SLC8A3: Sodium/Calcium Exchanger 3
A key regulator of calcium homeostasis in excitable tissues
Gene Information Card
| Symbol | SLC8A3 |
|---|---|
| Full Name | Solute Carrier Family 8 Member A3 |
| Gene Type | Protein coding |
| Chromosomal Location | 14q24.2 |
| NCBI Gene ID | 6547 ncbi.nlm.nih.gov/gene/6547 |
| Ensembl ID | ENSG00000100678 |
| UniProt ID | P57103 |
| OMIM ID | 601901 |
| HGNC ID | 11006 |
| Aliases | NCX3, SLC8A3, solute carrier family 8 (sodium/calcium exchanger), member 3 |
Description
SLC8A3 encodes the sodium/calcium exchanger 3 (NCX3), a plasma membrane protein that extrudes calcium from cells using the electrochemical gradient of sodium. It is predominantly expressed in brain and skeletal muscle, playing a critical role in calcium homeostasis, neuronal excitability, and muscle contraction. Alternative splicing generates multiple isoforms with distinct regulatory properties.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hearing loss, autosomal dominant 82 | Impaired calcium extrusion in cochlear hair cells due to SLC8A3 mutations | ClinVar, OMIM |
| Epileptic encephalopathy, early infantile, 80 | Disrupted neuronal calcium homeostasis leading to hyperexcitability | ClinVar, OMIM |
| Myopathy, distal, with rimmed vacuoles | Altered calcium handling in skeletal muscle fibers | OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | High |
| Skeletal muscle | 8.3 | Medium |
| Heart | 4.1 | Low |
| Kidney | 2.0 | Low |
| Liver | 0.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.2 | High expression |
| U-87 MG (glioblastoma) | 9.8 | Medium expression |
| C2C12 (myoblast) | 7.1 | Medium expression |
| HEK 293 (embryonic kidney) | 1.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.107G>A (p.Arg36His) | Missense | <0.01% | Reduced calcium extrusion activity |
| c.1340C>T (p.Thr447Met) | Missense | <0.01% | Altered ion selectivity |
| c.1825G>A (p.Gly609Arg) | Missense | <0.01% | Loss of function, associated with hearing loss |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.Gly609Arg) impair calcium efflux, leading to cellular calcium overload.
Gain of Function (GOF)
Not reported in SLC8A3.
Dominant Negative (DN)
Not reported in SLC8A3.
View complete mutation data：
Gene Ontology (GO)
| • calcium:sodium antiporter activity (GO:0005432) | • calcium ion transport (GO:0006816) |
| • sodium ion transport (GO:0006814) | • integral component of membrane (GO:0016021) |
| • plasma membrane (GO:0005886) | • transmembrane transport (GO:0055085) |
Pathways
• Calcium signaling pathway (KEGG: hsa04020)
• Cardiac muscle contraction (KEGG: hsa04260)
• Ion transport by P-type ATPases (Reactome: R-HSA-936837)
Protein Summary
NCX3 is a 10-transmembrane domain protein that catalyzes the electrogenic exchange of 3 Na+ for 1 Ca2+ across the plasma membrane. It contains two calcium-binding domains (CBD1 and CBD2) in the large intracellular loop that regulate exchanger activity. The protein is essential for rapid calcium clearance in neurons and muscle cells, and its dysfunction is linked to neurological and muscular disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLC8A3 Knockout HEK293 Cell Line | EDJ-KQ1433 | Human | 6547 | Details Get a Quote |
| SLC8A3 Knockout HeLa Cell Line | EDJ-KQ54501 | Human | 6547 | Details Get a Quote |
| SLC8A3 Knockout A-549 Cell Line | EDJ-KQ62987 | Human | 6547 | Details Get a Quote |
| SLC8A3 Knockout HCT 116 Cell Line | EDJ-KQ71458 | Human | 6547 | Details Get a Quote |
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