Protein / target
Neuronal acetylcholine receptor subunit alpha-4
Protein at a glance
Biological role
Acetylcholine-gated monoatomic cation-selective channel
Primary biology
Neuronal / synaptic signalling
Strongest disease association
Autosomal dominant nocturnal frontal lobe epilepsy
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
Component of neuronal acetylcholine receptors (nAChRs) that function as pentameric, ligand-gated cation channels with high calcium permeability among other activities.
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Component of neuronal acetylcholine receptors (nAChRs) that function as pentameric, ligand-gated cation channels with high calcium permeability among other activities. nAChRs are excitatory neurotrasnmitter receptors formed by a collection of nAChR subunits known to mediate synaptic transmission in the nervous system and the neuromuscular junction. Each nAchR subunit confers differential attributes to channel properties, including activation, deactivation and desensitization kinetics, pH sensitivity, cation permeability, and binding to allosteric modulators (PubMed:22361591, PubMed:27698419, PubMed:29720657, PubMed:38454578). CHRNA4 forms heteropentameric neuronal acetylcholine receptors with CHRNB2 and CHRNB4, as well as CHRNA5 and CHRNB3 as accesory subunits. Is the most abundant nAChR subtype expressed in the central nervous system (PubMed:16835356, PubMed:22361591, PubMed:27698419, PubMed:29720657, PubMed:38454578). Found in two major stoichiometric forms,(CHRNA4)3:(CHRNB2)2 and (CHRNA4)2:(CHRNB2)3, the two stoichiometric forms differ in their unitary conductance, calcium permeability, ACh sensitivity and potentiation by divalent cation (PubMed:27698419, PubMed:29720657, PubMed:38454578). Involved in the modulation of calcium-dependent signaling pathways, influences the release of neurotransmitters, including dopamine, glutamate and GABA (By similarity)
Subcellular location
Domains and Gene Ontology detail (40)Hide
Gene Ontology
- Cacetylcholine-gated channel complex
- Ccation channel complex
- Cdendrite
- Cexternal side of plasma membrane
- Cmembrane
- Cneuron projection
- Cneuronal cell body
- Cneurotransmitter receptor complex
- Cplasma membrane
- Cpostsynaptic membrane
- Cpresynaptic membrane
- Csynapse
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
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Ligand-gated signalling
- ·Component of neuronal acetylcholine receptors (nAChRs) that function as pentameric, liga…
- ·ligand-gated monoatomic ion channel activity
Ion channel gating
- ·acetylcholine-gated channel complex
- ·ligand-gated monoatomic ion channel activity
- ·monoatomic ion transmembrane transport
Inhibitory neurotransmission
- ·inhibitory postsynaptic potential
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Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.
Interaction neighbourhood
Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.
Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.
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.
3 medicines meet Open Targets' target-level approved-medicine definition; the 2 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.
Neuronal acetylcholine receptor; alpha4/beta2 agonist
Indicated for Tobacco Use Disorder
Neuronal acetylcholine receptor; alpha4/beta2 antagonist
Neuronal acetylcholine receptor; alpha4/beta2 partial agonist
Indicated for Eye Diseases, Tobacco Use Disorder
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 CHRNA4
Gene-level evidence surfaced through the gene CHRNA4that 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.
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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
16 compounds recorded · 3 approved · 12 in clinical development · 1 earlier-stage
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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 (8)Hide
Raw Open Targets tractability assessment buckets, by modality.
Safety-related annotations
Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.
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.
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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 3 drugs that target 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.
- New publicationElectronic cigarettes and cardiovascular disease: epidemiological and biological links.
- New publicationA Pilot Randomized Trial of Transdermal Nicotine for Pulmonary Sarcoidosis.
- New publicationEffects of varenicline versus transdermal nicotine replacement therapy on cigarette demand on quit day in individuals with substance use disorders.
- New publicationEffects of Nicotine Patch vs Varenicline vs Combination Nicotine Replacement Therapy on Smoking Cessation at 26 Weeks: A Randomized Clinical Trial.
- New publicationCombination varenicline and bupropion SR for tobacco-dependence treatment in cigarette smokers: a randomized trial.
- New publicationNicotine replacement therapy for smoking cessation.
- New publicationEffects of 21 days of varenicline versus placebo on smoking behaviors and urges among non-treatment seeking smokers.
- New publicationA pilot study of the efficacy of varenicline for the treatment of smokeless tobacco users in Midwestern United States.
- New publicationEffects of the alpha4beta2 partial agonist varenicline on brain activity and working memory in abstinent smokers.
- New publicationPicomolar amyloid-beta positively modulates synaptic plasticity and memory in hippocampus.
- Regulatory approval
Approval: Champix (EMA)
- New publicationThe brain metabolite kynurenic acid inhibits alpha7 nicotinic receptor activity and increases non-alpha7 nicotinic receptor expression: physiopathological implications.
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.