U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Links from MedGen

    • Showing Current items.

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

    Gene ID: 5167, updated on 20-Apr-2024

    Summary

    Go to the top of the page Help
    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
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    Go to the top of the page Help
    Location:
    6q23.2
    Exon count:
    25
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (131808020..131895155)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (133002962..133090181)
    105.20220307 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

    Go to the top of the page Help

    Go to nucleotide: Graphics FASTA GenBank

    Expression

    Go to the top of the page Help
    • Project title: 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

    Go to the top of the pageHelp

    Related articles in PubMed

    1. Effects of food, fasting, and exercise on plasma pyrophosphate levels and ENPP1 activity in healthy adults. Khursigara G, et al. Bone, 2023 Jun. PMID 37003563
    2. ENPP1 deficiency: A clinical update on the relevance of individual variants using a locus-specific patient database. Mercurio SA, et al. Hum Mutat, 2022 Dec. PMID 36150100
    3. ENPP1 variants in patients with GACI and PXE expand the clinical and genetic heterogeneity of heritable disorders of ectopic calcification. Ralph D, et al. PLoS Genet, 2022 Apr. PMID 35482848, Free PMC Article
    4. Mutation update: Variants of the ENPP1 gene in pathologic calcification, hypophosphatemic rickets, and cutaneous hypopigmentation with punctate keratoderma. Ralph D, et al. Hum Mutat, 2022 Sep. PMID 35475527, Free PMC Article
    5. Tumor ENPP1 (CD203a)/Haptoglobin Axis Exploits Myeloid-Derived Suppressor Cells to Promote Post-Radiotherapy Local Recurrence in Breast Cancer. Ruiz-Fernández de Córdoba B, et al. Cancer Discov, 2022 May 2. PMID 35191482, Free PMC Article

    See all (263) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. 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.
    2. Targeting ENPP1 for cancer immunotherapy: Killing two birds with one stone.
      Title: Targeting ENPP1 for cancer immunotherapy: Killing two birds with one stone.
    3. 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.
    4. 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.
    5. 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.
    6. 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.
    7. 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.
    8. Mutation update: Variants of the ENPP1 gene in pathologic calcification, hypophosphatemic rickets, and cutaneous hypopigmentation with punctate keratoderma.
      Title: Mutation update: Variants of the ENPP1 gene in pathologic calcification, hypophosphatemic rickets, and cutaneous hypopigmentation with punctate keratoderma.
    9. ENPP1 variants in patients with GACI and PXE expand the clinical and genetic heterogeneity of heritable disorders of ectopic calcification.
      Title: ENPP1 variants in patients with GACI and PXE expand the clinical and genetic heterogeneity of heritable disorders of ectopic calcification.
    10. ENPP1's regulation of extracellular cGAMP is a ubiquitous mechanism of attenuating STING signaling.
      Title: ENPP1's regulation of extracellular cGAMP is a ubiquitous mechanism of attenuating STING signaling.
    Submit: New GeneRIF Correction See all GeneRIFs (192)

    Phenotypes

    Go to the top of the page Help

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

    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

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

    Variation

    Go to the top of the page Help

    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Pathways from PubChem

    Go to the top of the page

    Interactions

    Go to the top of the page Help
    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Go to the top of the page Help

    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 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 glucose import 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 response to inorganic substance 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

    Go to the top of the page Help
    Preferred Names
    ectonucleotide pyrophosphatase/phosphodiesterase family member 1
    Names
    E-NPP 1
    Ly-41 antigen
    alkaline phosphodiesterase 1
    membrane component, chromosome 6, surface marker 1
    phosphodiesterase I/nucleotide pyrophosphatase 1
    plasma-cell membrane glycoprotein 1
    plasma-cell membrane glycoprotein PC-1
    NP_006199.2

    NCBI Reference Sequences (RefSeq)

    Go to the top of the page Help

    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_2023_10

    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.

    Chemical Information
    Medical
    Molecular Biology Databases
    Research Materials
    Tools
    Miscellaneous