ENPP4
protein-codingectonucleotide pyrophosphatase/phosphodiesterase 4, the group of Ectonucleotide pyrophosphatase/phosphodiesterase family
Gene summary
Enables bis(5'-adenosyl)-triphosphatase activity. Involved in positive regulation of blood coagulation and purine ribonucleoside catabolic process. Located in extracellular exosome and membrane. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~16.7 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 ENPP4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014936.5. 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 | 67 | 1 | 68 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 68 | 1 | 0 | 69 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_055751.1 | 3 | MANE Select | |
| Ensembl | ENSP00000318066.3 | 3 | MANE Select | |
| Ensembl | ENSP00000529858.1 | 3 | Standard | |
| Ensembl | ENSP00000529858.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Purine metabolism - Homo sapiens (human)
- Neutrophil degranulation
- Innate Immune System
- Immune System
Biological Process
- blood coagulation
- positive regulation of blood coagulation
- neutrophil degranulation
- purine ribonucleoside catabolic process
Molecular Function
- metal ion binding
- bis(5'-adenosyl)-triphosphatase activity
Cellular Component
- plasma membrane
- membrane
- integral component of membrane
- extracellular exosome
- ficolin-1-rich granule membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000321037
- Coding exons
- 3
- Length
- 16707
- Individuals with no LoFs
- 125571
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 22
- Defined
- 125593
- p
- 0.0000876
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.803 | 204 | 239 | 0.854 | 0.0000113 | 3025 |
| Missense (PolyPhen) | 38 | 65.575 | 0.57949 | 799 | ||
| Synonymous | 0.320 | 84 | 87.8 | 0.957 | 0.00000458 | 844 |
| Loss of Function | 2.45 | 4 | 13.9 | 0.289 | 6.47e-7 | 190 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.000092 | 0.000092 | rare |
| European (Non-Finnish) | 0.00011 | 0.00011 | rare |
| South Asian | 0.00016 | 0.00016 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Hydrolyzes extracellular Ap3A into AMP and ADP, and Ap4A into AMP and ATP. Ap3A and Ap4A are diadenosine polyphosphates thought to induce proliferation of vascular smooth muscle cells. Acts as a procoagulant, mediating platelet aggregation at the site of nascent thrombus via release of ADP from Ap3A and activation of ADP receptors. {ECO:0000269|PubMed:22995898, ECO:0000269|PubMed:24338010}.;
Recessive Scores
- pRec
- 0.101
Intolerance Scores
- LoFtool
- 0.686
- RVIS EVS
- 0.37
- RVIS percentile EVS
- 75.29
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.159
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |