SLC12A1: Solute Carrier Family 12 Member 1
Key regulator of renal ion transport and blood pressure homeostasis
Gene Information Card
| Symbol | SLC12A1 |
|---|---|
| Full Name | Solute Carrier Family 12 Member 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 15q21.1 |
| NCBI Gene ID | 6557 ncbi.nlm.nih.gov/gene/6557 |
| Ensembl ID | ENSG00000074803 |
| UniProt ID | Q13621 |
| OMIM ID | 600839 |
| HGNC ID | 10910 |
| Aliases | NKCC2, BSC1, FLJ61975 |
Description
SLC12A1 encodes the Na-K-2Cl cotransporter NKCC2, a membrane protein primarily expressed in the kidney. It mediates electroneutral transport of sodium, potassium, and chloride ions across the apical membrane of thick ascending limb cells, playing a critical role in urine concentration and blood pressure regulation. Mutations in this gene cause Bartter syndrome type 1, a renal tubular disorder characterized by salt wasting, hypokalemic alkalosis, and hypercalciuria.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Bartter syndrome type 1 | Loss-of-function mutations impair NKCC2-mediated ion reabsorption in the thick ascending limb, leading to salt wasting and electrolyte imbalance. | OMIM #601678; ClinVar pathogenic variants |
| Hypokalemic alkalosis with hypercalciuria | Defective NaCl transport reduces medullary osmotic gradient, causing polyuria and electrolyte disturbances. | NCBI GeneReviews |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 45.2 | High |
| Testis | 1.3 | Low |
| Adrenal gland | 0.8 | Low |
| Liver | 0.2 | Not detected |
| Heart | 0.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 0.0 | No endogenous expression |
| HK-2 (kidney proximal tubule) | 0.0 | No endogenous expression |
| Primary thick ascending limb cells | 120.0 | High expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.119C>T (p.Pro40Leu) | Missense | <0.01% | Loss of function; associated with Bartter syndrome type 1 |
| c.1456G>A (p.Gly486Arg) | Missense | <0.01% | Loss of function; impaired ion transport |
| c.2221C>T (p.Arg741*) | Nonsense | <0.01% | Loss of function; truncated protein |
Mutation functional classification
Loss of Function (LOF)
Most SLC12A1 mutations cause loss of function, reducing or abolishing NKCC2 cotransport activity, leading to Bartter syndrome type 1.
Gain of Function (GOF)
No gain-of-function mutations reported in SLC12A1.
Dominant Negative (DN)
No dominant-negative mutations reported; inheritance is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • GO:0008511 – sodium:potassium:chloride symporter activity | • GO:0015379 – potassium:chloride symporter activity |
| • GO:0015293 – symporter activity | • GO:0005886 – plasma membrane |
| • GO:0016324 – apical plasma membrane | • GO:0070588 – calcium ion transmembrane transport |
| • GO:0002024 – diet induced thermogenesis | • GO:0003091 – renal water homeostasis |
Pathways
• Electrolyte and water transport (Reactome: R-HSA-425366)
• Ion transport by P-type ATPases (Reactome: R-HSA-936837)
• Transport of inorganic cations/anions (Reactome: R-HSA-425393)
Protein Summary
The SLC12A1 protein (NKCC2) is a 1099-amino acid transmembrane cotransporter with 12 transmembrane domains. It functions as a homodimer and is essential for NaCl reabsorption in the kidney's thick ascending limb. The protein is activated by phosphorylation via WNK kinases and is the target of loop diuretics such as furosemide. Defects cause Bartter syndrome type 1.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLC12A1 Knockout HEK293 Cell Line | EDJ-KQ5795 | Human | 6557 | Details Get a Quote |
| SLC12A1 Knockout HeLa Cell Line | EDC90152 | Human | 6557 | Details Get a Quote |
| SLC12A1 Knockout A-549 Cell Line | EDJ-KQ62991 | Human | 6557 | Details Get a Quote |
| SLC12A1 Knockout HCT 116 Cell Line | EDJ-KQ71462 | Human | 6557 | Details Get a Quote |
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