinium hydroxide 5'-ester with adenosine 5'-pyrophosphate (see all 28)53-84-9--

    2 DrugBank Compounds for ENPP1    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    AmifostineAmifostine Ethiofos (see all 7)20537-88-6targetinducer17139284 17016423
    RibavirinRBV (see all 4)36791-04-5targetinhibitor17139284 17016423

    Selected Novoseek inferred chemical compound relationships for ENPP1 gene (see all 21)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    npps 90.2 52 12509614 (7), 11202013 (6), 15834329 (6), 10453738 (4) (see all 9)
    pdnp 79.7 4 11352238 (1), 10524196 (1)
    pyrophosphate 79.7 25 17552941 (4), 17906411 (3), 16546821 (2), 16369898 (1) (see all 15)
    5'-nucleotide 79.6 5 7737162 (1), 18500657 (1), 8003067 (1), 7998960 (1) (see all 5)
    glucose 46 30 8826966 (6), 16968801 (3), 16278247 (3), 10389840 (2) (see all 15)
    tyrosine 40.8 51 10615944 (5), 8923458 (4), 10871198 (3), 9518262 (3) (see all 23)
    metformin 34.9 9 10634965 (4), 12803833 (2), 15209435 (1)
    rapamycin 30 1 12441313 (1)
    phosphodiester 29.7 1 11202013 (1)
    hydroxyapatite 27.6 7 11159191 (1), 15569637 (1), 11352238 (1), 15075217 (1) (see all 5)



    Find genes that share compounds with ENPP1           About GenesLikeMe



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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    REFSEQ mRNAs for ENPP1 gene: 
    NM_006208.2  

    Unigene Cluster for ENPP1:

    Ectonucleotide pyrophosphatase/phosphodiesterase 1
    Hs.527295  [show with all ESTs]
    Unigene Representative Sequence: NM_006208
    4 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000486853 ENST00000360971(uc011ecf.2) ENST00000513998 ENST00000459624(uc003qcy.3)

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    Selected qRT-PCR Assays for microRNAs that regulate ENPP1 (see all 45):
    hsa-miR-607 hsa-miR-513a-5p hsa-miR-3653 hsa-miR-105 hsa-miR-9 hsa-miR-3658 hsa-miR-520g hsa-miR-181b
    SwitchGear 3'UTR luciferase reporter plasmidENPP1 3' UTR sequence
    Inhib. RNA
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    Primer
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      QuantiTect SYBR Green Assays in human, mouse, rat ENPP1
      QuantiFast Probe-based Assays in human, mouse, rat ENPP1

    Additional mRNA sequence: 

    AK314870.1 BC033008.1 BC059375.1 D12485.1 M57736.1 

    8 DOTS entries:

    DT.316590  DT.410845  DT.443506  DT.100695274  DT.100838471  DT.121354988  DT.95365401  DT.121403534 

    Selected AceView cDNA sequences (see all 135):

    BM785436 AA417961 CD101720 AA236029 AI089081 BM770219 BQ186971 NM_006208 
    BM756291 BX113968 AW205890 M57736 AA384887 AI990893 BX537580 D12485 
    AI342149 CA447028 AI433710 BC059375 AI090484 BQ771937 AA771740 AA234217 

    GeneLoc Exon Structure

    2 Alternative Splicing Database (ASD) splice patterns (SP) for ENPP1    About this scheme

    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:            


    ECgene alternative splicing isoforms for ENPP1

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    ENPP1 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: AGTGCTTTCA
    ENPP1 Expression
    About this image


    ENPP1 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 3) fully expand
     
     Neural Crest (Gastrulation Derivatives)
             PureStem 7SMOO32, NCr-fac & Meso Progenitor
     
     Liver (Hepatobiliary System)
             Perivenous Hepatocytes Liver Lobule
     
     Mesoderm (Gastrulation Derivatives)
             PureStem 7SMOO32, NCr-fac & Meso Progenitor
    ENPP1 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    ENPP1 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.527295

    UniProtKB/Swiss-Prot: ENPP1_HUMAN, P22413
    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

        Pathway & Disease-focused RT2 Profiler PCR Array including ENPP1: 
              Diabetes in human mouse rat

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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of eukaryotes.

    Orthologs for ENPP1 gene from Selected species (see all 16)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Enpp11 , 5 ectonucleotide pyrophosphatase/phosphodiesterase 11, 5 81.15(n)1
    80.78(a)1
      10 (12.26 cM)5
    186051  NM_008813.31  NP_032839.31 
     246379145 
    chicken
    (Gallus gallus)
    Aves ENPP11 ectonucleotide pyrophosphatase/phosphodiesterase 1 70.9(n)
    66.93(a)
      426929  XM_424539.4  XP_424539.4 
    lizard
    (Anolis carolinensis)
    Reptilia ENPP16
    ectonucleotide pyrophosphatase/phosphodiesterase 1...
    63(a)
    1 ↔ 1
    1(204285991-204337055)
    tropical clawed frog
    (Xenopus tropicalis)
    Amphibia enpp11 ectonucleotide pyrophosphatase/phosphodiesterase 1 64.53(n)
    60.87(a)
      100422807  XM_002936314.2  XP_002936360.2 
    zebrafish
    (Danio rerio)
    Actinopterygii enpp11 ectonucleotide pyrophosphatase/phosphodiesterase 1 59.85(n)
    56.58(a)
      562399  NM_001030168.1  NP_001025339.1 
    worm
    (Caenorhabditis elegans)
    Secernentea C27A7.13
    CELE_C27A7.11
    Human plasma-cell membrane glycoprotein
    PC-1 like3
    CELE_C27A7.11
    28(a)
    (best of 2)3
    46.27(n)1
    35.38(a)1
      V(12134089-12139865)3
    1796631  NM_001047621.11  NP_001041086.11 
    baker's yeast
    (Saccharomyces cerevisiae)
    Saccharomycetes NPP26
    NPP16
    Nucleotide pyrophosphatase/phosphodiesterase famil...
    Nucleotide pyrophosphatase/phosphodiesterase famil...
    23(a)
    21(a)
    many ↔ many
    many ↔ many
    V(124737-126218) YEL016C
    III(164111-166339) YCR026C
    thale cress
    (Arabidopsis thaliana)
    eudicotyledons AT4G296801 AT4G29680 50.54(n)
    42.7(a)
      829089  NM_119113.3  NP_194697.1 
    rice
    (Oryza sativa)
    Liliopsida Os01g01966001 Os01g0196600 50.54(n)
    45.14(a)
      4327327  NM_001048830.1  NP_001042295.1 


    ENSEMBL Gene Tree for ENPP1 (if available)
    TreeFam Gene Tree for ENPP1 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
    About This Section

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    Paralogs for ENPP1 gene
    ENPP62  ENPP32  ENPP52  ENPP72  ENPP42  ENPP22  
    8 SIMAP similar genes for ENPP1 using alignment to 2 protein entries:     ENPP1_HUMAN (see all proteins):
    PDNP1    DKFZp686P13218    ENPP3    ENPP2    PDNP3    ENPP4
    ENPP5    ENPP6

    Find genes that share paralogs with ENPP1           About GenesLikeMe



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for ENPP1 (see all 2141)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 6 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs1909471441,2,,4
    COssification of the posterior longitudinal ligament of the spine (OPLL)4 --132182832(+) TGCTTC/TCTTTT 2 S F mis10--------
    VAR_0679144
    Arterial calcification of infancy, generalized, 1 (GACI1)4--see VAR_0679142 G R mis40--------
    VAR_0707834
    Cole disease (COLED)4--see VAR_0707832 C S mis40--------
    VAR_0141414
    Ossification of the posterior longitudinal ligament of the spine (OPLL)4--see VAR_0141412 L P mis40--------
    VAR_0185144
    Arterial calcification of infancy, generalized, 1 (GACI1)4--see VAR_0185142 L F mis40--------
    VAR_0374334
    Arterial calcification of infancy, generalized, 1 (GACI1)4--see VAR_0374332 G V mis40--------
    VAR_0679124
    Arterial calcification of infancy, generalized, 1 (GACI1)4--see VAR_0679122 P T mis40--------
    VAR_0679104
    Arterial calcification of infancy, generalized, 1 (GACI1)4--see VAR_0679102 P L mis40--------
    VAR_0707824
    Cole disease (COLED)4--see VAR_0707822 C S mis40--------
    VAR_0679134
    Arterial calcification of infancy, generalized, 1 (GACI1)4--see VAR_0679132 D H mis40--------

    HapMap Linkage Disequilibrium report for ENPP1 (132129156 - 132216295 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 4 variations for ENPP1:    About this table    
    Variant IDTypeSubtypePubMed ID
    nsv5479CNV Loss18451855
    dgv88n68CNV Loss17160897
    nsv7968CNV Loss18304495
    dgv6993n71CNV Gain21882294

    Human Gene Mutation Database (HGMD): ENPP1
    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing ENPP1
    DNA2.0 Custom Variant and Variant Library Synthesis for ENPP1

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
    About This Section

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    OMIM gene information: 173335   
    OMIM disorders: 602475  125853  601665  208000  613312  615522  
    UniProtKB/Swiss-Prot: ENPP1_HUMAN, P22413
  • 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. 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. 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. 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. Note=The disease is caused by mutations affecting the gene
    represented in this entry

  • 15 diseases for ENPP1:    
    About MalaCards
    ossification of the posterior longitudinal ligament of the spine    arterial calcification, generalized, of infancy, 1    cole disease    hypophosphatemic rickets, autosomal recessive 2
    arterial calcification of infancy    bile duct disease    hypophosphatemic rickets, ar    hypophosphatasia
    type 2 diabetes mellitus    pseudogout    calcinosis    rickets
    obesity    ankylosis    insulin resistance

    6 diseases from the University of Copenhagen DISEASES database for ENPP1:
    Generalized arterial calcification of infancy     Ankylosis     Diabetes mellitus     Hypophosphatasia
    Pseudogout     Pseudoxanthoma elasticum

    Find genes that share disorders with ENPP1           About GenesLikeMe

    Selected Novoseek inferred disease relationships for ENPP1 gene (see all 36)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    adpkd 83.6 58 17090781 (4), 16567633 (3), 16778383 (3), 12633844 (3) (see all 23)
    insulin resistance 76.6 125 17563456 (6), 15209435 (5), 10499882 (4), 10389840 (3) (see all 58)
    chondrocalcinosis 74.7 3 11764218 (1), 12744817 (1), 17043047 (1)
    polycystic kidney diseases 71.8 9 16778383 (1), 17102641 (1), 19759016 (1), 17715262 (1) (see all 8)
    insulin sensitivity 64 20 15126519 (3), 19577557 (2), 10523005 (2), 10634965 (2) (see all 13)
    calcification 56.9 45 11352238 (3), 17848394 (3), 15625282 (3), 11159191 (2) (see all 18)
    ossification heterotopic 55.5 5 11856874 (2), 11771660 (1), 15834329 (1), 10453738 (1)
    renal cyst 54.5 3 17102641 (1), 16399078 (1), 18845692 (1)
    niddm 53.4 27 10499882 (4), 7830796 (3), 9609127 (2), 16941279 (2) (see all 14)
    obesity 51.9 42 8826966 (4), 16025115 (4), 17065358 (4), 16968801 (3) (see all 19)

    Genetic Association Database (GAD): ENPP1
    Human Genome Epidemiology (HuGE) Navigator: ENPP1 (100 documents)

    Export disorders for ENPP1 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for ENPP1 gene, integrated from 10 sources (see all 301):
    (articles sorted by number of sources associating them with ENPP1)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Association of the human NPPS gene with ossification of the posterior longitudinal ligament of the spine (OPLL). (PubMed id 10453738)1, 2, 4, 9 Nakamura I.... Nakamura Y. (Hum. Genet. 1999)
    2. The K121Q polymorphism of the ENPP1/PC-1 gene is associated with insulin resistance/atherogenic phenotypes, including earlier onset of type 2 diabetes and myocardial infarction. (PubMed id 16186408)1, 2, 4 Bacci S....Trischitta V. (Diabetes 2005)
    3. Molecular cloning of cDNAs for human fibroblast nucleotide pyrophosphatase. (PubMed id 1315502)1, 2, 3 Funakoshi I.... Yamashina I. (Arch. Biochem. Biophys. 1992)
    4. Membrane glycoprotein PC-1 inhibition of insulin receptor function occurs via direct interaction with the receptor alpha-subunit. (PubMed id 10615944)1, 2, 9 Maddux B.A. and Goldfine I.D. (Diabetes 2000)
    5. Autophosphorylation of PC-1 (alkaline phosphodiesterase I/nucleotide pyrophosphatase) and analysis of the active site. (PubMed id 7737162)1, 2, 9 Belli S.I.... Goding J.W. (Eur. J. Biochem. 1995)
    6. Biochemical characterization of human PC-1, an enzyme possessing alkaline phosphodiesterase I and nucleotide pyrophosphatase activities. (PubMed id 8001561)1, 2, 9 Belli S.I. and Goding J.W. (Eur. J. Biochem. 1994)
    7. A cluster of three single nucleotide polymorphisms in the 3'-untranslated region of human glycoprotein PC-1 gene stabilizes PC-1 mRNA and is associated with increased PC-1 protein content and insulin resistance-related abnormalities. (PubMed id 11473061)1, 4, 9 Frittitta L....Trischitta V. (Diabetes 2001)
    8. Investigation of the role of ENPP1 and TNAP genes in chondrocalcinosis. (PubMed id 17043047)1, 4, 9 Zhang Y....Wordsworth B.P. (Rheumatology (Oxford) 2007)
    9. The association of the K121Q polymorphism of the plasma cell glycoprotein-1 gene with type 2 diabetes and hypertension depends on size at birth. (PubMed id 15126519)1, 4, 9 Kubaszek A....Laakso M. (J. Clin. Endocrinol. Metab. 2004)
    10. New polymorphism of ENPP1 (PC-1) is associated with increased risk of type 2 diabetes among obese individuals. (PubMed id 16936213)1, 4, 9 Bochenski J....Krolewski A.S. (Diabetes 2006)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 5167 HGNC: 3356 AceView: ENPP1 Ensembl:ENSG00000197594 euGenes: HUgn5167
    ECgene: ENPP1 Kegg: 5167 H-InvDB: ENPP1

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for ENPP1 Pharmacogenomics, SNPs, Pathways

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for ENPP1 gene:
    Search GeneIP for patents involving ENPP1

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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