ENPP3
protein-codingectonucleotide pyrophosphatase/phosphodiesterase 3, the group of CD molecules|Ectonucleotide pyrophosphatase/phosphodiesterase family
Gene summary
The protein encoded by this gene belongs to a series of ectoenzymes that are involved in hydrolysis of extracellular nucleotides. These ectoenzymes possess ATPase and ATP pyrophosphatase activities and are type II transmembrane proteins. Expression of the related rat mRNA has been found in a subset of immature glial cells and in the alimentary tract. The corresponding rat protein has been detected in the pancreas, small intestine, colon, and liver. The human mRNA is expressed in glioma cells, prostate, and uterus. Expression of the human protein has been detected in uterus, basophils, and mast cells. Two transcript variants, one protein coding and the other non-protein coding, have been found for this gene. [provided by RefSeq, Oct 2015]
- PDNP3
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~119.0 kbGenCC 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 ENPP3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005021.5. 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.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 108 | 6 | 2 | 116 | ||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 113 | 7 | 2 | 122 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005012.2 | 25 | MANE Select | |
| Ensembl | ENSP00000350265.3 | 25 | MANE Select | |
| Ensembl | ENSP00000350964.5 | 21 | Standard | |
| Ensembl | ENSP00000350964.6 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Pyrimidine metabolism - Homo sapiens (human)
- Nicotinate and nicotinamide metabolism - Homo sapiens (human)
- Starch and sucrose metabolism - Homo sapiens (human)
- Pantothenate and CoA biosynthesis - Homo sapiens (human)
- Riboflavin metabolism - Homo sapiens (human)
Biological Process
- basophil activation involved in immune response
- pyrimidine nucleotide metabolic process
- phosphate-containing compound metabolic process
- receptor-mediated endocytosis
- nucleoside triphosphate catabolic process
Molecular Function
- nucleic acid binding
- phosphodiesterase I activity
- scavenger receptor activity
- calcium ion binding
- zinc ion binding
Cellular Component
- external side of plasma membrane
- integral component of membrane
- apical plasma membrane
- perinuclear region of cytoplasm
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000414305
- Coding exons
- 25
- Length
- 118972
- Individuals with no LoFs
- 125073
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 672
- Defined
- 125746
- p
- 0.00268
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.0744 | 463 | 468 | 0.990 | 0.0000229 | 5805 |
| Missense (PolyPhen) | 175 | 192.54 | 0.90889 | 2439 | ||
| Synonymous | -0.491 | 169 | 161 | 1.05 | 0.00000805 | 1557 |
| Loss of Function | 1.40 | 41 | 51.9 | 0.790 | 0.00000260 | 647 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0030 | 0.0030 | notable |
| Latino/Admixed American | 0.0018 | 0.0018 | notable |
| Ashkenazi Jewish | 0.00070 | 0.00069 | rare |
| East Asian | 0.0016 | 0.0015 | notable |
| Finnish | 0.0021 | 0.0021 | notable |
| European (Non-Finnish) | 0.0028 | 0.0028 | notable |
| South Asian | 0.0050 | 0.0049 | notable |
| Other | 0.0026 | 0.0026 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Hydrolase that metabolizes extracellular nucleotides, including ATP, GTP, UTP and CTP (PubMed:29717535). Limits mast cell and basophil responses during inflammation and during the chronic phases of allergic responses by eliminating the extracellular ATP that functions as signaling molecule and activates basophils and mast cells and induces the release of inflammatory cytokines. Metabolizes extracellular ATP in the lumen of the small intestine, and thereby prevents ATP-induced apoptosis of intestinal plasmacytoid dendritic cells (By similarity). Has also alkaline phosphodiesterase activity (PubMed:11342463). {ECO:0000250|UniProtKB:Q6DYE8, ECO:0000269|PubMed:11342463, ECO:0000269|PubMed:29717535}.;
Recessive Scores
- pRec
- 0.423
Intolerance Scores
- LoFtool
- 0.935
- RVIS EVS
- 0.39
- RVIS percentile EVS
- 75.68
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.599
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |