SLC12A5
Function
Mediates electroneutral potassium-chloride cotransport in mature neurons and is required for neuronal Cl(-) homeostasis (PubMed:12106695). As major extruder of intracellular chloride, it establishes the low neuronal Cl(-) levels required for chloride influx after binding of GABA-A and glycine to their receptors, with subsequent hyperpolarization and neuronal inhibition (By similarity). Involved in the regulation of dendritic spine formation and maturation (PubMed:24668262).
Involvement in disease
Developmental and epileptic encephalopathy 34
DEE34
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE34 is characterized by onset of refractory migrating focal seizures in infancy. Affected children show developmental regression and are severely impaired globally.
None
The disease is caused by variants affecting the gene represented in this entry.
Epilepsy, idiopathic generalized 14
EIG14
An autosomal dominant form of idiopathic generalized epilepsy, a disorder characterized by recurring generalized seizures in the absence of detectable brain lesions and/or metabolic abnormalities. Generalized seizures arise diffusely and simultaneously from both hemispheres of the brain. Seizure types include juvenile myoclonic seizures, absence seizures, and generalized tonic-clonic seizures.
None
Disease susceptibility is associated with variants affecting the gene represented in this entry.
Post-translational modifications
Phosphorylated at Thr-929 and Thr-1030 by OXSR1/OSR1 and STK39/SPAK downstream of WNK kinases (WNK1, WNK2, WNK3 or WNK4), inhibiting the potassium-chloride cotransport activity.
Sequence Similarities
Belongs to the SLC12A transporter family. K/Cl co-transporter subfamily.
Tissue Specificity
Brain specific. Detected in neuronal cells.
Cellular localization
- Cell membrane
- Multi-pass membrane protein
- Cell projection
- Dendrite
- Detected on dendrites, but not on axons of spinal cord neurons and at GPHN-positive inhibitory synapses.
Alternative names
KCC2, KIAA1176, SLC12A5, Solute carrier family 12 member 5, Electroneutral potassium-chloride cotransporter 2, K-Cl cotransporter 2, Neuronal K-Cl cotransporter, hKCC2