DGIdb - CHRNA4 Gene Record

CHRNA4 1137 Druggable Genome

Alternate Names:

1137
CHOLINERGIC RECEPTOR NICOTINIC ALPHA 4 SUBUNIT
CHRNA4
BFNC
EBN
EBN1
NACHR
NACHRA4
NACRA4
118504
1958
ENSG00000101204
OTTHUMG00000033080
P43681
ACHA4_HUMAN
465
nicotinic acetylcholine receptor α4 subunit
NICOTINIC ACETYLCHOLINE RECEPTOR
BE0000849
NEURONAL ACETYLCHOLINE RECEPTOR SUBUNIT ALPHA-4
NEURONAL ACETYLCHOLINE RECEPTOR PROTEIN, ALPHA-4 SUBUNIT PRECURSOR. [SOURCE:UNIPROT/SWISSPROT;ACC:P43681]
PA26490
T78111
Neuronal acetylcholine receptor alpha-4
T70967
NM_000744
NP_000735

Gene Info:

Target Class	Receptors
Target Subclass	TC:1.A.9
Uniprot Status	Swiss-Prot
Interpro Type	Domain
Interpro Name	Neurotransmitter-gated ion-channel ligand-binding
Human Readable Name	DRUGGABLE GENOME
Interpro Short Name	Neur_chan_lig-bd
Interpro Name	Neurotransmitter-gated ion-channel
Interpro Type	Family
Uniprot Evidence	1: Evidence at protein level
Interpro Acc	IPR006202
Interpro Short Name	Neur_channel
Human Readable Name	ION CHANNEL
Interpro Acc	IPR006201
Transmembrane Helix Count	4
Target Subclass	Ligand_gated_ion_channels
Target Subclass	Channels
Target Subclass	cys-loop
Target Main Class	Receptors
Gene Biotype	PROTEIN_CODING
GuideToPharmacology Gene Category Name	Nicotinic acetylcholine receptors
GuideToPharmacology Gene Category ID	76

(11 More Sources)

Gene Categories: Category Details

DNA REPAIR
ION CHANNEL
EXTERNAL SIDE OF PLASMA MEMBRANE
DRUGGABLE GENOME

Publications:

Arias et al., 2005, Anesthetics as chemical tools to study the structure and function of nicotinic acetylcholine receptors., Curr. Protein Pept. Sci.
Yamakura et al., 2001, Anesthetics and ion channels: molecular models and sites of action., Annu. Rev. Pharmacol. Toxicol.
Krasowski et al., 1999, General anaesthetic actions on ligand-gated ion channels., Cell. Mol. Life Sci.
Stauderman KA et al., 1998, Characterization of human recombinant neuronal nicotinic acetylcholine receptor subunit combinations alpha2beta4, alpha3beta4 and alpha4beta4 stably expressed in HEK293 cells., J Pharmacol Exp Ther
Klaassen et al., 2006, Seizures and enhanced cortical GABAergic inhibition in two mouse models of human autosomal dominant nocturnal frontal lobe epilepsy., Proc. Natl. Acad. Sci. U.S.A.
Ehringer et al., 2007, Association of the neuronal nicotinic receptor beta2 subunit gene (CHRNB2) with subjective responses to alcohol and nicotine., Am. J. Med. Genet. B Neuropsychiatr. Genet.
Mansvelder et al., 2009, Nicotinic modulation of synaptic transmission and plasticity in cortico-limbic circuits., Semin. Cell Dev. Biol.
Zaniewska et al., Nicotine dependence - human and animal studies, current pharmacotherapies and future perspectives., Pharmacol Rep
Espeseth et al., 2007, Nicotine receptor gene CHRNA4 modulates early event-related potentials in auditory and visual oddball target detection tasks., Neuroscience
Winterer et al., 2007, Association of attentional network function with exon 5 variations of the CHRNA4 gene., Hum. Mol. Genet.
Narahashi et al., 2000, Symposium overview: mechanism of action of nicotine on neuronal acetylcholine receptors, from molecule to behavior., Toxicol. Sci.
De Luca et al., 2006, Genetic interaction between alpha4 and beta2 subunits of high affinity nicotinic receptor: analysis in schizophrenia., Exp Brain Res
Jackson et al., 2010, Role of alpha5 nicotinic acetylcholine receptors in pharmacological and behavioral effects of nicotine in mice., J. Pharmacol. Exp. Ther.
Gu F et al., 2020, Association Between Nicotine-dependent Gene Polymorphism and Smoking Cessation in Patients With Lung Cancer., Clin Lung Cancer
Chu CJ et al., 2011, Association of nicotinic acetylcholine receptor subunit alpha-4 polymorphisms with smoking behaviors in Chinese male smokers., Chin Med J (Engl)
Hoft NR et al., 2011, CHRNB2 promoter region: association with subjective effects to nicotine and gene expression differences., Genes Brain Behav
Breitling LP et al., 2009, Association of nicotinic acetylcholine receptor subunit alpha 4 polymorphisms with nicotine dependence in 5500 Germans., Pharmacogenomics J
Li MD et al., 2005, Ethnic- and gender-specific association of the nicotinic acetylcholine receptor alpha4 subunit gene (CHRNA4) with nicotine dependence., Hum Mol Genet
Matera C et al., 2015, Bifunctional compounds targeting both D2 and non-α7 nACh receptors: design, synthesis and pharmacological characterization., Eur J Med Chem
Rollema et al., 2007, Rationale, pharmacology and clinical efficacy of partial agonists of alpha4beta2 nACh receptors for smoking cessation., Trends Pharmacol. Sci.
Steensland et al., 2007, Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, selectively decreases ethanol consumption and seeking., Proc. Natl. Acad. Sci. U.S.A.
McColl et al., 2008, Human abuse liability of the smoking cessation drug varenicline in smokers and nonsmokers., Clin. Pharmacol. Ther.
Chen et al., 2002, TTD: Therapeutic Target Database., Nucleic Acids Res.
Nakamura et al., 2007, Efficacy and tolerability of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, in a 12-week, randomized, placebo-controlled, dose-response study with 40-week follow-up for smoking cessation in Japanese smokers., Clin Ther
Rocha Santos J et al., 2015, CHRNA4 rs1044396 is associated with smoking cessation in varenicline therapy., Front Genet
Walker et al., 2014, Cytisine versus nicotine for smoking cessation., N. Engl. J. Med.
Houlihan et al., 2001, Activity of cytisine and its brominated isosteres on recombinant human alpha7, alpha4beta2 and alpha4beta4 nicotinic acetylcholine receptors., J. Neurochem.
Eaton JB et al., 2003, Characterization of human alpha 4 beta 2-nicotinic acetylcholine receptors stably and heterologously expressed in native nicotinic receptor-null SH-EP1 human epithelial cells., Mol Pharmacol
Kim SA et al., 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
Dopico et al., 2009, Acute alcohol action and desensitization of ligand-gated ion channels., Pharmacol. Rev.
Hendrickson et al., 2013, Neuronal nicotinic acetylcholine receptors: common molecular substrates of nicotine and alcohol dependence., Front Psychiatry
Damaj et al., 2005, Effect of dextrometorphan and dextrorphan on nicotine and neuronal nicotinic receptors: in vitro and in vivo selectivity., J. Pharmacol. Exp. Ther.
Smulders CJ et al., 2005, Cholinergic drugs potentiate human nicotinic alpha4beta2 acetylcholine receptors by a competitive mechanism., Eur J Pharmacol
Matsubayashi H et al., 1997, Amantadine inhibits nicotinic acetylcholine receptor function in hippocampal neurons., J Pharmacol Exp Ther
Yamashita M et al., 2005, Isoflurane modulation of neuronal nicotinic acetylcholine receptors expressed in human embryonic kidney cells., Anesthesiology
Flood P et al., 2002, Isoflurane hyperalgesia is modulated by nicotinic inhibition., Anesthesiology
Brannigan G et al., 2010, Multiple binding sites for the general anesthetic isoflurane identified in the nicotinic acetylcholine receptor transmembrane domain., Proc Natl Acad Sci U S A
Paradiso K et al., 2001, The C terminus of the human nicotinic alpha4beta2 receptor forms a binding site required for potentiation by an estrogenic steroid., J Neurosci
Jin X et al., 2011, A portable site: a binding element for 17β-estradiol can be placed on any subunit of a nicotinic α4β2 receptor., J Neurosci
Talka R et al., 2015, Methadone's effect on nAChRs--a link between methadone use and smoking?, Biochem Pharmacol
Talka R et al., 2015, Methadone is a non-competitive antagonist at the α4β2 and α3* nicotinic acetylcholine receptors and an agonist at the α7 nicotinic acetylcholine receptor., Basic Clin Pharmacol Toxicol
Ortells MO et al., 2002, Molecular modelling of the interactions of carbamazepine and a nicotinic receptor involved in the autosomal dominant nocturnal frontal lobe epilepsy., Br J Pharmacol
Di Resta C et al., 2010, Effect of carbamazepine and oxcarbazepine on wild-type and mutant neuronal nicotinic acetylcholine receptors linked to nocturnal frontal lobe epilepsy., Eur J Pharmacol
Bertrand D, 2002, Neuronal Nicotinic Acetylcholine Receptors and Epilepsy., Epilepsy Curr

VARENICLINE CHRNA4

Interaction Score: 1.37

Interaction Types & Directionality:

partial agonist (activating)

agonist (activating)

Interaction Info:

Trial Name varenicline, CP-526

Novel drug target Established target

Details of the Assay for Interaction In vitro affinity for recombinant human α4β2 receptors in membranes from transfected CHO-K1 cells, determined by displacement of [3H]-(−)-cytisine.

PMIDs:
17573127 17626178 18288085 11752352 17692720 25774163

Sources:
DrugBank TdgClinicalTrial TEND GuideToPharmacology PharmGKB

ISPRONICLINE CHRNA4

Interaction Score: 1.0

Interaction Types & Directionality:

partial agonist (activating)

Interaction Info:

Novel drug target Established target

Trial Name TC-1734, AZD-3480, ispronicline

Mechanism of Interaction Neuronal acetylcholine receptor; alpha4/beta2 partial agonist

PMIDs:
None found

Sources:
TdgClinicalTrial ChemblInteractions
CHEMBL59986 CHRNA4

Interaction Score: 1.0

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
TTD
DEXMECAMYLAMINE CHRNA4

Interaction Score: 1.0

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Novel drug target Established target

Trial Name TC-5214

Mechanism of Interaction Neuronal acetylcholine receptor; alpha4/beta2 antagonist

PMIDs:
None found

Sources:
TdgClinicalTrial ChemblInteractions
POZANICLINE CHRNA4

Interaction Score: 0.75

Interaction Types & Directionality:

partial agonist (activating)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction Nicotinic acetylcholine receptor alpha4/beta2/alpha5 partial agonist

Trial Name pozanicline , ABT-089

PMIDs:
None found

Sources:
DrugBank TdgClinicalTrial ChemblInteractions
HEXOBARBITAL CHRNA4

Interaction Score: 0.6

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Trial Name -

Novel drug target Established target

PMIDs:
16248797 11264449 10487207

Sources:
DrugBank TdgClinicalTrial TEND
BUTETHAL CHRNA4

Interaction Score: 0.6

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Trial Name -

Novel drug target Established target

PMIDs:
16248797 11264449 10487207

Sources:
DrugBank TdgClinicalTrial TEND
CYTISINICLINE CHRNA4

Interaction Score: 0.57

Interaction Types & Directionality:

agonist (activating)

Interaction Info:

PMIDs:
25517706 11553677

Sources:
DrugBank TTD
SECOBARBITAL CHRNA4

Interaction Score: 0.54

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Novel drug target Established target

Trial Name -

PMIDs:
16248797 11264449 10487207

Sources:
DrugBank TdgClinicalTrial TEND
TRIMETHAPHAN CHRNA4

Interaction Score: 0.5

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
TTD
TEBANICLINE CHRNA4

Interaction Score: 0.5

Interaction Types & Directionality:

agonist (activating)

Interaction Info:

Mechanism of Interaction Neuronal acetylcholine receptor; alpha4/beta2 agonist

Direct Interaction yes

PMIDs:
None found

Sources:
ChemblInteractions
AZD1446 CHRNA4

Interaction Score: 0.5

Interaction Types & Directionality:

agonist (activating)

Interaction Info:

Mechanism of Interaction Neuronal acetylcholine receptor; alpha4/beta2 agonist

Direct Interaction yes

PMIDs:
None found

Sources:
ChemblInteractions
VARENICLINE TARTRATE CHRNA4

Interaction Score: 0.5

Interaction Types & Directionality:

agonist (activating)

Interaction Info:

Mechanism of Interaction Neuronal acetylcholine receptor; alpha4/beta2 agonist

Direct Interaction yes

PMIDs:
None found

Sources:
ChemblInteractions
ABT-560 CHRNA4

Interaction Score: 0.5

Interaction Types & Directionality:

modulator

Interaction Info:

Mechanism of Interaction Neuronal acetylcholine receptor; alpha4/beta2 modulator

Direct Interaction yes

PMIDs:
None found

Sources:
ChemblInteractions
NICOTINE POLACRILEX CHRNA4

Interaction Score: 0.5

Interaction Types & Directionality:

agonist (activating)

Interaction Info:

Mechanism of Interaction Neuronal acetylcholine receptor; alpha4/beta2 agonist

Direct Interaction yes

PMIDs:
None found

Sources:
ChemblInteractions
TC-2216 CHRNA4

Interaction Score: 0.5

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction Neuronal acetylcholine receptor; alpha4/beta2 antagonist

PMIDs:
None found

Sources:
ChemblInteractions
THIOPENTAL CHRNA4

Interaction Score: 0.5

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Trial Name -

Novel drug target Established target

PMIDs:
16248797 11264449 10487207

Sources:
DrugBank TdgClinicalTrial TEND
ALTINICLINE CHRNA4

Interaction Score: 0.5

Interaction Types & Directionality:

agonist (activating)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction Neuronal acetylcholine receptor; alpha4/beta2 agonist

PMIDs:
None found

Sources:
ChemblInteractions
SOFINICLINE CHRNA4

Interaction Score: 0.5

Interaction Types & Directionality:

agonist (activating)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction Neuronal acetylcholine receptor; alpha4/beta2 agonist

PMIDs:
None found

Sources:
ChemblInteractions
TC-6499 CHRNA4

Interaction Score: 0.5

Interaction Types & Directionality:

agonist (activating)

Interaction Info:

Trial Name TC-6499

Novel drug target Established target

Mechanism of Interaction Neuronal acetylcholine receptor; alpha4/beta2 agonist

PMIDs:
None found

Sources:
TdgClinicalTrial ChemblInteractions
MEPHOBARBITAL CHRNA4

Interaction Score: 0.46

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Trial Name -

Novel drug target Established target

PMIDs:
16248797 11264449 10487207

Sources:
DrugBank TdgClinicalTrial TEND

NICOTINE CHRNA4

Interaction Score: 0.42

Interaction Types & Directionality:

agonist (activating)

Interaction Info:

Details of the Assay for Interaction In vitro affinity for recombinant human α4β2 receptors in membranes from transfected CHO-K1 cells, determined by displacement of [3H]-(−)-cytisine.

Specific Action of the Ligand Agonist

Details of Interaction α4β2

AMOBARBITAL CHRNA4

Interaction Score: 0.4

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

PMIDs:
16248797 11264449 10487207

Sources:
DrugBank
BARBITAL CHRNA4

Interaction Score: 0.4

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

PMIDs:
16248797 11264449 10487207

Sources:
DrugBank
HEPTABARBITAL CHRNA4

Interaction Score: 0.4

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

PMIDs:
16248797 11264449 10487207

Sources:
DrugBank

ATRACURIUM CHRNA4

Interaction Score: 0.4

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Details of the Assay for Interaction Antagonism of ACh activation of human α4β2 nACh receptors expressed in Xenopus oocytes, at different ACh concentrations.

Specific Action of the Ligand Antagonist

Endogenous Drug? False

PMIDs:
None found

Sources:
GuideToPharmacology TTD

APROBARBITAL CHRNA4

Interaction Score: 0.4

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

PMIDs:
16248797 11264449 10487207

Sources:
DrugBank
MECAMYLAMINE CHRNA4

Interaction Score: 0.36

Interaction Types & Directionality:

blocker (inhibitory)

Interaction Info:

Specific Action of the Ligand None

Details of Interaction α4β4

Endogenous Drug? False

PMIDs:
14645658

Sources:
DrugBank GuideToPharmacology TTD
PHYSOSTIGMINE CHRNA4

Interaction Score: 0.33

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
14645658

Sources:
DrugBank
DECAMETHONIUM CHRNA4

Interaction Score: 0.33

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
14645658

Sources:
DrugBank
CP-601927 CHRNA4

Interaction Score: 0.33

Interaction Types & Directionality:

partial agonist (activating)

Interaction Info:

Mechanism of Interaction Neuronal acetylcholine receptor; alpha4/beta2 partial agonist

Direct Interaction yes

PMIDs:
None found

Sources:
ChemblInteractions
DEXEFAROXAN CHRNA4

Interaction Score: 0.33

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
TTD
CHEMBL490153 CHRNA4

Interaction Score: 0.33

Interaction Types & Directionality:

blocker (inhibitory)

Interaction Info:

Specific Action of the Ligand None

Details of Interaction α4β2

Endogenous Drug? False

PMIDs:
None found

Sources:
GuideToPharmacology
RIVANICLINE CHRNA4

Interaction Score: 0.33

Interaction Types & Directionality:

agonist (activating)

Interaction Info:

Direct Interaction? False

Endogenous Drug? False

Specific Action of the Ligand Agonist

PMIDs:
None found

Sources:
GuideToPharmacology
TALBUTAL CHRNA4

Interaction Score: 0.3

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Trial Name -

Novel drug target Established target

PMIDs:
16248797 11264449 10487207

Sources:
DrugBank TdgClinicalTrial TEND
METHARBITAL CHRNA4

Interaction Score: 0.3

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Novel drug target Established target

Trial Name -

PMIDs:
16248797 11264449 10487207

Sources:
DrugBank TdgClinicalTrial TEND
BUTALBITAL CHRNA4

Interaction Score: 0.3

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Trial Name -

Novel drug target Established target

PMIDs:
16248797 11264449 10487207

Sources:
DrugBank TdgClinicalTrial TEND
EPIBATIDINE CHRNA4

Interaction Score: 0.28

Interaction Types & Directionality:

agonist (activating)

Interaction Info:

PMIDs:
9454827

Sources:
DrugBank
BUTABARBITAL CHRNA4

Interaction Score: 0.28

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Trial Name -

Novel drug target Established target

PMIDs:
16248797 11264449 10487207

Sources:
TdgClinicalTrial TEND
PENTOBARBITAL CHRNA4

Interaction Score: 0.27

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Trial Name -

Novel drug target Established target

PMIDs:
16248797 11264449 10487207

Sources:
DrugBank TdgClinicalTrial TEND
SCOPOLAMINE CHRNA4

Interaction Score: 0.25

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
15733544

Sources:
DrugBank
HEXAMETHONIUM CHRNA4

Interaction Score: 0.25

Interaction Types & Directionality:

blocker (inhibitory)

Interaction Info:

Specific Action of the Ligand None

Details of Interaction α4β2

Endogenous Drug? False

PMIDs:
None found

Sources:
GuideToPharmacology
PENTOLINIUM CHRNA4

Interaction Score: 0.25

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
TTD
AMANTADINE CHRNA4

Interaction Score: 0.2

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

PMIDs:
9152392

Sources:
DrugBank
PANCURONIUM CHRNA4

Interaction Score: 0.2

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
TTD
PRIMIDONE CHRNA4

Interaction Score: 0.19

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Trial Name -

Novel drug target Established target

PMIDs:
16248797 11264449 10487207

Sources:
DrugBank TdgClinicalTrial TEND
PHENOBARBITAL CHRNA4

Interaction Score: 0.16

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Trial Name -

Novel drug target Established target

PMIDs:
16248797 11264449 10487207

Sources:
DrugBank TdgClinicalTrial TEND
ESTRADIOL BENZOATE CHRNA4

Interaction Score: 0.15

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
11517245

Sources:
DrugBank
ASM-024 CHRNA4

Interaction Score: 0.14

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
TTD
ATROPINE CHRNA4

Interaction Score: 0.13

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
15733544

Sources:
DrugBank
ISOFLURANE CHRNA4

Interaction Score: 0.12

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

PMIDs:
15618790 12131122 20660787

Sources:
DrugBank
DEXTROMETHORPHAN CHRNA4

Interaction Score: 0.1

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

PMIDs:
15356218

Sources:
DrugBank
COTININE CHRNA4

Interaction Score: 0.1

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
TTD
METHADONE CHRNA4

Interaction Score: 0.09

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

PMIDs:
26231941 25196810

Sources:
DrugBank
ESTRADIOL CHRNA4

Interaction Score: 0.09

Interaction Types & Directionality:

binder

Interaction Info:

PMIDs:
11517245 21451042

Sources:
DrugBank
CARBAMAZEPINE CHRNA4

Interaction Score: 0.08

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
12110613 20561518 15309115

Sources:
DrugBank
ALCOHOL CHRNA4

Interaction Score: 0.04

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
15902904 19270242 23641218

Sources:
DrugBank PharmGKB

Ensembl: ENSG00000101204
- Version: 101_38
Alternate Names:

CHRNA4 Ensembl Gene Name

Gene Info:

Gene Biotype PROTEIN_CODING

Publications:
TdgClinicalTrial: P43681
- Version: January-2014
Alternate Names:

CHRNA4 Gene Symbol

Gene Info:

Target Class Receptors

Target Subclass TC:1.A.9

Publications:
RussLampel: ENSG00000101204
- Version: 26-July-2011
Alternate Names:

ENSG00000101204 Ensembl Gene Id

CHRNA4 Display Id

NEURONAL ACETYLCHOLINE RECEPTOR PROTEIN, ALPHA-4 SUBUNIT PRECURSOR. [SOURCE:UNIPROT/SWISSPROT;ACC:P43681] Description

Gene Info:

Human Readable Name DRUGGABLE GENOME

Gene Categories:

DRUGGABLE GENOME

Publications:
HopkinsGroom: P43681
- Version: 11-September-2012
Alternate Names:

ACHA4_HUMAN Uniprot Id

CHRNA4 Uniprot Gene Name

ENSG00000101204 Ensembl Gene Id

Gene Info:

Uniprot Status Swiss-Prot

Interpro Type Domain

Interpro Name Neurotransmitter-gated ion-channel ligand-binding

Gene Categories:

ION CHANNEL, DRUGGABLE GENOME

Publications:
TEND: P43681
- Version: 01-August-2011
Alternate Names:

ACHA4_HUMAN Uniprot Id

ENSG00000101204 Ensembl Gene Id

1137 Entrez Gene Id

Gene Info:

Transmembrane Helix Count 4

Target Subclass Ligand_gated_ion_channels

Target Subclass Channels

Publications:
GuideToPharmacology: 1137
- Version: 29-September-2020
Alternate Names:

1958 HUGO Gene ID

1958 HUGO Gene Symbol

cholinergic receptor nicotinic alpha 4 subunit HUGO Gene Name

Gene Info:

GuideToPharmacology Gene Category Name Nicotinic acetylcholine receptors

GuideToPharmacology Gene Category ID 76

Gene Categories:

ION CHANNEL

Publications:

PharmGKB: CHRNA4

Version: 18-August-2020

Alternate Names:

PA26490 PharmGKB ID

Gene Info:

Publications:

Rocha Santos J et al., 2015, CHRNA4 rs1044396 is associated with smoking cessation in varenicline therapy., Front Genet

Li MD et al., 2005, Ethnic- and gender-specific association of the nicotinic acetylcholine receptor alpha4 subunit gene (CHRNA4) with nicotine dependence., Hum Mol Genet

Breitling LP et al., 2009, Association of nicotinic acetylcholine receptor subunit alpha 4 polymorphisms with nicotine dependence in 5500 Germans., Pharmacogenomics J

DrugBank: BE0000849

Version: 5.1.7

Alternate Names:

CHRNA4 DrugBank Gene Name

P43681 UniProt Accession

1137 Entrez Gene Id

Gene Info:

Publications:

De Luca et al., 2006, Genetic interaction between alpha4 and beta2 subunits of high affinity nicotinic receptor: analysis in schizophrenia., Exp Brain Res

Narahashi et al., 2000, Symposium overview: mechanism of action of nicotine on neuronal acetylcholine receptors, from molecule to behavior., Toxicol. Sci.

Mansvelder et al., 2009, Nicotinic modulation of synaptic transmission and plasticity in cortico-limbic circuits., Semin. Cell Dev. Biol.

TTD: Nicotinic acetylcholine receptor

Version: 2020.06.01

Alternate Names:

nAChR TTD Gene Abbreviation

T78111 TTD Target ID

Gene Info:

Publications:

Sunaga H et al., 2010, Gantacurium and CW002 do not potentiate muscarinic receptor-mediated airway smooth muscle constriction in guinea pigs., Anesthesiology

Casella G et al., 2010, Therapeutic advances in the treatment of nicotine addiction: present and future., Ther Adv Chronic Dis

DTC: CHRNA4
- Version: 02-September-2020
Alternate Names:

Gene Info:

Publications:

Matera C et al., 2015, Bifunctional compounds targeting both D2 and non-α7 nACh receptors: design, synthesis and pharmacological characterization., Eur J Med Chem
HingoraniCasas: ENSG00000101204
- Version: 31-May-2017
Alternate Names:

ENSG00000101204 Gene Symbol

CHRNA4 Ensembl Id

Gene Info:

Gene Categories:

DRUGGABLE GENOME

Publications:
ChemblInteractions: NACRA4
- Version: chembl_23
Alternate Names:

NACRA4 GENE_SYMBOL

CHRNA4 GENE_SYMBOL

Neuronal acetylcholine receptor subunit alpha-4 UNIPROT

Gene Info:

Publications:
Pharos: CHRNA4
- Version: 03-September-2020
Alternate Names:

Neuronal acetylcholine receptor subunit alpha-4 Gene Name

P43681 UniProt ID

Gene Info:

Gene Categories:

ION CHANNEL

Publications:
GO: CHRNA4
- Version: 05-September-2020
Alternate Names:

NACRA4 GO Gene Synonym

Gene Info:

Gene Categories:

DNA REPAIR, EXTERNAL SIDE OF PLASMA MEMBRANE

Publications:
TTD: Neuronal acetylcholine receptor alpha-4
- Version: 2020.06.01
Alternate Names:

CHRNA4 TTD Gene Abbreviation

T70967 TTD Target ID

Gene Info:

Publications:

Trial Name	varenicline, CP-526
Novel drug target	Established target
Details of the Assay for Interaction	<i>In vitro</i> affinity for recombinant human α4β2 receptors in membranes from transfected CHO-K1 cells, determined by displacement of [<sup>3</sup>H]-(−)-cytisine.

Direct Interaction	yes
Mechanism of Interaction	Nicotinic acetylcholine receptor alpha4/beta2/alpha5 partial agonist
Trial Name	pozanicline , ABT-089

Mechanism of Interaction	Neuronal acetylcholine receptor; alpha4/beta2 agonist
Direct Interaction	yes

Trial Name	TC-6499
Novel drug target	Established target
Mechanism of Interaction	Neuronal acetylcholine receptor; alpha4/beta2 agonist

Details of the Assay for Interaction	<i>In vitro</i> affinity for recombinant human α4β2 receptors in membranes from transfected CHO-K1 cells, determined by displacement of [<sup>3</sup>H]-(−)-cytisine.
Specific Action of the Ligand	Agonist
Details of Interaction	α4β2

Details of the Assay for Interaction	Antagonism of ACh activation of human α4β2 nACh receptors expressed in <i>Xenopus</i> oocytes, at different ACh concentrations.
Specific Action of the Ligand	Antagonist
Endogenous Drug?	False

Specific Action of the Ligand	None
Details of Interaction	α4β4
Endogenous Drug?	False

Direct Interaction?	False
Endogenous Drug?	False
Specific Action of the Ligand	Agonist

ENSG00000101204	Ensembl Gene Id
CHRNA4	Display Id
NEURONAL ACETYLCHOLINE RECEPTOR PROTEIN, ALPHA-4 SUBUNIT PRECURSOR. [SOURCE:UNIPROT/SWISSPROT;ACC:P43681]	Description

ACHA4_HUMAN	Uniprot Id
CHRNA4	Uniprot Gene Name
ENSG00000101204	Ensembl Gene Id

1958	HUGO Gene ID
1958	HUGO Gene Symbol
cholinergic receptor nicotinic alpha 4 subunit	HUGO Gene Name

CHRNA4	DrugBank Gene Name
P43681	UniProt Accession
1137	Entrez Gene Id

NACRA4	GENE_SYMBOL
CHRNA4	GENE_SYMBOL
Neuronal acetylcholine receptor subunit alpha-4	UNIPROT

Neuronal acetylcholine receptor subunit alpha-4	Gene Name
P43681	UniProt ID

CHRNA4 Gene Record

CHRNA4 1137 Druggable Genome

Alternate Names:

Gene Info:

Gene Categories: Category Details

Publications:

Interaction Types & Directionality: partial agonist (activating) agonist (activating)

PMIDs: 17573127 17626178 18288085 11752352 17692720 25774163

Sources: DrugBank TdgClinicalTrial TEND GuideToPharmacology PharmGKB

Interaction Types & Directionality: partial agonist (activating)

Interaction Info: Novel drug target Established target Trial Name TC-1734, AZD-3480, ispronicline Mechanism of Interaction Neuronal acetylcholine receptor; alpha4/beta2 partial agonist

PMIDs: None found

Sources: TdgClinicalTrial ChemblInteractions

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: None found

Sources: TTD

Interaction Types & Directionality: antagonist (inhibitory)

Interaction Info: Novel drug target Established target Trial Name TC-5214 Mechanism of Interaction Neuronal acetylcholine receptor; alpha4/beta2 antagonist

PMIDs: None found

Sources: TdgClinicalTrial ChemblInteractions

Interaction Types & Directionality: partial agonist (activating)

Interaction Info: Direct Interaction yes Mechanism of Interaction Nicotinic acetylcholine receptor alpha4/beta2/alpha5 partial agonist Trial Name pozanicline , ABT-089

PMIDs: None found

Sources: DrugBank TdgClinicalTrial ChemblInteractions

Interaction Types & Directionality: antagonist (inhibitory)

Interaction Info: Trial Name - Novel drug target Established target

PMIDs: 16248797 11264449 10487207

Sources: DrugBank TdgClinicalTrial TEND

Interaction Types & Directionality: antagonist (inhibitory)

Interaction Info: Trial Name - Novel drug target Established target

PMIDs: 16248797 11264449 10487207

Sources: DrugBank TdgClinicalTrial TEND

Interaction Types & Directionality: agonist (activating)

Interaction Info:

PMIDs: 25517706 11553677

Sources: DrugBank TTD

Interaction Types & Directionality: antagonist (inhibitory)

Interaction Info: Novel drug target Established target Trial Name -

PMIDs: 16248797 11264449 10487207

Sources: DrugBank TdgClinicalTrial TEND

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: None found

Sources: TTD

Interaction Types & Directionality: agonist (activating)

Interaction Info: Mechanism of Interaction Neuronal acetylcholine receptor; alpha4/beta2 agonist Direct Interaction yes

PMIDs: None found

Sources: ChemblInteractions

Interaction Types & Directionality: agonist (activating)

Interaction Info: Mechanism of Interaction Neuronal acetylcholine receptor; alpha4/beta2 agonist Direct Interaction yes

PMIDs: None found

Sources: ChemblInteractions

Interaction Types & Directionality: agonist (activating)

Interaction Info: Mechanism of Interaction Neuronal acetylcholine receptor; alpha4/beta2 agonist Direct Interaction yes

PMIDs: None found

Sources: ChemblInteractions

Interaction Types & Directionality: modulator

Interaction Info: Mechanism of Interaction Neuronal acetylcholine receptor; alpha4/beta2 modulator Direct Interaction yes

PMIDs: None found

Sources: ChemblInteractions

Interaction Types & Directionality: agonist (activating)

Interaction Info: Mechanism of Interaction Neuronal acetylcholine receptor; alpha4/beta2 agonist Direct Interaction yes

PMIDs: None found

Sources: ChemblInteractions

Interaction Types & Directionality: antagonist (inhibitory)

Interaction Info: Direct Interaction yes Mechanism of Interaction Neuronal acetylcholine receptor; alpha4/beta2 antagonist

PMIDs: None found

Sources: ChemblInteractions

Interaction Types & Directionality: antagonist (inhibitory)

Interaction Info: Trial Name - Novel drug target Established target

PMIDs: 16248797 11264449 10487207

Sources: DrugBank TdgClinicalTrial TEND

Interaction Types & Directionality: agonist (activating)

Interaction Info: Direct Interaction yes Mechanism of Interaction Neuronal acetylcholine receptor; alpha4/beta2 agonist

PMIDs: None found

Sources: ChemblInteractions

Interaction Types & Directionality: agonist (activating)

Interaction Info: Direct Interaction yes Mechanism of Interaction Neuronal acetylcholine receptor; alpha4/beta2 agonist

PMIDs: None found

Interaction Types & Directionality:

partial agonist (activating)

agonist (activating)

PMIDs:
17573127 17626178 18288085 11752352 17692720 25774163

Sources:
DrugBank TdgClinicalTrial TEND GuideToPharmacology PharmGKB

Interaction Types & Directionality:

partial agonist (activating)

Interaction Info:

Novel drug target Established target

Trial Name TC-1734, AZD-3480, ispronicline

Mechanism of Interaction Neuronal acetylcholine receptor; alpha4/beta2 partial agonist

PMIDs:
None found

Sources:
TdgClinicalTrial ChemblInteractions

Interaction Types & Directionality:

n/a

PMIDs:
None found

Sources:
TTD

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Novel drug target Established target

Trial Name TC-5214

Mechanism of Interaction Neuronal acetylcholine receptor; alpha4/beta2 antagonist

PMIDs:
None found

Sources:
TdgClinicalTrial ChemblInteractions

Interaction Types & Directionality:

partial agonist (activating)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction Nicotinic acetylcholine receptor alpha4/beta2/alpha5 partial agonist

Trial Name pozanicline , ABT-089

PMIDs:
None found

Sources:
DrugBank TdgClinicalTrial ChemblInteractions

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Trial Name -

Novel drug target Established target

PMIDs:
16248797 11264449 10487207

Sources:
DrugBank TdgClinicalTrial TEND

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Trial Name -

Novel drug target Established target

PMIDs:
16248797 11264449 10487207

Sources:
DrugBank TdgClinicalTrial TEND

Interaction Types & Directionality:

agonist (activating)

PMIDs:
25517706 11553677

Sources:
DrugBank TTD

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Novel drug target Established target

Trial Name -

PMIDs:
16248797 11264449 10487207

Sources:
DrugBank TdgClinicalTrial TEND

Interaction Types & Directionality:

n/a

PMIDs:
None found

Sources:
TTD

Interaction Types & Directionality:

agonist (activating)

Interaction Info:

Mechanism of Interaction Neuronal acetylcholine receptor; alpha4/beta2 agonist

Direct Interaction yes

PMIDs:
None found

Sources:
ChemblInteractions

Interaction Types & Directionality:

agonist (activating)

Interaction Info:

Mechanism of Interaction Neuronal acetylcholine receptor; alpha4/beta2 agonist

Direct Interaction yes

PMIDs:
None found

Sources:
ChemblInteractions

Interaction Types & Directionality:

agonist (activating)

Interaction Info:

Mechanism of Interaction Neuronal acetylcholine receptor; alpha4/beta2 agonist

Direct Interaction yes

PMIDs:
None found

Sources:
ChemblInteractions

Interaction Types & Directionality:

modulator

Interaction Info:

Mechanism of Interaction Neuronal acetylcholine receptor; alpha4/beta2 modulator

Direct Interaction yes

PMIDs:
None found

Sources:
ChemblInteractions

Interaction Types & Directionality:

agonist (activating)

Interaction Info:

Mechanism of Interaction Neuronal acetylcholine receptor; alpha4/beta2 agonist

Direct Interaction yes

PMIDs:
None found

Sources:
ChemblInteractions

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction Neuronal acetylcholine receptor; alpha4/beta2 antagonist

PMIDs:
None found

Sources:
ChemblInteractions

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Trial Name -

Novel drug target Established target

PMIDs:
16248797 11264449 10487207

Sources:
DrugBank TdgClinicalTrial TEND

Interaction Types & Directionality:

agonist (activating)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction Neuronal acetylcholine receptor; alpha4/beta2 agonist

PMIDs:
None found

Sources:
ChemblInteractions

Interaction Types & Directionality:

agonist (activating)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction Neuronal acetylcholine receptor; alpha4/beta2 agonist

PMIDs:
None found

Sources:
ChemblInteractions

Interaction Types & Directionality:

agonist (activating)

Interaction Info:

Trial Name TC-6499

Novel drug target Established target

Mechanism of Interaction Neuronal acetylcholine receptor; alpha4/beta2 agonist

PMIDs:
None found

Sources:
TdgClinicalTrial ChemblInteractions

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Trial Name -

Novel drug target Established target

PMIDs:
16248797 11264449 10487207

Sources:
DrugBank TdgClinicalTrial TEND