SMPD3: Sphingomyelin Phosphodiesterase 3
Key enzyme in ceramide metabolism and bone development
Gene Information Card
| Symbol | SMPD3 |
|---|---|
| Full Name | Sphingomyelin Phosphodiesterase 3 |
| Gene Type | Protein-coding |
| Chromosomal Location | 16q22.1 |
| NCBI Gene ID | 55512 ncbi.nlm.nih.gov/gene/55512 |
| Ensembl ID | ENSG00000103056 |
| UniProt ID | Q9NY59 |
| OMIM ID | 605777 |
| HGNC ID | 14249 |
| Aliases | nSMase2, NSMASE2, NSMASE-2, SMD-3 |
Description
SMPD3 encodes sphingomyelin phosphodiesterase 3, also known as neutral sphingomyelinase 2 (nSMase2). This enzyme catalyzes the hydrolysis of sphingomyelin to ceramide and phosphocholine, playing a critical role in sphingolipid metabolism, cell signaling, apoptosis, and bone mineralization. Mutations in SMPD3 are associated with skeletal dysplasias and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Osteogenesis Imperfecta Type XXIV | Loss-of-function mutations impair ceramide-mediated signaling in osteoblasts, leading to defective bone mineralization and fragility. | ClinVar, OMIM |
| Chondrodysplasia with Platyspondyly | Disrupted sphingomyelin metabolism affects chondrocyte differentiation and endochondral ossification. | OMIM, PubMed |
| Hereditary Sensory Neuropathy Type 1 (possible) | Altered ceramide levels may impact neuronal membrane stability and signaling. | NCBI Gene, UniProt |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Bone Marrow | 8.2 | Low |
| Liver | 6.1 | Low |
| Kidney | 5.4 | Low |
| Lung | 4.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 10.3 | Moderate expression |
| HEK293 | 7.6 | Detectable |
| SH-SY5Y | 15.1 | High expression in neuronal cells |
| HepG2 | 5.9 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1003C>T (p.Arg335Ter) | Nonsense | Rare | Loss of function; associated with osteogenesis imperfecta |
| c.1462G>A (p.Gly488Arg) | Missense | Rare | Impaired catalytic activity |
| c.1726C>T (p.Arg576Trp) | Missense | Rare | Reduced enzyme stability |
Mutation functional classification
Loss of Function (LOF)
Nonsense and missense mutations that reduce or abolish nSMase2 activity lead to impaired ceramide production and bone mineralization defects.
Gain of Function (GOF)
No gain-of-function mutations have been reported for SMPD3.
Dominant Negative (DN)
No dominant-negative mutations have been characterized for SMPD3.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004767 – sphingomyelin phosphodiesterase activity | • GO:0006685 – sphingomyelin catabolic process |
| • GO:0006672 – ceramide metabolic process | • GO:0005886 – plasma membrane |
| • GO:0005737 – cytoplasm | • GO:0042981 – regulation of apoptotic process |
Pathways
• Sphingolipid metabolism (KEGG: hsa00600)
• Sphingomyelin signaling pathway
• Ceramide biosynthesis and signaling
Protein Summary
SMPD3 encodes neutral sphingomyelinase 2 (nSMase2), a 655-amino-acid protein localized to the plasma membrane and cytoplasm. It contains a catalytic domain responsible for sphingomyelin hydrolysis and a sterile alpha motif (SAM) domain involved in protein-protein interactions. nSMase2 is activated by various stimuli including cytokines, oxidative stress, and growth factors, and its activity is essential for ceramide-mediated signaling in bone development, neuronal function, and apoptosis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SMPD3 Knockout HEK293 Cell Line | EDJ-KQ3537 | Human | 55512 | Details Get a Quote |
| SMPD3 Knockout HeLa Cell Line | EDJ-KQ56593 | Human | 55512 | Details Get a Quote |
| SMPD3 Knockout A-549 Cell Line | EDC90436 | Human | 55512 | Details Get a Quote |
| SMPD3 Knockout HCT 116 Cell Line | EDJ-KQ73539 | Human | 55512 | Details Get a Quote |
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