ENPP7: Ectonucleotide Pyrophosphatase/Phosphodiesterase 7
Sphingomyelin Phosphodiesterase and Lipid Metabolism Regulator
Gene Information Card
| Symbol | ENPP7 |
|---|---|
| Full Name | Ectonucleotide Pyrophosphatase/Phosphodiesterase 7 |
| Gene Type | Protein coding |
| Chromosomal Location | 17q25.3 |
| NCBI Gene ID | 339221 ncbi.nlm.nih.gov/gene/339221 |
| Ensembl ID | ENSG00000182199 |
| UniProt ID | Q6UWV6 |
| OMIM ID | 612696 |
| HGNC ID | 23766 |
| Aliases | NPP7, ALK-SMase, SMase2, E-NPP 7 |
Description
ENPP7 encodes ectonucleotide pyrophosphatase/phosphodiesterase 7, also known as alkaline sphingomyelinase. This enzyme hydrolyzes sphingomyelin to ceramide and phosphocholine, playing a key role in sphingolipid metabolism, intestinal lipid digestion, and cell signaling. It is primarily expressed in the intestinal tract and liver, and its activity is implicated in colorectal cancer and inflammatory bowel disease.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal Cancer | Reduced ENPP7 expression leads to decreased ceramide production, promoting tumor cell proliferation and survival. | PMID: 19258510; COSMIC |
| Inflammatory Bowel Disease | Altered sphingomyelinase activity disrupts intestinal barrier function and inflammation regulation. | PMID: 21880725 |
| Metabolic Syndrome | ENPP7 variants may influence lipid absorption and cholesterol metabolism. | OMIM: 612696 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Small Intestine | 45.2 | High |
| Colon | 32.8 | High |
| Liver | 18.5 | Medium |
| Kidney | 6.1 | Low |
| Pancreas | 4.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Caco-2 (Colorectal) | 38.7 | Intestinal epithelial model |
| HepG2 (Liver) | 22.1 | Hepatocellular carcinoma line |
| HT-29 (Colorectal) | 29.4 | Colon adenocarcinoma line |
| SW480 (Colorectal) | 15.3 | Primary colorectal cancer line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1045C>T (p.Arg349Trp) | Missense | 0.02% (gnomAD) | Reduced enzymatic activity |
| c.1237G>A (p.Gly413Ser) | Missense | 0.01% (gnomAD) | Unknown functional effect |
| c.1462_1463del (p.Leu488fs) | Frameshift | <0.01% (COSMIC) | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense variants (e.g., p.Leu488fs) lead to truncated protein and loss of sphingomyelinase activity.
Gain of Function (GOF)
No gain-of-function mutations reported in ENPP7.
Dominant Negative (DN)
No dominant-negative mutations described for ENPP7.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Sphingolipid metabolism (Reactome: R-HSA-428157)
• Sphingomyelin metabolism (KEGG: hsa00600)
• Ceramide signaling (WikiPathways: WP4720)
Protein Summary
ENPP7 encodes a 474-amino acid type II transmembrane glycoprotein with a single N-terminal transmembrane domain and a conserved phosphodiesterase domain. The enzyme is active at alkaline pH (optimum pH 8.5-9.0) and requires bile salts for full activity. It is the only known sphingomyelinase that is resistant to proteolysis in the intestinal lumen, enabling its role in dietary sphingomyelin digestion. The protein is N-glycosylated and localized to the brush border membrane of intestinal epithelial cells.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ENPP7 Knockout HEK293 Cell Line | EDJ-KQ12515 | Human | 339221 | Details Get a Quote |
| ENPP7 Knockout HeLa Cell Line | EDJ-KQ59634 | Human | 339221 | Details Get a Quote |
| ENPP7 Knockout A-549 Cell Line | EDJ-KQ68101 | Human | 339221 | Details Get a Quote |
| ENPP7 Knockout HCT 116 Cell Line | EDJ-KQ76476 | Human | 339221 | Details Get a Quote |
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