CHRNA3 Gene

HGNC Family	Cholinergic receptors, Ion channels
Name	cholinergic receptor, nicotinic, alpha 3 (neuronal)
Description	This locus encodes a member of the nicotinic acetylcholine receptor family of proteins. Members of this family of proteins form pentameric complexes comprised of both alpha and beta subunits. This locus encodes an alpha-type subunit, as it contains characteristic adjacent cysteine residues. The encoded protein is a ligand-gated ion channel that likely plays a role in neurotransmission. Polymorphisms in this gene have been associated with an increased risk of smoking initiation and an increased susceptibility to lung cancer. Alternatively spliced transcript variants have been described. [provided by RefSeq, Nov 2009]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The nicotinic acetylcholine receptor subunit gene "}, {"type": "b", "children": [{"type": "t", "text": "CHRNA3"}]}, {"type": "t", "text": ", located on chromosome 15q25.1, encodes a component of neuronal nicotinic receptors that modulate cellular responses to nicotine and tobacco‐derived carcinogens. Genetic variation in CHRNA3 has been consistently linked with multiple tobacco‐related phenotypes, including increased lung cancer risk, greater smoking intensity, and heightened susceptibility to chronic obstructive pulmonary disease. Studies have demonstrated that CHRNA3, together with its gene cluster partners (CHRNA5 and CHRNB4), is expressed not only in neural tissues but also in lung epithelial and pulmonary neuroendocrine cells, where it influences receptor behavior and the extent of nicotine extraction per cigarette smoked."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition, common polymorphisms in CHRNA3 (for example, rs1051730 and rs578776) have been robustly associated with higher cigarettes-per-day consumption and enhanced internal exposure to nicotine and tobacco-specific nitrosamines, thereby elevating lung cancer risk independent of self-reported smoking levels."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Further research, which includes replication studies and functional analyses, supports that distinct variants within the CHRNA5–CHRNA3–CHRNB4 cluster contribute independently to the development of nicotine dependence and modify risks for both lung cancer and airflow obstruction."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Moreover, carriers of risk alleles within this region have been shown to extract more nicotine per cigarette, suggesting that CHRNA3 plays a key role in regulating smoking behavior and determining individual exposure to tobacco carcinogens."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Collectively, these findings underscore the clinical relevance of CHRNA3 in the neurobiological pathways of nicotine addiction and in modulating tobacco-related disease susceptibility.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Christopher I Amos, Xifeng Wu, Peter Broderick, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.109"}], "href": "https://doi.org/10.1038/ng.109"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18385676"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18385676"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Rayjean J Hung, James D McKay, Valerie Gaborieau, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature06885"}], "href": "https://doi.org/10.1038/nature06885"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18385738"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18385738"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Unknown Authors "}, {"type": "b", "children": [{"type": "t", "text": "Genome-wide meta-analyses identify multiple loci associated with smoking behavior."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.571"}], "href": "https://doi.org/10.1038/ng.571"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20418890"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20418890"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Sreekumar G Pillai, Dongliang Ge, Guohua Zhu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A genome-wide association study in chronic obstructive pulmonary disease (COPD): identification of two major susceptibility loci."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pgen.1000421"}], "href": "https://doi.org/10.1371/journal.pgen.1000421"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19300482"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19300482"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Laura Jean Bierut, Jerry A Stitzel, Jen C Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Variants in nicotinic receptors and risk for nicotine dependence."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Psychiatry (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1176/appi.ajp.2008.07111711"}], "href": "https://doi.org/10.1176/appi.ajp.2008.07111711"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18519524"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18519524"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Nancy L Saccone, Scott F Saccone, Anthony L Hinrichs, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Multiple distinct risk loci for nicotine dependence identified by dense coverage of the complete family of nicotinic receptor subunit (CHRN) genes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet B Neuropsychiatr Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.b.30828"}], "href": "https://doi.org/10.1002/ajmg.b.30828"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19259974"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19259974"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Loïc Le Marchand, Kiersten S Derby, Sharon E Murphy, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Smokers with the CHRNA lung cancer-associated variants are exposed to higher levels of nicotine equivalents and a carcinogenic tobacco-specific nitrosamine."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-08-2271"}], "href": "https://doi.org/10.1158/0008-5472.CAN-08-2271"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19010884"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19010884"}]}]}]}
Synonyms	PAOD2, NACHRA3
Proteins	ACHA3_HUMAN
NCBI Gene ID	1136
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

CHRNA3 has 5,876 functional associations with biological entities spanning 9 categories (molecular profile, organism, disease, phenotype or trait, functional term, phrase or reference, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 121 datasets.

Click the + buttons to view associations for CHRNA3 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

CHRNA3 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 CHRNA3 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 CHRNA3 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 CHRNA3 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of CHRNA3 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of CHRNA3 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 CHRNA3 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 CHRNA3 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 CHRNA3 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 CHRNA3 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 CHRNA3 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 CHRNA3 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 CHRNA3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with CHRNA3 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with CHRNA3 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 CHRNA3 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of CHRNA3 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 CHRNA3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with CHRNA3 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing CHRNA3 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of CHRNA3 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing CHRNA3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing CHRNA3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with CHRNA3 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 CHRNA3 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with CHRNA3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with CHRNA3 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with CHRNA3 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with CHRNA3 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by CHRNA3 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with CHRNA3 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with CHRNA3 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 CHRNA3 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 CHRNA3 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 CHRNA3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with CHRNA3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for CHRNA3 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at CHRNA3 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 CHRNA3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of CHRNA3 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 CHRNA3 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.