HCN2
Domain
The segment S4 is the voltage-sensor and is characterized by a series of positively charged amino acids at every third position. The ion-conducting pore region is between segment S5 and S6.
The cytosolic C-terminal domain contains the cyclic nucleotide-binding domain (CNBD), which mediates modulation by cyclic nucleotides.
Function
Hyperpolarization-activated ion channel that is permeable to sodium and potassium ions. Displays lower selectivity for K(+) over Na(+) ions (PubMed:10228147, PubMed:22006928). Contributes to the native pacemaker currents in heart (If) and in neurons (Ih) (PubMed:10228147, PubMed:10524219). Can also transport ammonium in the distal nephron (By similarity). Involved in the initiation of neuropathic pain in sensory neurons (By similarity).
Involvement in disease
Epilepsy, idiopathic generalized 17
EIG17
A 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. Both autosomal dominant and autosomal recessive EIG17 inheritance have been reported.
None
Disease susceptibility is associated with variants affecting the gene represented in this entry.
Febrile seizures, familial, 2
FEB2
Seizures associated with febrile episodes in childhood without any evidence of intracranial infection or defined pathologic or traumatic cause. It is a common condition, affecting 2-5% of children aged 3 months to 5 years. The majority are simple febrile seizures (generally defined as generalized onset, single seizures with a duration of less than 30 minutes). Complex febrile seizures are characterized by focal onset, duration greater than 30 minutes, and/or more than one seizure in a 24 hour period. The likelihood of developing epilepsy following simple febrile seizures is low. Complex febrile seizures are associated with a moderately increased incidence of epilepsy. FEB2 transmission pattern is consistent with autosomal dominant inheritance.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Phosphorylation at Ser-668 by PRKG2 shifts the voltage-dependence to more negative voltages, hence counteracting the stimulatory effect of cGMP on gating.
S-palmitoylated.
N-glycosylated; required for cell surface trafficking of HCN2.
Sequence Similarities
Belongs to the potassium channel HCN family.
Tissue Specificity
Highly expressed throughout the brain. Detected at low levels in heart.
Cellular localization
- Cell membrane
- Multi-pass membrane protein
Alternative names
BCNG2, HCN2, Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2, Brain cyclic nucleotide-gated channel 2, BCNG-2