SLC12A7: Solute Carrier Family 12 Member 7
Potassium-Chloride Cotransporter KCC4
Gene Information Card
| Symbol | SLC12A7 |
|---|---|
| Full Name | Solute Carrier Family 12 Member 7 |
| Gene Type | Protein-coding |
| Chromosomal Location | 5p15.33 |
| NCBI Gene ID | 10723 ncbi.nlm.nih.gov/gene/10723 |
| Ensembl ID | ENSG00000113594 |
| UniProt ID | Q9Y666 |
| OMIM ID | 604878 |
| HGNC ID | 10916 |
| Aliases | KCC4, hKCC4, FLJ40451 |
Description
SLC12A7 encodes the potassium-chloride cotransporter KCC4, a member of the SLC12 family of electroneutral cation-chloride cotransporters. KCC4 mediates coupled K+ and Cl- efflux across the plasma membrane, playing critical roles in cell volume regulation, ion homeostasis, and transepithelial ion transport. The gene is expressed in multiple tissues including kidney, brain, and erythrocytes.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Deafness, autosomal recessive 89 (DFNB89) | Loss-of-function mutations in SLC12A7 disrupt KCC4-mediated ion transport in inner ear hair cells, impairing auditory function. | OMIM #604878; ClinVar |
| Epileptic encephalopathy, early infantile, 83 | Missense variants in SLC12A7 alter neuronal chloride homeostasis, leading to hyperexcitability. | OMIM #618830; ClinVar |
| Renal tubular acidosis (possible) | KCC4 dysfunction in kidney intercalated cells may impair acid-base balance. | UniProt; literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 12.5 | Medium |
| Brain | 8.3 | Medium |
| Lung | 6.1 | Low |
| Heart | 4.7 | Low |
| Liver | 2.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.2 | High expression |
| SH-SY5Y | 9.8 | Medium expression |
| A549 | 5.4 | Low expression |
| HepG2 | 3.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.118C>T (p.Arg40*) | Nonsense | <0.01% | Loss of function; associated with DFNB89 |
| c.625G>A (p.Gly209Arg) | Missense | <0.01% | Loss of function; associated with epileptic encephalopathy |
| c.1045_1046del (p.Leu349Valfs*3) | Frameshift | <0.01% | Loss of function; likely pathogenic |
Mutation functional classification
Loss of Function (LOF)
Nonsense, frameshift, and missense variants (e.g., p.Arg40*, p.Leu349Valfs*3, p.Gly209Arg) impair KCC4 transport activity, leading to deafness or epilepsy.
Gain of Function (GOF)
No gain-of-function mutations reported in SLC12A7.
Dominant Negative (DN)
No dominant-negative mutations reported in SLC12A7.
View complete mutation data：
Gene Ontology (GO)
| • potassium:chloride symporter activity (GO:0015379) | • plasma membrane (GO:0005886) |
| • potassium ion transport (GO:0006813) | • chloride transport (GO:0006821) |
| • cell volume homeostasis (GO:0006884) |
Pathways
• Ion transport by P-type ATPases (Reactome: R-HSA-936837)
• SLC-mediated transmembrane transport (Reactome: R-HSA-425407)
Protein Summary
KCC4 (UniProt Q9Y666) is a 1083-amino acid multi-pass membrane protein with 12 transmembrane domains. It functions as a K+/Cl- cotransporter, mediating electroneutral efflux of potassium and chloride ions. KCC4 is activated by cell swelling and dephosphorylation, contributing to regulatory volume decrease. The protein is expressed in basolateral membranes of renal collecting duct intercalated cells and in cochlear hair cells, where it is essential for hearing and acid-base balance.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLC12A7 Knockout HEK293 Cell Line | EDJ-KQ7141 | Human | 10723 | Details Get a Quote |
| SLC12A7 Knockout A-549 Cell Line | EDJ-KQ32030 | Human | 10723 | Details Get a Quote |
| SLC12A7 Knockout HCT 116 Cell Line | EDJ-KQ32031 | Human | 10723 | Details Get a Quote |
| SLC12A7 Knockout HeLa Cell Line | EDJ-KQ32032 | Human | 10723 | Details Get a Quote |
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