CHRNA4 Gene

HGNC Family	Cholinergic receptors, Ion channels
Name	cholinergic receptor, nicotinic, alpha 4 (neuronal)
Description	This gene encodes a nicotinic acetylcholine receptor, which belongs to a superfamily of ligand-gated ion channels that play a role in fast signal transmission at synapses. These pentameric receptors can bind acetylcholine, which causes an extensive change in conformation that leads to the opening of an ion-conducting channel across the plasma membrane. This protein is an integral membrane receptor subunit that can interact with either nAChR beta-2 or nAChR beta-4 to form a functional receptor. Mutations in this gene cause nocturnal frontal lobe epilepsy type 1. Polymorphisms in this gene that provide protection against nicotine addiction have been described. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2012]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The gene "}, {"type": "b", "children": [{"type": "t", "text": "CHRNA4"}]}, {"type": "t", "text": " encodes the α4 subunit of the neuronal nicotinic acetylcholine receptor, a key component of the predominant heteromeric α4β2 receptor in the brain that mediates fast synaptic transmission. Structural investigations have revealed that the assembly, ligand recognition, ion permeation, and desensitization properties of these receptors are tightly regulated by the α4 subunit (see, for example."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In parallel, genetic association studies across diverse populations have implicated common and rare CHRNA4 variants in several neuropsychiatric and neurological phenotypes. In the realm of nicotine dependence, multiple studies have demonstrated that specific single‐nucleotide polymorphisms (SNPs) and haplotypes in CHRNA4 are significantly associated with smoking behaviors – including measures of heaviness, initiation, cessation, and subjective responses to nicotine – thereby influencing vulnerability to addiction."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "2", "end_ref": "6"}]}, {"type": "t", "text": " Beyond addiction, CHRNA4 has also been evaluated as a candidate gene in attention‐deficit/hyperactivity disorder"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "and has been shown to interact with other factors (for example, APOE genotype) to modulate attentional processing."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " In addition, rare mutations in CHRNA4, such as the S284L substitution, have been identified as the cause of autosomal dominant nocturnal frontal lobe epilepsy"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": ", further attesting to its crucial role in maintaining normal neuronal excitability. Collectively, these findings underscore the multifunctional role of CHRNA4 in regulating cholinergic neurotransmission, shaping responses to nicotine, influencing cognitive functions, and contributing to seizure susceptibility.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Claudio L Morales-Perez, Colleen M Noviello, Ryan E Hibbs "}, {"type": "b", "children": [{"type": "t", "text": "X-ray structure of the human α4β2 nicotinic receptor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature19785"}], "href": "https://doi.org/10.1038/nature19785"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27698419"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27698419"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Ming D Li, Joke Beuten, Jennie Z Ma, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ethnic- and gender-specific association of the nicotinic acetylcholine receptor alpha4 subunit gene (CHRNA4) with nicotine dependence."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddi132"}], "href": "https://doi.org/10.1093/hmg/ddi132"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15790597"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15790597"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yan Feng, Tianhua Niu, Houxun Xing, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A common haplotype of the nicotine acetylcholine receptor alpha 4 subunit gene is associated with vulnerability to nicotine addiction in men."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1086/422194"}], "href": "https://doi.org/10.1086/422194"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15154117"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15154117"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "D B Hancock, G W Reginsson, N C Gaddis, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-wide meta-analysis reveals common splice site acceptor variant in CHRNA4 associated with nicotine dependence."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Transl Psychiatry (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/tp.2015.149"}], "href": "https://doi.org/10.1038/tp.2015.149"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26440539"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26440539"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "L P Breitling, N Dahmen, K Mittelstrass, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of nicotinic acetylcholine receptor subunit alpha 4 polymorphisms with nicotine dependence in 5500 Germans."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pharmacogenomics J (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/tpj.2009.6"}], "href": "https://doi.org/10.1038/tpj.2009.6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19290018"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19290018"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Kent E Hutchison, David L Allen, Francesca M Filbey, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CHRNA4 and tobacco dependence: from gene regulation to treatment outcome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arch Gen Psychiatry (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1001/archpsyc.64.9.1078"}], "href": "https://doi.org/10.1001/archpsyc.64.9.1078"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17768273"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17768273"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Jessica Lasky-Su, Benjamin M Neale, Barbara Franke, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-wide association scan of quantitative traits for attention deficit hyperactivity disorder identifies novel associations and confirms candidate gene associations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet B Neuropsychiatr Genet (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.b.30867"}], "href": "https://doi.org/10.1002/ajmg.b.30867"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18821565"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18821565"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Aaron J Bobb, Anjene M Addington, Ellen Sidransky, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Support for association between ADHD and two candidate genes: NET1 and DRD1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet B Neuropsychiatr Genet (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.b.30142"}], "href": "https://doi.org/10.1002/ajmg.b.30142"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15717291"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15717291"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Thomas Espeseth, Pamela M Greenwood, Ivar Reinvang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interactive effects of APOE and CHRNA4 on attention and white matter volume in healthy middle-aged and older adults."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cogn Affect Behav Neurosci (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3758/cabn.6.1.31"}], "href": "https://doi.org/10.3758/cabn.6.1.31"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16869227"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16869227"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "A Rigbi, K Kanyas, A Yakir, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Why do young women smoke? V. Role of direct and interactive effects of nicotinic cholinergic receptor gene variation on neurocognitive function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Brain Behav (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1601-183X.2007.00329.x"}], "href": "https://doi.org/10.1111/j.1601-183X.2007.00329.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17559419"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17559419"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Agata Rozycka, Elzbieta Skorupska, Andrzej Kostyrko, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Evidence for S284L mutation of the CHRNA4 in a white family with autosomal dominant nocturnal frontal lobe epilepsy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Epilepsia (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1046/j.1528-1157.2003.07603.x"}], "href": "https://doi.org/10.1046/j.1528-1157.2003.07603.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12887446"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12887446"}]}]}]}
Synonyms	BFNC, NACHR, EBN, NACRA4, EBN1, NACHRA4
Proteins	ACHA4_HUMAN
NCBI Gene ID	1137
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

CHRNA4 has 5,885 functional associations with biological entities spanning 9 categories (molecular profile, organism, disease, phenotype or trait, chemical, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 112 datasets.

Click the + buttons to view associations for CHRNA4 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

CHRNA4 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by CHRNA4 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of CHRNA4 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of CHRNA4 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of CHRNA4 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of CHRNA4 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of CHRNA4 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of CHRNA4 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of CHRNA4 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of CHRNA4 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of CHRNA4 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of CHRNA4 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with CHRNA4 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of CHRNA4 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of CHRNA4 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of CHRNA4 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with CHRNA4 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of CHRNA4 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing CHRNA4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing CHRNA4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with CHRNA4 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with CHRNA4 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing CHRNA4 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of CHRNA4 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with CHRNA4 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with CHRNA4 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with CHRNA4 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by CHRNA4 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving CHRNA4 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving CHRNA4 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with CHRNA4 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with CHRNA4 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with CHRNA4 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with CHRNA4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with CHRNA4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for CHRNA4 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at CHRNA4 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of CHRNA4 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of CHRNA4 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing CHRNA4 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with CHRNA4 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.