SMPD2: Sphingomyelin Phosphodiesterase 2
Gene encoding neutral sphingomyelinase 2 (nSMase2), a key enzyme in sphingolipid metabolism and ceramide production.
Gene Information Card
| Symbol | SMPD2 |
|---|---|
| Full Name | Sphingomyelin Phosphodiesterase 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 6q21 |
| NCBI Gene ID | 6610 ncbi.nlm.nih.gov/gene/6610 |
| Ensembl ID | ENSG00000112294 |
| UniProt ID | O60906 |
| OMIM ID | 603498 |
| HGNC ID | 11121 |
| Aliases | nSMase2, NSMASE2, NSMASE-2, SMase2 |
Description
SMPD2 encodes neutral sphingomyelinase 2 (nSMase2), a membrane-bound enzyme that catalyzes the hydrolysis of sphingomyelin to ceramide and phosphocholine. This enzyme is involved in sphingolipid signaling, cell differentiation, apoptosis, and stress responses. nSMase2 is activated by various stimuli including cytokines, oxidative stress, and DNA damage, and plays a role in exosome biogenesis and neurodegenerative processes.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Niemann-Pick disease type B (potential modifier) | Altered sphingomyelinase activity may contribute to sphingomyelin accumulation | PMID: 10958799 |
| Alzheimer's disease | Increased nSMase2 activity linked to ceramide accumulation and amyloid-beta pathology | PMID: 20080793 |
| Cancer (breast, colon) | Dysregulated ceramide production via nSMase2 affects apoptosis and tumor progression | PMID: 23543789 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Lung | 8.3 | Low |
| Liver | 6.1 | Low |
| Kidney | 9.7 | Low |
| Heart | 7.4 | Low |
| Spleen | 5.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | Moderate expression |
| HeLa | 10.8 | Low expression |
| SH-SY5Y | 18.5 | Higher expression in neuronal cells |
| MCF7 | 7.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1045C>T (p.Arg349Trp) | Missense | <0.01% | Reduced enzyme activity in vitro |
| c.1282G>A (p.Glu428Lys) | Missense | <0.01% | Altered substrate binding |
| c.1468_1470del (p.Phe490del) | Deletion | <0.01% | Loss of function |
Mutation functional classification
Loss of Function (LOF)
p.Phe490del and p.Arg349Trp reduce or abolish catalytic activity, impairing ceramide production.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in SMPD2.
Dominant Negative (DN)
Not established; SMPD2 functions as a monomer, dominant-negative effects are unlikely.
View complete mutation data：
Gene Ontology (GO)
| • sphingomyelin phosphodiesterase activity (GO:0004767) | • sphingomyelin catabolic process (GO:0006685) |
| • ceramide metabolic process (GO:0006672) | • integral component of membrane (GO:0016021) |
| • cytoplasm (GO:0005737) |
Pathways
• Sphingolipid metabolism (Reactome: R-HSA-428157)
• Ceramide signaling (KEGG: hsa00600)
• Apoptosis (KEGG: hsa04210)
Protein Summary
Neutral sphingomyelinase 2 (nSMase2) is a 591-amino acid protein with a single transmembrane domain, localized to the plasma membrane and Golgi. It contains a catalytic domain with a conserved HKD motif essential for sphingomyelin hydrolysis. nSMase2 is regulated by phosphorylation, palmitoylation, and interaction with proteins such as p62 and TRAF2. Its activity generates ceramide, a bioactive lipid involved in cell signaling, senescence, and exosome release.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SMPD2 Knockout HEK293 Cell Line | EDJ-KQ50640 | Human | 6610 | Details Get a Quote |
| SMPD2 Knockout HeLa Cell Line | EDJ-KQ54528 | Human | 6610 | Details Get a Quote |
| SMPD2 Knockout A-549 Cell Line | EDJ-KQ63011 | Human | 6610 | Details Get a Quote |
| SMPD2 Knockout HCT 116 Cell Line | EDJ-KQ71486 | Human | 6610 | Details Get a Quote |
