HCN4 encodes a member of the hyperpolarization-activated cyclic nucleotide-gated potassium channels. The protein shows slow kinetics of activation and inactivation, and is necessary for the cardiac pacemaking process. This channel may also mediate responses to sour stimuli. Mutations in this gene have been linked to sick sinus syndrome 2, also known as atrial fibrillation with bradyarrhythmia or familial sinus bradycardia. Two pseudogenes have been identified on chromosome 15. The HCN4 cDNA predicts a protein of 1,203 amino acids. HCN4 contains 6 putative transmembrane segments, a pore region, and a cyclic nucleotide-binding domain (CNBD). Northern blot and PCR analyses showed that HCN4 is expressed at heart ventricle and atrium.