SPART Gene (Spastin)
SPART (Spastin) is a protein-coding gene associated with hereditary spastic paraplegia and microtubule dynamics.
Gene Information Card
| Symbol | SPART |
|---|---|
| Full Name | Spastin |
| Gene Type | Protein coding |
| Chromosomal Location | 2p22.3 |
| NCBI Gene ID | 6684 ncbi.nlm.nih.gov/gene/6684 |
| Ensembl ID | ENSG00000164171 |
| UniProt ID | Q9UBP0 |
| OMIM ID | 604277 |
| HGNC ID | 11233 |
| Aliases | SPG4, KIAA1083, spastin |
Description
The SPART gene encodes spastin, a member of the AAA (ATPases Associated with diverse cellular Activities) protein family. Spastin functions as a microtubule-severing protein, regulating microtubule dynamics and cytoskeletal organization. Mutations in SPART are the most common cause of hereditary spastic paraplegia type 4 (SPG4), a neurodegenerative disorder characterized by progressive spasticity and weakness of the lower limbs.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary Spastic Paraplegia 4 (SPG4) | Loss-of-function mutations impair microtubule severing, leading to axonal degeneration of corticospinal tract neurons. | ClinVar, OMIM |
| Spastic Paraplegia, Autosomal Dominant | Dominant-negative or haploinsufficiency mechanisms disrupt microtubule dynamics in motor neurons. | OMIM, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Spinal Cord | 10.2 | Medium |
| Testis | 8.9 | Low |
| Heart | 6.1 | Low |
| Liver | 3.4 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.3 | High expression |
| HeLa (cervical carcinoma) | 8.7 | Moderate expression |
| HEK293 (embryonic kidney) | 6.2 | Low expression |
| HepG2 (hepatocellular carcinoma) | 4.1 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1496C>T (p.Pro499Leu) | Missense | Common | Reduced ATPase activity and microtubule severing |
| c.1684C>T (p.Arg562*) | Nonsense | Rare | Premature truncation, loss of function |
| c.1413+1G>A | Splice site | Rare | Exon skipping, frameshift, loss of function |
| c.1090C>T (p.Arg364Cys) | Missense | Rare | Impaired microtubule binding |
Mutation functional classification
Loss of Function (LOF)
Most SPART mutations cause loss of function via haploinsufficiency or dominant-negative effects, reducing microtubule-severing activity.
Gain of Function (GOF)
No evidence of gain-of-function mutations in SPART.
Dominant Negative (DN)
Some missense mutations (e.g., p.Pro499Leu) act via dominant-negative mechanism, interfering with wild-type spastin function.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Microtubule dynamics (Reactome: R-HSA-983231)
• Axonal transport (KEGG: hsa04728)
Protein Summary
Spastin is a 616-amino acid protein with an N-terminal microtubule-interacting and trafficking (MIT) domain and a C-terminal AAA ATPase domain. It forms hexameric rings that use ATP hydrolysis to sever microtubules, regulating their length and distribution. Spastin is critical for neuronal development and maintenance, particularly in long axons of the corticospinal tract.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SPART Knockout HEK293 Cell Line | EDJ-KQ7836 | Human | 23111 | Details Get a Quote |
| SPART Knockout A-549 Cell Line | EDJ-KQ33376 | Human | 23111 | Details Get a Quote |
| SPART Knockout HeLa Cell Line | EDJ-KQ33377 | Human | 23111 | Details Get a Quote |
| SPART Knockout HCT 116 Cell Line | EDJ-KQ72629 | Human | 23111 | Details Get a Quote |
