BSCL2
Seipin, a key regulator of lipid droplet biogenesis and adipogenesis
Gene Information Card
| Symbol | BSCL2 |
|---|---|
| Full Name | BSCL2 lipid droplet biogenesis associated, seipin |
| Gene Type | Protein coding |
| Chromosomal Location | 11q12.3 |
| NCBI Gene ID | 26580 ncbi.nlm.nih.gov/gene/26580 |
| Ensembl ID | ENSG00000168000 |
| UniProt ID | Q96G97 |
| OMIM ID | 606158 |
| HGNC ID | 13532 |
| Aliases | SPG17, HMN5, seipin, GNG3LG, MGC26269 |
Description
The BSCL2 gene encodes seipin, a transmembrane protein localized to the endoplasmic reticulum that is essential for lipid droplet biogenesis, adipocyte differentiation, and lipid homeostasis. Mutations in BSCL2 cause Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) and are also associated with motor neuron diseases such as Silver syndrome (SPG17) and distal hereditary motor neuropathy type V (HMN5).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) | Loss-of-function mutations in BSCL2 disrupt seipin function, impairing lipid droplet formation and adipogenesis, leading to near-total loss of adipose tissue. | OMIM #269700 |
| Silver syndrome (SPG17) | Dominant missense mutations (e.g., N88S, S90L) cause seipin misfolding and ER stress, leading to motor neuron degeneration. | OMIM #270685 |
| Distal hereditary motor neuropathy type V (HMN5) | Same dominant missense mutations as SPG17, resulting in progressive distal muscle weakness and atrophy. | OMIM #600794 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adipose tissue | High | High |
| Brain | Moderate | Moderate |
| Testis | Moderate | Moderate |
| Liver | Low | Low |
| Skeletal muscle | Low | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Adipocytes (differentiated) | High | Key role in adipogenesis |
| Neuroblastoma SH-SY5Y | Moderate | Neuronal expression relevant to motor neuron disease |
| HeLa | Low | Minimal expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| N88S | Missense | Rare (dominant) | Gain-of-toxic function; causes ER stress and motor neuron disease (SPG17/HMN5) |
| S90L | Missense | Rare (dominant) | Similar to N88S; misfolding and ER stress |
| c.985C>T (p.Arg329*) | Nonsense | Rare (recessive) | Loss of function; causes congenital lipodystrophy type 2 |
| c.974dupG (p.Val326Glyfs*12) | Frameshift | Rare (recessive) | Loss of function; causes congenital lipodystrophy type 2 |
Mutation functional classification
Loss of Function (LOF)
Recessive mutations (nonsense, frameshift) cause complete loss of seipin function, leading to congenital lipodystrophy type 2.
Gain of Function (GOF)
Dominant missense mutations (N88S, S90L) confer a toxic gain of function via protein misfolding and ER stress, causing motor neuron diseases.
Dominant Negative (DN)
Not clearly established; dominant mutations likely act through gain-of-toxic function rather than dominant-negative effects.
View complete mutation data：
Gene Ontology (GO)
| • integral component of membrane (GO:0016021) | • endoplasmic reticulum (GO:0005783) |
| • positive regulation of lipid storage (GO:0010884) | • fat cell differentiation (GO:0045444) |
| • lipid droplet (GO:0005811) | • response to insulin (GO:0032868) |
Pathways
• Lipid droplet biogenesis (Reactome: R-HSA-8979227)
• Adipogenesis (WikiPathways: WP236)
• Endoplasmic reticulum stress response (KEGG: hsa04141)
Protein Summary
Seipin is a 398-amino-acid transmembrane protein with two transmembrane domains and a conserved luminal loop. It localizes to the endoplasmic reticulum and is critical for lipid droplet formation, adipogenesis, and lipid homeostasis. Seipin interacts with lipid droplet-associated proteins and calcium channels, and its dysfunction leads to severe lipodystrophy or neurodegeneration depending on mutation type.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| BSCL2 Knockout HEK293 Cell Line | EDJ-KQ2595 | Human | 26580 | Details Get a Quote |
| BSCL2 Knockout A-549 Cell Line | EDJ-KQ23290 | Human | 26580 | Details Get a Quote |
| BSCL2 Knockout HCT 116 Cell Line | EDJ-KQ23291 | Human | 26580 | Details Get a Quote |
| BSCL2 Knockout HeLa Cell Line | EDJ-KQ23292 | Human | 26580 | Details Get a Quote |
