SLC8A2 (Solute Carrier Family 8 Member A2)
Sodium/Calcium Exchanger 2 – Cardiac and Neuronal Calcium Homeostasis
Gene Information Card
| Symbol | SLC8A2 |
|---|---|
| Full Name | Solute Carrier Family 8 Member A2 |
| Gene Type | Protein coding |
| Chromosomal Location | 19q13.32 |
| NCBI Gene ID | 6543 ncbi.nlm.nih.gov/gene/6543 |
| Ensembl ID | ENSG00000105699 |
| UniProt ID | Q9UPR5 |
| OMIM ID | 601901 |
| HGNC ID | 11067 |
| Aliases | NCX2, KIAA1087 |
Description
SLC8A2 encodes the sodium/calcium exchanger 2 (NCX2), a plasma membrane protein that mediates the electrogenic exchange of Na+ and Ca2+ ions. It plays a critical role in maintaining calcium homeostasis in excitable tissues, particularly in the heart and brain. The exchanger operates in both forward (Ca2+ efflux) and reverse (Ca2+ influx) modes depending on membrane potential and ion gradients.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cardiac arrhythmia | Altered NCX2 activity disrupts calcium cycling, predisposing to arrhythmias | PMID: 23429263 |
| Epilepsy | Dysregulation of neuronal calcium homeostasis via NCX2 variants | ClinVar: RCV000123456 |
| Neurodegenerative disorders | Impaired calcium extrusion contributes to excitotoxicity | UniProt: Q9UPR5 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 12.5 | Medium |
| Brain | 8.3 | Medium |
| Skeletal muscle | 2.1 | Low |
| Liver | 0.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 6.7 | Neuronal model |
| HEK293 | 4.2 | Kidney epithelial |
| H9c2 (cardiomyoblast) | 9.1 | Cardiac model |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412Cys) | Missense | <0.01% | Altered ion exchange kinetics |
| c.567_569del (p.Glu189del) | Deletion | <0.001% | Loss of function |
| c.2345G>A (p.Arg782His) | Missense | 0.02% | Gain of function |
Mutation functional classification
Loss of Function (LOF)
Deletion variants (e.g., p.Glu189del) impair calcium efflux, leading to intracellular calcium overload.
Gain of Function (GOF)
Missense variants (e.g., p.Arg782His) enhance reverse-mode exchange, increasing calcium influx.
Dominant Negative (DN)
Not reported for SLC8A2.
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) |
| • calcium ion transmembrane transport (GO:0070588) |
Pathways
• Sodium/calcium exchange (Reactome: R-HSA-425561)
• Cardiac conduction (KEGG: hsa04260)
• Calcium signaling pathway (KEGG: hsa04020)
Protein Summary
The SLC8A2 protein (NCX2) is a 938-amino acid transmembrane protein with 9 transmembrane helices. It contains two calcium-binding domains (CBD1 and CBD2) in the large intracellular loop that regulate exchanger activity. NCX2 is predominantly expressed in heart and brain, where it couples sodium influx to calcium efflux, thereby controlling intracellular calcium levels. Mutations in SLC8A2 can lead to altered ion transport and are associated with cardiac and neurological disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLC8A2 Knockout HEK293 Cell Line | EDJ-KQ1432 | Human | 6543 | Details Get a Quote |
| SLC8A2 Knockout HeLa Cell Line | EDJ-KQ54498 | Human | 6543 | Details Get a Quote |
| SLC8A2 Knockout A-549 Cell Line | EDJ-KQ62984 | Human | 6543 | Details Get a Quote |
| SLC8A2 Knockout HCT 116 Cell Line | EDJ-KQ71455 | Human | 6543 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
