CHRNA4: Cholinergic Receptor Nicotinic Alpha 4 Subunit
A key neuronal nicotinic acetylcholine receptor subunit implicated in epilepsy, addiction, and cognitive disorders.
Gene Information Card
| Symbol | CHRNA4 |
|---|---|
| Full Name | Cholinergic Receptor Nicotinic Alpha 4 Subunit |
| Gene Type | protein coding |
| Chromosomal Location | 20q13.33 |
| NCBI Gene ID | 1137 ncbi.nlm.nih.gov/gene/1137 |
| Ensembl ID | ENSG00000101204 |
| UniProt ID | P43681 |
| OMIM ID | 118504 |
| HGNC ID | 1958 |
| Aliases | BFNC, EBN, EBN1, NACRA4, NACHRA4, N-AChRA4 |
Description
CHRNA4 encodes the alpha-4 subunit of neuronal nicotinic acetylcholine receptors (nAChRs), which are pentameric ligand-gated ion channels. These receptors mediate fast synaptic transmission in the central nervous system and are involved in cognitive function, reward pathways, and seizure susceptibility. Mutations in CHRNA4 are a well-established cause of autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) | Gain-of-function or loss-of-function mutations in CHRNA4 alter nAChR channel properties, leading to hyperexcitability in frontal lobe circuits during sleep. | ClinVar, OMIM |
| Nicotine dependence | Variants in CHRNA4 influence receptor sensitivity to nicotine, affecting smoking behavior and addiction risk. | NCBI, ClinVar |
| Epilepsy, nocturnal frontal lobe, type 1 (EBN1) | Specific missense mutations (e.g., S248F, 776ins3) cause altered calcium permeability and receptor desensitization. | OMIM, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (frontal cortex) | 12.5 | Medium |
| Brain (cerebellum) | 8.3 | Low |
| Brain (hippocampus) | 10.1 | Medium |
| Brain (thalamus) | 9.7 | Medium |
| Adrenal gland | 4.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.3 | High expression; used for nAChR studies |
| SK-N-SH (neuroblastoma) | 11.8 | Moderate expression |
| HEK293 (embryonic kidney) | 0.5 | Low endogenous; common for recombinant expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| S248F | Missense | Rare | Gain-of-function; increased ACh sensitivity; ADNFLE |
| 776ins3 (L264_L265insL) | Insertion | Rare | Loss-of-function; altered channel gating; ADNFLE |
| T265I | Missense | Rare | Reduced calcium permeability; ADNFLE |
| R336C | Missense | Rare | Impaired receptor trafficking; ADNFLE |
Mutation functional classification
Loss of Function (LOF)
776ins3, R336C: reduce channel expression or function.
Gain of Function (GOF)
S248F: increases receptor sensitivity to acetylcholine.
Dominant Negative (DN)
Some ADNFLE mutations (e.g., T265I) may exert dominant-negative effects on wild-type subunits.
View complete mutation data：
Gene Ontology (GO)
| • acetylcholine-gated monoatomic cation channel activity | • ion channel activity |
| • extracellular ligand-gated monoatomic ion channel activity | • plasma membrane |
| • synapse | • neuronal cell body |
| • response to nicotine | • chemical synaptic transmission |
Pathways
• Nicotine addiction (KEGG: hsa05033)
• Neuroactive ligand-receptor interaction (KEGG: hsa04080)
• Cholinergic synapse (KEGG: hsa04725)
Protein Summary
The CHRNA4 protein (UniProt P43681) is 627 amino acids long and contains four transmembrane domains (M1-M4). It assembles with beta-2 subunits (CHRNB2) to form functional (alpha4)2(beta2)3 nAChRs. These receptors are highly expressed in the brain, particularly in the thalamus and cortex, and mediate fast excitatory neurotransmission. Post-translational modifications include glycosylation and phosphorylation, which modulate receptor trafficking and function.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CHRNA4 Knockout HEK293 Cell Line | EDJ-KQ4275 | Human | 1137 | Details Get a Quote |
| CHRNA4 Knockout HeLa Cell Line | EDJ-KQ52903 | Human | 1137 | Details Get a Quote |
| CHRNA4 Knockout A-549 Cell Line | EDJ-KQ61371 | Human | 1137 | Details Get a Quote |
| CHRNA4 Knockout HCT 116 Cell Line | EDJ-KQ69867 | Human | 1137 | Details Get a Quote |
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