SPG11 Gene
SPG11: Spatacsin, Hereditary Spastic Paraplegia 11
Gene Information Card
| Symbol | SPG11 |
|---|---|
| Full Name | SPG11 vesicle trafficking associated, spatacsin |
| Gene Type | Protein coding |
| Chromosomal Location | 15q21.1 |
| NCBI Gene ID | 80208 ncbi.nlm.nih.gov/gene/80208 |
| Ensembl ID | ENSG00000104140 |
| UniProt ID | Q96JI7 |
| OMIM ID | 610844 |
| HGNC ID | 11232 |
| Aliases | KIAA1840, SPG11, spatacsin |
Description
The SPG11 gene encodes spatacsin, a large protein (2443 amino acids) that functions in vesicle trafficking, lysosomal biogenesis, and autophagy. It is widely expressed in the brain, particularly in neurons. Loss-of-function mutations in SPG11 are the most common cause of autosomal recessive hereditary spastic paraplegia (HSP) with thin corpus callosum (HSP-TCC), and are also associated with juvenile amyotrophic lateral sclerosis (ALS5) and Charcot-Marie-Tooth disease type 2X.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary spastic paraplegia 11 (SPG11) | Loss-of-function mutations impair spatacsin function, leading to axonal degeneration and accumulation of autophagic vesicles in neurons. | ClinVar, OMIM |
| Juvenile amyotrophic lateral sclerosis 5 (ALS5) | Biallelic SPG11 mutations cause motor neuron degeneration, with clinical overlap with HSP. | ClinVar, OMIM |
| Charcot-Marie-Tooth disease type 2X (CMT2X) | Rare SPG11 mutations cause axonal peripheral neuropathy. | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Cerebellum | 10.8 | Medium |
| Spinal cord | 9.2 | Medium |
| Testis | 8.1 | Medium |
| Heart | 4.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.2 | Neuronal model |
| HEK293 (embryonic kidney) | 8.7 | Common cell line |
| HeLa (cervical carcinoma) | 6.4 | Epithelial |
| U-87 MG (glioblastoma) | 11.0 | Glial |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.733_734delAT (p.Met245Valfs*2) | Frameshift | Common in European HSP | Loss of function |
| c.2436_2437delGA (p.Lys812Asnfs*14) | Frameshift | Recurrent in Japanese HSP | Loss of function |
| c.6100C>T (p.Arg2034*) | Nonsense | Reported in ALS5 | Loss of function |
| c.2671C>T (p.Arg891*) | Nonsense | Found in CMT2X | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Most SPG11 mutations are loss-of-function (nonsense, frameshift, splice-site), leading to truncated or absent spatacsin protein, impairing autophagy and lysosomal function.
Gain of Function (GOF)
No gain-of-function mutations reported for SPG11.
Dominant Negative (DN)
No dominant-negative mutations reported; SPG11 disease is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Autophagy - lysosome pathway
• Endosomal trafficking
Protein Summary
Spatacsin is a 2443-amino acid protein with a predicted N-terminal transmembrane domain and a C-terminal coiled-coil region. It localizes to the endoplasmic reticulum and endosomes, and is essential for autophagic lysosome reformation and clearance of autophagic vesicles. Loss of spatacsin leads to accumulation of autophagic substrates and axonal swelling, particularly in long corticospinal tract neurons.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SPG11 Knockout HEK293 Cell Line | EDJ-KQ9494 | Human | 80208 | Details Get a Quote |
| SPG11 Knockout HeLa Cell Line | EDJ-KQ34982 | Human | 80208 | Details Get a Quote |
| SPG11 Knockout A-549 Cell Line | EDJ-KQ36232 | Human | 80208 | Details Get a Quote |
| SPG11 Knockout HCT 116 Cell Line | EDJ-KQ36233 | Human | 80208 | Details Get a Quote |
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