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    ENPP1 ectonucleotide pyrophosphatase/phosphodiesterase 1 [ Homo sapiens (human) ]

    Gene ID: 5167, updated on 3-Nov-2024

    Summary

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    Official Symbol
    ENPP1provided by HGNC
    Official Full Name
    ectonucleotide pyrophosphatase/phosphodiesterase 1provided by HGNC
    Primary source
    HGNC:HGNC:3356
    See related
    Ensembl:ENSG00000197594 MIM:173335; AllianceGenome:HGNC:3356
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    M6S1; NPP1; NPPS; PC-1; PCA1; ARHR2; COLED; PDNP1
    Summary
    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]
    Expression
    Biased expression in placenta (RPKM 22.6), thyroid (RPKM 14.0) and 13 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See ENPP1 in Genome Data Viewer
    Location:
    6q23.2
    Exon count:
    25
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (131808020..131895155)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (133002962..133090181)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (132129160..132216295)

    Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene ribosomal protein L15 pseudogene 9 Neighboring gene microRNA 548h-5 Neighboring gene leucine rich repeat containing 8 VRAC subunit B pseudogene Neighboring gene selenoprotein K pseudogene 2 Neighboring gene RN7SK pseudogene 245 Neighboring gene NANOG hESC enhancer GRCh37_chr6:132180698-132181244 Neighboring gene HNF4 motif-containing MPRA enhancer 74 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr6:132222462-132223015 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:132223016-132223568 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr6:132228019-132228545 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr6:132228546-132229072 Neighboring gene Sharpr-MPRA regulatory region 1543 Neighboring gene CCN2 antisense RNA 1 Neighboring gene Sharpr-MPRA regulatory region 2799 Neighboring gene cellular communication network factor 2 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr6:132324214-132325413 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25069 Neighboring gene microRNA 548aj-1

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Association of a genetic polymorphism in ectonucleotide pyrophosphatase/phosphodiesterase 1 with hepatitis C virus infection and hepatitis C virus core antigen levels in subjects in a hyperendemic area of Japan. Takahama Y, et al. J Gastroenterol, 2008. PMID 19107338
    2. Quantitative correlation of ENPP1 pathogenic variants with disease phenotype. Ansh AJ, et al. Bone, 2024 Sep. PMID 38806089,
    3. ENPP1/PC-1 K121Q polymorphism and genetic susceptibility to type 2 diabetes in North Indians. Bhatti JS, et al. Mol Cell Biochem, 2010 Dec. PMID 20820885
    4. [Association and meta-analysis of ENPP1 K121Q with type 2 diabetes in Han Chinese.]. Wang M, et al. Yi Chuan, 2010 Aug. PMID 20709678
    5. Family-based study of association between ENPP1 genetic variants and craniofacial morphology. Ermakov S, et al. Ann Hum Biol, 2010 Nov. PMID 20446819

    See all (275) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Tumor Exosomal ENPP1 Hydrolyzes cGAMP to Inhibit cGAS-STING Signaling.
      Title: Tumor Exosomal ENPP1 Hydrolyzes cGAMP to Inhibit cGAS-STING Signaling.
    2. Quantitative correlation of ENPP1 pathogenic variants with disease phenotype.
      Title: Quantitative correlation of ENPP1 pathogenic variants with disease phenotype.
    3. TET3 boosts hepatocyte autophagy and impairs non-alcoholic fatty liver disease by increasing ENPP1 promoter hypomethylation.
      Title: TET3 boosts hepatocyte autophagy and impairs non-alcoholic fatty liver disease by increasing ENPP1 promoter hypomethylation.
    4. ENPP1 inhibits the transcription activity of the hepatitis B virus pregenomic promoter by upregulating the acetylation of LMNB1.
      Title: ENPP1 inhibits the transcription activity of the hepatitis B virus pregenomic promoter by upregulating the acetylation of LMNB1.
    5. Targeting ENPP1 for cancer immunotherapy: Killing two birds with one stone.
      Title: Targeting ENPP1 for cancer immunotherapy: Killing two birds with one stone.
    6. Role of ENPP1 Gene Variants in the Susceptibility to Diabetic Nephropathy in Patients with type 2 Diabetes Mellitus.
      Title: Role of ENPP1 Gene Variants in the Susceptibility to Diabetic Nephropathy in Patients with type 2 Diabetes Mellitus.
    7. ENPP1 in Blood and Bone: Skeletal and Soft Tissue Diseases Induced by ENPP1 Deficiency.
      Title: ENPP1 in Blood and Bone: Skeletal and Soft Tissue Diseases Induced by ENPP1 Deficiency.
    8. ENPP1 is an innate immune checkpoint of the anticancer cGAMP-STING pathway in breast cancer.
      Title: ENPP1 is an innate immune checkpoint of the anticancer cGAMP-STING pathway in breast cancer.
    9. Effects of food, fasting, and exercise on plasma pyrophosphate levels and ENPP1 activity in healthy adults.
      Title: Effects of food, fasting, and exercise on plasma pyrophosphate levels and ENPP1 activity in healthy adults.
    10. ENPP1 deficiency: A clinical update on the relevance of individual variants using a locus-specific patient database.
      Title: ENPP1 deficiency: A clinical update on the relevance of individual variants using a locus-specific patient database.
    Submit: New GeneRIF Correction See all GeneRIFs (195)

    Phenotypes

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

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Arterial calcification, generalized, of infancy, 1
    MedGen: C4551985 OMIM: 208000 GeneReviews: Generalized Arterial Calcification of Infancy
    		not available
    Hypophosphatemic rickets, autosomal recessive, 2
    MedGen: C2750078 OMIM: 613312 GeneReviews: Not available
    		not available
    Hypopigmentation-punctate palmoplantar keratoderma syndrome
    MedGen: C3809781 OMIM: 615522 GeneReviews: Not available
    		not available
    Inherited obesity
    MedGen: C4054476 OMIM: 601665 GeneReviews: Not available
    		not available
    Type 2 diabetes mellitus
    MedGen: C0011860 OMIM: 125853 GeneReviews: WFS1 Spectrum Disorder
    		not available

    EBI GWAS Catalog

    Description
    Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables 3',5'-cyclic-AMP phosphodiesterase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables 3'-phosphoadenosine 5'-phosphosulfate binding IC
    Inferred by Curator
    more info
    		 PubMed 
    enables ATP binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables ATP diphosphatase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables GTP diphosphatase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables UTP diphosphatase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables calcium ion binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables cyclic-GMP-AMP hydrolase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables dinucleotide phosphatase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables dinucleotide phosphatase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables exonuclease activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables insulin receptor binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables nucleic acid binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables nucleoside triphosphate diphosphatase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables phosphatase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables phosphodiesterase I activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables phosphodiesterase I activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables phosphodiesterase I activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables polysaccharide binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein homodimerization activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables scavenger receptor activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables zinc ion binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Process Evidence Code Pubs
    involved_in 3'-phosphoadenosine 5'-phosphosulfate metabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in ATP metabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in ATP metabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in ATP metabolic process ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in bone mineralization IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in cellular response to insulin stimulus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in gene expression IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in generation of precursor metabolites and energy IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in immune response IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in inorganic diphosphate transport IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in inorganic diphosphate transport IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in intracellular phosphate ion homeostasis IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in melanocyte differentiation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of D-glucose import IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of bone mineralization ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in negative regulation of cell growth IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of fat cell differentiation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in negative regulation of fat cell differentiation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of glycogen biosynthetic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of hh target transcription factor activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in negative regulation of insulin receptor signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of protein autophosphorylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in nucleic acid metabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in nucleoside triphosphate catabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in nucleoside triphosphate catabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in phosphate ion homeostasis IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in phosphate-containing compound metabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of bone mineralization IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in regulation of bone mineralization IC
    Inferred by Curator
    more info
    		 PubMed 
    involved_in response to ATP IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in sequestering of triglyceride IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in vesicle-mediated transport IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in basolateral plasma membrane NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    is_active_in cell surface IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cell surface IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in extracellular space IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in lysosomal membrane HDA PubMed 
    located_in membrane ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    is_active_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in plasma membrane ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    ectonucleotide pyrophosphatase/phosphodiesterase family member 1
    Names
    E-NPP 1
    Ly-41 antigen
    NPPase
    alkaline phosphodiesterase 1
    alkaline phosphodiesterase I
    membrane component, chromosome 6, surface marker 1
    nucleotide diphosphatase
    nucleotide pyrophosphatase
    phosphodiesterase I/nucleotide pyrophosphatase 1
    plasma-cell membrane glycoprotein 1
    plasma-cell membrane glycoprotein PC-1
    NP_006199.2

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_008206.1 RefSeqGene

      Range
      5005..92140
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_1288

    mRNA and Protein(s)

    1. NM_006208.3 → NP_006199.2  ectonucleotide pyrophosphatase/phosphodiesterase family member 1

      See identical proteins and their annotated locations for NP_006199.2

      Status: REVIEWED

      Source sequence(s)
      AL117378, AL139805
      Consensus CDS
      CCDS5150.2
      UniProtKB/Swiss-Prot
      P22413, Q5T9R6, Q9NPZ3, Q9P1P6, Q9UP61, Q9Y6K3
      UniProtKB/TrEMBL
      B2RBY8
      Related
      ENSP00000498074.1, ENST00000647893.1
      Conserved Domains (3) summary
      smart00201
      Location:145 → 188
      SO; Somatomedin B -like domains
      smart00477
      Location:676 → 907
      NUC; DNA/RNA non-specific endonuclease
      pfam01663
      Location:212 → 538
      Phosphodiest; Type I phosphodiesterase / nucleotide pyrophosphatase

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000006.12 Reference GRCh38.p14 Primary Assembly

      Range
      131808020..131895155
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060930.1 Alternate T2T-CHM13v2.0

      Range
      133002962..133090181
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P22413.2 GenPept UniProtKB/Swiss-Prot:P22413

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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