SLC24A4: Sodium/Potassium/Calcium Exchanger 4
A member of the potassium-dependent sodium/calcium exchanger family involved in calcium homeostasis, pigmentation, and neurodevelopment.
Gene Information Card
| Symbol | SLC24A4 |
|---|---|
| Full Name | Solute Carrier Family 24 Member 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 14q32.12 |
| NCBI Gene ID | 123041 ncbi.nlm.nih.gov/gene/123041 |
| Ensembl ID | ENSG00000100823 |
| UniProt ID | Q8NFF2 |
| OMIM ID | 609840 |
| HGNC ID | 10975 |
| Aliases | NCKX4, SLC24A2, solute carrier family 24 (sodium/potassium/calcium exchanger), member 4 |
Description
SLC24A4 encodes NCKX4, a potassium-dependent sodium/calcium exchanger that transports Ca2+ in exchange for Na+ and K+. It is essential for calcium homeostasis in enamel-forming ameloblasts, melanocytes, and neurons. Mutations in SLC24A4 cause autosomal recessive amelogenesis imperfecta (AI) type IIC, characterized by hypomineralized enamel. The gene is also associated with normal variation in skin and hair pigmentation, and has been implicated in neurodevelopmental processes.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Amelogenesis Imperfecta Type IIC (AI1C) | Loss-of-function mutations impair calcium extrusion from ameloblasts, leading to defective enamel mineralization. | OMIM #613206; ClinVar |
| Pigmentation traits (hair/skin color) | Variants in SLC24A4 influence melanin synthesis via calcium-dependent signaling in melanocytes. | GWAS studies; NCBI |
| Neurodevelopmental disorders (suggested) | Altered calcium homeostasis in neurons may affect synaptic function and development. | PubMed; limited evidence |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Salivary gland | 8.2 | Low |
| Skin | 6.1 | Low |
| Thyroid | 5.0 | Low |
| Testis | 4.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.2 | Neuronal model |
| HaCaT (keratinocyte) | 9.8 | Skin model |
| HMC3 (microglia) | 7.4 | Brain immune cells |
| A549 (lung carcinoma) | 2.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1192C>T (p.Arg398*) | Nonsense | Rare | Loss of function; associated with AI1C |
| c.1465C>T (p.Arg489Trp) | Missense | Rare | Impaired calcium transport; AI1C |
| c.1666C>T (p.Arg556*) | Nonsense | Rare | Loss of function; AI1C |
| rs12821256 (intronic) | SNP | Common (European) | Associated with blond hair color |
Mutation functional classification
Loss of Function (LOF)
Nonsense and missense mutations (e.g., p.Arg398*, p.Arg489Trp) reduce or abolish calcium exchange activity, leading to enamel hypomineralization.
Gain of Function (GOF)
Not reported.
Dominant Negative (DN)
Not reported.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Calcium signaling pathway (KEGG: hsa04020)
• Ion transport by P-type ATPases (Reactome: R-HSA-936837)
• Transport of inorganic cations/anions (Reactome: R-HSA-425393)
Protein Summary
NCKX4 (SLC24A4) is a 658-amino acid multi-pass membrane protein with 10 transmembrane domains. It functions as a potassium-dependent sodium/calcium exchanger, coupling the efflux of one Ca2+ and one K+ to the influx of four Na+. The protein is highly expressed in brain, salivary glands, and skin, and localizes to the plasma membrane. Its activity is critical for calcium extrusion in ameloblasts during enamel maturation, and it modulates melanocyte function. Structural studies indicate a conserved ion-binding pocket essential for transport.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLC24A4 Knockout HEK293 Cell Line | EDJ-KQ8172 | Human | 123041 | Details Get a Quote |
| SLC24A4 Knockout HeLa Cell Line | EDJ-KQ58112 | Human | 123041 | Details Get a Quote |
| SLC24A4 Knockout A-549 Cell Line | EDJ-KQ66600 | Human | 123041 | Details Get a Quote |
| SLC24A4 Knockout HCT 116 Cell Line | EDJ-KQ75017 | Human | 123041 | Details Get a Quote |
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