CHRNA2 Gene

HGNC Family	Ion channels, Cholinergic receptors
Name	cholinergic receptor, nicotinic, alpha 2 (neuronal)
Description	Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels formed by a pentameric arrangement of alpha and beta subunits to create distinct muscle and neuronal receptors. Neuronal receptors are found throughout the peripheral and central nervous system where they are involved in fast synaptic transmission. This gene encodes an alpha subunit that is widely expressed in the brain. The proposed structure for nAChR subunits is a conserved N-terminal extracellular domain followed by three conserved transmembrane domains, a variable cytoplasmic loop, a fourth conserved transmembrane domain, and a short C-terminal extracellular region. Mutations in this gene cause autosomal dominant nocturnal frontal lobe epilepsy type 4. Single nucleotide polymorphisms (SNPs) in this gene have been associated with nicotine dependence. [provided by RefSeq, Nov 2009]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The neuronal nicotinic acetylcholine receptor α2 subunit, encoded by CHRNA2, plays a multifaceted role in the regulation of neuronal excitability, network synchronization, behavioral responses to nicotine, epileptogenesis, and even energy metabolism. In the central nervous system, rare missense mutations in CHRNA2 have been identified in families with sleep‐related focal epilepsies—including autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE)—where alterations in receptor structure markedly increase sensitivity to acetylcholine and disrupt normal neuronal signaling."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Furthermore, CHRNA2 is expressed in specific interneuronal populations. For example, its expression in layer 5 Martinotti cells has been shown to regulate the timing and synchronization of pyramidal cell activity in the cortex, a finding that underscores its importance in cortical information processing and cognitive control."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Outside its classical neuronal roles, CHRNA2 is also implicated in peripheral metabolic regulation. In beige adipocytes, activation of CHRNA2 triggers cAMP- and protein kinase A–dependent pathways that enhance thermogenesis, thereby contributing to energy homeostasis and resisting diet-induced metabolic dysfunction."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, both human genetic studies and animal models indicate that CHRNA2 influences nicotine-related behaviors. Variants in CHRNA2 are associated with altered nicotine-induced analgesia, enhanced self-administration and withdrawal responses, and an increased risk of nicotine dependence."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, the absence of CHRNA2 in select interneuronal populations is linked to impaired synaptic plasticity and memory deficits—for instance, by affecting the hippocampal response during nicotine withdrawal—highlighting its role in modulating network activity and cognitive outcomes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings demonstrate that CHRNA2 exerts diverse functions in both the central nervous system and peripheral tissues, making it a critical modulator of excitability, behavior, and metabolism.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Paolo Aridon, Carla Marini, Chiara Di Resta, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Increased sensitivity of the neuronal nicotinic receptor alpha 2 subunit causes familial epilepsy with nocturnal wandering and ictal fear."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1086/506459"}], "href": "https://doi.org/10.1086/506459"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16826524"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16826524"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Fernando Díaz-Otero, Mar Quesada, José Morales-Corraliza, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Autosomal dominant nocturnal frontal lobe epilepsy with a mutation in the CHRNB2 gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Epilepsia (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1528-1167.2007.01328.x"}], "href": "https://doi.org/10.1111/j.1528-1167.2007.01328.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17900292"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17900292"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Valerio Conti, Patrizia Aracri, Laura Chiti, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nocturnal frontal lobe epilepsy with paroxysmal arousals due to CHRNA2 loss of function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurology (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1212/WNL.0000000000001471"}], "href": "https://doi.org/10.1212/WNL.0000000000001471"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25770198"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25770198"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Markus M Hilscher, Richardson N Leão, Steven J Edwards, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Chrna2-Martinotti Cells Synchronize Layer 5 Type A Pyramidal Cells via Rebound Excitation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Biol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pbio.2001392"}], "href": "https://doi.org/10.1371/journal.pbio.2001392"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28182735"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28182735"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Heejin Jun, Hui Yu, Jianke Gong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "An immune-beige adipocyte communication via nicotinic acetylcholine receptor signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Med (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41591-018-0032-8"}], "href": "https://doi.org/10.1038/s41591-018-0032-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29785025"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29785025"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "J Yang, S Wang, Z Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The contribution of rare and common variants in 30 genes to risk nicotine dependence."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Psychiatry (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/mp.2014.156"}], "href": "https://doi.org/10.1038/mp.2014.156"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25450229"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25450229"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Shahrdad Lotfipour, Janet S Byun, Prescott Leach, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Targeted deletion of the mouse α2 nicotinic acetylcholine receptor subunit gene (Chrna2) potentiates nicotine-modulated behaviors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.4731-12.2013"}], "href": "https://doi.org/10.1523/JNEUROSCI.4731-12.2013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23637165"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23637165"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Ana I Robles, Ping Yang, Jin Jen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A DRD1 polymorphism predisposes to lung cancer among those exposed to secondhand smoke during childhood."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Prev Res (Phila) (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1940-6207.CAPR-14-0158"}], "href": "https://doi.org/10.1158/1940-6207.CAPR-14-0158"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25281486"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25281486"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Shahrdad Lotfipour, Celina Mojica, Sakura Nakauchi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "α2* Nicotinic acetylcholine receptors influence hippocampus-dependent learning and memory in adolescent mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Learn Mem (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/lm.045369.117"}], "href": "https://doi.org/10.1101/lm.045369.117"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28507032"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28507032"}]}]}]}
Proteins	ACHA2_HUMAN
NCBI Gene ID	1135
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

CHRNA2 has 3,820 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 118 datasets.

Click the + buttons to view associations for CHRNA2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

CHRNA2 Gene

Functional Associations

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

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of CHRNA2 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 CHRNA2 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 CHRNA2 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 CHRNA2 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of CHRNA2 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 CHRNA2 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 CHRNA2 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 CHRNA2 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of CHRNA2 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of CHRNA2 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 CHRNA2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of CHRNA2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of CHRNA2 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 CHRNA2 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 CHRNA2 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with CHRNA2 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of CHRNA2 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of CHRNA2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing CHRNA2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing CHRNA2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with CHRNA2 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 CHRNA2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of CHRNA2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with CHRNA2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with CHRNA2 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with CHRNA2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by CHRNA2 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DGIdb Drug Targets 2026	interacting drugs for CHRNA2 protein from the DGIdb Drug Targets 2026 dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving CHRNA2 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving CHRNA2 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with CHRNA2 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 CHRNA2 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 CHRNA2 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 CHRNA2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with CHRNA2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for CHRNA2 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at CHRNA2 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 CHRNA2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of CHRNA2 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 CHRNA2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.