HCN1: Hyperpolarization-Activated Cyclic Nucleotide-Gated Potassium Channel 1
Key regulator of neuronal pacemaker activity and cardiac rhythm
Gene Information Card
| Symbol | HCN1 |
|---|---|
| Full Name | Hyperpolarization Activated Cyclic Nucleotide Gated Potassium Channel 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 5p12 |
| NCBI Gene ID | 348980 ncbi.nlm.nih.gov/gene/348980 |
| Ensembl ID | ENSG00000164588 |
| UniProt ID | O60741 |
| OMIM ID | 602780 |
| HGNC ID | 4845 |
| Aliases | BCNG-1, HAC-1 |
Description
HCN1 encodes a member of the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel family. These channels are activated by membrane hyperpolarization and modulated by cyclic nucleotides. HCN1 contributes to the Ih current (funny current) in cardiac pacemaker cells and regulates neuronal excitability and rhythmic activity in the brain. It is highly expressed in the sinoatrial node, hippocampus, and cortex.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Epileptic encephalopathy, early infantile, 24 | Loss-of-function mutations in HCN1 reduce Ih current, leading to neuronal hyperexcitability and seizures. | ClinVar, OMIM |
| Generalized epilepsy with febrile seizures plus, type 10 | Missense variants alter channel gating, impairing neuronal pacemaking and increasing seizure susceptibility. | ClinVar, OMIM |
| Cardiac arrhythmia, sinus node dysfunction | Reduced HCN1 expression or function disrupts sinoatrial node automaticity, causing bradycardia. | NCBI Gene, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | High |
| Heart | 8.3 | Medium |
| Retina | 6.1 | Medium |
| Testis | 2.4 | Low |
| Liver | 0.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.2 | Neuronal model |
| HEK293 (embryonic kidney) | 0.8 | Low endogenous expression |
| iPSC-derived cardiomyocytes | 9.7 | Cardiac model |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1186C>T (p.Arg396Cys) | Missense | Rare | Reduced channel conductance; associated with epileptic encephalopathy |
| c.1730G>A (p.Arg577His) | Missense | Rare | Altered voltage dependence; linked to generalized epilepsy |
| c.229delG (p.Val77fs) | Frameshift | Very rare | Loss of function; truncation of protein |
Mutation functional classification
Loss of Function (LOF)
Reduced or absent Ih current due to impaired channel opening or trafficking; associated with epileptic encephalopathy.
Gain of Function (GOF)
Enhanced channel activity or altered voltage dependence; reported in some epilepsy syndromes.
Dominant Negative (DN)
Mutant subunits co-assemble with wild-type, suppressing overall channel function; observed in certain missense variants.
View complete mutation data：
Gene Ontology (GO)
| • voltage-gated ion channel activity (GO:0005244) | • protein binding (GO:0005515) |
| • plasma membrane (GO:0005886) | • integral component of membrane (GO:0016021) |
| • cAMP binding (GO:0030552) | • potassium ion transmembrane transport (GO:0071805) |
Pathways
• cAMP signaling pathway (Reactome: R-HSA-382556)
• Cardiac conduction (Reactome: R-HSA-5576891)
• Neuronal system (Reactome: R-HSA-112316)
Protein Summary
HCN1 is a 6-transmembrane domain protein that forms homotetrameric or heterotetrameric channels permeable to K+ and Na+. It is activated by hyperpolarization and modulated by intracellular cAMP binding to its cyclic nucleotide-binding domain. The channel mediates the Ih current, critical for pacemaker activity in cardiac sinoatrial node cells and for regulating neuronal firing patterns. Mutations in HCN1 disrupt channel function, leading to neurological and cardiac disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HCN1 Knockout HEK293 Cell Line | EDJ-KQ2829 | Human | 348980 | Details Get a Quote |
| HCN1 Knockout HeLa Cell Line | EDJ-KQ59841 | Human | 348980 | Details Get a Quote |
| HCN1 Knockout A-549 Cell Line | EDJ-KQ68307 | Human | 348980 | Details Get a Quote |
| HCN1 Knockout HCT 116 Cell Line | EDJ-KQ76681 | Human | 348980 | Details Get a Quote |
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