SLC24A3: Solute Carrier Family 24 Member 3 (Na+/K+/Ca2+ Exchanger)
A key regulator of calcium homeostasis in excitable tissues, linked to auditory and neurological disorders.
Gene Information Card
| Symbol | SLC24A3 |
|---|---|
| Full Name | Solute Carrier Family 24 Member 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 20p13 |
| NCBI Gene ID | 57419 ncbi.nlm.nih.gov/gene/57419 |
| Ensembl ID | ENSG00000125846 |
| UniProt ID | Q9HC58 |
| OMIM ID | 609841 |
| HGNC ID | 10976 |
| Aliases | NCKX3, SLC24A3 |
Description
SLC24A3 (Solute Carrier Family 24 Member 3) encodes a potassium-dependent sodium/calcium exchanger (NCKX3) that mediates the electrogenic exchange of 4 Na+ for 1 Ca2+ and 1 K+ across the plasma membrane. It is critical for calcium extrusion in excitable cells, particularly in neurons, smooth muscle, and auditory hair cells. The gene is located on chromosome 20p13 and is associated with autosomal recessive hearing loss and susceptibility to hypokalemic periodic paralysis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Autosomal recessive nonsyndromic hearing loss (DFNB) | Loss of NCKX3 function disrupts calcium homeostasis in cochlear hair cells, leading to cell death and hearing impairment. | ClinVar, OMIM #609841 |
| Hypokalemic periodic paralysis (susceptibility) | Altered calcium handling in skeletal muscle due to SLC24A3 variants may predispose to episodic muscle weakness. | ClinVar, OMIM #609841 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 8.3 | Low |
| Skeletal muscle | 6.1 | Low |
| Cochlea | 15.2 | High |
| Kidney | 4.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 14.0 | High expression |
| HEK293 (embryonic kidney) | 5.2 | Moderate expression |
| HMC3 (microglia) | 9.8 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1462C>T (p.Arg488*) | Nonsense | <0.01% | Premature stop; loss of exchanger function |
| c.832G>A (p.Gly278Arg) | Missense | <0.01% | Impaired calcium transport; associated with hearing loss |
| c.1121T>C (p.Leu374Pro) | Missense | <0.01% | Reduced protein stability; linked to periodic paralysis |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift variants (e.g., p.Arg488*) lead to truncated, non-functional NCKX3 protein, causing autosomal recessive hearing loss.
Gain of Function (GOF)
No gain-of-function variants reported in SLC24A3.
Dominant Negative (DN)
No dominant-negative variants reported in SLC24A3.
View complete mutation data：
Gene Ontology (GO)
| • calcium:sodium antiporter activity (GO:0005432) | • protein binding (GO:0005515) |
| • calcium ion transport (GO:0006816) | • sodium ion transport (GO:0006814) |
| • plasma membrane (GO:0005886) | • integral component of membrane (GO:0016021) |
Pathways
• Calcium signaling pathway (KEGG: hsa04020)
• Ion transport by P-type ATPases (Reactome: R-HSA-936837)
Protein Summary
NCKX3 (UniProt Q9HC58) is a 658-amino acid multi-pass membrane protein with 10 transmembrane helices. It functions as a K+-dependent Na+/Ca2+ exchanger, exporting Ca2+ from cells using the inward Na+ gradient. Expressed predominantly in brain, cochlea, and smooth muscle, it is essential for maintaining low intracellular calcium levels. Mutations cause calcium overload and cellular dysfunction, particularly in auditory and neuromuscular tissues.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLC24A3 Knockout HEK293 Cell Line | EDJ-KQ15307 | Human | 57419 | Details Get a Quote |
| SLC24A3 Knockout HeLa Cell Line | EDJ-KQ56837 | Human | 57419 | Details Get a Quote |
| SLC24A3 Knockout A-549 Cell Line | EDJ-KQ65348 | Human | 57419 | Details Get a Quote |
| SLC24A3 Knockout HCT 116 Cell Line | EDJ-KQ73787 | Human | 57419 | Details Get a Quote |
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