HCN3: Hyperpolarization-Activated Cyclic Nucleotide-Gated Potassium Channel 3
Key regulator of cardiac pacemaker activity and neuronal excitability
Gene Information Card
| Symbol | HCN3 |
|---|---|
| Full Name | Hyperpolarization Activated Cyclic Nucleotide Gated Potassium Channel 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 1q22 |
| NCBI Gene ID | 57657 ncbi.nlm.nih.gov/gene/57657 |
| Ensembl ID | ENSG00000143630 |
| UniProt ID | Q9P1Z3 |
| OMIM ID | 609773 |
| HGNC ID | 19170 |
| Aliases | HAC3, KIAA1538 |
Description
HCN3 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. HCN3 contributes to the pacemaker current (Ih) in cardiac and neuronal tissues, regulating rhythmic activity and excitability.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Sinus node dysfunction | Altered HCN3 channel function may disrupt cardiac pacemaker activity | ClinVar |
| Epilepsy | HCN3 variants implicated in neuronal hyperexcitability | ClinVar |
| Cardiac arrhythmia | Dysregulation of Ih current due to HCN3 mutations | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 12.5 | Medium |
| Brain | 8.3 | Medium |
| Kidney | 6.1 | Low |
| Liver | 2.4 | Low |
| Lung | 4.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | High expression in recombinant systems |
| SH-SY5Y | 7.8 | Neuronal model |
| H9c2 | 9.1 | Cardiomyoblast line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234G>A | Missense | 0.01% | Reduced channel conductance |
| c.567C>T | Nonsense | 0.005% | Premature truncation, loss of function |
| c.890A>G | Missense | 0.02% | Altered cyclic nucleotide sensitivity |
Mutation functional classification
Loss of Function (LOF)
c.567C>T nonsense variant leads to truncated non-functional protein
Gain of Function (GOF)
Not reported in HCN3
Dominant Negative (DN)
c.1234G>A missense may exert dominant-negative effect on wild-type channels
View complete mutation data：
Gene Ontology (GO)
| • GO:0005244 (GO:0005244) | • GO:0005515 (GO:0005515) |
| • GO:0005886 (GO:0005886) | • GO:0016021 (GO:0016021) |
| • GO:0071805 (GO:0071805) |
Pathways
• Cardiac pacemaker pathway (KEGG: hsa04260)
• cAMP signaling pathway (KEGG: hsa04024)
Protein Summary
HCN3 is a 779-amino acid transmembrane protein that forms tetrameric channels selective for K+ and Na+. It contains a cyclic nucleotide-binding domain (CNBD) in the C-terminus and six transmembrane segments (S1-S6). The channel opens upon hyperpolarization and is modulated by cAMP, contributing to the pacemaker current Ih in cardiac and neuronal cells.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HCN3 Knockout HEK293 Cell Line | EDJ-KQ13728 | Human | 57657 | Details Get a Quote |
| HCN3 Knockout A-549 Cell Line | EDJ-KQ43483 | Human | 57657 | Details Get a Quote |
| HCN3 Knockout HCT 116 Cell Line | EDJ-KQ43484 | Human | 57657 | Details Get a Quote |
| HCN3 Knockout HeLa Cell Line | EDJ-KQ43485 | Human | 57657 | Details Get a Quote |
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