Affinage

CHRNA4

Neuronal acetylcholine receptor subunit alpha-4 · UniProt P43681

Length
627 aa
Mass
70.0 kDa
Annotated
2026-04-28
100 papers in source corpus 13 papers cited in narrative 13 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CHRNA4 encodes the α4 subunit of neuronal nicotinic acetylcholine receptors (nAChRs), principally forming α4β2 heteropentameric ligand-gated cation channels that mediate fast cholinergic neurotransmission and modulate GABAergic and glutamatergic circuits. Disease-causing mutations clustered in the M2 transmembrane domain (e.g., S248F insertion, S252L, T265I, S284L) alter ACh sensitivity, calcium permeability, and the ratio of high- to low-affinity receptor states, while a polymorphism in the second intracellular loop (A529T) controls ethanol and nicotine sensitivity of the channel and associated behavioral responses (PMID:9175743, PMID:12823585, PMID:12871652, PMID:12766617, PMID:20061993). Gain-of-function or altered-function CHRNA4 mutations cause autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) by disrupting the balance of synaptic inhibition and excitation during slow-wave sleep (PMID:10563623, PMID:19020039). Beyond the nervous system, hepatocyte-expressed CHRNA4 couples acetylcholine or nicotine stimulation to calcium influx and inflammatory signaling that drives metabolic dysfunction-associated steatohepatitis (MASH), and its expression is post-transcriptionally regulated by METTL3-dependent m6A modification (PMID:38056431, PMID:37495067).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1996 Medium

    Determination of the six-exon genomic structure of CHRNA4 provided the foundation for systematic mutation scanning across all coding and transmembrane domains.

    Evidence Genomic sequencing and exon-intron boundary mapping of the CHRNA4 locus

    PMID:8833159

    Open questions at the time
    • no functional data from this study alone
    • regulatory elements outside coding exons not characterized
  2. 1997 High

    Reconstitution of an ADNFLE-associated M2 domain insertion mutant established that CHRNA4 mutations do not abolish channel function but instead alter ACh affinity and reduce calcium permeability, defining a gain-of-function/altered-function disease mechanism.

    Evidence Heterologous expression of wild-type and 776ins3 α4β2 receptors with electrophysiology and calcium permeability measurements

    PMID:9175743

    Open questions at the time
    • mechanism linking reduced calcium permeability to seizure generation not resolved
    • stoichiometry effects not tested
  3. 1999 Medium

    Identification of the S252L mutation in a Japanese ADNFLE family confirmed that the M2 transmembrane domain is a recurrent mutational hotspot for epilepsy, broadening the allelic spectrum beyond the original Australian kindred.

    Evidence SSCP screening, Sanger sequencing, and segregation analysis in a Japanese pedigree

    PMID:10563623

    Open questions at the time
    • no electrophysiological characterization of S252L in this study
    • penetrance modifiers not explored
  4. 2003 High

    Functional studies of the T265I mutation and the mouse A529T intracellular-loop polymorphism demonstrated that both the extracellular end of M2 and the second intracellular loop tune ACh sensitivity and the equilibrium between high- and low-affinity receptor populations, extending functional determinants beyond the channel pore lining.

    Evidence Xenopus oocyte electrophysiology (T265I); heterologous expression and 86Rb+ efflux in synaptosomes across inbred mouse strains and F2 animals (A529T)

    PMID:12766617 PMID:12823585 PMID:12871652

    Open questions at the time
    • structural basis for intracellular-loop modulation of affinity states unknown
    • whether human orthologue polymorphism has identical effects not tested
  5. 2008 High

    A transgenic rat carrying the S284L mutation revealed the downstream circuit-level mechanism: the mutant α4 subunit attenuates GABAergic inhibition and causes abnormal glutamate release selectively during slow-wave sleep, producing an ADNFLE-like phenotype.

    Evidence Transgenic knock-in rat with electrophysiological recording of synaptic currents and behavioral seizure monitoring

    PMID:19020039

    Open questions at the time
    • whether GABAergic attenuation is direct (presynaptic α4β2 on GABAergic terminals) or indirect not fully resolved
    • relevance of specific mutation (S284L) versus other ADNFLE alleles not compared in same model
  6. 2010 High

    Knock-in of the Chrna4 A529 allele in mice confirmed that the intracellular-loop polymorphism modulates nicotine pharmacology in vivo, altering hypothermia sensitivity, voluntary nicotine consumption, and reward-related behavior, linking receptor-level affinity changes to whole-animal addiction-relevant phenotypes.

    Evidence Knock-in mouse model with behavioral pharmacology and midbrain synaptosome 86Rb+ efflux

    PMID:20061993

    Open questions at the time
    • human translational relevance of A529T not established
    • downstream signaling mediating behavioral differences not identified
  7. 2014 High

    Characterization of rare human coding variants (R336C, P451L, R487Q) showed they alter surface expression, interactome composition, and agonist responsiveness of α4β2 receptors, establishing that CHRNA4 variation outside M2 also produces functional consequences relevant to nicotine dependence risk.

    Evidence [3H]epibatidine binding, LC-MS/MS interactome profiling, Xenopus oocyte electrophysiology, HEK293 expression

    PMID:24385388

    Open questions at the time
    • interactome changes not validated by reciprocal pull-downs
    • in vivo consequences of these rare variants not tested
  8. 2016 Medium

    Follow-up electrophysiology on the R336C variant demonstrated that it specifically reduces agonist sensitivity after chronic nicotine exposure, suggesting this variant alters receptor desensitization or upregulation dynamics rather than baseline function.

    Evidence Electrophysiology of α4β2 channels carrying R336C with nicotine pre-incubation

    PMID:26952864

    Open questions at the time
    • molecular mechanism of altered upregulation not resolved
    • single variant tested in isolation
  9. 2023 High

    Discovery of functional CHRNA4 expression in hepatocytes established a non-neuronal role: acetylcholine or nicotine activates hepatocyte α4-containing nAChRs to drive calcium influx and downstream inflammatory signaling that promotes MASH, and liver-specific Chrna4 deletion protects against diet-induced steatohepatitis.

    Evidence Liver-specific Chrna4 knockout mice, calcium imaging, inflammatory pathway readouts, dietary MASH model, human liver expression correlation

    PMID:38056431

    Open questions at the time
    • precise stoichiometry and partner subunits of hepatocyte nAChR not defined
    • whether hepatocyte CHRNA4 contributes to other liver diseases unknown
  10. 2023 Medium

    METTL3-mediated m6A methylation of Chrna4 mRNA was identified as a post-transcriptional regulatory mechanism controlling α4 subunit expression in hippocampal neurons, with functional consequences for synaptic transmission and spatial memory.

    Evidence MeRIP-seq, METTL3 shRNA knockdown and pharmacological inhibition, electrophysiology, and behavioral testing in BPA-exposed rats

    PMID:37495067

    Open questions at the time
    • whether m6A regulation of CHRNA4 operates under physiological (non-BPA) conditions unknown
    • reader protein mediating Chrna4 mRNA decay not identified
    • single-lab finding

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural basis for how intracellular-loop and non-M2 variants allosterically modulate channel gating, the subunit composition of hepatocyte nAChRs containing α4, and the physiological regulators of CHRNA4 m6A modification remain unresolved.
  • no high-resolution structure of disease-mutant α4β2 receptors
  • hepatocyte nAChR stoichiometry undefined
  • m6A regulation of CHRNA4 not confirmed outside BPA exposure context

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 6
Localization
GO:0005886 plasma membrane 4
Pathway
R-HSA-112316 Neuronal System 5 R-HSA-1643685 Disease 3 R-HSA-162582 Signal Transduction 1
Partners
CHRNB2METTL3
Complex memberships
α4β2 nicotinic acetylcholine receptor

Evidence

Reading pass · 13 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 An insertion of three nucleotides (GCT) at position 776 in the M2 domain of CHRNA4 does not prevent receptor function but increases apparent affinity for ACh and significantly lowers calcium permeability, corresponding to a loss of function at the cellular level. Receptor reconstitution and physiological investigation in heterologous expression system Human molecular genetics High 9175743
1999 The S252L (Ser252Leu) missense mutation in the M2 transmembrane domain of CHRNA4, affecting a conserved serine, causes autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) in a Japanese family, implicating this residue in channel function. SSCP, direct sequencing, and segregation analysis Neurology Medium 10563623
2003 The CHRNA4 α4-T265I mutation at the extracellular end of TM2 increases ACh sensitivity of reconstituted receptors, as demonstrated by expression in Xenopus oocytes. Expression in Xenopus oocytes and electrophysiology Epilepsia High 12823585
2003 The mouse Chrna4 A529T polymorphism in the second intracellular loop alters the ratio of high- to low-affinity α4β2 nAChR populations and changes receptor sensitivity to DHβE blockade when expressed heterologously, identifying this domain as a functional determinant of receptor affinity states. Heterologous expression of variant α4 subunits with β2 subunit; electrophysiology Neuropharmacology High 12871652
2003 The mouse Chrna4 A/T polymorphism at position 529 modulates enhancement of α4β2 nAChR function by ethanol: strains carrying the A variant show ethanol-induced increases in maximal ion flux, while strains with the T variant do not, indicating the polymorphism controls ethanol sensitivity of the receptor. 86Rb+ efflux assay in thalamic synaptosomes from inbred mouse strains and F2 intercross animals Alcoholism, clinical and experimental research High 12766617
2008 Transgenic rats harboring the CHRNA4 S284L mutation exhibit attenuation of synaptic and extrasynaptic GABAergic transmission and abnormal glutamate release during slow-wave sleep, producing an ADNFLE-like seizure phenotype. Transgenic rat model; electrophysiological measurements of GABAergic and glutamatergic neurotransmission; behavioral seizure monitoring The Journal of neuroscience High 19020039
2010 Chrna4 A529 knock-in mice show greater sensitivity to nicotine-induced hypothermia, reduced oral nicotine consumption, lack of conditioned place preference, and altered α4β2* nAChR function (maximal efflux and high-sensitivity receptor proportion) in midbrain, confirming that the T529A polymorphism in the second intracellular loop modulates α4β2* receptor function and behavioral responses to nicotine. Knock-in mouse model; behavioral pharmacology; 86Rb+ efflux assay from midbrain synaptosomes Pharmacogenetics and genomics High 20061993
2014 Rare CHRNA4 variants (α4R336C, α4P451L, α4R487Q) alter α4β2 nAChR expression, subcellular distribution, sensitivity to nicotine-induced receptor upregulation, intracellular interactome composition (by LC-MS/MS), and functional parameters of agonist activation in Xenopus oocytes, demonstrating that these variants produce receptors more sensitive to nicotine than those with the common variant. [3H]epibatidine binding, immunoprecipitation/LC-MS/MS proteomics, voltage-clamp electrophysiology in Xenopus oocytes, HEK293 cell expression The Journal of pharmacology and experimental therapeutics High 24385388
2015 A splice site acceptor variant (rs2273500-C) in CHRNA4 results in an alternate transcript predicted to be targeted for nonsense-mediated decay and is associated with decreased CHRNA4 expression in postmortem human brain, establishing rs2273500 as a functional regulatory variant. GWAS meta-analysis combined with eQTL analysis of brain expression data Translational psychiatry Medium 26440539
2023 CHRNA4 is expressed specifically in hepatocytes and functions as a subunit of nicotinic acetylcholine receptors activated by acetylcholine from immune cells or nicotine, inducing calcium influx and activation of inflammatory signaling pathways that promote MASH (metabolic dysfunction-associated steatohepatitis); genetic and pharmacological inhibition of CHRNA4 protected mice from diet-induced MASH. Liver-specific Chrna4 knockout mice, calcium influx assays, inflammatory signaling readouts, dietary MASH mouse model, human patient correlation Cell metabolism High 38056431
2023 METTL3-mediated m6A modification is enriched on Chrna4 mRNA in hippocampal neurons following BPA exposure, leading to decreased Chrna4 expression; inhibition of METTL3 restored Chrna4 levels and rescued abnormal synaptic transmission and spatial memory deficits. m6A sequencing/MeRIP, METTL3 knockdown (shRNA) and pharmacological inhibition, electrophysiology, behavioral testing in rats Environmental research Medium 37495067
1996 CHRNA4 consists of six exons distributed over approximately 17 kb of genomic DNA, enabling PCR-based amplification of the complete coding region including the functionally critical transmembrane domains. Genomic sequencing and exon-intron structure determination Genomics Medium 8833159
2016 The rare CHRNA4 R336C missense variant reduces the sensitivity of the human α4β2 channel isoform to its agonists following nicotine incubation, as shown by functional studies of the channel. Functional electrophysiology of α4β2 channels carrying R336C variant Molecular psychiatry Medium 26952864

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 An insertion mutation of the CHRNA4 gene in a family with autosomal dominant nocturnal frontal lobe epilepsy. Human molecular genetics 300 9175743
2004 The genome sequence of an anaerobic aromatic-degrading denitrifying bacterium, strain EbN1. Archives of microbiology 190 15551059
1999 A novel mutation of CHRNA4 responsible for autosomal dominant nocturnal frontal lobe epilepsy. Neurology 169 10563623
2005 Ethnic- and gender-specific association of the nicotinic acetylcholine receptor alpha4 subunit gene (CHRNA4) with nicotine dependence. Human molecular genetics 158 15790597
2004 A novel mutation in KCNQ2 associated with BFNC, drug resistant epilepsy, and mental retardation. Neurology 127 15249611
2007 CHRNA4 and tobacco dependence: from gene regulation to treatment outcome. Archives of general psychiatry 93 17768273
2002 Genes involved in the anaerobic degradation of ethylbenzene in a denitrifying bacterium, strain EbN1. Archives of microbiology 88 12420173
2005 Substrate-dependent regulation of anaerobic degradation pathways for toluene and ethylbenzene in a denitrifying bacterium, strain EbN1. Journal of bacteriology 75 15687214
2007 Functional proteomic view of metabolic regulation in "Aromatoleum aromaticum" strain EbN1. Proteomics 74 17549795
2015 Genome-wide meta-analysis reveals common splice site acceptor variant in CHRNA4 associated with nicotine dependence. Translational psychiatry 73 26440539
2006 Crystal structure and enzyme kinetics of the (S)-specific 1-phenylethanol dehydrogenase of the denitrifying bacterium strain EbN1. Biochemistry 72 16388583
2006 Interactive effects of APOE and CHRNA4 on attention and white matter volume in healthy middle-aged and older adults. Cognitive, affective & behavioral neuroscience 72 16869227
1999 Autosomal dominant nocturnal frontal lobe epilepsy in a Spanish family with a Ser252Phe mutation in the CHRNA4 gene. Archives of neurology 72 10448807
2000 Independent occurrence of the CHRNA4 Ser248Phe mutation in a Norwegian family with nocturnal frontal lobe epilepsy. Epilepsia 68 10802757
2003 A new Chrna4 mutation with low penetrance in nocturnal frontal lobe epilepsy. Epilepsia 66 12823585
2007 Association of attentional network function with exon 5 variations of the CHRNA4 gene. Human molecular genetics 59 17613539
2010 The association between dopamine DRD2 polymorphisms and working memory capacity is modulated by a functional polymorphism on the nicotinic receptor gene CHRNA4. Journal of cognitive neuroscience 56 19803686
2008 Solvent stress response of the denitrifying bacterium "Aromatoleum aromaticum" strain EbN1. Applied and environmental microbiology 55 18263750
2004 Genes involved in the anaerobic degradation of toluene in a denitrifying bacterium, strain EbN1. Archives of microbiology 55 14735297
2008 Gene-gene interactions among CHRNA4, CHRNB2, BDNF, and NTRK2 in nicotine dependence. Biological psychiatry 52 18534558
2008 Rats harboring S284L Chrna4 mutation show attenuation of synaptic and extrasynaptic GABAergic transmission and exhibit the nocturnal frontal lobe epilepsy phenotype. The Journal of neuroscience : the official journal of the Society for Neuroscience 52 19020039
2012 The role of the CHRNA4 gene in Internet addiction: a case-control study. Journal of addiction medicine 48 22722381
2001 (S)-1-phenylethanol dehydrogenase of Azoarcus sp. strain EbN1, an enzyme of anaerobic ethylbenzene catabolism. Archives of microbiology 47 11479712
2003 Evidence for S284L mutation of the CHRNA4 in a white family with autosomal dominant nocturnal frontal lobe epilepsy. Epilepsia 44 12887446
2008 Anaerobic degradation of p-ethylphenol by "Aromatoleum aromaticum" strain EbN1: pathway, regulation, and involved proteins. Journal of bacteriology 43 18539747
2000 Benign familial neonatal convulsions (BFNC) resulting from mutation of the KCNQ2 voltage sensor. European journal of human genetics : EJHG 43 11175290
1996 Exon-intron structure of the human neuronal nicotinic acetylcholine receptor alpha 4 subunit (CHRNA4). Genomics 40 8833159
2016 In vitro and in vivo mechanism of immunomodulatory and antiviral activity of Edible Bird's Nest (EBN) against influenza A virus (IAV) infection. Journal of ethnopharmacology 39 26976767
2005 Modulation of nicotine but not ethanol preference by the mouse Chrna4 A529T polymorphism. Behavioral neuroscience 39 15727510
2005 Functional genomics of an anaerobic aromatic-degrading denitrifying bacterium, strain EbN1. Applied microbiology and biotechnology 39 16041578
2004 Candidate gene association studies of the alpha 4 (CHRNA4) and beta 2 (CHRNB2) neuronal nicotinic acetylcholine receptor subunit genes in Alzheimer's disease. Neuroscience letters 38 15026168
2007 Nicotine receptor gene CHRNA4 modulates early event-related potentials in auditory and visual oddball target detection tasks. Neuroscience 37 17590520
2004 Association of polymorphisms in nicotinic acetylcholine receptor alpha 4 subunit gene (CHRNA4), mu-opioid receptor gene (OPRM1), and ethanol-metabolizing enzyme genes with alcoholism in Korean patients. Alcohol (Fayetteville, N.Y.) 37 15902904
2003 A polymorphism in the alpha4 nicotinic receptor gene (Chrna4) modulates enhancement of nicotinic receptor function by ethanol. Alcoholism, clinical and experimental research 36 12766617
2008 A novel mutation of the nicotinic acetylcholine receptor gene CHRNA4 in sporadic nocturnal frontal lobe epilepsy. Epilepsy research 35 19058950
2011 Effects of edible bird's nest (EBN) on cultured rabbit corneal keratocytes. BMC complementary and alternative medicine 34 21992551
1997 Neuronal nicotinic acetylcholine receptor alpha 4 subunit (CHRNA4) and panic disorder: an association study. American journal of medical genetics 34 9129724
2012 A cognitive phenotype for a polymorphism in the nicotinic receptor gene CHRNA4. Neuroscience and biobehavioral reviews 32 22373960
2005 Polymorphisms of the CHRNA4 gene encoding the alpha4 subunit of nicotinic acetylcholine receptor as related to the oxidative DNA damage and the level of apoptotic proteins in lymphocytes of the patients with Alzheimer's disease. DNA and cell biology 29 16332175
1994 A nonsense mutation in the alpha4 subunit of the nicotinic acetylcholine receptor (CHRNA4) cosegregates with 20q-linked benign neonatal familial convulsions (EBNI). Neurobiology of disease 29 9216991
2012 Physiological and proteomic adaptation of "Aromatoleum aromaticum" EbN1 to low growth rates in benzoate-limited, anoxic chemostats. Journal of bacteriology 28 22366417
2011 The nicotinic acetylcholine receptor gene CHRNA4 is associated with negative emotionality. Emotion (Washington, D.C.) 28 21500914
2020 Remarkable effect of transdermal nicotine in children with CHRNA4-related autosomal dominant sleep-related hypermotor epilepsy. Epilepsy & behavior : E&B 27 32097883
2016 A rare missense mutation in CHRNA4 associates with smoking behavior and its consequences. Molecular psychiatry 27 26952864
2012 Proteogenomic evidence for β-oxidation of plant-derived 3-phenylpropanoids in "Aromatoleum aromaticum" EbN1. Proteomics 27 22589189
2009 Deletions involving both KCNQ2 and CHRNA4 present with benign familial neonatal seizures. Neurology 27 19822871
2011 Association of CHRNA4 polymorphism with depression and loneliness in elderly males. Genes, brain, and behavior 25 22008229
2007 Association study of the nicotinic acetylcholine receptor alpha4 subunit gene, CHRNA4, in attention-deficit hyperactivity disorder. Genes, brain, and behavior 25 17504247
2006 A novel splicing mutation in KCNQ2 in a multigenerational family with BFNC followed for 25 years. Epilepsia 25 16686649
2018 CHRNA4 variant causes paroxysmal kinesigenic dyskinesia and genetic epilepsy with febrile seizures plus? Seizure 24 29454195
2011 Benzoate mediates repression of C(4)-dicarboxylate utilization in "Aromatoleum aromaticum" EbN1. Journal of bacteriology 24 22081395
2016 Production kinetics of polyhydroxyalkanoates by using Pseudomonas aeruginosa gamma ray mutant strain EBN-8 cultured on soybean oil. 3 Biotech 23 28330214
2013 Nominal association with CHRNA4 variants and nicotine dependence. Genes, brain, and behavior 23 23350800
2011 Association of CHRNA4 polymorphisms with smoking behavior in two populations. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 23 21445957
2003 The mouse Chrna4 A529T polymorphism alters the ratio of high to low affinity alpha 4 beta 2 nAChRs. Neuropharmacology 23 12871652
2019 Characterization of an Aldehyde Oxidoreductase From the Mesophilic Bacterium Aromatoleum aromaticum EbN1, a Member of a New Subfamily of Tungsten-Containing Enzymes. Frontiers in microbiology 22 30766522
2005 Functional analysis of novel KCNQ2 and KCNQ3 gene variants found in a large pedigree with benign familial neonatal convulsions (BFNC). Neurogenetics 22 16235065
1997 Benign childhood epilepsy with centrotemporal spikes and electroencephalography trait are not linked to EBN1 and EBN2 of benign neonatal familial convulsions. Epilepsia 22 9579905
2010 Nicotinic receptor gene CHRNA4 interacts with processing load in attention. PloS one 21 21203548
1999 SER252PHE and 776INS3 mutations in the CHRNA4 gene are rare in the Italian ADNFLE population. Sleep 21 10450598
2023 Hepatocyte CHRNA4 mediates the MASH-promotive effects of immune cell-produced acetylcholine and smoking exposure in mice and humans. Cell metabolism 20 38056431
2015 Molecular Genetic and Crystal Structural Analysis of 1-(4-Hydroxyphenyl)-Ethanol Dehydrogenase from 'Aromatoleum aromaticum' EbN1. Journal of molecular microbiology and biotechnology 20 26488297
2012 The dopamine D2 receptor gene DRD2 and the nicotinic acetylcholine receptor gene CHRNA4 interact on striatal gray matter volume: evidence from a genetic imaging study. NeuroImage 20 22947540
2017 The association between the nicotinic acetylcholine receptor α4 subunit gene (CHRNA4) rs1044396 and Internet gaming disorder in Korean male adults. PloS one 19 29240768
2010 Chrna4 A529 knock-in mice exhibit altered nicotine sensitivity. Pharmacogenetics and genomics 19 20061993
2007 Ring chromosome 20 syndrome without deletions of the subtelomeric and CHRNA4--KCNQ2 genes loci. European journal of medical genetics 19 17851150
2006 Mass spectrometric identification of proteins in complex post-genomic projects. Soluble proteins of the metabolically versatile, denitrifying 'Aromatoleum' sp. strain EbN1. Journal of molecular microbiology and biotechnology 19 16825790
2020 Characterization of Polar and Non-Polar Compounds of House Edible Bird's Nest (EBN) from Johor, Malaysia. Chemistry & biodiversity 18 31721431
2009 Financial and psychological risk attitudes associated with two single nucleotide polymorphisms in the nicotine receptor (CHRNA4) gene. PloS one 18 19693267
2009 Polymorphisms in the neural nicotinic acetylcholine receptor α4 subunit (CHRNA4) are associated with ADHD in a genetic isolate. Attention deficit and hyperactivity disorders 18 21432576
2014 Rare human nicotinic acetylcholine receptor α4 subunit (CHRNA4) variants affect expression and function of high-affinity nicotinic acetylcholine receptors. The Journal of pharmacology and experimental therapeutics 17 24385388
2009 The 1674+11C>T polymorphism of CHRNA4 is associated with juvenile myoclonic epilepsy. Seizure 17 19577488
2020 Recovery of value-added glycopeptides from edible bird's nest (EBN) co-products: enzymatic hydrolysis, physicochemical characteristics and bioactivity. Journal of the science of food and agriculture 16 32468613
2015 Nicotinergic Modulation of Attention-Related Neural Activity Differentiates Polymorphisms of DRD2 and CHRNA4 Receptor Genes. PloS one 16 26079805
2008 Development of a genetic system for the denitrifying bacterium 'Aromatoleum aromaticum' strain EbN1. Journal of molecular microbiology and biotechnology 16 18818489
2017 Overdominant Effect of a CHRNA4 Polymorphism on Cingulo-Opercular Network Activity and Cognitive Control. The Journal of neuroscience : the official journal of the Society for Neuroscience 15 28877969
2014 Association of the CHRNA4 neuronal nicotinic receptor subunit gene with frequency of binge drinking in young adults. Alcoholism, clinical and experimental research 15 24428733
2018 Effects of EBN on embryo implantation, plasma concentrations of reproductive hormones, and uterine expressions of genes of PCNA, steroids, growth factors and their receptors in rats. Theriogenology 14 30605790
2011 Autosomal dominant nocturnal frontal lobe epilepsy: a genotypic comparative study of Japanese and Korean families carrying the CHRNA4 Ser284Leu mutation. Journal of human genetics 13 21753767
2009 Lack of potassium current in W309R mutant KCNQ3 channel causing benign familial neonatal convulsions (BFNC). Epilepsy research 13 19167866
2000 Failure to replicate association between the gene for the neuronal nicotinic acetylcholine receptor alpha 4 subunit (CHRNA4) and IGE. American journal of medical genetics 13 11121188
2023 Decreased expression of Chrna4 by METTL3-mediated m6A modification participates in BPA-induced spatial memory deficit. Environmental research 12 37495067
2014 Massive withdrawal symptoms and affective vulnerability are associated with variants of the CHRNA4 gene in a subgroup of smokers. PloS one 12 24498031
1992 The genes coding for phosphoenolpyruvate carboxykinase-1 (PCK1) and neuronal nicotinic acetylcholine receptor alpha 4 subunit (CHRNA4) map to human chromosome 20, extending the known region of homology with mouse chromosome 2. Annals of human genetics 12 1492743
2020 Variants in CHRNB2 and CHRNA4 Identified in Patients with Insular Epilepsy. The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques 11 32536355
2016 CHRNA4 and ANKK1 Polymorphisms Influence Smoking-Induced Nicotinic Acetylcholine Receptor Upregulation. Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco 11 27611310
2015 Individual response speed is modulated by variants of the gene encoding the alpha 4 sub-unit of the nicotinic acetylcholine receptor (CHRNA4). Behavioural brain research 11 25639542
2015 Modulation of nicotine effects on selective attention by DRD2 and CHRNA4 gene polymorphisms. Psychopharmacology 11 25647695
2012 Possible association of nicotinic acetylcholine receptor gene (CHRNA4 and CHRNB2) polymorphisms with nicotine dependence in Japanese males: an exploratory study. Pharmacopsychiatry 11 23037950
2012 A novel differential susceptibility gene: CHRNA4 and moderation of the effect of maltreatment on child personality. Journal of child psychology and psychiatry, and allied disciplines 11 23240931
2007 Effects of APOE and CHRNA4 genotypes on retinal nerve fibre layer thickness at the optic disc and on risk for developing exfoliation syndrome. Acta ophthalmologica Scandinavica 11 17488453
2007 A novel missense mutation (N258S) in the KCNQ2 gene in a Turkish family afflicted with benign familial neonatal convulsions (BFNC). The Turkish journal of pediatrics 11 18246739
1995 Detection of a CfoI polymorphism within exon 5 of the human neuronal nicotinic acetylcholine receptor alpha 4 subunit gene (CHRNA4). Human genetics 11 7607646
2022 Systems Biology of Aromatic Compound Catabolism in Facultative Anaerobic Aromatoleum aromaticum EbN1T. mSystems 10 36445109
2010 Stress-induced changes of phospholipids in betaproteobacterium Aromatoleum aromaticum strain EbN1 due to alkylbenzene growth substrates. Journal of molecular microbiology and biotechnology 10 20185932
2010 Epistasis between APOE and nicotinic receptor gene CHRNA4 in age related cognitive function and decline. Journal of the International Neuropsychological Society : JINS 10 20331911
2008 Genetic association analysis of tagging SNPs in alpha4 and beta2 subunits of neuronal nicotinic acetylcholine receptor genes (CHRNA4 and CHRNB2) with schizophrenia in the Japanese population. Journal of neural transmission (Vienna, Austria : 1996) 10 18762859
2021 Responsiveness of Aromatoleum aromaticum EbN1T to Lignin-Derived Phenylpropanoids. Applied and environmental microbiology 9 33741621
2017 The influence of CHRNA4, COMT, and maternal sensitivity on orienting and executive attention in 6-month-old infants. Brain and cognition 9 28582665
2015 Mutational analysis of CHRNB2, CHRNA2 and CHRNA4 genes in Chinese population with autosomal dominant nocturnal frontal lobe epilepsy. International journal of clinical and experimental medicine 9 26309560