ENTPD5
protein-codingectonucleoside triphosphate diphosphohydrolase 5 (inactive), the group of Ectonucleoside triphosphate diphosphohydrolase family
Gene summary
The protein encoded by this gene is similar to E-type nucleotidases (NTPases)/ecto-ATPase/apyrases. NTPases, such as CD39, mediate catabolism of extracellular nucleotides. ENTPD5 contains 4 apyrase-conserved regions which is characteristic of NTPases. [provided by RefSeq, Jan 2009]
- CD39L4
- PCPH
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~61.4 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 ENTPD5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001249.5. 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 | 52 | 1 | 53 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 56 | 1 | 0 | 57 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001240.1 | 13 | MANE Select | |
| Ensembl | ENSP00000335246.6 | 13 | MANE Select | |
| RefSeq | NP_001308913.1 | 13 | Standard | |
| RefSeq | NP_001308914.1 | 13 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| entpd5a | Danio rerio | Structure: whole organism Quality: dead abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Pyrimidine metabolism - Homo sapiens (human)
- Purine metabolism - Homo sapiens (human)
- Purine Nucleoside Phosphorylase Deficiency
- Mercaptopurine Action Pathway
- Azathioprine Action Pathway
Biological Process
- protein N-linked glycosylation
- cell population proliferation
- regulation of phosphatidylinositol 3-kinase signaling
- nucleobase-containing small molecule catabolic process
- positive regulation of glycolytic process
Molecular Function
- guanosine-diphosphatase activity
- protein binding
- nucleoside-diphosphatase activity
- uridine-diphosphatase activity
Cellular Component
- extracellular region
- endoplasmic reticulum
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000334696
- Coding exons
- 13
- Length
- 61390
- Individuals with no LoFs
- 125632
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 115
- Defined
- 125747
- p
- 0.000457
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.412 | 210 | 227 | 0.923 | 0.0000111 | 2785 |
| Missense (PolyPhen) | 89 | 101.74 | 0.87476 | 1241 | ||
| Synonymous | -0.180 | 88 | 85.9 | 1.02 | 0.00000441 | 828 |
| Loss of Function | 2.77 | 12 | 27.7 | 0.433 | 0.00000152 | 303 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0026 | 0.0026 | notable |
| Latino/Admixed American | 0.00017 | 0.00017 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000092 | 0.000092 | rare |
| European (Non-Finnish) | 0.00040 | 0.00039 | rare |
| South Asian | 0.00065 | 0.00065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Uridine diphosphatase (UDPase) that promotes protein N- glycosylation and ATP level regulation. UDP hydrolysis promotes protein N-glycosylation and folding in the endoplasmic reticulum, as well as elevated ATP consumption in the cytosol via an ATP hydrolysis cycle. Together with CMPK1 and AK1, constitutes an ATP hydrolysis cycle that converts ATP to AMP and results in a compensatory increase in aerobic glycolysis. The nucleotide hydrolyzing preference is GDP > IDP > UDP, but not any other nucleoside di-, mono- or triphosphates, nor thiamine pyrophosphate. Plays a key role in the AKT1-PTEN signaling pathway by promoting glycolysis in proliferating cells in response to phosphoinositide 3-kinase (PI3K) signaling. {ECO:0000269|PubMed:10400613}.;
Recessive Scores
- pRec
- 0.177
Intolerance Scores
- LoFtool
- 0.868
- RVIS EVS
- 0.42
- RVIS percentile EVS
- 76.96
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.474
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |