SCN5A Gene: Cardiac Sodium Channel Alpha Subunit
Genetic insights into cardiac excitability, arrhythmias, and cardiomyopathy
Gene Information Card
| Symbol | SCN5A |
|---|---|
| Full Name | sodium voltage-gated channel alpha subunit 5 |
| Gene Type | protein-coding |
| Chromosomal Location | 3p22.2 |
| NCBI Gene ID | 6331 ncbi.nlm.nih.gov/gene/6331 |
| Ensembl ID | ENSG00000183873 |
| UniProt ID | Q14524 |
| OMIM ID | 600163 |
| HGNC ID | 10593 |
| Aliases | Nav1.5; CMD1E; CMPD2; HB1; HB2; HH1; IVF; LQT3; PFHB1; SCN5A |
Description
The SCN5A gene encodes the alpha subunit of the cardiac sodium channel (Nav1.5), which is critical for the initiation and propagation of action potentials in cardiac myocytes. This channel mediates the rapid influx of sodium ions during phase 0 of the cardiac action potential, influencing myocardial excitability and conduction. Mutations in SCN5A are associated with a spectrum of cardiac disorders, including Brugada syndrome, long QT syndrome type 3, cardiac conduction disease, and dilated cardiomyopathy.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Brugada syndrome | Loss-of-function mutations reduce sodium current, leading to ST-segment elevation and ventricular arrhythmias. | ClinVar, OMIM |
| Long QT syndrome type 3 | Gain-of-function mutations delay sodium channel inactivation, prolonging the action potential and QT interval. | ClinVar, OMIM |
| Cardiac conduction disease | Loss-of-function mutations impair conduction, causing progressive conduction block. | ClinVar, OMIM |
| Dilated cardiomyopathy | Mutations may disrupt sodium channel function, affecting myocyte structure and contractility. | OMIM, NCBI |
| Sick sinus syndrome | Reduced sodium current in sinoatrial node cells leads to bradycardia and sinus node dysfunction. | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | High (nTPM ~ 100) | Predominant expression in cardiac muscle |
| Skeletal Muscle | Low (nTPM ~ 5) | Minor expression |
| Brain | Low (nTPM ~ 2) | Low expression in some regions |
| Liver | Not detected | No significant expression |
| Kidney | Not detected | No significant expression |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cardiomyocytes | High | Primary cell type expressing Nav1.5 |
| HEK293 (transfected) | High (overexpression) | Used for functional studies |
| iPSC-derived cardiomyocytes | High | Model for cardiac electrophysiology |
| HeLa (transfected) | Moderate (overexpression) | Used for heterologous expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.4213C>T (p.Arg1405Cys) | Missense | Rare | Gain-of-function; associated with LQT3 |
| c.4868T>C (p.Leu1623Pro) | Missense | Rare | Loss-of-function; associated with Brugada syndrome |
| c.3932C>T (p.Thr1311Met) | Missense | Rare | Loss-of-function; associated with conduction disease |
| c.665G>A (p.Arg222Gln) | Missense | Rare | Gain-of-function; associated with LQT3 |
| c.1673A>G (p.His558Arg) | Missense | Common polymorphism | Modulates channel function; may affect disease severity |
Mutation functional classification
Loss of Function (LOF)
Reduces sodium current density or alters channel gating, leading to decreased excitability. Associated with Brugada syndrome, conduction disease, and sick sinus syndrome.
Gain of Function (GOF)
Enhances sodium current, often by impairing inactivation, leading to prolonged action potential. Associated with long QT syndrome type 3.
Dominant Negative (DN)
Mutant subunits may co-assemble with wild-type subunits, reducing overall functional channel expression. This mechanism is observed in some loss-of-function mutations.
View complete mutation data：
Gene Ontology (GO)
| • voltage-gated sodium channel activity | • sodium ion transmembrane transport |
| • action potential propagation | • cardiac muscle contraction |
| • membrane depolarization | • ion channel complex |
Pathways
• Cardiac conduction
• Voltage-gated sodium channel pathway
• Arrhythmogenic right ventricular cardiomyopathy (ARVC) pathway
• Ion channel transport
Protein Summary
The SCN5A protein (Nav1.5) is a large, pore-forming alpha subunit of the cardiac sodium channel. It consists of four homologous domains (I-IV), each with six transmembrane segments (S1-S6). The S4 segments serve as voltage sensors, while the loop between domains III and IV is involved in fast inactivation. Nav1.5 is essential for the rapid depolarization phase of the cardiac action potential. Post-translational modifications, such as phosphorylation and glycosylation, modulate its function. Mutations affecting this protein lead to various cardiac channelopathies.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SCN5A Knockout HEK293 Cell Line | EDJ-KQ4969 | Human | 6331 | Details Get a Quote |
| SCN5A Knockout HCT 116 Cell Line | EDJ-KQ29110 | Human | 6331 | Details Get a Quote |
| SCN5A Knockout HeLa Cell Line | EDJ-KQ54403 | Human | 6331 | Details Get a Quote |
| SCN5A Knockout A-549 Cell Line | EDJ-KQ62894 | Human | 6331 | Details Get a Quote |
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