HCN2

Chr 19AD

hyperpolarization activated cyclic nucleotide gated potassium and sodium channel 2

Also known as: BCNG-2, BCNG2, EIG17, FEB2, GEFSP11, HAC-1

NCBI Gene: 610 ENSG00000099822 UniProt: Q9UL51 OMIM: 602781

The protein is a hyperpolarization-activated cation channel that generates pacemaker currents in the heart and brain by conducting sodium and potassium ions. Mutations cause autosomal dominant epilepsy syndromes including generalized epilepsy with febrile seizures plus, familial febrile seizures, and idiopathic generalized epilepsy. Disease can result from multiple mechanisms depending on the specific variant, with some mutations potentially causing gain-of-function effects that alter normal channel properties.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

The protein encoded by this gene is a hyperpolarization-activated cation channel involved in the generation of native pacemaker activity in the heart and in the brain. The encoded protein is activated by cAMP and can produce a fast, large current. Defects in this gene were noted as a possible cause of some forms of epilepsy. [provided by RefSeq, Jan 2017]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

{Epilepsy, idiopathic generalized, susceptibility to, 17}MIM #602477

Febrile seizures, familial, 2MIM #602477

Generalized epilepsy with febrile seizures plus, type 11MIM #602477

Clinical highlights

Gene-disease validity (ClinGen)

complex neurodevelopmental disorder · ARDefinitivesufficient evidence for diagnostic panels3 gene-disease associations curated in total

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.45

LOEUF

Multiple*

Mechanism· predicted