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

Gene ID: 5167, updated on 14-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
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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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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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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)

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 8-oxo-(d)RTP hydrolase activity IEA
Inferred from Electronic Annotation
more info
  
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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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.

Chemical Information
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