SPAST (Spastin) Gene
Microtubule-severing protein associated with hereditary spastic paraplegia
Gene Information Card
| Symbol | SPAST |
|---|---|
| Full Name | Spastin |
| Gene Type | Protein coding |
| Chromosomal Location | 2p22.3 |
| NCBI Gene ID | 6683 ncbi.nlm.nih.gov/gene/6683 |
| Ensembl ID | ENSG00000100413 |
| UniProt ID | Q9UBP0 |
| OMIM ID | 604277 |
| HGNC ID | 11233 |
| Aliases | SPG4, ADPSP, FSP2, KIAA1083 |
Description
The SPAST gene encodes spastin, an ATP-dependent microtubule-severing protein that regulates microtubule dynamics and is essential for axonal transport and neuronal survival. Mutations in SPAST are the most common cause of autosomal dominant hereditary spastic paraplegia type 4 (SPG4), characterized by progressive lower limb spasticity and weakness.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary spastic paraplegia type 4 (SPG4) | Loss-of-function mutations impair microtubule severing, leading to axonal degeneration of corticospinal tracts | ClinVar, OMIM |
| Spastic paraplegia, autosomal dominant | Heterozygous mutations in SPAST disrupt spastin function, causing dominant inheritance | OMIM, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 nTPM | Medium |
| Spinal cord | 10.2 nTPM | Medium |
| Testis | 8.9 nTPM | Low |
| Heart | 6.1 nTPM | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.3 nTPM | Neuronal model |
| HeLa (cervical carcinoma) | 7.8 nTPM | Epithelial |
| HEK293 (embryonic kidney) | 9.4 nTPM | Common cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1496G>A (p.Arg499His) | Missense | Common | Reduced ATPase activity and microtubule severing |
| c.1684C>T (p.Arg562*) | Nonsense | Rare | Premature truncation, loss of function |
| c.1098_1099delCT (p.Phe367Leufs*3) | Frameshift | Rare | Loss of function via nonsense-mediated decay |
Mutation functional classification
Loss of Function (LOF)
Most SPAST mutations cause haploinsufficiency, reducing spastin levels and impairing microtubule severing.
Gain of Function (GOF)
Not reported for SPAST.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by interfering with wild-type spastin oligomerization.
View complete mutation data：
Gene Ontology (GO)
| • Microtubule severing (GO:0051013) | • ATP binding (GO:0005524) |
| • Microtubule binding (GO:0008017) | • ATPase activity (GO:0016887) |
| • Neuron projection development (GO:0031175) |
Pathways
• Microtubule dynamics (Reactome R-HSA-983189)
• Axon guidance (KEGG hsa04360)
Protein Summary
Spastin is a 616-amino acid protein belonging to the AAA (ATPases Associated with diverse cellular Activities) family. It forms hexameric rings that use ATP hydrolysis to sever microtubules, regulating their length and distribution. Spastin is critical for neuronal development, axonal transport, and synaptic function. Mutations cause hereditary spastic paraplegia by disrupting microtubule homeostasis in long corticospinal tract axons.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SPAST Knockout HEK293 Cell Line | EDJ-KQ5832 | Human | 6683 | Details Get a Quote |
| SPAST Knockout A-549 Cell Line | EDJ-KQ29274 | Human | 6683 | Details Get a Quote |
| SPAST Knockout HCT 116 Cell Line | EDJ-KQ29275 | Human | 6683 | Details Get a Quote |
| SPAST Knockout HeLa Cell Line | EDJ-KQ29276 | Human | 6683 | Details Get a Quote |
