SMPD4: Sphingomyelin Phosphodiesterase 4
A key enzyme in sphingolipid metabolism, associated with neurodevelopmental disorders and cancer.
Gene Information Card
| Symbol | SMPD4 |
|---|---|
| Full Name | Sphingomyelin Phosphodiesterase 4 |
| Gene Type | Protein-coding |
| Chromosomal Location | 2q21.1 |
| NCBI Gene ID | 55627 ncbi.nlm.nih.gov/gene/55627 |
| Ensembl ID | ENSG00000115956 |
| UniProt ID | Q9NXE4 |
| OMIM ID | 610457 |
| HGNC ID | 14221 |
| Aliases | nSMase3, NSMASE3, FLJ20297 |
Description
SMPD4 encodes sphingomyelin phosphodiesterase 4, a neutral sphingomyelinase (nSMase3) that catalyzes the hydrolysis of sphingomyelin to ceramide and phosphocholine. This enzyme is involved in sphingolipid signaling, cell differentiation, apoptosis, and stress responses. It is localized to the endoplasmic reticulum and Golgi apparatus.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neurodevelopmental disorder with microcephaly, seizures, and brain atrophy | Loss-of-function mutations impair ceramide production, disrupting neuronal development and survival | ClinVar, OMIM |
| Breast cancer | Altered SMPD4 expression may influence ceramide-mediated apoptosis and tumor progression | COSMIC, NCBI |
| Colorectal cancer | Somatic mutations and expression changes linked to sphingolipid metabolism dysregulation | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 10.2 | Medium |
| Heart | 8.5 | Medium |
| Liver | 6.1 | Low |
| Kidney | 7.8 | Medium |
| Testis | 12.4 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 9.3 | Embryonic kidney cells |
| HeLa | 7.1 | Cervical cancer cells |
| MCF7 | 6.8 | Breast cancer cells |
| HepG2 | 5.5 | Liver cancer cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1096C>T (p.Arg366Ter) | Nonsense | Rare | Loss of function; associated with neurodevelopmental disorder |
| c.1432G>A (p.Gly478Arg) | Missense | Rare | Impaired enzyme activity; reported in ClinVar |
| c.1745_1746del (p.Leu582fs) | Frameshift | Rare | Loss of function; linked to microcephaly |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations in SMPD4 lead to truncated or absent protein, reducing ceramide production and disrupting neuronal development.
Gain of Function (GOF)
No gain-of-function mutations have been reported for SMPD4.
Dominant Negative (DN)
No dominant-negative mutations have been described for SMPD4.
View complete mutation data：
Gene Ontology (GO)
| • Sphingomyelin phosphodiesterase activity | • Ceramide biosynthetic process |
| • Sphingomyelin catabolic process | • Apoptotic process |
| • Endoplasmic reticulum membrane | • Golgi apparatus |
Pathways
• Sphingolipid metabolism
• Ceramide signaling pathway
• Apoptosis
Protein Summary
SMPD4 encodes neutral sphingomyelinase 3 (nSMase3), a 582-amino acid protein with a single transmembrane domain. It localizes to the endoplasmic reticulum and Golgi, where it converts sphingomyelin to ceramide. Ceramide acts as a second messenger in stress responses, differentiation, and apoptosis. Mutations in SMPD4 cause a severe neurodevelopmental disorder, and altered expression is observed in several cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SMPD4 Knockout HEK293 Cell Line | EDJ-KQ15403 | Human | 55627 | Details Get a Quote |
| SMPD4 Knockout A-549 Cell Line | EDJ-KQ46168 | Human | 55627 | Details Get a Quote |
| SMPD4 Knockout HeLa Cell Line | EDJ-KQ46170 | Human | 55627 | Details Get a Quote |
| SMPD4 Knockout HCT 116 Cell Line | EDJ-KQ44924 | Human | 55627 | Details Get a Quote |
