HCN2: Hyperpolarization-Activated Cyclic Nucleotide-Gated Potassium Channel 2
Key regulator of cardiac pacemaker activity and neuronal excitability
Gene Information Card
| Symbol | HCN2 |
|---|---|
| Full Name | Hyperpolarization Activated Cyclic Nucleotide Gated Potassium And Sodium Channel 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 19p13.3 |
| NCBI Gene ID | 610 ncbi.nlm.nih.gov/gene/610 |
| Ensembl ID | ENSG00000105699 |
| UniProt ID | Q9UL51 |
| OMIM ID | 602761 |
| HGNC ID | 4846 |
| Aliases | HCN2, BCNG-2, HAC-1 |
Description
HCN2 encodes a member of the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel family. These channels are activated by membrane hyperpolarization and modulated by intracellular cyclic nucleotides. HCN2 contributes to the pacemaker current (Ih) in cardiac sinoatrial node cells and regulates neuronal excitability in the brain. The protein forms a tetrameric channel permeable to Na+ and K+ ions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Epilepsy, generalized, with febrile seizures plus, type 8 | Altered channel gating leading to neuronal hyperexcitability | ClinVar, OMIM |
| Cardiac arrhythmia, sinus node dysfunction | Reduced If current in sinoatrial node | ClinVar, OMIM |
| Autism spectrum disorder | Rare variants affecting neuronal Ih current | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 12.3 | Medium |
| Brain | 8.7 | Medium |
| Testis | 4.2 | Low |
| Kidney | 2.1 | Low |
| Liver | 0.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.0 | High expression in recombinant systems |
| SH-SY5Y | 6.5 | Neuronal model |
| HL-1 | 9.8 | Cardiac atrial myocyte line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1456C>T (p.Arg486Cys) | Missense | <0.01% | Reduced cAMP sensitivity |
| c.1738G>A (p.Gly580Ser) | Missense | <0.01% | Loss of function |
| c.2149G>A (p.Gly717Arg) | Missense | <0.01% | Gain of function |
Mutation functional classification
Loss of Function (LOF)
p.Gly580Ser reduces channel conductance and Ih current amplitude.
Gain of Function (GOF)
p.Gly717Arg increases channel open probability and shifts activation curve to more depolarized potentials.
Dominant Negative (DN)
p.Arg486Cys co-assembles with wild-type subunits and suppresses total current.
View complete mutation data：
Gene Ontology (GO)
| • voltage-gated ion channel activity (GO:0005244) | • protein binding (GO:0005515) |
| • voltage-gated potassium channel complex (GO:0008076) | • integral component of membrane (GO:0016021) |
| • cAMP binding (GO:0030552) | • potassium ion transmembrane transport (GO:0071805) |
Pathways
• cAMP signaling pathway (Reactome: R-HSA-163615)
• Cardiac conduction (Reactome: R-HSA-5576891)
• Ion channel transport (KEGG: hsa04010)
Protein Summary
HCN2 is a 889-amino acid transmembrane protein with six transmembrane segments (S1-S6), a pore-forming loop between S5 and S6, and a cyclic nucleotide-binding domain (CNBD) in the C-terminus. It forms homotetrameric or heterotetrameric channels that conduct the hyperpolarization-activated inward current (Ih). The channel is modulated by cAMP binding to the CNBD, which shifts activation to less negative potentials. HCN2 is critical for cardiac pacemaking and neuronal rhythmic activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HCN2 Knockout HEK293 Cell Line | EDJ-KQ50152 | Human | 610 | Details Get a Quote |
| HCN2 Knockout HeLa Cell Line | EDJ-KQ52713 | Human | 610 | Details Get a Quote |
| HCN2 Knockout A-549 Cell Line | EDJ-KQ61184 | Human | 610 | Details Get a Quote |
| HCN2 Knockout HCT 116 Cell Line | EDJ-KQ69675 | Human | 610 | Details Get a Quote |
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