HCN4 encodes hyperpolarization activated cyclic nucleotide gated potassium channel 4 (1,203 aa). Hyperpolarization-activated ion channel that are permeable to Na(+) and K(+) ions with very slow activation and inactivation. Exhibits higher selectivity for K(+) over Na(+) ions. Highest expression in Testis (19.6 TPM) and Heart Atrial Appendage (8.0 TPM).

Sick sinus syndrome 2, autosomal dominant is caused by mutations in the HCN4 gene on chromosome 15.

The HCN4 protein participates in HCN channel Homomer of subunit HCN4 and HCNs:cAMP bind SNIs pathways.

HCN4 is classified as a druggable target (Druggable Genome, Ion Channel, and Transporter categories) with score 17.4.

Genetic testing for HCN4 is available. Testing is considered confirmatory for diagnosis.

Phenotype severity distribution: 11 always present features, 1 very common feature, 2 common features.

No clinical trials have been registered for sick sinus syndrome 2, autosomal dominant.

12 publications have been identified in PubMed for sick sinus syndrome 2, autosomal dominant. Research spans Case Report / Case Series (58%), Basic Science / Preclinical (25%), and Review / Meta-Analysis (8%).

Recent Publications

• Hirota Y (2025). [PMID: 41260694](https://pubmed.ncbi.nlm.nih.gov/41260694/). *Circulation journal : official journal of the Japanese Circulation Society*. [Case Report / Case Series]

• Zhang F (2025). [PMID: 40613349](https://pubmed.ncbi.nlm.nih.gov/40613349/). *Channels (Austin, Tex.)*. [Case Report / Case Series]

• Nomura Y (2025). [PMID: 40697198](https://pubmed.ncbi.nlm.nih.gov/40697198/). *Journal of cardiology cases*. [Case Report / Case Series]

• He L (2025). [PMID: 41004863](https://pubmed.ncbi.nlm.nih.gov/41004863/). *Journal of pharmacological and toxicological methods*. [Gene Therapy / Novel Therapeutics]

• Hamidi J (2025). [PMID: 40414080](https://pubmed.ncbi.nlm.nih.gov/40414080/). *Stem cell research*. [Case Report / Case Series]

• Yang B (2025). [PMID: 40609213](https://pubmed.ncbi.nlm.nih.gov/40609213/). *Journal of molecular and cellular cardiology*. [Case Report / Case Series]

• Gao J (2025). [PMID: 39838659](https://pubmed.ncbi.nlm.nih.gov/39838659/). *Current cardiology reviews*. [Review / Meta-Analysis]

• Hou P (2024). [PMID: 39723092](https://pubmed.ncbi.nlm.nih.gov/39723092/). *Food science & nutrition*. [Basic Science / Preclinical]

• Yonehara K (2024). [PMID: 39698436](https://pubmed.ncbi.nlm.nih.gov/39698436/). *Annals of pediatric cardiology*. [Case Report / Case Series]

• Kahnert K (2024). [PMID: 38661182](https://pubmed.ncbi.nlm.nih.gov/38661182/). *Cardiovascular research*. [Basic Science / Preclinical]