SGMS2: Sphingomyelin Synthase 2
Key enzyme in sphingolipid metabolism and bone mineralization
Gene Information Card
| Symbol | SGMS2 |
|---|---|
| Full Name | Sphingomyelin Synthase 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 4q25 |
| NCBI Gene ID | 166929 ncbi.nlm.nih.gov/gene/166929 |
| Ensembl ID | ENSG00000164023 |
| UniProt ID | Q8NHU3 |
| OMIM ID | 611574 |
| HGNC ID | 28380 |
| Aliases | SMS2, FLJ20489, MGC138290 |
Description
SGMS2 (sphingomyelin synthase 2) encodes a transmembrane protein that catalyzes the conversion of phosphatidylcholine and ceramide to sphingomyelin and diacylglycerol. This enzyme is involved in sphingolipid metabolism, membrane lipid homeostasis, and bone mineralization. Mutations in SGMS2 are associated with autosomal dominant osteoporosis and skeletal dysplasia.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Osteoporosis, autosomal dominant, with calvarial wormian bones | Loss-of-function mutations impair sphingomyelin synthesis, disrupting bone matrix mineralization | PMID: 30595372 |
| Skeletal dysplasia, SGMS2-related | Missense mutations alter enzyme activity, leading to abnormal bone development | PMID: 30595372 |
| Osteogenesis imperfecta-like phenotype | Reduced sphingomyelin levels affect osteoblast function and collagen deposition | PMID: 30595372 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Kidney | 8.2 | Medium |
| Liver | 6.1 | Low |
| Bone | 4.3 | Low |
| Heart | 3.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.0 | High expression |
| HeLa | 10.5 | Moderate expression |
| HepG2 | 7.8 | Moderate expression |
| U2OS | 5.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.148C>T (p.Arg50Cys) | Missense | Rare | Reduced enzyme activity; associated with osteoporosis |
| c.185G>A (p.Arg62His) | Missense | Rare | Impaired sphingomyelin synthesis; skeletal dysplasia |
| c.1A>G (p.Met1Val) | Start loss | Very rare | Loss of protein expression; severe phenotype |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.Arg50Cys) reduce catalytic activity, leading to decreased sphingomyelin levels and impaired bone mineralization.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
Heterozygous mutations may exert dominant-negative effects by disrupting dimerization or enzyme complex formation.
View complete mutation data：
Gene Ontology (GO)
| • sphingomyelin synthase activity (GO:0004767) | • sphingomyelin biosynthetic process (GO:0006686) |
| • integral component of membrane (GO:0016021) | • endoplasmic reticulum (GO:0005783) |
| • Golgi apparatus (GO:0005794) |
Pathways
• Sphingolipid metabolism (Reactome R-HSA-428157)
• Sphingomyelin de novo biosynthesis (KEGG map00600)
Protein Summary
SGMS2 is a 365-amino acid transmembrane protein localized to the endoplasmic reticulum and Golgi. It catalyzes the transfer of phosphocholine from phosphatidylcholine to ceramide, producing sphingomyelin and diacylglycerol. The enzyme is critical for membrane lipid composition and bone matrix mineralization. Loss-of-function mutations cause autosomal dominant osteoporosis with calvarial wormian bones.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SGMS2 Knockout HEK293 Cell Line | EDJ-KQ1742 | Human | 166929 | Details Get a Quote |
| SGMS2 Knockout A-549 Cell Line | EDJ-KQ21596 | Human | 166929 | Details Get a Quote |
| SGMS2 Knockout HCT 116 Cell Line | EDJ-KQ21597 | Human | 166929 | Details Get a Quote |
| SGMS2 Knockout HeLa Cell Line | EDJ-KQ21598 | Human | 166929 | Details Get a Quote |
| SGMS2 Knockout Hep-G2 Cell Line | EDJ-KZ453 | Human | 166929 | Details Get a Quote |
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