SLC12A2: Solute Carrier Family 12 Member 2
Na-K-Cl Cotransporter 1 (NKCC1) – Key regulator of ion homeostasis and cell volume
Gene Information Card
| Symbol | SLC12A2 |
|---|---|
| Full Name | Solute carrier family 12 member 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 5q23.3 |
| NCBI Gene ID | 6558 ncbi.nlm.nih.gov/gene/6558 |
| Ensembl ID | ENSG00000064651 |
| UniProt ID | P55011 |
| OMIM ID | 600840 |
| HGNC ID | 10911 |
| Aliases | NKCC1, BSC2, PPP1R143 |
Description
SLC12A2 encodes the Na-K-Cl cotransporter 1 (NKCC1), a membrane protein that mediates electroneutral transport of sodium, potassium, and chloride ions across the plasma membrane. It is widely expressed and plays critical roles in cell volume regulation, ion homeostasis, and neuronal chloride gradient maintenance. Mutations in SLC12A2 are associated with neurodevelopmental disorders and hearing loss.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Deafness, autosomal dominant 79 (DFNA79) | Missense mutations impair NKCC1 function in inner ear epithelial cells, disrupting endolymph ion homeostasis | ClinVar, OMIM |
| Neurodevelopmental disorder with hypotonia and variable brain anomalies | Loss-of-function variants reduce NKCC1 activity, altering neuronal chloride transport and brain development | ClinVar, OMIM |
| Seizures, early-onset, with or without developmental delay | Gain-of-function or dominant-negative mutations affect NKCC1-mediated ion balance, increasing neuronal excitability | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 12.3 | Medium |
| Brain (cerebellum) | 8.7 | Medium |
| Lung | 6.5 | Low |
| Heart | 4.2 | Low |
| Liver | 1.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.2 | High expression |
| SH-SY5Y | 9.8 | Moderate expression |
| A549 | 7.3 | Low expression |
| HepG2 | 2.1 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1012C>T (p.Arg338Trp) | Missense | <0.01% | Impaired ion transport; associated with DFNA79 |
| c.1670G>A (p.Arg557His) | Missense | <0.01% | Reduced cotransport activity; neurodevelopmental phenotype |
| c.2443C>T (p.Arg815*) | Nonsense | <0.01% | Loss of function; severe developmental delay |
Mutation functional classification
Loss of Function (LOF)
Nonsense and missense variants (e.g., p.Arg815*) that reduce or abolish NKCC1 ion transport activity, leading to hearing loss and neurodevelopmental disorders.
Gain of Function (GOF)
Rare missense changes (e.g., p.Arg557His) that increase NKCC1 activity, associated with early-onset seizures.
Dominant Negative (DN)
Some missense mutations (e.g., p.Arg338Trp) may interfere with wild-type NKCC1 function in a dominant manner, contributing to autosomal dominant deafness.
View complete mutation data：
Gene Ontology (GO)
| • GO:0008511 – sodium:potassium:chloride symporter activity | • GO:0005886 – plasma membrane |
| • GO:0006813 – potassium ion transport | • GO:0006814 – sodium ion transport |
| • GO:0006821 – chloride transport | • GO:0006884 – cell volume homeostasis |
Pathways
• Ion transport by P-type ATPases (Reactome: R-HSA-936837)
• Transport of inorganic cations/anions (Reactome: R-HSA-425393)
• Chloride transport (Reactome: R-HSA-425407)
Protein Summary
NKCC1 (UniProt P55011) is a 1212-amino acid integral membrane protein with 12 transmembrane domains. It mediates electroneutral Na+-K+-2Cl- cotransport, critical for cell volume regulation, epithelial ion secretion, and neuronal chloride homeostasis. The protein is phosphorylated and regulated by WNK kinases and SPAK/OSR1. Defects cause hearing loss and neurodevelopmental disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLC12A2 Knockout HEK293 Cell Line | EDC90549 | Human | 6558 | Details Get a Quote |
| SLC12A2 Knockout A-549 Cell Line | EDJ-KQ29200 | Human | 6558 | Details Get a Quote |
| SLC12A2 Knockout HCT 116 Cell Line | EDJ-KQ29201 | Human | 6558 | Details Get a Quote |
| SLC12A2 Knockout HeLa Cell Line | EDJ-KQ29202 | Human | 6558 | Details Get a Quote |
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