SNTA1 (Syntrophin Alpha 1): Genetic Structure, Function, and Clinical Significance
A comprehensive biomedical overview of the SNTA1 gene, its protein product, associated diseases, expression patterns, and mutational landscape.
Gene Information Card
| Symbol | SNTA1 |
|---|---|
| Full Name | Syntrophin alpha 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 20q11.21 |
| NCBI Gene ID | 6647 ncbi.nlm.nih.gov/gene/6647 |
| Ensembl ID | ENSG00000101442 |
| UniProt ID | Q13424 |
| OMIM ID | 601017 |
| HGNC ID | 11167 |
| Aliases | TACIP1, PRO0895, SNT1 |
Description
The SNTA1 gene encodes alpha-1-syntrophin, a peripheral membrane protein that is a component of the dystrophin-associated glycoprotein complex (DGC). This protein is crucial for linking the extracellular matrix to the cytoskeleton, particularly in muscle cells. It contains a PDZ domain, a pleckstrin homology (PH) domain, and a syntrophin unique (SU) domain, which mediate protein-protein interactions. SNTA1 plays a vital role in maintaining the structural integrity of muscle fibers and in localizing signaling proteins, such as neuronal nitric oxide synthase (nNOS), to the sarcolemma. Mutations in SNTA1 are associated with inherited cardiac conditions, notably Long QT syndrome and dilated cardiomyopathy.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Disease | Mechanism | Evidence |
| Long QT Syndrome (LQTS) | Mutations in SNTA1 disrupt the interaction with the cardiac sodium channel (Nav1.5) and nNOS, leading to increased late sodium current (I_NaL) and prolonged action potential duration, predisposing to arrhythmias. | ClinVar, OMIM (601017) |
| Dilated Cardiomyopathy (DCM) | SNTA1 variants can impair the stability of the DGC in cardiac myocytes, leading to membrane fragility, altered signaling, and progressive ventricular dilation and systolic dysfunction. | ClinVar, NCBI Gene |
| Muscular Dystrophy (e.g., Duchenne/Becker) | While not a primary cause, SNTA1 is a component of the DGC. Its expression and localization are altered in Duchenne Muscular Dystrophy (DMD) due to the loss of dystrophin, contributing to the pathological phenotype. | UniProt, NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Tissue | nTPM | Level |
| Skeletal Muscle | ~500 | High |
| Heart | ~200 | Medium |
| Brain | ~50 | Low |
| Liver | ~10 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cell Line | nTPM | Notes |
| RH-30 (Rhabdomyosarcoma) | ~100 | High expression in muscle-derived cell line. |
| SK-UT-1 (Leiomyosarcoma) | ~50 | Moderate expression in smooth muscle tumor line. |
| HepG2 (Liver cancer) | ~5 | Low expression in non-muscle cell line. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| Variant | Type | Frequency | Effect |
| p.A261V (c.782C>T) | Missense | Rare (found in LQTS cohorts) | Disrupts PDZ domain interaction with Nav1.5, increasing late sodium current. |
| p.P109L (c.326C>T) | Missense | Rare (found in DCM cohorts) | Alters protein stability and localization within the DGC. |
| p.G460S (c.1378G>A) | Missense | Rare | Impairs nNOS binding, leading to altered nitric oxide signaling in cardiac tissue. |
Mutation functional classification
Loss of Function (LOF)
Most SNTA1 mutations associated with disease are considered loss-of-function, as they disrupt critical protein-protein interactions (e.g., with Nav1.5, nNOS) or destabilize the DGC, leading to impaired cellular signaling and structural integrity.
Gain of Function (GOF)
There is no clear evidence of gain-of-function mutations for SNTA1. The primary pathogenic mechanism is a loss of normal regulatory function.
Dominant Negative (DN)
Some missense mutations may act in a dominant-negative manner. For example, a mutant SNTA1 protein could compete with the wild-type protein for binding to the DGC or ion channels, but fail to perform its normal function, thereby disrupting the entire complex.
View complete mutation data：
Gene Ontology (GO)
| • PDZ domain binding | • protein domain specific binding |
| • scaffold protein binding | • structural constituent of muscle |
| • cytoskeletal protein binding | • signal transducer activity |
| • plasma membrane | • sarcolemma |
| • dystrophin-associated glycoprotein complex | • cytoskeleton |
| • cell junction | • Z disc |
| • muscle contraction | • signal transduction |
| • maintenance of muscle cell membrane integrity |
Pathways
• Dystrophin-associated glycoprotein complex (DGC) pathway
• Nitric oxide signaling pathway (via nNOS)
• Cardiac conduction and arrhythmia pathways (via Nav1.5 regulation)
Protein Summary
Alpha-1-syntrophin is a modular adapter protein predominantly expressed in skeletal and cardiac muscle. It contains a PDZ domain that binds to the C-termini of ion channels and receptors, and a PH domain that mediates membrane association. As a core component of the DGC, it links the actin cytoskeleton to the extracellular matrix. It is essential for the proper localization of neuronal nitric oxide synthase (nNOS) to the sarcolemma, where nitric oxide production regulates muscle blood flow and contraction. Through its interaction with the cardiac sodium channel (Nav1.5), it modulates cardiac excitability. Disruption of these interactions via mutations leads to cardiac and muscular pathologies.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SNTA1 Knockout HEK293 Cell Line | EDJ-KQ5814 | Human | 6640 | Details Get a Quote |
| SNTA1 Knockout A-549 Cell Line | EDJ-KQ29237 | Human | 6640 | Details Get a Quote |
| SNTA1 Knockout HCT 116 Cell Line | EDJ-KQ29238 | Human | 6640 | Details Get a Quote |
| SNTA1 Knockout HeLa Cell Line | EDJ-KQ29239 | Human | 6640 | Details Get a Quote |
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