CHRNB3

Summary

CHRNB3 (cholinergic receptor nicotinic beta 3 subunit, HGNC:1963) is a protein-coding gene on chromosome 8p11.21, encoding Neuronal acetylcholine receptor subunit beta-3 (Q05901). Component of neuronal acetylcholine receptors (nAChRs) that function as pentameric, ligand-gated cation channels with high calcium permeability among other activities. nAChRs are excitatory neurotrasnmitter receptors formed by a collection of nAChR subunits known to mediate syna….

The nicotinic acetylcholine receptors (nAChRs) are members of a superfamily of ligand-gated ion channels that mediate fast signal transmission at synapses. The nAChRs are (hetero)pentamers composed of homologous subunits. The subunits that make up the muscle and neuronal forms of nAChRs are encoded by separate genes and have different primary structure. There are several subtypes of neuronal nAChRs that vary based on which homologous subunits are arranged around the central channel. They are classified as alpha-subunits if, like muscle alpha-1 (MIM 100690), they have a pair of adjacent cysteines as part of the presumed acetylcholine binding site. Subunits lacking these cysteine residues are classified as beta-subunits (Groot Kormelink and Luyten, 1997 [PubMed 9009220]). Elliott et al. (1996) [PubMed 8906617] stated that the proposed structure for each subunit is a conserved N-terminal extracellular domain followed by 3 conserved transmembrane domains, a variable cytoplasmic loop, a fourth conserved transmembrane domain, and a short C-terminal extracellular region.

Source: NCBI Gene 1142 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 75 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000749

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1963
Approved symbol	CHRNB3
Name	cholinergic receptor nicotinic beta 3 subunit
Location	8p11.21
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000147432
Ensembl biotype	protein_coding
OMIM	118508
Entrez	1142

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000289957, ENST00000531610, ENST00000534391

RefSeq mRNA: 2 — MANE Select: NM_000749 NM_000749, NM_001347717

CCDS: CCDS6134

Canonical transcript exons

ENST00000289957 — 6 exons

Exon	Start	End
ENSE00001090338	42731667	42732549
ENSE00001121232	42736484	42737407
ENSE00001240507	42730594	42730703
ENSE00001240532	42697366	42697598
ENSE00001612761	42710390	42710434
ENSE00003562206	42708717	42708868

Expression profiles

Bgee: expression breadth broad, 71 present calls, max score 77.18.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0911 / max 23.2726, expressed in 44 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
88700	0.0423	18
88699	0.0312	12
88701	0.0176	7

Top tissues by expression

253 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.18	gold quality
pancreatic ductal cell	CL:0002079	65.96	silver quality
ileal mucosa	UBERON:0000331	62.86	gold quality
tibialis anterior	UBERON:0001385	60.60	silver quality
right testis	UBERON:0004534	59.80	gold quality
cerebellar cortex	UBERON:0002129	59.08	gold quality
cerebellar hemisphere	UBERON:0002245	58.91	gold quality
left testis	UBERON:0004533	58.85	gold quality
prefrontal cortex	UBERON:0000451	58.20	gold quality
cerebellum	UBERON:0002037	57.80	gold quality
testis	UBERON:0000473	57.37	gold quality
substantia nigra	UBERON:0002038	56.90	gold quality
decidua	UBERON:0002450	56.55	gold quality
endometrium epithelium	UBERON:0004811	56.31	gold quality
body of pancreas	UBERON:0001150	55.96	gold quality
right hemisphere of cerebellum	UBERON:0014890	55.62	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	55.35	gold quality
midbrain	UBERON:0001891	55.23	gold quality
frontal cortex	UBERON:0001870	52.91	gold quality
hair follicle	UBERON:0002073	52.43	gold quality
neocortex	UBERON:0001950	51.55	gold quality
Brodmann (1909) area 9	UBERON:0013540	51.39	gold quality
cerebellar vermis	UBERON:0004720	50.99	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	50.84	gold quality
right frontal lobe	UBERON:0002810	50.64	gold quality
quadriceps femoris	UBERON:0001377	50.54	gold quality
frontal pole	UBERON:0002795	50.41	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
paraflocculus	UBERON:0005351	50.18	gold quality
Brodmann (1909) area 10	UBERON:0013541	50.18	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-25	yes	8.23
E-ANND-3	yes	3.77
E-MTAB-7303	no	502.55

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

17 targeting CHRNB3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-4320	99.75	65.80	793
HSA-MIR-2116-3P	99.74	64.32	889
HSA-MIR-4784	99.15	67.41	1733
HSA-MIR-3190-5P	98.87	64.89	1345
HSA-MIR-3150B-3P	98.81	67.21	1728
HSA-MIR-11399	98.71	65.69	869
HSA-MIR-4660	97.79	67.44	1328
HSA-MIR-4639-3P	97.54	67.12	787
HSA-MIR-4689	96.97	65.79	1209
HSA-MIR-6858-5P	96.05	64.59	1020

Literature-anchored findings (GeneRIF, showing 28)

• absence of differences in the pharmacological profile of nicotinic receptor alpha3beta4 argues against role for incorporated beta3 subunit in formation of agonist binding sites while changes in channel kinetics suggest important effect on receptor gating (PMID:12912995)
• CHRNB3 is associated with subjective responses to tobacco. (PMID:18055561)
• Together these results further implicate the region downstream of CHRNA6 and the region upstream of CHRNB3 in risk of nicotine dependence. (PMID:18704094)
• There was no evidence of association of any of the SNPs in CHRNAB2 (rs2072661, rs4845378) or CHRNAB3 (rs4953, rs6474413) with smoking status (p=0.30) or, among daily smokers, of association with cotinine levels (p=0.08). (PMID:19482438)
• Three single nucleotide polymorphisms (SNPs) in CHRNA6 and one SNP in CHRNB3 are associated with a composite of alcohol phenotypes. (PMID:19500157)
• CHRNB3-CHRNA6 and CYP2A6 sequence variants affect smoking behavior (PMID:20418888)
• Concatameric pentamers and pentamers formed from combinations of trimers, dimers, and monomers of alpha6beta2beta3* acetylcholine receptors exhibit similar properties, indicating that the linkers between subunits do not alter their functional properties. (PMID:20923852)
• Variants in CHRNB3/CHRNA6 are independently associated with bipolar disorder. (PMID:21191315)
• The GG genotype of SNP rs13261190 in the CHRNB3 was associated with increased novelty seeking in alcohol-dependent individuals. (PMID:21606657)
• CHRNB3 and CHRNA6 polymorphisms are associated with smoking behavior and lung cancer susceptibility in Chinese Han population. (PMID:21831805)
• beta3 subunit coexpression promotes function of alpha6*-nAChR (PMID:22315221)
• The results indicate the genetic locus for the CHRNB3 gene is strongly associated with nicotine dependence. (PMID:22524403)
• this study provides convincing evidence for a role of CHRNB3 in Nicotine Dependence. (PMID:23319001)
• Results demonstrate the association between SNPs in CHRNB3 nicotinic acetylcholine receptor genes and the risk of smoking in ADHD (PMID:23899432)
• Level of cigarettes per day during adolescence and young adulthood is associated with CHRNB3A6, CHRNA5A3B4, and CHRNA2 (PMID:23943838)
• This patient’s chromosomal abnormality affected only one gene that is highly expressed in the brainstem and brain, involved in neurotransmission, and could be related to her Duane retraction syndrome. (PMID:24001015)
• Rare missense variants in CHRNB3 and CHRNA3 are associated with risk of alcohol and cocaine dependence. (PMID:24057674)
• The common variant rs13273442 in the CHRNB3-CHNRA6 region is associated significantly with nicotine dependence in European Americans and African Americans. (PMID:24401102)
• the CHRNB3-A6 locus contains multiple variants affecting risk for vulnerability to cocaine and nicotine dependence as well as bipolar disorder, suggesting that they have pleiotropic effects. (PMID:24675634)
• CHRNB3 c.-57A>G alteration affects the promoter activity and is associated with Parkinson’s disease (PD), and smoking in PD patients. (PMID:24731518)
• these results demonstrate that the combined effect of rs6474412-C/T polymorphism in smoking-related CHRNB3-CHRNA6 region gene and smoking behavior may not confer risk to psoriasis vulgaris (PV), but may have impact on PV severity in Chinese Han population. (PMID:24792900)
• Data show efficient expression of (alpha6beta2)2beta3 nicotinic acetylcholine receptors (AChRs) in Xenopus oocytes using free subunits with only small changes in alpha6 subunits, while not altering AChR pharmacology or channel structure. (PMID:25068303)
• Polymorphism in CHRNB3 gene is associated with esophageal adenocarcinoma. (PMID:25823894)
• Data provide evidence that the protective genetic variant at rs6474413 identified in human genetic studies reduces gene expression and that decreased beta3 gene expression in mice reduces nicotine intake (PMID:26318101)
• More low frequency variants in the CHRNA6/CHRNB3 gene region were observed in cases compared to controls. (PMID:27085880)
• To gain a better understanding of the pathological processes underlying ND and ND-related behaviors and to promote the development of effective smoking cessation therapies, we here present the most recent studies concerning the genetic effects of the CHRNB3-CHRNA6 gene cluster in ND. (PMID:27327258)
• This study shows that unorthodox acetylcholine binding sites can form at the alpha5/alpha4 and beta3/alpha4 interfaces in (alpha4beta2)2alpha5 and (alpha4beta2)2beta3 nicotinic acetylcholine receptors (nAChRs) and at the alpha4/alpha5 in (beta2alpha4)2alpha5 nAChRs. (PMID:27645992)
• This study is the first showing that CHRNB3/A6 are highly associated with nicotine dependence in a large Chinese Han sample. (PMID:28851948)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	chrnb3b	ENSDARG00000038508
danio_rerio	chrnb3a	ENSDARG00000052764
mus_musculus	Chrnb3	ENSMUSG00000031492
rattus_norvegicus	Chrnb3	ENSRNOG00000012448

Paralogs (45): GABRA3 (ENSG00000011677), GABRA1 (ENSG00000022355), CHRNA3 (ENSG00000080644), GABRP (ENSG00000094755), CHRNA4 (ENSG00000101204), GLRA2 (ENSG00000101958), GABRE (ENSG00000102287), CHRNE (ENSG00000108556), GABRA4 (ENSG00000109158), GLRB (ENSG00000109738), GABRR2 (ENSG00000111886), GABRG2 (ENSG00000113327), CHRNB4 (ENSG00000117971), CHRNA2 (ENSG00000120903), CHRNA10 (ENSG00000129749), CHRND (ENSG00000135902), CHRNA1 (ENSG00000138435), GLRA3 (ENSG00000145451), GABRA6 (ENSG00000145863), GABRB2 (ENSG00000145864), GLRA1 (ENSG00000145888), GABRR1 (ENSG00000146276), CHRNA6 (ENSG00000147434), HTR3B (ENSG00000149305), GABRA2 (ENSG00000151834), CHRNB2 (ENSG00000160716), GABRG1 (ENSG00000163285), GABRB1 (ENSG00000163288), GABRB3 (ENSG00000166206), CHRFAM7A (ENSG00000166664), HTR3A (ENSG00000166736), CHRNA5 (ENSG00000169684), CHRNB1 (ENSG00000170175), CHRNA9 (ENSG00000174343), CHRNA7 (ENSG00000175344), HTR3C (ENSG00000178084), GABRG3 (ENSG00000182256), GABRR3 (ENSG00000183185), HTR3E (ENSG00000186038), HTR3D (ENSG00000186090)

Protein

Protein identifiers

Neuronal acetylcholine receptor subunit beta-3 — Q05901 (reviewed: Q05901)

All UniProt accessions (2): Q05901, A0A1D5RMT8

UniProt curated annotations — full annotation on UniProt →

Function. Component of neuronal acetylcholine receptors (nAChRs) that function as pentameric, ligand-gated cation channels with high calcium permeability among other activities. nAChRs are excitatory neurotrasnmitter receptors formed by a collection of nAChR subunits known to mediate synaptic transmission in the nervous system and the neuromuscular junction. Each nAchR subunit confers differential attributes to channel properties, including activation, deactivation and desensitization kinetics, pH sensitivity, cation permeability, and binding to allosteric modulators. Has an accessory rather than functional role and is only able to form functional nAChRs when co-assembled with another beta subunit. Participates in pentameric assemblies along with CHRNA3, CHRNA4, CHRNA6, CHRNB2 and CHRNB4. Modulates receptor assembly and increases receptor sensitivity to nicotine when associated with CHRNB2, CHRNA4 and/or CHRNA6 as well as CHRNA3 and CHRNB4. Seems to play a role in nicotine addiction.

Subunit / interactions. Neuronal AChR seems to be composed of two different type of subunits: alpha and beta. CHRNB3/beta-3 subunit is only able to form functional nAChRs when co-assembled with another beta subunit. Participates in pentameric assemblies along with CHRNA4/alpha-4 and CHRNB2/beta-2 subunits and with CHRNA6/alpha-6 as well, forming stoichiometries such as (CHRNA3:CHRNB4)2:CHRNB3, (CHRNA4:CHRNB2)2:CHRNB3 or (CHRNA6:CHRNB2)2:CHRNB3.

Subcellular location. Synaptic cell membrane. Cell membrane.

Activity regulation. Activated by a myriad of ligands such as acetylcholine, cytisine, nicotine, choline and epibatidine.

Similarity. Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Beta-3/CHRNB3 sub-subfamily.

RefSeq proteins (2): NP_000740, NP_001334646 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002394	Nicotinic_acetylcholine_rcpt	Family
IPR006029	Neurotrans-gated_channel_TM	Domain
IPR006201	Neur_channel	Family
IPR006202	Neur_chan_lig-bd	Domain
IPR018000	Neurotransmitter_ion_chnl_CS	Conserved_site
IPR036719	Neuro-gated_channel_TM_sf	Homologous_superfamily
IPR036734	Neur_chan_lig-bd_sf	Homologous_superfamily
IPR038050	Neuro_actylchol_rec	Homologous_superfamily

Pfam: PF02931, PF02932

Catalyzed reactions (Rhea), 3 shown:

• K(+)(in) = K(+)(out) (RHEA:29463)
• Ca(2+)(in) = Ca(2+)(out) (RHEA:29671)
• Na(+)(in) = Na(+)(out) (RHEA:34963)

UniProt features (33 total): strand 13, transmembrane region 4, glycosylation site 3, helix 3, turn 2, topological domain 2, signal peptide 1, chain 1, disulfide bond 1, sequence variant 1, mutagenesis site 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8A5U	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q05901-F1	83.65	0.54

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (1): 153–167

Glycosylation sites (3): 166, 51, 138

Mutagenesis-validated functional residues (1):

Position	Phenotype
273	increases potency of agonists.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-629594	Highly calcium permeable postsynaptic nicotinic acetylcholine receptors
R-HSA-629597	Highly calcium permeable nicotinic acetylcholine receptors
R-HSA-112314	Neurotransmitter receptors and postsynaptic signal transmission
R-HSA-112315	Transmission across Chemical Synapses
R-HSA-112316	Neuronal System
R-HSA-181431	Acetylcholine binding and downstream events
R-HSA-622323	Presynaptic nicotinic acetylcholine receptors
R-HSA-622327	Postsynaptic nicotinic acetylcholine receptors

MSigDB gene sets: 107 (showing top): GOBP_MEMBRANE_DEPOLARIZATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, MODULE_328, MODULE_274, MODULE_64, GOBP_SYNAPTIC_TRANSMISSION_CHOLINERGIC, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_CELL_CELL_SIGNALING, GOBP_REGULATION_OF_POSTSYNAPTIC_MEMBRANE_POTENTIAL, TGIF_01, KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_CELLULAR_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_SYNAPTIC_SIGNALING, GOBP_RESPONSE_TO_NICOTINE

GO Biological Process (11): signal transduction (GO:0007165), synaptic transmission, cholinergic (GO:0007271), neuromuscular synaptic transmission (GO:0007274), monoatomic ion transmembrane transport (GO:0034220), response to nicotine (GO:0035094), membrane depolarization (GO:0051899), acetylcholine receptor signaling pathway (GO:0095500), presynaptic modulation of chemical synaptic transmission (GO:0099171), monoatomic ion transport (GO:0006811), regulation of postsynaptic membrane potential (GO:0060078), excitatory postsynaptic potential (GO:0060079)

GO Molecular Function (8): transmembrane signaling receptor activity (GO:0004888), channel activity (GO:0015267), acetylcholine-gated monoatomic cation-selective channel activity (GO:0022848), acetylcholine binding (GO:0042166), heterocyclic compound binding (GO:1901363), monoatomic ion channel activity (GO:0005216), extracellular ligand-gated monoatomic ion channel activity (GO:0005230), acetylcholine receptor activity (GO:0015464)

GO Cellular Component (12): plasma membrane (GO:0005886), acetylcholine-gated channel complex (GO:0005892), membrane (GO:0016020), cation channel complex (GO:0034703), neuron projection (GO:0043005), synapse (GO:0045202), postsynaptic membrane (GO:0045211), dopaminergic synapse (GO:0098691), presynapse (GO:0098793), neurotransmitter receptor complex (GO:0098878), protein-containing complex (GO:0032991), synaptic membrane (GO:0097060)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Acetylcholine binding and downstream events	2
Postsynaptic nicotinic acetylcholine receptors	1
Presynaptic nicotinic acetylcholine receptors	1
Transmission across Chemical Synapses	1
Neuronal System	1
Neurotransmitter receptors and postsynaptic signal transmission	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
synapse	3
chemical synaptic transmission	2
regulation of membrane potential	2
postsynaptic neurotransmitter receptor activity	2
monoatomic ion channel complex	2
plasma membrane signaling receptor complex	2
cellular anatomical structure	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
monoatomic ion transport	1
transmembrane transport	1
response to chemical	1
acetylcholine receptor activity	1
postsynaptic signal transduction	1
cellular response to acetylcholine	1
modulation of chemical synaptic transmission	1
presynapse	1
transport	1
regulation of postsynaptic membrane potential	1
chemical synaptic transmission, postsynaptic	1
signaling receptor activity	1
passive transmembrane transporter activity	1
excitatory extracellular ligand-gated monoatomic ion channel activity	1
ligand-gated monoatomic cation channel activity	1
transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential	1
cation binding	1
small molecule binding	1
monoatomic ion transmembrane transporter activity	1
channel activity	1
ligand-gated monoatomic ion channel activity	1
transmembrane signaling receptor activity	1
synaptic transmission, cholinergic	1
acetylcholine binding	1
membrane	1
cell periphery	1
plasma membrane bounded cell projection	1
cell junction	1

Protein interactions and networks

STRING

822 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHRNB3	CYP2A6	P00190	807
CHRNB3	CYP2B6	P20813	704
CHRNB3	EGLN2	Q96KS0	606
CHRNB3	CHRNA6	Q15825	567
CHRNB3	GABBR2	O75899	554
CHRNB3	FAM163B	P0C2L3	520
CHRNB3	SLC17A6	Q9P2U8	512
CHRNB3	CHRM2	P08172	477
CHRNB3	SLC17A7	Q9P2U7	458
CHRNB3	SYNGR1	O43759	438
CHRNB3	CHRM5	P08912	438
CHRNB3	DRD2	P14416	420
CHRNB3	TAS2R38	P59533	418
CHRNB3	CNTNAP4	Q9C0A0	410
CHRNB3	DDC	P20711	406
CHRNB3	RPTN	Q6XPR3	406

IntAct

5 interactions, top by confidence:

A	B	Type	Score
CHRNB3	TYRO3	psi-mi:“MI:0914”(association)	0.530
CHRNB3	HNRNPAB	psi-mi:“MI:0915”(physical association)	0.400
CHRNB3	GAMT	psi-mi:“MI:0914”(association)	0.350

BioGRID (14): TYRO3 (Affinity Capture-MS), LEMD2 (Affinity Capture-MS), ZG16B (Affinity Capture-MS), TYRO3 (Affinity Capture-MS), LEMD2 (Affinity Capture-MS), CHRNB3 (Synthetic Lethality), HNRNPAB (Proximity Label-MS), TYRO3 (Affinity Capture-MS), LEMD2 (Affinity Capture-MS), GAMT (Affinity Capture-MS), NPW (Affinity Capture-MS), CHRNB3 (Positive Genetic), HNRNPAB (Cross-Linking-MS (XL-MS)), CHRNB3 (Affinity Capture-MS)

ESM2 similar proteins: G5EBR3, O00591, O09028, O14764, O16926, O18276, P02710, P02711, P04755, P04757, P09479, P09481, P18506, P18845, P20420, P20781, P22456, P22933, P25162, P26152, P32297, P41849, P43143, P45963, P48167, P48168, P48181, P48182, P49581, Q05901, Q07263, Q09453, Q15825, Q18812, Q21005, Q23022, Q27218, Q5EA06, Q5IS75, Q5IS76

Diamond homologs: A8WQK3, O16926, O70174, P02708, P02709, P02710, P02711, P02712, P02713, P02716, P02717, P04755, P04756, P04757, P04758, P04759, P05377, P09478, P09479, P09480, P09481, P09482, P09483, P09484, P09628, P09690, P11230, P12389, P12390, P12391, P12392, P13908, P17644, P17787, P18257, P18845, P19370, P20420, P22456, P22770

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
acetylcholine	“up-regulates activity”	CHRNB3	“chemical activation”
nicotine	“up-regulates activity”	CHRNB3	“chemical activation”
AGRN	“up-regulates activity”	CHRNB3	binding
CHRNB3	“up-regulates activity”	APC	binding
CHRNB3	“form complex”	“Neuronal nicotinic acetylcholine receptor complex, alpha3-alpha6-beta2-beta3”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

75 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	67
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1047 predictions. Top by Δscore:

Variant	Effect	Δscore
8:42697599:G:C	donor_loss	1.0000
8:42730590:GCA:G	acceptor_loss	1.0000
8:42730592:A:AC	acceptor_loss	1.0000
8:42730593:GGAAT:G	acceptor_gain	1.0000
8:42730699:GAAAA:G	donor_gain	1.0000
8:42730700:AAAA:A	donor_gain	1.0000
8:42730700:AAAAG:A	donor_loss	1.0000
8:42730701:AAA:A	donor_gain	1.0000
8:42730701:AAAGT:A	donor_loss	1.0000
8:42730702:AA:A	donor_gain	1.0000
8:42730702:AAGTA:A	donor_loss	1.0000
8:42730703:AGTA:A	donor_loss	1.0000
8:42730704:G:GG	donor_gain	1.0000
8:42730705:TAAG:T	donor_loss	1.0000
8:42731665:A:AG	acceptor_gain	1.0000
8:42731665:AGT:A	acceptor_gain	1.0000
8:42731666:G:GA	acceptor_gain	1.0000
8:42731666:GT:G	acceptor_gain	1.0000
8:42731666:GTG:G	acceptor_gain	1.0000
8:42731666:GTGCT:G	acceptor_gain	1.0000
8:42710388:A:AG	acceptor_gain	0.9900
8:42710389:G:GG	acceptor_gain	0.9900
8:42710432:CAG:C	donor_loss	0.9900
8:42710434:G:GA	donor_loss	0.9900
8:42710435:GT:G	donor_loss	0.9900
8:42730592:A:AG	acceptor_gain	0.9900
8:42730593:G:GG	acceptor_gain	0.9900
8:42730593:GGA:G	acceptor_gain	0.9900
8:42730706:AA:A	donor_loss	0.9900
8:42731661:TTGCA:T	acceptor_loss	0.9900

AlphaMissense

3009 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:42730597:T:A	W85R	1.000
8:42730597:T:C	W85R	1.000
8:42730675:T:A	W111R	1.000
8:42730675:T:C	W111R	1.000
8:42731765:G:A	C153Y	1.000
8:42731808:C:G	C167W	1.000
8:42731908:T:A	W201R	1.000
8:42731908:T:C	W201R	1.000
8:42731910:G:C	W201C	1.000
8:42731910:G:T	W201C	1.000
8:42730599:G:C	W85C	0.999
8:42730599:G:T	W85C	0.999
8:42730618:T:A	W92R	0.999
8:42730618:T:C	W92R	0.999
8:42730620:G:C	W92C	0.999
8:42730620:G:T	W92C	0.999
8:42730677:G:C	W111C	0.999
8:42730677:G:T	W111C	0.999
8:42731758:A:C	S151R	0.999
8:42731760:C:A	S151R	0.999
8:42731760:C:G	S151R	0.999
8:42731764:T:A	C153S	0.999
8:42731764:T:C	C153R	0.999
8:42731765:G:C	C153S	0.999
8:42731766:C:G	C153W	0.999
8:42731786:T:G	F160C	0.999
8:42731788:C:T	P161S	0.999
8:42731789:C:A	P161Q	0.999
8:42731806:T:A	C167S	0.999
8:42731806:T:C	C167R	0.999

dbSNP variants (sampled 300 via entrez): RS1000002402 (8:42702759 C>A), RS1000153408 (8:42729979 A>G), RS1000225289 (8:42695747 G>A), RS1000426782 (8:42713981 A>G), RS1000600997 (8:42734093 T>A,G), RS1000633482 (8:42733942 C>T), RS1000652925 (8:42735952 G>C), RS1000750883 (8:42728875 C>A), RS1000758605 (8:42729460 T>A,C), RS1000833576 (8:42707442 C>A), RS1001099975 (8:42715845 T>A), RS1001159160 (8:42700756 T>C,G), RS1001202370 (8:42714434 G>A), RS1001207366 (8:42728646 G>C), RS1001306825 (8:42730351 G>A)

Disease associations

OMIM: gene MIM:118508 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST000667_4	Smoking behavior	1.000000e-08
GCST001490_1	Nicotine dependence	7.000000e-16
GCST003185_3	Nicotine dependence	1.000000e-06
GCST003225_24	Pelvic organ prolapse (moderate/severe)	2.000000e-07
GCST007602_2	Smoking behaviour (cigarettes smoked per day)	2.000000e-21
GCST008547_2	Time to smoke first cigarette in the morning	8.000000e-09
GCST008803_5	Smoking behaviour (cigarette pack-years)	1.000000e-15
GCST008809_4	Smoking behaviour (cigarettes smoked per day)	3.000000e-16
GCST011754_3	Nicotine dependence	2.000000e-09

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004318	smoking behavior
EFO:0006525	cigarettes per day measurement
EFO:0010126	time to first cigarette measurement
EFO:0009115	tobacco smoke exposure measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2109233 (PROTEIN COMPLEX), CHEMBL2111384 (PROTEIN COMPLEX GROUP), CHEMBL4524133 (PROTEIN COMPLEX GROUP), CHEMBL4804182 (PROTEIN COMPLEX GROUP)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 184,969 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL3	NICOTINE	4	184,969

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs4950	CHRNB3		0.00	0
rs13280604	CHRNB3		0.00	0
rs6474413	CHRNB3		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: lgic — Nicotinic acetylcholine receptors (nACh)

Binding affinities (BindingDB)

3 measured of 3 human assays (3 total across all organisms); most potent 3 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL3329540	EC50	53 nM
CHEMBL3329544	KI	310 nM
CHEMBL3329545	EC50	540 nM

ChEMBL bioactivities

86 potent at pChembl≥5 of 96 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.02	Ki	0.95	nM	CHEMBL2177538
9.02	IC50	0.95	nM	CHEMBL3104238
9.00	Ki	1	nM	CHEMBL2177537
9.00	IC50	1	nM	CHEMBL406906
8.59	Ki	2.6	nM	CHEMBL2177543
8.32	Ki	4.8	nM	CHEMBL2177545
8.26	IC50	5.55	nM	CHEMBL4872191
8.13	EC50	7.4	nM	CHEMBL2024094
8.08	IC50	8.3	nM	CHEMBL2409631
8.05	EC50	9	nM	CHEMBL2409627
8.01	IC50	9.7	nM	CHEMBL2024094
7.85	Ki	14	nM	CHEMBL3329543
7.68	Ki	21	nM	CHEMBL3329528
7.63	EC50	23.5	nM	CHEMBL2409631
7.62	IC50	23.9	nM	CHEMBL2409627
7.57	Ki	27	nM	CHEMBL3329537
7.37	Ki	43	nM	CHEMBL3329540
7.29	EC50	51.5	nM	CHEMBL2409625
7.29	EC50	51	nM	CHEMBL3329543
7.28	EC50	53	nM	CHEMBL3329540
7.26	Ki	55	nM	CHEMBL3329538
7.21	EC50	62	nM	CHEMBL3329537
7.12	Ki	75	nM	CHEMBL3329546
7.10	EC50	80	nM	CHEMBL3329528
7.07	IC50	84.8	nM	NICOTINE
7.06	EC50	88	nM	CHEMBL3329538
7.04	Ki	92	nM	CHEMBL3329541
7.00	EC50	100	nM	CHEMBL3329546
6.90	EC50	127	nM	NICOTINE
6.87	IC50	135	nM	CHEMBL4869892
6.77	Ki	170	nM	CHEMBL3329542
6.75	EC50	180	nM	CHEMBL3329530
6.72	Ki	190	nM	CHEMBL3329530
6.65	IC50	223	nM	CHEMBL2409625
6.62	Ki	240	nM	CHEMBL3329533
6.60	Ki	250	nM	CHEMBL3329545
6.52	Ki	300	nM	CHEMBL2177540
6.52	EC50	300	nM	CHEMBL3329531
6.51	Ki	310	nM	CHEMBL3329544
6.50	Ki	320	nM	CHEMBL2177539
6.46	Ki	350	nM	CHEMBL3329531
6.43	EC50	370	nM	CHEMBL3329533
6.31	Ki	490	nM	CHEMBL3329539
6.27	EC50	540	nM	CHEMBL3329545
6.24	Ki	580	nM	CHEMBL3329532
6.21	Ki	610	nM	CHEMBL3329529
6.21	EC50	620	nM	CHEMBL3329539
6.16	Ki	690	nM	CHEMBL2177544
6.16	IC50	690	nM	CHEMBL160950
6.12	EC50	750	nM	CHEMBL3329529

PubChem BioAssay actives

86 with measured affinity, of 140 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(1S,5R)-7-pyridin-3-yl-3-azabicyclo[3.3.1]non-6-ene	705800: Displacement of [125I]epibatidine from human alpha6/alpha3beta2beta3 nAChR expressed in HEK293T cells	ki	0.0009	uM
(3S)-3-[[(2S)-2-amino-5-carbamimidamidopentanoyl]amino]-4-[(2S)-2-[[(1R,6R,9S,12S,15S,21S,24S,27S,30S,33R,36S,39S,45S,48S,53R)-21,45-bis(2-amino-2-oxoethyl)-12-(3-amino-3-oxopropyl)-9-[(2S)-butan-2-yl]-6-carbamoyl-30-[(1R)-1-hydroxyethyl]-48-(hydroxymethyl)-24-(1H-imidazol-5-ylmethyl)-8,11,14,20,23,26,29,32,35,38,44,47,50,52-tetradecaoxo-27,36-di(propan-2-yl)-3,4,55,56-tetrathia-7,10,13,19,22,25,28,31,34,37,43,46,49,51-tetradecazatetracyclo[31.17.7.015,19.039,43]heptapentacontan-53-yl]carbamoyl]pyrrolidin-1-yl]-4-oxobutanoic acid	1062465: Antagonist activity at human alpha6/alpha3beta2beta3 nAChR expressed in Xenopus oocytes assessed as inhibition of ACh-induced current by voltage clamp electrophysiology method	ic50	0.0009	uM
(3S)-3-amino-4-[(2S)-2-[[(2R)-1-[[(2R)-1-[[(2S)-1-[[(2S)-4-amino-1-[(2S)-2-[[(2S)-1-[[(2R)-1-[[(2S,3R)-1-[[(2S)-1-[[(2S)-1-[[(2S)-4-amino-1-[(2S)-2-[[(2S)-5-amino-1-[[(2S,3S)-1-[[(2R)-1-amino-1-oxo-3-sulfanylpropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]carbamoyl]pyrrolidin-1-yl]-1,4-dioxobutan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1-oxo-3-sulfanylpropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]carbamoyl]pyrrolidin-1-yl]-1,4-dioxobutan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-1-oxo-3-sulfanylpropan-2-yl]amino]-1-oxo-3-sulfanylpropan-2-yl]carbamoyl]pyrrolidin-1-yl]-4-oxobutanoic acid	242400: Inhibitory concentration against Nicotinic acetylcholine receptor alpha-6-alpha-3-beta-2-beta-3; Range is 0.7-1 nM	ic50	0.0010	uM
(1R,5S)-7-pyridin-3-yl-3-azabicyclo[3.3.1]non-6-ene	705800: Displacement of [125I]epibatidine from human alpha6/alpha3beta2beta3 nAChR expressed in HEK293T cells	ki	0.0010	uM
7-(5-propan-2-yloxy-3-pyridinyl)-3-azabicyclo[3.3.1]non-6-ene	705800: Displacement of [125I]epibatidine from human alpha6/alpha3beta2beta3 nAChR expressed in HEK293T cells	ki	0.0026	uM
7-(5-phenoxy-3-pyridinyl)-3-azabicyclo[3.3.1]non-6-ene	705800: Displacement of [125I]epibatidine from human alpha6/alpha3beta2beta3 nAChR expressed in HEK293T cells	ki	0.0048	uM
(1R,6R,9S,12S,15S,18S,21S,24S,27S,30R,33S,36S,42S,45S,50R)-50-[(2-aminoacetyl)amino]-15,21,27-tris(3-carbamimidamidopropyl)-45-(hydroxymethyl)-18,42-bis(1H-imidazol-5-ylmethyl)-12,24-dimethyl-9-(2-methylpropyl)-8,11,14,17,20,23,26,29,32,35,41,44,47,49-tetradecaoxo-33-propan-2-yl-3,4,52,53-tetrathia-7,10,13,16,19,22,25,28,31,34,40,43,46,48-tetradecazatricyclo[28.17.7.036,40]tetrapentacontane-6-carboxamide	1753076: Inhibition of human alpha6/alpha3beta2beta3 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced current response by two-electrode voltage-clamp method	ic50	0.0056	uM
3-[[(2S)-azetidin-2-yl]methoxy]-5-[(1S,2R)-2-(2-methoxyethyl)cyclopropyl]pyridine	761160: Agonist activity at human alpha6/alpha3beta2beta3 nAChR expressed in human SHEP1 cells assessed as stimulation of 86Rb+ ion efflux after 5 mins by liquid scintillation counting analysis	ec50	0.0074	uM
3-[(1S,2R)-2-(2-methoxyethyl)cyclopropyl]-5-[[(3R)-pyrrolidin-3-yl]methoxy]pyridine;2,2,2-trifluoroacetic acid	761152: Antagonist activity at human alpha6/alpha3beta2beta3 nAChR expressed in human SHEP1 cells assessed as inhibition of carbamylcholine-induced 86Rb+ ion efflux preincubated for 10 mins by liquid scintillation counting analysis	ic50	0.0083	uM
3-[(1S,2R)-2-(2-methoxyethyl)cyclopropyl]-5-[[(2S)-1-methylpyrrolidin-2-yl]methoxy]pyridine;2,2,2-trifluoroacetic acid	761160: Agonist activity at human alpha6/alpha3beta2beta3 nAChR expressed in human SHEP1 cells assessed as stimulation of 86Rb+ ion efflux after 5 mins by liquid scintillation counting analysis	ec50	0.0090	uM
3,6-diazabicyclo[3.1.1]heptan-3-yl-[(1R,2R)-2-methylcyclopropyl]methanone	1188741: Displacement of [3H]epibatidine from human alpha6/alpha3beta2beta3 nAChR transfected in CHO cells by liquid scintillation counting	ki	0.0140	uM
cyclopropyl(3,6-diazabicyclo[3.1.1]heptan-3-yl)methanone	1188741: Displacement of [3H]epibatidine from human alpha6/alpha3beta2beta3 nAChR transfected in CHO cells by liquid scintillation counting	ki	0.0210	uM
3,6-diazabicyclo[3.1.1]heptan-3-yl-[(1R,2R)-2-fluorocyclopropyl]methanone	1188741: Displacement of [3H]epibatidine from human alpha6/alpha3beta2beta3 nAChR transfected in CHO cells by liquid scintillation counting	ki	0.0270	uM
3,6-diazabicyclo[3.1.1]heptan-3-yl-[(1S,2R)-2-fluorocyclopropyl]methanone	1188741: Displacement of [3H]epibatidine from human alpha6/alpha3beta2beta3 nAChR transfected in CHO cells by liquid scintillation counting	ki	0.0430	uM
3-[(1S,2R)-2-(2-methoxyethyl)cyclopropyl]-5-[[(2S)-pyrrolidin-2-yl]methoxy]pyridine;2,2,2-trifluoroacetic acid	761160: Agonist activity at human alpha6/alpha3beta2beta3 nAChR expressed in human SHEP1 cells assessed as stimulation of 86Rb+ ion efflux after 5 mins by liquid scintillation counting analysis	ec50	0.0515	uM
3,6-diazabicyclo[3.1.1]heptan-3-yl-[(1S,2S)-2-fluorocyclopropyl]methanone	1188741: Displacement of [3H]epibatidine from human alpha6/alpha3beta2beta3 nAChR transfected in CHO cells by liquid scintillation counting	ki	0.0550	uM
3,6-diazabicyclo[3.1.1]heptan-3-yl-(2,2-difluorocyclopropyl)methanone	1188741: Displacement of [3H]epibatidine from human alpha6/alpha3beta2beta3 nAChR transfected in CHO cells by liquid scintillation counting	ki	0.0750	uM
Nicotine	761152: Antagonist activity at human alpha6/alpha3beta2beta3 nAChR expressed in human SHEP1 cells assessed as inhibition of carbamylcholine-induced 86Rb+ ion efflux preincubated for 10 mins by liquid scintillation counting analysis	ic50	0.0848	uM
3,6-diazabicyclo[3.1.1]heptan-3-yl-[(1S,2R)-2-methylcyclopropyl]methanone	1188741: Displacement of [3H]epibatidine from human alpha6/alpha3beta2beta3 nAChR transfected in CHO cells by liquid scintillation counting	ki	0.0920	uM
3-[(1R,6R,9S,12S,15S,21S,24S,27S,30S,33R,36S,39S,45S,48S,53R)-53-[(2-aminoacetyl)amino]-24,30-bis(2-amino-2-oxoethyl)-9-[(2S)-butan-2-yl]-6-carbamoyl-48-(hydroxymethyl)-21,45-bis(1H-imidazol-5-ylmethyl)-8,11,14,20,23,26,29,32,35,38,44,47,50,52-tetradecaoxo-27,36-di(propan-2-yl)-3,4,55,56-tetrathia-7,10,13,19,22,25,28,31,34,37,43,46,49,51-tetradecazatetracyclo[31.17.7.015,19.039,43]heptapentacontan-12-yl]propanoic acid	1753076: Inhibition of human alpha6/alpha3beta2beta3 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced current response by two-electrode voltage-clamp method	ic50	0.1350	uM
3,6-diazabicyclo[3.1.1]heptan-3-yl-[(1R,2S)-2-methylcyclopropyl]methanone	1188741: Displacement of [3H]epibatidine from human alpha6/alpha3beta2beta3 nAChR transfected in CHO cells by liquid scintillation counting	ki	0.1700	uM
1-(3,6-diazabicyclo[3.1.1]heptan-3-yl)propan-1-one	1188746: Agonist activity at human alpha6/alpha3beta2beta3 nAChR transfected in CHO cells assessed as calcium flux by FLIPR assay	ec50	0.1800	uM
cyclobutyl(3,6-diazabicyclo[3.1.1]heptan-3-yl)methanone	1188741: Displacement of [3H]epibatidine from human alpha6/alpha3beta2beta3 nAChR transfected in CHO cells by liquid scintillation counting	ki	0.2400	uM
3,6-diazabicyclo[3.1.1]heptan-3-yl-(2,2-dimethylcyclopropyl)methanone	1188741: Displacement of [3H]epibatidine from human alpha6/alpha3beta2beta3 nAChR transfected in CHO cells by liquid scintillation counting	ki	0.2500	uM
(1S,5R)-3-methyl-7-pyridin-3-yl-3-azabicyclo[3.3.1]non-6-ene	705800: Displacement of [125I]epibatidine from human alpha6/alpha3beta2beta3 nAChR expressed in HEK293T cells	ki	0.3000	uM
1-(3,6-diazabicyclo[3.1.1]heptan-3-yl)butan-1-one	1188746: Agonist activity at human alpha6/alpha3beta2beta3 nAChR transfected in CHO cells assessed as calcium flux by FLIPR assay	ec50	0.3000	uM
3,6-diazabicyclo[3.1.1]heptan-3-yl-[(1S,2S)-2-methylcyclopropyl]methanone	1188741: Displacement of [3H]epibatidine from human alpha6/alpha3beta2beta3 nAChR transfected in CHO cells by liquid scintillation counting	ki	0.3100	uM
(1R,5S)-3-methyl-7-pyridin-3-yl-3-azabicyclo[3.3.1]non-6-ene	705800: Displacement of [125I]epibatidine from human alpha6/alpha3beta2beta3 nAChR expressed in HEK293T cells	ki	0.3200	uM
3,6-diazabicyclo[3.1.1]heptan-3-yl-[(1R,2S)-2-fluorocyclopropyl]methanone	1188741: Displacement of [3H]epibatidine from human alpha6/alpha3beta2beta3 nAChR transfected in CHO cells by liquid scintillation counting	ki	0.4900	uM
1-(3,6-diazabicyclo[3.1.1]heptan-3-yl)-2-methylpropan-1-one	1188741: Displacement of [3H]epibatidine from human alpha6/alpha3beta2beta3 nAChR transfected in CHO cells by liquid scintillation counting	ki	0.5800	uM
1-(3,6-diazabicyclo[3.1.1]heptan-3-yl)ethanone	1188741: Displacement of [3H]epibatidine from human alpha6/alpha3beta2beta3 nAChR transfected in CHO cells by liquid scintillation counting	ki	0.6100	uM
3-[[(2S)-1-methylpyrrolidin-2-yl]methoxy]-5-naphthalen-1-ylpyridine	145503: Antagonistic activity against neuronal nicotinic acetylcholine receptor (alpha3-betaX subunit) in IMR 32 cell line using 100 uM of (-)-nicotine as agonist	ic50	0.6900	uM
3-methyl-7-(5-propan-2-yloxy-3-pyridinyl)-3-azabicyclo[3.3.1]non-6-ene	705800: Displacement of [125I]epibatidine from human alpha6/alpha3beta2beta3 nAChR expressed in HEK293T cells	ki	0.6900	uM
3-[[(2S)-1-methylpyrrolidin-2-yl]methoxy]-5-(2-phenylethynyl)pyridine	145503: Antagonistic activity against neuronal nicotinic acetylcholine receptor (alpha3-betaX subunit) in IMR 32 cell line using 100 uM of (-)-nicotine as agonist	ic50	0.7900	uM
3-(4-methylphenyl)-5-[[(2S)-1-methylpyrrolidin-2-yl]methoxy]pyridine	145503: Antagonistic activity against neuronal nicotinic acetylcholine receptor (alpha3-betaX subunit) in IMR 32 cell line using 100 uM of (-)-nicotine as agonist	ic50	0.8000	uM
3-(2,4-dichlorophenyl)-5-[[(2S)-1-methylpyrrolidin-2-yl]methoxy]pyridine	145503: Antagonistic activity against neuronal nicotinic acetylcholine receptor (alpha3-betaX subunit) in IMR 32 cell line using 100 uM of (-)-nicotine as agonist	ic50	0.8900	uM
3-[[(2S)-1-methylpyrrolidin-2-yl]methoxy]-5-(2-phenylethyl)pyridine	145503: Antagonistic activity against neuronal nicotinic acetylcholine receptor (alpha3-betaX subunit) in IMR 32 cell line using 100 uM of (-)-nicotine as agonist	ic50	1.1000	uM
cyclopent-3-en-1-yl(3,6-diazabicyclo[3.1.1]heptan-3-yl)methanone	1188741: Displacement of [3H]epibatidine from human alpha6/alpha3beta2beta3 nAChR transfected in CHO cells by liquid scintillation counting	ki	1.1000	uM
3-(2-methylphenyl)-5-[[(2S)-1-methylpyrrolidin-2-yl]methoxy]pyridine	145503: Antagonistic activity against neuronal nicotinic acetylcholine receptor (alpha3-betaX subunit) in IMR 32 cell line using 100 uM of (-)-nicotine as agonist	ic50	1.2500	uM
3-[2-(4-methylphenyl)ethynyl]-5-[[(2S)-1-methylpyrrolidin-2-yl]methoxy]pyridine	145503: Antagonistic activity against neuronal nicotinic acetylcholine receptor (alpha3-betaX subunit) in IMR 32 cell line using 100 uM of (-)-nicotine as agonist	ic50	1.5000	uM
cyclopentyl(3,6-diazabicyclo[3.1.1]heptan-3-yl)methanone	1188746: Agonist activity at human alpha6/alpha3beta2beta3 nAChR transfected in CHO cells assessed as calcium flux by FLIPR assay	ec50	1.6000	uM
3-[[(2S)-1-methylpyrrolidin-2-yl]methoxy]-5-thiophen-2-ylpyridine	145503: Antagonistic activity against neuronal nicotinic acetylcholine receptor (alpha3-betaX subunit) in IMR 32 cell line using 100 uM of (-)-nicotine as agonist	ic50	1.7000	uM
3-(4-chlorophenyl)-5-[[(2S)-1-methylpyrrolidin-2-yl]methoxy]pyridine	145503: Antagonistic activity against neuronal nicotinic acetylcholine receptor (alpha3-betaX subunit) in IMR 32 cell line using 100 uM of (-)-nicotine as agonist	ic50	1.9900	uM
3-[[(2S)-1-methylpyrrolidin-2-yl]methoxy]-5-(3-nitrophenyl)pyridine	145503: Antagonistic activity against neuronal nicotinic acetylcholine receptor (alpha3-betaX subunit) in IMR 32 cell line using 100 uM of (-)-nicotine as agonist	ic50	2.3300	uM
3-[3,5-bis(trifluoromethyl)phenyl]-5-[[(2S)-1-methylpyrrolidin-2-yl]methoxy]pyridine	145503: Antagonistic activity against neuronal nicotinic acetylcholine receptor (alpha3-betaX subunit) in IMR 32 cell line using 100 uM of (-)-nicotine as agonist	ic50	2.3500	uM
2-cyclopent-2-en-1-yl-1-(3,6-diazabicyclo[3.1.1]heptan-3-yl)ethanone	1188741: Displacement of [3H]epibatidine from human alpha6/alpha3beta2beta3 nAChR transfected in CHO cells by liquid scintillation counting	ki	2.5000	uM
3-methyl-5-[[(2S)-1-methylpyrrolidin-2-yl]methoxy]pyridine	146168: Stimulation of cation efflux in Nicotinic acetylcholine receptor alpha3-betaX subtype expressing IMR-32 cells	ec50	2.9000	uM
3-(1-benzofuran-2-yl)-5-[[(2S)-1-methylpyrrolidin-2-yl]methoxy]pyridine	145503: Antagonistic activity against neuronal nicotinic acetylcholine receptor (alpha3-betaX subunit) in IMR 32 cell line using 100 uM of (-)-nicotine as agonist	ic50	2.9000	uM
3-[[(2S)-1-methylpyrrolidin-2-yl]methoxy]-5-naphthalen-2-ylpyridine	145503: Antagonistic activity against neuronal nicotinic acetylcholine receptor (alpha3-betaX subunit) in IMR 32 cell line using 100 uM of (-)-nicotine as agonist	ic50	3.4000	uM
3-[[(2S)-1-methylpyrrolidin-2-yl]methoxy]-5-[(E)-2-phenylethenyl]pyridine	145503: Antagonistic activity against neuronal nicotinic acetylcholine receptor (alpha3-betaX subunit) in IMR 32 cell line using 100 uM of (-)-nicotine as agonist	ic50	4.8000	uM

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Resveratrol	affects cotreatment, decreases expression	2
Benzo(a)pyrene	increases mutagenesis, decreases methylation, increases methylation	2
bisphenol A	decreases methylation	1
benzo(e)pyrene	decreases methylation	1
AM 251	increases expression	1
bisphenol S	increases methylation	1
Amiodarone	increases expression	1
Amphotericin B	increases expression	1
Atrazine	increases expression	1
Carmustine	decreases expression	1
Copper	affects cotreatment, decreases expression	1
Folic Acid	decreases expression	1
Methapyrilene	decreases methylation	1
Phthalic Acids	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	affects response to substance	1
Gold Compounds	decreases expression	1
Sirolimus	decreases reaction, increases expression	1

ChEMBL screening assays

25 unique, capped per target: 20 binding, 4 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2187460	Binding	Displacement of [125I]epibatidine from human alpha6/alpha3beta2beta3 nAChR expressed in HEK293T cells	Structure-activity studies of 7-heteroaryl-3-azabicyclo[3.3.1]non-6-enes: a novel class of highly potent nicotinic receptor ligands. — J Med Chem
CHEMBL750055	Functional	Stimulation of cation efflux in Nicotinic acetylcholine receptor alpha3-betaX subtype expressing IMR-32 cells	Synthesis and structure-activity relationships of pyridine-modified analogs of 3-[2-((S)-pyrrolidinyl)methoxy]pyridine, A-84543, a potent nicotinic acetylcholine receptor agonist. — Bioorg Med Chem Lett
CHEMBL4810209	ADMET	Inhibition of neuronal nicotinic receptor (unknown origin) at 0.1 to 1 uM	Discovery of Pemigatinib: A Potent and Selective Fibroblast Growth Factor Receptor (FGFR) Inhibitor. — J Med Chem

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.