SMPD1 Gene: Sphingomyelin Phosphodiesterase 1 (Acid Sphingomyelinase)
Genetic insights into SMPD1: function, associated diseases, expression, and mutation landscape.
Gene Information Card
| Symbol | SMPD1 |
|---|---|
| Full Name | Sphingomyelin phosphodiesterase 1, acid lysosomal |
| Gene Type | Protein coding |
| Chromosomal Location | 11p15.4 |
| NCBI Gene ID | 6609 ncbi.nlm.nih.gov/gene/6609 |
| Ensembl ID | ENSG00000166311 |
| UniProt ID | P17405 |
| OMIM ID | 607608 |
| HGNC ID | 11120 |
| Aliases | ASM, ASMASE, NPD, SMPD1 |
Description
The SMPD1 gene encodes acid sphingomyelinase, a lysosomal enzyme that hydrolyzes sphingomyelin to ceramide and phosphocholine. This enzyme is critical for sphingolipid metabolism and cellular signaling. Mutations in SMPD1 lead to Niemann-Pick disease types A and B, characterized by lysosomal accumulation of sphingomyelin. The gene is also implicated in other conditions such as Parkinson's disease and certain cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Niemann-Pick disease type A | Loss-of-function mutations in SMPD1 result in deficient acid sphingomyelinase activity, leading to accumulation of sphingomyelin in lysosomes, particularly in macrophages and neurons. | ClinVar, OMIM |
| Niemann-Pick disease type B | Similar to type A but with residual enzyme activity, causing a milder phenotype with visceral involvement and less neurological impairment. | ClinVar, OMIM |
| Parkinson's disease | Heterozygous SMPD1 mutations are associated with increased risk of Parkinson's disease, possibly through altered ceramide metabolism and mitochondrial dysfunction. | ClinVar, PubMed |
| Hepatocellular carcinoma | Reduced SMPD1 expression or activity may contribute to tumor progression via dysregulated sphingolipid signaling. | COSMIC, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 20.1 | High |
| Spleen | 15.3 | High |
| Lung | 10.2 | Medium |
| Brain | 8.5 | Medium |
| Kidney | 7.4 | Medium |
| Heart | 5.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 25.3 | Liver cancer cell line, high expression |
| A549 | 12.1 | Lung carcinoma, moderate expression |
| SH-SY5Y | 9.8 | Neuroblastoma, moderate expression |
| HeLa | 6.4 | Cervical carcinoma, low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Arg496Leu | Missense | Common in Niemann-Pick type A (Ashkenazi Jewish) | Loss of enzyme activity |
| p.Leu302Pro | Missense | Found in Niemann-Pick type B | Reduced enzyme activity |
| c.996delC | Frameshift | Rare, causes severe type A | Loss of function |
| p.Phe333Ser | Missense | Associated with Parkinson's disease risk | Partial loss of function |
Mutation functional classification
Loss of Function (LOF)
Most SMPD1 mutations are loss-of-function, leading to reduced or absent acid sphingomyelinase activity, causing lysosomal sphingomyelin accumulation.
Gain of Function (GOF)
No gain-of-function mutations have been reported for SMPD1.
Dominant Negative (DN)
Some missense mutations may exert a dominant-negative effect when co-expressed with wild-type enzyme, but this is not well established.
View complete mutation data：
Gene Ontology (GO)
| • sphingomyelin phosphodiesterase activity | • ceramide biosynthetic process |
| • lysosome | • lipid catabolic process |
| • response to stress |
Pathways
• Sphingolipid metabolism
• Sphingomyelin metabolism
• Lysosome
Protein Summary
The SMPD1 protein is a lysosomal acid sphingomyelinase that catalyzes the hydrolysis of sphingomyelin to ceramide and phosphocholine. It is a glycoprotein that requires proteolytic processing for full activity. The enzyme plays a role in membrane turnover, apoptosis, and cell signaling. Defects in this protein lead to Niemann-Pick disease types A and B.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SMPD1 Knockout HEK293 Cell Line | EDJ-KQ1740 | Human | 6609 | Details Get a Quote |
| SMPD1 Knockout A-549 Cell Line | EDJ-KQ21590 | Human | 6609 | Details Get a Quote |
| SMPD1 Knockout HCT 116 Cell Line | EDJ-KQ21591 | Human | 6609 | Details Get a Quote |
| SMPD1 Knockout HeLa Cell Line | EDJ-KQ21592 | Human | 6609 | Details Get a Quote |
| SMPD1 Knockout Hep-G2 Cell Line | EDJ-KZ482 | Human | 6609 | Details Get a Quote |
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