KCNH5
Domain
Contains a voltage sensor domain (VSD) formed from the S1-S4 transmembrane helices, a pore domain formed from the S5-pore loop-S6 domain and the C-terminal cyclic nucleotide binding homology domain (CNBHD).
The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position.
Function
Pore-forming (alpha) subunit of a voltage-gated delayed rectifier potassium channel that mediates outward-rectifying potassium currents which, on depolarization, reaches a steady-state level and do not inactivate (PubMed:11943152, PubMed:12135768, PubMed:24133262, PubMed:36928654). The kinetic is characterized by a slow activation time course and a small voltage dependence of the activation time constants, therefore, starts to open at more negative voltages (PubMed:11943152, PubMed:12135768). The activation kinetics depend on the prepulse potential and external divalent cation concentration (PubMed:11943152, PubMed:24133262). The time course of activation is biphasic with a fast and a slowly activating current component (PubMed:11943152, PubMed:12135768, PubMed:36928654). With negative prepulses, the current activation is delayed and slowed down several fold, whereas more positive prepulses speed up activation, therefore the activation rate depends on holding potential (PubMed:11943152, PubMed:12135768, PubMed:36928654).
Involvement in disease
Developmental and epileptic encephalopathy 112
DEE112
A form of epileptic encephalopathy, a heterogeneous group of 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. DEE112 is an autosomal dominant form characterized by onset in infancy, and a wide range of seizure types including focal and generalized seizures. Cognitive outcomes range from normal intellect to profound intellectual development impairment.
None
The disease is caused by variants affecting the gene represented in this entry.
Sequence Similarities
Belongs to the potassium channel family. H (Eag) (TC 1.A.1.20) subfamily. Kv10.2/KCNH5 sub-subfamily.
Tissue Specificity
Detected in brain, skeletal muscle, heart, placenta, lung and liver, and at low levels in kidney.
Cellular localization
- Membrane
- Multi-pass membrane protein
Alternative names
EAG2, KCNH5, Voltage-gated delayed rectifier potassium channel KCNH5, Ether-a-go-go potassium channel 2, Potassium voltage-gated channel subfamily H member 5, Voltage-gated potassium channel subunit Kv10.2, hEAG2