SPTAN1 Gene: Structure, Function, and Clinical Significance
Alpha-II Spectrin: A Cytoskeletal Protein Linked to Neurological and Hematological Disorders
Gene Information Card
| Symbol | SPTAN1 |
|---|---|
| Full Name | Spectrin alpha, non-erythrocytic 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 9q34.11 |
| NCBI Gene ID | 6709 ncbi.nlm.nih.gov/gene/6709 |
| Ensembl ID | ENSG00000197694 |
| UniProt ID | Q13813 |
| OMIM ID | 182810 |
| HGNC ID | 11273 |
| Aliases | alpha-II spectrin, SPTA2, NEAS |
Description
The SPTAN1 gene encodes alpha-II spectrin, a cytoskeletal protein that forms heterotetramers with beta spectrins. It is widely expressed in various tissues, with high levels in the brain and muscle. Alpha-II spectrin is involved in maintaining cell membrane integrity, organizing membrane domains, and facilitating intracellular transport. Mutations in SPTAN1 are associated with a spectrum of neurological disorders, including early infantile epileptic encephalopathy, hereditary spastic paraplegia, and intellectual disability.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Early infantile epileptic encephalopathy 5 (EIEE5) | Missense mutations in the spectrin repeat domain disrupt protein folding and stability, leading to dominant-negative effects on the cytoskeleton. | ClinVar, OMIM |
| Hereditary spastic paraplegia (HSP) | Loss-of-function mutations (e.g., frameshift, nonsense) cause haploinsufficiency, impairing axonal transport and neuronal survival. | ClinVar, OMIM |
| Intellectual disability with or without seizures | De novo missense mutations in the calponin homology domain affect actin binding, leading to altered neuronal morphology. | ClinVar, OMIM |
| Spinocerebellar ataxia (SCA) | Rare missense variants in the spectrin repeat region are associated with cerebellar degeneration, though the mechanism is not fully defined. | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | High (e.g., ~50 nTPM) | Highest expression in cerebral cortex and cerebellum |
| Muscle | Moderate (e.g., ~20 nTPM) | Skeletal and cardiac muscle |
| Kidney | Moderate (e.g., ~15 nTPM) | Tubular cells |
| Liver | Low (e.g., ~5 nTPM) | Hepatocytes |
| Lung | Low (e.g., ~3 nTPM) | Alveolar cells |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | High (e.g., ~80 nTPM) | Neuronal-like cells; used for neurotoxicity studies |
| HeLa (cervical carcinoma) | Moderate (e.g., ~30 nTPM) | Epithelial-like; common for cytoskeletal studies |
| A549 (lung carcinoma) | Low (e.g., ~10 nTPM) | Alveolar basal epithelial |
| HepG2 (hepatocellular carcinoma) | Low (e.g., ~8 nTPM) | Liver cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.617G>A (p.Arg206His) | Missense | Rare (de novo) | Disrupts calponin homology domain; associated with EIEE5 |
| c.2314C>T (p.Arg772Ter) | Nonsense | Rare (familial) | Premature stop; causes haploinsufficiency in HSP |
| c.2369_2370del (p.Glu790GlyfsTer23) | Frameshift | Rare (de novo) | Loss of function; intellectual disability |
| c.739G>A (p.Gly247Arg) | Missense | Rare (de novo) | Alters spectrin repeat stability; epileptic encephalopathy |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations leading to premature termination codons result in reduced protein levels (haploinsufficiency), impairing cytoskeletal integrity in neurons.
Gain of Function (GOF)
Some missense mutations may confer toxic gain-of-function by producing misfolded proteins that aggregate, disrupting cellular processes.
Dominant Negative (DN)
Missense mutations in the spectrin repeat domain often act in a dominant-negative manner, interfering with the assembly of functional spectrin tetramers.
View complete mutation data：
Gene Ontology (GO)
| • actin binding | • calcium ion binding |
| • cytoskeletal protein binding | • structural constituent of cytoskeleton |
| • protein heterodimerization activity | • SH3 domain binding |
Pathways
• Formation of the cornified envelope
• Cell junction organization
• Cytoskeletal signaling
• Axon guidance
• Spectrin-associated cytoskeleton
Protein Summary
Alpha-II spectrin is a large (≈285 kDa) cytoskeletal protein composed of multiple spectrin repeats, an SH3 domain, and a calponin homology domain. It forms antiparallel heterodimers with beta spectrins, which further assemble into tetramers and higher-order networks. These networks provide mechanical support to the plasma membrane, anchor membrane proteins, and facilitate vesicular trafficking. In neurons, alpha-II spectrin is enriched in axons and synapses, where it regulates synaptic vesicle recycling and axonal transport. Post-translational modifications, such as phosphorylation and calpain cleavage, modulate its function and are implicated in neurodegeneration.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SPTAN1 Knockout HEK293 Cell Line | EDJ-KQ5837 | Human | 6709 | Details Get a Quote |
| SPTAN1 Knockout A-549 Cell Line | EDJ-KQ29286 | Human | 6709 | Details Get a Quote |
| SPTAN1 Knockout HCT 116 Cell Line | EDJ-KQ29287 | Human | 6709 | Details Get a Quote |
| SPTAN1 Knockout HeLa Cell Line | EDJ-KQ29288 | Human | 6709 | Details Get a Quote |
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