ENPP7
protein-codingectonucleotide pyrophosphatase/phosphodiesterase 7, the group of Ectonucleotide pyrophosphatase/phosphodiesterase family
Gene summary
The protein encoded by this gene is an intestinal alkaline sphingomyelin phosphodiesterase that converts sphingomyelin to ceramide and phosphocholine. The encoded protein is anchored in the cell membrane, and it may function to protect the intestinal mucosa from inflammation and tumorigenesis. This protein is glycosylated and also exhibits lysophosphatidylcholine hydrolase activity. [provided by RefSeq, Oct 2016]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~11.3 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 ENPP7 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_178543.5. 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 | 2 | 2 | ||||
| missense | 88 | 13 | 101 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 89 | 15 | 0 | 104 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_848638.3 | 5 | MANE Select | |
| Ensembl | ENSP00000332656.5 | 5 | MANE Select | |
| Ensembl | ENSP00000460429.1 | 3 | Standard | |
| Ensembl | ENSP00000534539.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Sphingolipid metabolism - Homo sapiens (human)
- Sphingolipid Metabolism
- Gaucher Disease
- Globoid Cell Leukodystrophy
- Metachromatic Leukodystrophy (MLD)
Biological Process
- sphingomyelin metabolic process
- sphingomyelin catabolic process
- glycosphingolipid metabolic process
- negative regulation of DNA replication
- negative regulation of cell population proliferation
Molecular Function
- sphingomyelin phosphodiesterase activity
- zinc ion binding
Cellular Component
- Golgi apparatus
- plasma membrane
- integral component of plasma membrane
- microvillus
- membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000328313
- Coding exons
- 5
- Length
- 11341
- Individuals with no LoFs
- 121845
- Homozygous LoFs
- 237
- Heterozygous LoFs
- 3666
- Defined
- 125748
- p
- 0.0156
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.478 | 326 | 303 | 1.08 | 0.0000212 | 2989 |
| Missense (PolyPhen) | 130 | 119.33 | 1.0894 | 1320 | ||
| Synonymous | 0.333 | 136 | 141 | 0.964 | 0.0000117 | 941 |
| Loss of Function | -0.961 | 19 | 15.0 | 1.27 | 7.32e-7 | 161 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0018 | 0.0017 | notable |
| Latino/Admixed American | 0.12 | 0.11 | notable |
| Ashkenazi Jewish | 0.0032 | 0.0031 | notable |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.00046 | 0.00046 | rare |
| European (Non-Finnish) | 0.00044 | 0.00043 | rare |
| South Asian | 0.00023 | 0.00023 | rare |
| Other | 0.012 | 0.011 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Converts sphingomyelin to ceramide and phosphocholine (PubMed:12885774, PubMed:12671034, PubMed:15205117, PubMed:28292932). Has also phospholipase C activity and can cleave phosphocholine from palmitoyl lyso-phosphatidylcholine (PubMed:12885774). Does not have nucleotide pyrophosphatase activity (PubMed:12885774). {ECO:0000269|PubMed:12671034, ECO:0000269|PubMed:12885774, ECO:0000269|PubMed:15205117, ECO:0000269|PubMed:28292932}.;
Recessive Scores
- pRec
- 0.143
Intolerance Scores
- LoFtool
- 0.715
- RVIS EVS
- 0.52
- RVIS percentile EVS
- 80.36
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.979
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |