GeneBe

ENPP2

protein-coding

ectonucleotide pyrophosphatase/phosphodiesterase 2, the group of Ectonucleotide pyrophosphatase/phosphodiesterase family

Gene summary

The protein encoded by this gene functions as both a phosphodiesterase, which cleaves phosphodiester bonds at the 5' end of oligonucleotides, and a phospholipase, which catalyzes production of lysophosphatidic acid (LPA) in extracellular fluids. LPA evokes growth factor-like responses including stimulation of cell proliferation and chemotaxis. This gene product stimulates the motility of tumor cells and has angiogenic properties, and its expression is upregulated in several kinds of carcinomas. The gene product is secreted and further processed to make the biologically active form. Several alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Aug 2008]

Previous symbols:
  • PDNP2

MANE transcript

NM_001040092.3

Inheritance

—

ClinVar variants

U:132B:6

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.28

Max pathogenic AF

—

Genomic locus

chr8:119,557,086-119,673,453

External References & Databases

Ensembl (ENSG00000136960)NCBI Gene (5168)OMIM (601060)HGNC:3357GenCCUniProt (Q13822)AlphaFoldClinVar (ENPP2)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~116.4 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ENPP2 variants in ClinVar

2 Conditions Cataloged
not specifiedTotal: 123
not providedTotal: 10

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001040092.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
2
clinvar
2
clinvar
 4
missense
116
clinvar
3
clinvar
1
clinvar
 120
nonsense
1
clinvar
 1
start loss
0
frameshift
2
clinvar
 2
splice donor/acceptor (+/-2bp)
11
clinvar
 11
Total0013251138
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 49 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_001040092.3RefSeqNP_001035181.125MANE Select
ENST00000075322.11EnsemblENSP00000075322.625MANE Select
NM_001130863.3RefSeqNP_001124335.126Standard
NM_001330600.2RefSeqNP_001317529.126Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
enpp2Danio rerio

Structure: nucleate erythrocyte

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Ether lipid metabolism - Homo sapiens (human)
  • Vitamin B2 (riboflavin) metabolism
  • Vitamin B3 (nicotinate and nicotinamide) metabolism
  • Vitamin B5 - CoA biosynthesis from pantothenate
  • Nicotinate Nicotinamide metabolism

Biological Process

  • receptor-mediated endocytosis
  • chemotaxis
  • immune response
  • phospholipid catabolic process
  • positive regulation of epithelial cell migration

Molecular Function

  • nucleic acid binding
  • phosphodiesterase I activity
  • nucleotide diphosphatase activity
  • lysophospholipase activity
  • scavenger receptor activity

Cellular Component

  • extracellular space
  • plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000259486
Coding exons
26
Length
116368
Individuals with no LoFs
125718
Homozygous LoFs
0
Heterozygous LoFs
30
Defined
125748
p
0.000119
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense1.384255130.8280.00002756033
Missense (PolyPhen)136217.60.6252417
Synonymous-0.07131831821.010.00001021646
Loss of Function4.981656.40.2840.00000294690

Population LoF Frequency

PopulationCAFp-valueStatus
African0.0000620.000062rare
Latino/Admixed American0.000150.00014rare
Ashkenazi Jewish0.0000990.000099rare
East Asian00.0absent
Finnish0.0000460.000046rare
European (Non-Finnish)0.000120.00011rare
South Asian0.000300.00029rare
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Hydrolyzes lysophospholipids to produce the signaling molecule lysophosphatidic acid (LPA) in extracellular fluids (PubMed:15769751, PubMed:26371182, PubMed:27754931). Major substrate is lysophosphatidylcholine (PubMed:12176993, PubMed:27754931). Also can act on sphingosylphosphorylcholine producing sphingosine-1-phosphate, a modulator of cell motility. Can hydrolyze, in vitro, bis-pNPP, to some extent pNP-TMP, and barely ATP (PubMed:15769751, PubMed:12176993). Involved in several motility-related processes such as angiogenesis and neurite outgrowth. Acts as an angiogenic factor by stimulating migration of smooth muscle cells and microtubule formation (PubMed:11559573). Stimulates migration of melanoma cells, probably via a pertussis toxin-sensitive G protein (PubMed:1733949). May have a role in induction of parturition (PubMed:12176993). Possible involvement in cell proliferation and adipose tissue development (Probable). Tumor cell motility- stimulating factor (PubMed:1733949, PubMed:11559573). {ECO:0000269|PubMed:11559573, ECO:0000269|PubMed:12176993, ECO:0000269|PubMed:15769751, ECO:0000269|PubMed:1733949, ECO:0000269|PubMed:21240271, ECO:0000269|PubMed:26371182, ECO:0000269|PubMed:27754931, ECO:0000305|PubMed:15700135}.;

Recessive Scores

pRec
0.196

Intolerance Scores

LoFtool
0.650
RVIS EVS
0.16
RVIS percentile EVS
64.96

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.825

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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