Figure 1.

Schematic presentation of the HCN1 channel with 6 transmembrane domains (S1–S6), the locations of the pathogenic variants related to epilepsy and the altered protein functions. Most of mutations are located in S6, the intracellular linker between S6 and CNBD as well as in N-terminal. Notably, variants related to both epilepsy and SUDEP (p.G391D, p.G46V, and 187-195del) are located both in the N- and C-terminals and there is a hotspot in residue G391. Variants in blue correspond to gain-of-function (GOF) effects, variants in red correspond to loss-of-function (LOF) effects, and variants in black stand for the variants with unknown or clear effects.