Protein / target
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4
Protein at a glance
Biological role
CAMP-activated cation channel
Strongest disease association
Atrial Fibrillation
Therapeutic position
Established drug target
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function overview
Hyperpolarization-activated ion channel that are permeable to Na(+) and K(+) ions with very slow activation and inactivation.
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Hyperpolarization-activated ion channel that are permeable to Na(+) and K(+) ions with very slow activation and inactivation (PubMed:10228147, PubMed:10430953, PubMed:20829353). Exhibits higher selectivity for K(+) over Na(+) ions (PubMed:10228147). Contributes to the native pacemaker currents in heart (If) that regulate the rhythm of heart beat (Probable) (PubMed:10228147, PubMed:16407510, PubMed:19165230). Contributes to the native pacemaker currents in neurons (Ih) (Probable). May mediate responses to sour stimuli (By similarity)
Subcellular location
Domains and Gene Ontology detail (30)Hide
Gene Ontology
- Caxon
- Cdendrite
- CHCN channel complex
- Cperinuclear region of cytoplasm
- Cplasma membrane
- FcAMP binding
- Fintracellularly cAMP-activated cation channel activity
- Fvoltage-gated potassium channel activity
- Fvoltage-gated potassium channel activity involved in SA node cell action potential depolarization
- Fvoltage-gated sodium channel activity
- Pblood circulation
- Pcellular response to cAMP
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
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Ion channel gating
- ·intracellularly cAMP-activated cation channel activity
- ·potassium ion transmembrane transport
- ·sodium ion transmembrane transport
Muscle contraction
- ·muscle contraction
- ·regulation of cardiac muscle contraction
Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.
Approved medicines with mapped indications
Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.
Broader indication categories (1)Hide
Broad umbrella indications (e.g. “Neoplasms”). Shown here because every medicine also appears under a more specific disease above — kept for completeness, de-emphasised for clarity.
4 medicines meet Open Targets' target-level approved-medicine definition; the 1 shown here are those on this page with a canonical approved disease indication in the graph. Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.
Drugs targeting this protein
How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4 blocker
Indicated for Heart Failure, Cardiovascular Diseases
ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.
Translational evidence
Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.
Strongest disease associations · via encoding gene HCN4
Gene-level evidence surfaced through the gene HCN4 that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.
View evidence synthesis (5)Hide
The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.
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Drug development
4 compounds recorded · 4 approved
View all recorded compounds (4)Hide
Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.
Tractability
Small molecules — Strong
Antibodies — Emerging
Protein degraders — Emerging
View underlying tractability evidence (10)Hide
Raw Open Targets tractability assessment buckets, by modality.
Clinical trials
Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.
View all trials (26)Hide
ClinicalTrials.gov via the drug-target graph.
What's happening now
Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for a drug that targets this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.
- Product recall
Recall (Class II): IVABRADINE
- Product recall
Recall (Class II): IVABRADINE
- Regulatory approval
Approval: Ivabradine Anpharm (EMA)
- Safety communication
Drug Safety Update: Ivabradine: carefully monitor for bradycardia
- New publicationIvabradine in stable coronary artery disease without clinical heart failure.
- New publicationRationale, design, and baseline characteristics of the Study assessInG the morbidity-mortality beNefits of the If inhibitor ivabradine in patients with coronarY artery disease (SIGNIFY trial): a randomized, double-blind, placebo-controlled trial of ivabradine in patients with stable coronary artery disease without clinical heart failure.
- New publicationHeart rate as a risk factor in chronic heart failure (SHIFT): the association between heart rate and outcomes in a randomised placebo-controlled trial.
- New publicationIvabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study.
- New publicationIvabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomised, double-blind, placebo-controlled trial.
Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.