SLC12A4: Solute Carrier Family 12 Member 4
Potassium-Chloride Cotransporter KCC1: Gene Function, Expression, and Clinical Relevance
Gene Information Card
| Symbol | SLC12A4 |
|---|---|
| Full Name | Solute Carrier Family 12 Member 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 16q22.1 |
| NCBI Gene ID | 6560 ncbi.nlm.nih.gov/gene/6560 |
| Ensembl ID | ENSG00000124067 |
| UniProt ID | Q9UP95 |
| OMIM ID | 604119 |
| HGNC ID | 10914 |
| Aliases | KCC1, hKCC1, MGC126674, MGC126675 |
Description
SLC12A4 encodes the potassium-chloride cotransporter KCC1, a member of the SLC12 family of electroneutral cation-chloride cotransporters. KCC1 mediates coupled K+ and Cl- efflux across the plasma membrane, playing a key role in cell volume regulation, ion homeostasis, and neuronal excitability. The gene is widely expressed in human tissues, with highest levels in erythroid cells and kidney. Mutations in SLC12A4 are associated with hereditary spherocytosis and may contribute to cancer cell volume regulation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary spherocytosis | Loss-of-function mutations impair KCC1 activity, leading to erythrocyte dehydration and reduced deformability | ClinVar, OMIM |
| Epilepsy (candidate) | Altered KCC1 expression may disrupt neuronal chloride homeostasis, affecting GABAergic signaling | NCBI Gene, literature |
| Cancer (general) | KCC1 overexpression promotes cell volume regulation and migration in solid tumors | COSMIC, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 12.5 | High |
| Erythroid cells | 18.2 | High |
| Brain | 8.3 | Medium |
| Liver | 6.1 | Medium |
| Heart | 4.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.3 | High expression |
| K562 (erythroleukemia) | 22.1 | Very high expression |
| HepG2 | 7.8 | Moderate expression |
| SH-SY5Y | 5.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.625C>T (p.Arg209Trp) | Missense | 0.001% | Loss of function; associated with hereditary spherocytosis |
| c.1124G>A (p.Arg375Gln) | Missense | 0.0005% | Likely loss of function; reported in ClinVar |
| c.1681delC (p.Leu561Cysfs*12) | Frameshift | Rare | Loss of function; truncation |
Mutation functional classification
Loss of Function (LOF)
Missense and frameshift mutations reduce KCC1 transport activity, leading to erythrocyte dehydration and spherocytosis.
Gain of Function (GOF)
No gain-of-function mutations reported in SLC12A4.
Dominant Negative (DN)
No dominant-negative mutations described for SLC12A4.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Ion transport by P-type ATPases (Reactome: R-HSA-936837)
• Transport of inorganic cations/anions (Reactome: R-HSA-425393)
• SLC-mediated transmembrane transport (Reactome: R-HSA-425407)
Protein Summary
KCC1 is a 1085-amino acid integral membrane protein with 12 transmembrane domains. It functions as a K+/Cl- cotransporter, coupling the movement of potassium and chloride ions across the plasma membrane. The protein is glycosylated and phosphorylated, with activity regulated by cell volume and kinase signaling. KCC1 is widely expressed, with highest levels in erythrocytes and kidney, where it contributes to ion homeostasis and cell volume regulation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLC12A4 Knockout HEK293 Cell Line | EDJ-KQ5783 | Human | 6560 | Details Get a Quote |
| SLC12A4 Knockout A-549 Cell Line | EDJ-KQ29203 | Human | 6560 | Details Get a Quote |
| SLC12A4 Knockout HCT 116 Cell Line | EDJ-KQ29204 | Human | 6560 | Details Get a Quote |
| SLC12A4 Knockout HeLa Cell Line | EDJ-KQ18242 | Human | 6560 | Details Get a Quote |
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