CHRNB4
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Summary
CHRNB4 (cholinergic receptor nicotinic beta 4 subunit, HGNC:1964) is a protein-coding gene on chromosome 15q25.1, encoding Neuronal acetylcholine receptor subunit beta-4 (P30926). 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….
This gene is found within a conserved gene cluster and encodes one of the beta subunits of the nicotinic acetylcholine receptor (nAChRs) superfamily which form ligand-gated ion channels with a central pore that forms a cation channel. Neuronal nAChRs are pentameric structures that can be either homomeric or heteromeric, with heteromeric structures containing both alpha and beta subunits. Each subunit contains an extracellular amino terminus and four transmembrane domains. Nicotine is one of the agonists that binds to the receptor. Variants in this gene have been associated with nicotine dependence and lung cancer. Alternative splicing results in multiple transcript variants encoding different isoforms.
Source: NCBI Gene 1143 — RefSeq curated summary.
At a glance
- Gene–disease (curated): lung cancer (Limited, GenCC)
- GWAS associations: 65
- Clinical variants (ClinVar): 67 total — 1 pathogenic, 2 likely-pathogenic
- Phenotypes (HPO): 1
- Druggable target: yes — 20 molecules with ChEMBL bioactivity
- MANE Select transcript:
NM_000750
Identifiers
Gene identifiers
| Field | Value |
|---|---|
| HGNC ID | HGNC:1964 |
| Approved symbol | CHRNB4 |
| Name | cholinergic receptor nicotinic beta 4 subunit |
| Location | 15q25.1 |
| Locus type | gene with protein product |
| Status | Approved |
| Ensembl gene | ENSG00000117971 |
| Ensembl biotype | protein_coding |
| OMIM | 118509 |
| Entrez | 1143 |
Gene structure
Transcript identifiers
Ensembl transcripts: 8 — 4 protein_coding, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay
ENST00000261751, ENST00000412074, ENST00000558216, ENST00000559849, ENST00000560511, ENST00000560868, ENST00000929174, ENST00000929175
RefSeq mRNA: 2 — MANE Select: NM_000750
NM_000750, NM_001256567
CCDS: CCDS10306, CCDS58392
Canonical transcript exons
ENST00000261751 — 6 exons
| Exon | Start | End |
|---|---|---|
| ENSE00000794044 | 78631076 | 78631185 |
| ENSE00001262649 | 78628967 | 78629945 |
| ENSE00001664559 | 78624111 | 78625291 |
| ENSE00003695137 | 78635439 | 78635587 |
| ENSE00003701007 | 78631288 | 78631332 |
| ENSE00003843453 | 78641079 | 78641210 |
Expression profiles
Bgee: expression breadth ubiquitous, 125 present calls, max score 82.37.
FANTOM5 (CAGE): breadth broad, TPM avg 0.6693 / max 115.2605, expressed in 209 samples.
FANTOM5 promoters (3 alternative TSS)
| Promoter ID | TPM avg | Samples expressed |
|---|---|---|
| 151124 | 0.3839 | 142 |
| 151123 | 0.2621 | 105 |
| 151125 | 0.0233 | 3 |
Top tissues by expression
232 total, by Bgee expression score (0-100, higher = more expressed):
| Tissue | Anatomy ID | Expression score | Quality |
|---|---|---|---|
| primordial germ cell in gonad | CL:0000670 ∩ UBERON:0000991 | 82.37 | gold quality |
| male germ line stem cell (sensu Vertebrata) in testis | CL:0000089 ∩ UBERON:0000473 | 80.21 | gold quality |
| right testis | UBERON:0004534 | 77.82 | gold quality |
| left testis | UBERON:0004533 | 77.69 | gold quality |
| testis | UBERON:0000473 | 75.27 | gold quality |
| buccal mucosa cell | CL:0002336 | 74.67 | silver quality |
| adrenal tissue | UBERON:0018303 | 73.03 | gold quality |
| ganglionic eminence | UBERON:0004023 | 71.36 | gold quality |
| cortical plate | UBERON:0005343 | 66.58 | gold quality |
| muscle layer of sigmoid colon | UBERON:0035805 | 60.81 | gold quality |
| ventricular zone | UBERON:0003053 | 58.67 | gold quality |
| sural nerve | UBERON:0015488 | 58.33 | silver quality |
| right adrenal gland | UBERON:0001233 | 57.67 | gold quality |
| adrenal gland | UBERON:0002369 | 57.61 | gold quality |
| vermiform appendix | UBERON:0001154 | 57.37 | gold quality |
| tendon of biceps brachii | UBERON:0008188 | 57.25 | gold quality |
| sigmoid colon | UBERON:0001159 | 57.03 | gold quality |
| left adrenal gland cortex | UBERON:0035825 | 56.52 | gold quality |
| metanephric glomerulus | UBERON:0004736 | 55.97 | gold quality |
| left adrenal gland | UBERON:0001234 | 55.62 | gold quality |
| adrenal cortex | UBERON:0001235 | 54.98 | gold quality |
| lower esophagus mucosa | UBERON:0035834 | 54.95 | gold quality |
| right adrenal gland cortex | UBERON:0035827 | 54.51 | gold quality |
| esophagus mucosa | UBERON:0002469 | 54.45 | gold quality |
| caecum | UBERON:0001153 | 53.58 | gold quality |
| thymus | UBERON:0002370 | 53.58 | silver quality |
| colon | UBERON:0001155 | 52.34 | gold quality |
| lymph node | UBERON:0000029 | 52.18 | gold quality |
| large intestine | UBERON:0000059 | 51.92 | gold quality |
| colonic epithelium | UBERON:0000397 | 51.30 | gold quality |
Single-cell (SCXA)
Detected in 1 experiment(s), a significant marker in 1.
| Experiment | Marker? | Max mean expression |
|---|---|---|
| E-ANND-3 | yes | 5.21 |
Regulation
Is transcription factor: no
Upstream regulators (CollecTRI, top): ASCL1, SOX10, SP1, SP3
miRNA regulators (miRDB)
41 targeting CHRNB4, 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-4747-5P | 100.00 | 67.90 | 2681 |
| HSA-MIR-5196-5P | 100.00 | 67.98 | 2761 |
| HSA-MIR-4534 | 99.99 | 66.58 | 1907 |
| HSA-MIR-8082 | 99.95 | 67.27 | 1170 |
| HSA-MIR-6780A-5P | 99.88 | 66.69 | 2776 |
| HSA-MIR-4728-5P | 99.85 | 69.39 | 4718 |
| HSA-MIR-6785-5P | 99.82 | 68.68 | 4428 |
| HSA-MIR-1273H-5P | 99.77 | 66.32 | 2471 |
| HSA-MIR-4306 | 99.72 | 70.50 | 3630 |
| HSA-MIR-4699-3P | 99.71 | 70.15 | 3142 |
| HSA-MIR-30B-3P | 99.70 | 65.76 | 2325 |
| HSA-MIR-3689A-3P | 99.70 | 65.73 | 2306 |
| HSA-MIR-3689B-3P | 99.70 | 65.71 | 2311 |
| HSA-MIR-3689C | 99.70 | 65.71 | 2311 |
| HSA-MIR-6779-5P | 99.70 | 65.76 | 2363 |
| HSA-MIR-6762-3P | 99.66 | 66.94 | 1188 |
| HSA-MIR-1827 | 99.63 | 68.57 | 3265 |
| HSA-MIR-7106-5P | 99.53 | 67.47 | 3574 |
| HSA-MIR-1275 | 99.47 | 67.90 | 2749 |
| HSA-MIR-940 | 99.37 | 66.14 | 2064 |
| HSA-MIR-4284 | 99.36 | 65.25 | 1293 |
| HSA-MIR-185-5P | 99.35 | 68.60 | 2497 |
| HSA-MIR-4644 | 99.35 | 69.12 | 2514 |
| HSA-MIR-1912-3P | 99.32 | 67.40 | 936 |
| HSA-MIR-6808-5P | 99.31 | 66.23 | 2150 |
| HSA-MIR-6893-5P | 99.31 | 66.25 | 2119 |
| HSA-MIR-4667-3P | 99.26 | 65.45 | 1608 |
| HSA-MIR-7974 | 99.24 | 65.48 | 1137 |
| HSA-MIR-6799-5P | 99.14 | 65.72 | 2093 |
| HSA-MIR-1295B-5P | 99.03 | 67.50 | 810 |
Literature-anchored findings (GeneRIF, showing 40)
- CHRNB4 subunit is expressed in the soma of the majority of pyramidal cells, with fairly consistent immunoreactivity observed throughout the different regions of the hippocampus. (PMID:12663058)
- 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)
- The receptors containing the R136W and M467V mutations (or variants) had a higher sensitivity to acetylcholine and lower EC50 than the wild-type. (PMID:15742216)
- In the 2,827 long-term smokers examined, common susceptibility and protective haplotypes at the CHRNA5-A3-B4 locus were associated with nicotine dependence severity. (PMID:18618000)
- Correlated SNPs in the cholinergic nicotinic receptor gene cluster CHRNA5-CHRNA3-CHRNB4, in a case-control study of cocaine dependence composed of 504 European-American and 583 African-Americans. (PMID:18759969)
- CHRNB4 seem to exert no relevant influence on smoking cessation probability in heavy smokers in the general population. (PMID:18996504)
- Two distinct variant groups in the CHRNA5-CHRNA3-CHRNB4 gene cluster are strongly associated with heavy smoking. The snp rs16969968 alters the coding sequence of these genes. (PMID:19029397)
- Genetic variant in the CHRNA5-CHRNA3-CHRNB4 gene cluster is associated with smoking cessation during pregnancy. (PMID:19429911)
- Missense mutation of CHRNB4, CHRNB3 and CHRNA4 are associated with sporadic amyotrophic lateral sclerosis. (PMID:19628475)
- Genetic variation at CHRNA5/CHRNA3/CHRNB4 cluster influences blood nicotine level. (PMID:19628476)
- These results indicate that variants within CHRNA3 and among CHRNA5, CHRNA3, and CHRNB4 contribute significantly to the etiology of ND through gene-gene interactions. (PMID:19859904)
- Data suggest that interactions between alpha3beta4 nAChRs and P2X2 receptors may modulate transmission at enteric synapses that use ATP and acetylcholine as co-transmitters. (PMID:20426799)
- The data of this study supported the importance of variants in the CHRNA5/A3/B4 gene cluster as mediators of the genetic risk for substance dependence. (PMID:20485328)
- Variation in the nicotinic acetylcholine receptor gene cluster CHRNA5-CHRNA3-CHRNB4 influences cognitive flexibility differently in African Americans and European Americans. (PMID:20631687)
- This review focuses on the clustered nicotinic acetylcholine receptor genes CHRNalpha5/alpha3/beta4 and evaluates their role in nicotine addiction and lung cancer. (PMID:20685379)
- associations of variants in the CHRNA5/A3/B4 cluster with smoking initiation, smoking quantity and smoking cessation (PMID:20808433)
- evidence that CHRNA5-CHRNA3-CHRNB4 gene cluster variants,particularly CHRNA5 variant rs16969968, could be associated with cognitive performance possibly mediating in part risk for developing nicotine dependence (PMID:20886544)
- functional properties of nAChRs containing beta4R349C subunit; mutation caused reduction in potency of ACh and nicotine, decreased density of whole-cell current evoked by maximal transmitter concentrations, altered kinetics of ACh-evoked whole-cell currents (PMID:21107856)
- CHRNA5-CHRNA3-CHRNB4 is involved in the transition toward heavy smoking in mid-adulthood and in smoking persistence. (PMID:21168125)
- Single nucleotide polymorphism (SNP) CHRNB4 on chromosome 15 is not associated with Parkinson’s disease risk in the overall anaylsis or after stratifying on smoking status. (PMID:21228559)
- Variant A of the rs1051730 SNP of CHRNA5-A3-B4 gene cluster was significantly associated with smoking quantity in 2 Italian populations, Val Borbera and Cilento, no association was found in Carlantino population. (PMID:21248747)
- neuronal nicotinic acetylcholine receptors alpha4beta4 and alpha7 show differential agonist binding modes (PMID:21343288)
- Single Nucleotide Polymorphisms in CHRNB4 is associated with smoking persistence in African Americans. (PMID:21436384)
- The A2A receptor reduces the desensitization of alpha3beta4 nAChR through the action of protein kinase A. Mutations disrupting the sequence 385RAES388 abolish PKA-induced changes in nAChR function. (PMID:21486776)
- Nicotinic acetylcholine receptor polymorphisms are associated with additional increased risk of lung cancer, bladder cancer, and chronic obstructive pulmonary disease after adjustment for smoking. (PMID:21646606)
- Variation in CHRNA5-A3-B4 was independently and additively associated with increased smoking, nicotine dependence, and lung cancer risk. (PMID:21747048)
- alpha6beta4* nAChRs are expressed and contribute to exocytosis in human chromaffin cells of the adrenal gland, the main source of adrenaline under stressful situations. (PMID:21917987)
- Overexpression of alpha3/alpha5/beta4 nicotinic acetylcholine receptor subunits produces changes in two specific aspects of executive functioning–working memory and response inhibition–that may be related to nicotine dependence vulnerability. (PMID:22024278)
- This study examines whether the CHRNA5/CHRNA3/CHRNB4 locus is correlated also with externalizing behaviors in three independent longitudinally assessed adolescent samples (PMID:22042234)
- Missense variants at conserved residues in CHRNB4 are associated with lower risk for nicotine dependence in African Americans and European Americans. (PMID:22042774)
- vivo evidence of the involvement of the CHRNA5, CHRNA3 and CHRNB4 genomic cluster in nicotine addiction (PMID:22101982)
- Single nucleotide polymorphisma in CHRNB4 showed suggestive association with the comorbidity of depression and nicotine dependence. (PMID:22241830)
- The genetic risks of nicotine dependence associated with the CHRNA5-A3-B4 subunit genes are specific, and not shared among commonly comorbid psychiatric disorders (PMID:22336398)
- Collectively, the presence of alpha7 and beta4 nAChRs in PDLSCs supports a key role of Nicotinic acetylcholine receptor (nAChRs) in the modulation of nicotine-induced apoptosis (PMID:22382680)
- study provides evidence for a general role of the CHRNA5/A3/B4 gene cluster in substance use initiation that is not limited to nicotine and alcohol. (PMID:22382757)
- Quantitative trait disequilibrium test (QTDT) significant association was detected between age at onset of daily smoking and variants located upstream of CHRNB4. (PMID:22438940)
- transgenic mice with human alpha 5, alpha 3, beta 4 subunit genes drank less ethanol than wild-type in a two-bottle (ethanol vs. water) preference test; results suggest a complex role for this receptor subunit gene cluster in the modulation of ethanol’s as well as nicotine’s effects (PMID:22459873)
- Compared with etomidate, carboetomidate’s higher hydrophobicity is associated with greater inhibition of alpha4/beta2 neuronal nicotinic acetylcholine receptors. (PMID:22543065)
- epigenetic deregulation of nicotinic acetylcholine receptor subunit (nAChR) genes which in the case of CHRNB4 is strongly associated with genetic lung cancer susceptibility variants and a functional impact on tumorigenic potential (PMID:22945651)
- Genetic variation in the 15q25 nicotinic acetylcholine receptor gene cluster (CHRNA5-CHRNA3-CHRNB4) interacts with maternal self-reported smoking status during pregnancy to influence birth weight. (PMID:22956269)
Cross-species orthologs
3 orthologs
| Organism | Symbol | Gene ID |
|---|---|---|
| danio_rerio | chrnb4 | ENSDARG00000101677 |
| mus_musculus | Chrnb4 | ENSMUSG00000035200 |
| rattus_norvegicus | Chrnb4 | ENSRNOG00000014427 |
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), CHRNA2 (ENSG00000120903), CHRNA10 (ENSG00000129749), CHRND (ENSG00000135902), CHRNA1 (ENSG00000138435), GLRA3 (ENSG00000145451), GABRA6 (ENSG00000145863), GABRB2 (ENSG00000145864), GLRA1 (ENSG00000145888), GABRR1 (ENSG00000146276), CHRNB3 (ENSG00000147432), 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-4 — P30926 (reviewed: P30926)
All UniProt accessions (2): P30926, H3BU02
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. CHRNB4 forms heteropentameric neuronal acetylcholine receptors with CHRNA2, CHRNA3 and CHRNA4, as well as CHRNA5 and CHRNB3 as accesory subunits. CHRNA3:CHRNB4 being predominant in neurons of the autonomic ganglia, it is known as ganglionic nicotinic receptor. CHRNA3:CHRNB4 or CHRNA3:CHRNA5:CHRNB4 play also an important role in the habenulo-interpeduncular tract, modulating the mesolimbic dopamine system and affecting reward circuits and addiction. Hypothalamic CHRNA3:CHRNB4 nAChR activation by nicotine leads to activation of POMC neurons and a decrease in food intake.
Subunit / interactions. Neuronal AChR is composed of two different types of subunits: alpha and beta. CHRNB4/Beta-4 subunit can be combined to CHRNA2/alpha-2, CHRNA3/alpha-3 or CHRNA4/alpha-4, CHRNA5/alpha-5 and CHRNB3/beta-3 to give rise to functional receptors. Forms stoichiometries such as (CHRNA3)2:(CHRNB4)3 or (CHRNA3:CHRNB4)2:CHRNB3. Interacts with RIC3; which is required for proper folding and assembly. Interacts with LYPD6.
Subcellular location. Synaptic cell membrane. Cell membrane.
Activity regulation. Activated by a myriad of ligands such as acetylcholine, cytisine, nicotine, choline and epibatidine. The heteropentamer CHRNA3:CHRNB4 activity is blocked by the alpha-conotoxin ImI and AuIB.
Similarity. Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Beta-4/CHRNB4 sub-subfamily.
Isoforms (2)
| UniProt ID | Names | Canonical? |
|---|---|---|
| P30926-1 | 1 | yes |
| P30926-2 | 2 |
RefSeq proteins (2): NP_000741, NP_001243496 (=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 (59 total): strand 15, helix 8, turn 7, topological domain 5, glycosylation site 4, sequence variant 4, transmembrane region 4, site 2, splice variant 2, sequence conflict 2, signal peptide 1, chain 1, region of interest 1, binding site 1, disulfide bond 1, mutagenesis site 1
Structure
Experimental structures (PDB)
4 structures.
| PDB | Method | Resolution (Å) |
|---|---|---|
| 8ZRN | ELECTRON MICROSCOPY | 3.25 |
| 8ZRP | ELECTRON MICROSCOPY | 3.32 |
| 6PV7 | ELECTRON MICROSCOPY | 3.34 |
| 6PV8 | ELECTRON MICROSCOPY | 3.87 |
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-P30926-F1 | 82.08 | 0.62 |
Antibody-complex structures (SAbDab): 2 — 6PV7, 6PV8
Functional residue map
Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.
Catalytic / active sites (2): 82 (key residue that facilitates effective access of the conotoxin buia to the channel binding site); 134 (key residue for a low dissociation (k(off)) from the conotoxin buia)
Ligand- & substrate-binding residues (1): 262
Disulfide bonds (1): 153–167
Glycosylation sites (4): 36, 93, 138, 166
Mutagenesis-validated functional residues (1):
| Position | Phenotype |
|---|---|
| 272 | increases potency of agonists. |
Function
Pathways and Gene Ontology
Reactome pathways
12 pathways
| ID | Pathway |
|---|---|
| R-HSA-629587 | Highly sodium permeable postsynaptic acetylcholine nicotinic receptors |
| R-HSA-629594 | Highly calcium permeable postsynaptic nicotinic acetylcholine receptors |
| R-HSA-629597 | Highly calcium permeable nicotinic acetylcholine receptors |
| R-HSA-6798695 | Neutrophil degranulation |
| R-HSA-112314 | Neurotransmitter receptors and postsynaptic signal transmission |
| R-HSA-112315 | Transmission across Chemical Synapses |
| R-HSA-112316 | Neuronal System |
| R-HSA-168249 | Innate Immune System |
| R-HSA-168256 | Immune 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: 196 (showing top):
GOBP_EXCRETION, MODULE_92, GOBP_MEMBRANE_DEPOLARIZATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, REACTOME_INNATE_IMMUNE_SYSTEM, MODULE_274, GOBP_BEHAVIOR, GOCC_SECRETORY_GRANULE, GOBP_ADULT_BEHAVIOR, MODULE_64, GOBP_SYNAPTIC_TRANSMISSION_CHOLINERGIC, GOBP_REGULATION_OF_SMOOTH_MUSCLE_CONTRACTION, GOBP_NEUROTRANSMITTER_TRANSPORT, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, MORF_RAD51L3
GO Biological Process (18): monoatomic ion transport (GO:0006811), smooth muscle contraction (GO:0006939), regulation of smooth muscle contraction (GO:0006940), signal transduction (GO:0007165), synaptic transmission, cholinergic (GO:0007271), locomotory behavior (GO:0007626), neuronal action potential (GO:0019228), monoatomic ion transmembrane transport (GO:0034220), behavioral response to nicotine (GO:0035095), regulation of neurotransmitter secretion (GO:0046928), membrane depolarization (GO:0051899), positive regulation of transmission of nerve impulse (GO:0051971), synaptic transmission involved in micturition (GO:0060084), acetylcholine receptor signaling pathway (GO:0095500), response to nicotine (GO:0035094), regulation of membrane potential (GO:0042391), regulation of postsynaptic membrane potential (GO:0060078), excitatory postsynaptic potential (GO:0060079)
GO Molecular Function (8): ligand-gated monoatomic ion channel activity (GO:0015276), acetylcholine receptor activity (GO:0015464), acetylcholine-gated monoatomic cation-selective channel activity (GO:0022848), transmembrane signaling receptor activity (GO:0004888), monoatomic ion channel activity (GO:0005216), extracellular ligand-gated monoatomic ion channel activity (GO:0005230), protein binding (GO:0005515), transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential (GO:1904315)
GO Cellular Component (13): plasma membrane (GO:0005886), acetylcholine-gated channel complex (GO:0005892), membrane (GO:0016020), specific granule membrane (GO:0035579), neuron projection (GO:0043005), synapse (GO:0045202), tertiary granule membrane (GO:0070821), neurotransmitter receptor complex (GO:0098878), cholinergic synapse (GO:0098981), postsynaptic specialization membrane (GO:0099634), cation channel complex (GO:0034703), postsynaptic membrane (GO:0045211), synaptic membrane (GO:0097060)
Reactome top-level categories
Rollup of top-8 pathways:
| Category | Pathways |
|---|---|
| Presynaptic nicotinic acetylcholine receptors | 2 |
| Postsynaptic nicotinic acetylcholine receptors | 2 |
| Acetylcholine binding and downstream events | 2 |
| Innate Immune System | 1 |
| Transmission across Chemical Synapses | 1 |
| Neuronal System | 1 |
| Immune System | 1 |
| Neurotransmitter receptors and postsynaptic signal transmission | 1 |
GO top-level categories
Rollup of top GO terms by namespace:
| Category | Terms |
|---|---|
| transmission of nerve impulse | 2 |
| regulation of membrane potential | 2 |
| regulation of postsynaptic membrane potential | 2 |
| postsynaptic neurotransmitter receptor activity | 2 |
| monoatomic ion channel complex | 2 |
| plasma membrane signaling receptor complex | 2 |
| secretory granule membrane | 2 |
| synapse | 2 |
| synaptic membrane | 2 |
| transport | 1 |
| muscle contraction | 1 |
| regulation of muscle contraction | 1 |
| smooth muscle contraction | 1 |
| cell communication | 1 |
| cellular process | 1 |
| signaling | 1 |
| regulation of cellular process | 1 |
| cellular response to stimulus | 1 |
| chemical synaptic transmission | 1 |
| behavior | 1 |
| action potential | 1 |
| monoatomic ion transport | 1 |
| transmembrane transport | 1 |
| adult behavior | 1 |
| response to nicotine | 1 |
| neurotransmitter secretion | 1 |
| modulation of chemical synaptic transmission | 1 |
| regulation of neurotransmitter transport | 1 |
| regulation of secretion by cell | 1 |
| positive regulation of cell communication | 1 |
| positive regulation of nervous system process | 1 |
| regulation of transmission of nerve impulse | 1 |
| neuromuscular synaptic transmission | 1 |
| micturition | 1 |
| acetylcholine receptor activity | 1 |
| postsynaptic signal transduction | 1 |
| cellular response to acetylcholine | 1 |
| response to chemical | 1 |
| monoatomic ion transmembrane transport | 1 |
| regulation of biological quality | 1 |
Protein interactions and networks
STRING
816 interactions, top by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| CHRNB4 | PSMA4 | P25789 | 938 |
| CHRNB4 | CHRNA3 | P32297 | 822 |
| CHRNB4 | RIC3 | Q7Z5B4 | 755 |
| CHRNB4 | HYKK | A2RU49 | 700 |
| CHRNB4 | DEGS2 | Q6QHC5 | 608 |
| CHRNB4 | IGBP1 | P78318 | 606 |
| CHRNB4 | CYP2A6 | P00190 | 603 |
| CHRNB4 | IREB2 | P48200 | 577 |
| CHRNB4 | GABBR2 | O75899 | 568 |
| CHRNB4 | NMUR2 | Q9GZQ4 | 559 |
| CHRNB4 | SLC6A4 | P31645 | 557 |
| CHRNB4 | CHRM2 | P08172 | 557 |
| CHRNB4 | SLC17A6 | Q9P2U8 | 538 |
| CHRNB4 | DRD1 | P21728 | 526 |
| CHRNB4 | HTR2A | P28223 | 514 |
IntAct
9 interactions, top by confidence:
| A | B | Type | Score |
|---|---|---|---|
| CHRNB4 | MEOX2 | psi-mi:“MI:0915”(physical association) | 0.560 |
| LYPD6 | CHRNB2 | psi-mi:“MI:0914”(association) | 0.350 |
| LYNX1 | CHRNB2 | psi-mi:“MI:0914”(association) | 0.350 |
| HCN1 | USP27X | psi-mi:“MI:0914”(association) | 0.350 |
| CHRNB4 | GPR89A | psi-mi:“MI:0914”(association) | 0.350 |
| CHRNB4 | MEOX2 | psi-mi:“MI:0915”(physical association) | 0.000 |
BioGRID (69): CHRNB4 (Affinity Capture-RNA), CHRNB4 (Affinity Capture-MS), CHRNB4 (Two-hybrid), CHRNB4 (Affinity Capture-MS), SQSTM1 (Affinity Capture-MS), ABHD14A (Affinity Capture-MS), RHBDD3 (Affinity Capture-MS), UBA52 (Affinity Capture-MS), BNIP1 (Affinity Capture-MS), HS6ST2 (Affinity Capture-MS), ANO6 (Affinity Capture-MS), RNF215 (Affinity Capture-MS), SPPL2B (Affinity Capture-MS), DNAJB9 (Affinity Capture-MS), PLD6 (Affinity Capture-MS)
ESM2 similar proteins: A8WQK3, O16926, P02708, P02709, P02710, P02711, P02712, P02718, P04755, P04756, P04757, P05377, P09478, P09479, P09481, P09484, P09628, P12389, P12392, P17644, P18845, P19370, P20420, P22456, P23414, P25108, P25162, P26152, P26153, P30926, P32297, P43143, P48180, P48181, P49579, P49581, P91766, Q07263, Q15825, Q23022
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
2 interactions.
| A | Effect | B | Mechanism |
|---|---|---|---|
| CHRNB4 | “form complex” | “Neuronal nicotinic acetylcholine receptor complex, alpha3-alpha5-beta4” | binding |
| CHRNB4 | “form complex” | “Neuronal nicotinic acetylcholine receptor complex, alpha3-alpha6-beta4” | binding |
Disease & clinical
Clinical variants and AI predictions
ClinVar
67 variants total. Per-class counts are floors (≥ shown; pagination cap):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 1 |
| Likely pathogenic | 2 |
| Uncertain significance | 43 |
| Likely benign | 8 |
| Benign | 8 |
Top pathogenic / likely-pathogenic (3)
| Variant ID | HGVS | Classification |
|---|---|---|
| 3336651 | NM_000750.5(CHRNB4):c.1411G>C (p.Val471Leu) | Pathogenic |
| 1344512 | NM_000750.5(CHRNB4):c.178C>T (p.Leu60Phe) | Likely pathogenic |
| 1344513 | NM_000750.5(CHRNB4):c.658G>A (p.Val220Met) | Likely pathogenic |
SpliceAI
1209 predictions. Top by Δscore:
| Variant | Effect | Δscore |
|---|---|---|
| 15:78628374:T:TA | donor_gain | 1.0000 |
| 15:78628375:C:A | donor_gain | 1.0000 |
| 15:78628965:A:AC | donor_gain | 1.0000 |
| 15:78628966:C:CC | donor_gain | 1.0000 |
| 15:78628966:CA:C | donor_gain | 1.0000 |
| 15:78628966:CACT:C | donor_gain | 1.0000 |
| 15:78629957:C:CT | acceptor_gain | 1.0000 |
| 15:78631070:ACTCA:A | donor_loss | 1.0000 |
| 15:78631073:CA:C | donor_loss | 1.0000 |
| 15:78631074:A:AC | donor_gain | 1.0000 |
| 15:78631075:C:CC | donor_gain | 1.0000 |
| 15:78631075:CTT:C | donor_gain | 1.0000 |
| 15:78631075:CTTG:C | donor_gain | 1.0000 |
| 15:78631181:CATTC:C | acceptor_gain | 1.0000 |
| 15:78631183:TTC:T | acceptor_gain | 1.0000 |
| 15:78631184:TC:T | acceptor_gain | 1.0000 |
| 15:78631185:CC:C | acceptor_gain | 1.0000 |
| 15:78631185:CCTGG:C | acceptor_loss | 1.0000 |
| 15:78631186:C:CC | acceptor_gain | 1.0000 |
| 15:78631186:CTGG:C | acceptor_loss | 1.0000 |
| 15:78631187:T:A | acceptor_loss | 1.0000 |
| 15:78635438:CCACG:C | donor_gain | 1.0000 |
| 15:78628356:AAAG:A | donor_gain | 0.9900 |
| 15:78628959:CAACT:C | donor_loss | 0.9900 |
| 15:78628960:AACTT:A | donor_loss | 0.9900 |
| 15:78628961:ACTTA:A | donor_loss | 0.9900 |
| 15:78628962:CTTAC:C | donor_loss | 0.9900 |
| 15:78628963:TT:T | donor_loss | 0.9900 |
| 15:78628964:TACA:T | donor_loss | 0.9900 |
| 15:78628965:A:C | donor_loss | 0.9900 |
AlphaMissense
3279 scored. Top likely-pathogenic:
| Variant | Protein change | am_pathogenicity |
|---|---|---|
| 15:78629702:C:A | W201C | 0.999 |
| 15:78629702:C:G | W201C | 0.999 |
| 15:78631104:A:G | W111R | 0.999 |
| 15:78631104:A:T | W111R | 0.999 |
| 15:78631182:A:G | W85R | 0.999 |
| 15:78631182:A:T | W85R | 0.999 |
| 15:78629704:A:G | W201R | 0.998 |
| 15:78629704:A:T | W201R | 0.998 |
| 15:78629793:A:G | F171S | 0.998 |
| 15:78631102:C:A | W111C | 0.998 |
| 15:78631102:C:G | W111C | 0.998 |
| 15:78631159:C:A | W92C | 0.998 |
| 15:78631159:C:G | W92C | 0.998 |
| 15:78631180:C:A | W85C | 0.998 |
| 15:78631180:C:G | W85C | 0.998 |
| 15:78629617:G:T | R230S | 0.997 |
| 15:78629790:C:G | R172P | 0.997 |
| 15:78629799:A:G | L169P | 0.997 |
| 15:78629852:G:C | S151R | 0.997 |
| 15:78629852:G:T | S151R | 0.997 |
| 15:78629854:T:G | S151R | 0.997 |
| 15:78631161:A:G | W92R | 0.997 |
| 15:78631161:A:T | W92R | 0.997 |
| 15:78631166:A:G | L90P | 0.997 |
| 15:78629804:G:C | C167W | 0.996 |
| 15:78629866:C:G | A147P | 0.996 |
| 15:78629889:C:A | G139V | 0.996 |
| 15:78629901:A:T | V135D | 0.996 |
| 15:78631097:G:T | P113H | 0.996 |
| 15:78631176:C:G | D87H | 0.996 |
dbSNP variants (sampled 300 via entrez): RS1000166231 (15:78650209 A>G), RS1000219662 (15:78634982 G>T), RS1000253384 (15:78638577 G>A), RS1000268528 (15:78656282 A>G), RS1000270355 (15:78635268 A>C), RS1000301146 (15:78656524 C>T), RS1000431036 (15:78661635 C>G,T), RS1000550482 (15:78636292 G>A,C), RS1000603007 (15:78636706 C>A), RS1000699238 (15:78624159 C>G,T), RS1000825099 (15:78634055 T>C), RS1000855837 (15:78661697 CCA>C), RS1000855914 (15:78662103 C>A), RS1001021909 (15:78628566 G>C), RS1001074098 (15:78653062 A>C,G,T)
Disease associations
OMIM: gene MIM:118509 | disease phenotypes: MIM:606963
GenCC curated gene-disease
| Disease | Classification | Inheritance |
|---|---|---|
| lung cancer | Limited | Autosomal dominant |
Mondo (5): frontotemporal dementia (MONDO:0017276), lung adenocarcinoma (MONDO:0005061), chronic obstructive pulmonary disease (MONDO:0005002), amyotrophic lateral sclerosis (MONDO:0004976), lung cancer (MONDO:0008903)
Orphanet (3): Frontotemporal dementia (Orphanet:282), Amyotrophic lateral sclerosis (Orphanet:803), NON RARE IN EUROPE: Adenocarcinoma of the lung (Orphanet:415268)
HPO phenotypes
1 total (1 of 1 shown, HPO-id order):
| HPO | Term |
|---|---|
| HP:0007354 | Amyotrophic lateral sclerosis |
GWAS associations
65 associations (top):
| Study | Trait | p-value |
|---|---|---|
| GCST000170_1 | Lung cancer | 5.000000e-20 |
| GCST000171_1 | Nicotine dependence | 6.000000e-20 |
| GCST000233_1 | Lung cancer | 1.000000e-08 |
| GCST001102_3 | Sudden cardiac arrest | 4.000000e-07 |
| GCST002539_77 | Schizophrenia | 2.000000e-13 |
| GCST002584_1 | Exhaled carbon monoxide levels | 2.000000e-09 |
| GCST003025_22 | Attention function in attention deficit hyperactive disorder | 6.000000e-06 |
| GCST003185_2 | Nicotine dependence | 4.000000e-17 |
| GCST003262_17 | Post bronchodilator FEV1 | 4.000000e-09 |
| GCST003262_22 | Post bronchodilator FEV1 | 7.000000e-07 |
| GCST003262_229 | Post bronchodilator FEV1 | 3.000000e-13 |
| GCST003262_407 | Post bronchodilator FEV1 | 2.000000e-11 |
| GCST003262_409 | Post bronchodilator FEV1 | 1.000000e-10 |
| GCST003262_51 | Post bronchodilator FEV1 | 7.000000e-09 |
| GCST003262_673 | Post bronchodilator FEV1 | 8.000000e-09 |
| GCST003262_739 | Post bronchodilator FEV1 | 6.000000e-08 |
| GCST003262_743 | Post bronchodilator FEV1 | 2.000000e-07 |
| GCST003262_757 | Post bronchodilator FEV1 | 7.000000e-08 |
| GCST003262_772 | Post bronchodilator FEV1 | 4.000000e-13 |
| GCST003262_800 | Post bronchodilator FEV1 | 5.000000e-09 |
| GCST003262_822 | Post bronchodilator FEV1 | 3.000000e-10 |
| GCST003262_916 | Post bronchodilator FEV1 | 2.000000e-14 |
| GCST003262_919 | Post bronchodilator FEV1 | 2.000000e-08 |
| GCST003262_957 | Post bronchodilator FEV1 | 3.000000e-09 |
| GCST003262_975 | Post bronchodilator FEV1 | 1.000000e-07 |
| GCST003264_1111 | Post bronchodilator FEV1/FVC ratio | 9.000000e-08 |
| GCST003264_1115 | Post bronchodilator FEV1/FVC ratio | 2.000000e-07 |
| GCST003264_1152 | Post bronchodilator FEV1/FVC ratio | 3.000000e-09 |
| GCST003264_1235 | Post bronchodilator FEV1/FVC ratio | 1.000000e-07 |
| GCST003264_1307 | Post bronchodilator FEV1/FVC ratio | 8.000000e-14 |
EFO canonical traits (10, from GWAS)
| EFO ID | Trait name |
|---|---|
| EFO:0004278 | sudden cardiac arrest |
| EFO:0004318 | smoking behavior |
| EFO:0006520 | carbon monoxide exhalation measurement |
| EFO:0007636 | attention function measurement |
| EFO:0004314 | forced expiratory volume |
| EFO:0004713 | FEV/FVC ratio |
| EFO:0004340 | body mass index |
| EFO:0009369 | diffusing capacity of the lung for carbon monoxide |
| EFO:0007874 | gut microbiome measurement |
| EFO:0006527 | smoking status measurement |
MeSH disease descriptors (3)
| Descriptor | Name | Tree numbers |
|---|---|---|
| D000690 | Amyotrophic Lateral Sclerosis | C10.228.854.139; C10.574.562.250; C10.574.950.050; C10.668.467.250; C18.452.845.800.050 |
| D057180 | Frontotemporal Dementia | C10.228.140.380.266.299; C10.574.950.300.299; C18.452.845.800.300.299; F03.615.400.380.299 |
| D029424 | Pulmonary Disease, Chronic Obstructive | C08.381.495.389; C23.550.291.500.875 |
Drugs & pharmacology
Drug and pharmacology data
Is drug target: yes
ChEMBL targets (11): CHEMBL1907591 (PROTEIN COMPLEX), CHEMBL1907594 (PROTEIN COMPLEX), CHEMBL2109230 (PROTEIN COMPLEX), CHEMBL2111384 (PROTEIN COMPLEX GROUP), CHEMBL2221346 (PROTEIN COMPLEX GROUP), CHEMBL3038459 (PROTEIN COMPLEX), CHEMBL3137273 (PROTEIN COMPLEX), CHEMBL3137285 (PROTEIN COMPLEX), CHEMBL3885595 (PROTEIN COMPLEX), CHEMBL4524133 (PROTEIN COMPLEX GROUP)
Molecules with ChEMBL bioactivity
20 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 426,191 (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 |
|---|---|---|---|
| CHEMBL1076903 | VARENICLINE | 4 | 5,807 |
| CHEMBL3 | NICOTINE | 4 | 184,969 |
| CHEMBL894 | BUPROPION | 4 | 36,982 |
| CHEMBL267936 | MECAMYLAMINE | 4 | 5,623 |
| CHEMBL46 | ONDANSETRON | 4 | 41,386 |
| CHEMBL56564 | TROPISETRON | 4 | 19,312 |
| CHEMBL667 | ACETYLCHOLINE | 4 | 124,626 |
| CHEMBL2103881 | DEXMECAMYLAMINE | 3 | 18 |
| CHEMBL497939 | CYTISINICLINE | 3 | 2,766 |
| CHEMBL111659 | ALTINICLINE | 2 | 129 |
| CHEMBL1172928 | RADAFAXINE | 2 | 1,079 |
| CHEMBL1230982 | ANABASEINE | 2 | 139 |
| CHEMBL1257065 | STILONIUM IODIDE | 2 | 751 |
| CHEMBL132966 | RIVANICLINE | 2 | 911 |
| CHEMBL134713 | GTS-21 | 2 | 269 |
| CHEMBL2179529 | AZD1446 | 2 | 78 |
| CHEMBL238465 | SOFINICLINE | 2 | 153 |
| CHEMBL430497 | TEBANICLINE | 2 | 1,155 |
| CHEMBL607048 | 18-METHOXYCORONARIDINE | 2 | 6 |
| CHEMBL504652 | TC-2216 | 1 | 32 |
PharmGKB: 1 entry (VIP=true, CPIC=false)
PharmGKB clinical annotations
5 annotations.
| Variant | Type | Level | Drugs | Phenotypes |
|---|---|---|---|---|
| rs10851907 | Metabolism/PK | 3 | cotinine | Tobacco Use Disorder |
| rs1948 | Toxicity | 3 | nicotine | Tobacco Use Disorder |
| rs2869950 | Toxicity | 3 | nicotine | Tobacco Use Disorder |
| rs3813567 | Toxicity | 3 | nicotine | Tobacco Use Disorder |
| rs7178270 | Toxicity | 3 | nicotine | Tobacco Use Disorder |
PharmGKB variants
6 variants.
| Variant | Genes | Level | Score | #Clin annots | Drugs |
|---|---|---|---|---|---|
| rs3813567 | CHRNB4 | 3 | 2.00 | 1 | nicotine |
| rs10851907 | CHRNB4 | 3 | 0.00 | 1 | cotinine |
| rs2869950 | CHRNB4, FAM13A | 3 | 0.00 | 1 | nicotine |
| rs1948 | CHRNB4 | 3 | 3.00 | 1 | nicotine |
| rs7178270 | CHRNB4 | 3 | 3.00 | 1 | nicotine |
| rs950776 | CHRNB4 | 0.00 | 0 |
GtoPdb / IUPHAR curated pharmacology
(IUPHAR/BPS Guide to Pharmacology — expert-curated)
Target class: lgic — Nicotinic acetylcholine receptors (nACh)
Binding affinities (BindingDB)
7 measured of 9 human assays (10 total across all organisms); most potent 7 below. Values come from heterogeneous assays and are not directly comparable.
| Ligand | Measure | Value |
|---|---|---|
| CHEMBL4453542 | KI | 2.5 nM |
| CHEMBL4450133 | KI | 6.7 nM |
| CHEMBL4440403 | KI | 20 nM |
| CHEMBL4535466 | KI | 138 nM |
| CHEMBL4463888 | KI | 631 nM |
| 18-methoxycoronaridine | KI | 700 nM |
| CHEMBL4468230 | KI | 1630 nM |
ChEMBL bioactivities
1230 potent at pChembl≥5 of 1586 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).
| pChembl | Type | Value | Unit | Molecule |
|---|---|---|---|---|
| 10.14 | Ki | 0.072 | nM | EPIBATIDINE |
| 10.04 | Ki | 0.091 | nM | EPIBATIDINE |
| 9.90 | Ki | 0.126 | nM | CHEMBL1209244 |
| 9.83 | Ki | 0.149 | nM | CHEMBL1209243 |
| 9.82 | Ki | 0.15 | nM | EPIBATIDINE |
| 9.82 | Ki | 0.15 | nM | (-)-EPIBATIDINE |
| 9.80 | Ki | 0.16 | nM | CHEMBL220476 |
| 9.80 | IC50 | 0.16 | nM | CHEMBL1269126 |
| 9.80 | Ki | 0.158 | nM | CHEMBL1209187 |
| 9.80 | EC50 | 0.16 | nM | CHEMBL1209244 |
| 9.73 | Ki | 0.186 | nM | CHEMBL1209124 |
| 9.72 | Ki | 0.191 | nM | EPIBATIDINE |
| 9.70 | Ki | 0.2 | nM | CHEMBL462846 |
| 9.70 | IC50 | 0.2 | nM | CHEMBL4869892 |
| 9.66 | Ki | 0.22 | nM | EPIBATIDINE |
| 9.64 | Ki | 0.23 | nM | EPIBATIDINE |
| 9.62 | IC50 | 0.24 | nM | CHEMBL4860756 |
| 9.61 | Ki | 0.243 | nM | CHEMBL1209187 |
| 9.55 | IC50 | 0.28 | nM | CHEMBL4876825 |
| 9.52 | Kd | 0.3 | nM | EPIBATIDINE |
| 9.52 | IC50 | 0.3 | nM | CHEMBL412032 |
| 9.52 | Kd | 0.3 | nM | (-)-EPIBATIDINE |
| 9.46 | IC50 | 0.35 | nM | CHEMBL4462550 |
| 9.43 | IC50 | 0.37 | nM | CHEMBL4454232 |
| 9.42 | Ki | 0.382 | nM | CHEMBL1209186 |
| 9.39 | IC50 | 0.41 | nM | CHEMBL4878931 |
| 9.34 | IC50 | 0.46 | nM | CHEMBL4556075 |
| 9.34 | Ki | 0.457 | nM | EPIBATIDINE |
| 9.29 | IC50 | 0.51 | nM | CHEMBL566208 |
| 9.28 | Ki | 0.527 | nM | HOMOEPIBATIDINE |
| 9.26 | IC50 | 0.55 | nM | CHEMBL4443845 |
| 9.24 | IC50 | 0.57 | nM | CHEMBL4585225 |
| 9.24 | IC50 | 0.58 | nM | CHEMBL566886 |
| 9.21 | IC50 | 0.62 | nM | CHEMBL566050 |
| 9.19 | IC50 | 0.65 | nM | CHEMBL4463134 |
| 9.19 | IC50 | 0.65 | nM | CHEMBL565844 |
| 9.16 | Ki | 0.684 | nM | CHEMBL4163848 |
| 9.15 | IC50 | 0.7 | nM | CHEMBL569465 |
| 9.13 | Ki | 0.748 | nM | CHEMBL1209124 |
| 9.12 | IC50 | 0.75 | nM | CHEMBL429557 |
| 9.10 | Ki | 0.799 | nM | CHEMBL4170527 |
| 9.09 | Ki | 0.818 | nM | CHEMBL4163257 |
| 9.07 | Ki | 0.856 | nM | CHEMBL1209126 |
| 9.05 | Ki | 0.882 | nM | CHEMBL1209072 |
| 9.04 | IC50 | 0.92 | nM | CHEMBL4531333 |
| 9.03 | Ki | 0.944 | nM | CHEMBL363973 |
| 9.03 | Ki | 0.925 | nM | HOMOEPIBATIDINE |
| 9.03 | IC50 | 0.93 | nM | CHEMBL425006 |
| 9.02 | IC50 | 0.95 | nM | CHEMBL4440025 |
| 9.02 | Ki | 0.957 | nM | CHEMBL1209184 |
PubChem BioAssay actives
1157 with measured affinity, of 2985 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 |
|---|---|---|---|---|
| 2-(6-chloro-3-pyridinyl)-7-azabicyclo[2.2.1]heptane | 1359525: Displacement of [3H]epibatidine from human alpha3beta4 nAChR expressed in HEK293 cell membranes | ki | 0.0001 | uM |
| N-[5-[2-[[(1R,5R,6S)-3-azabicyclo[3.2.1]octan-6-yl]oxy]phenyl]-3-pyridinyl]ethanesulfonamide;hydrochloride | 495033: Displacement of [3H]epibatidine from alpha3beta4 nicotinic receptor expressed in human HEK293 cells | ki | 0.0001 | uM |
| N-[5-[2-[[(1R,5R,6S)-3-azabicyclo[3.2.1]octan-6-yl]oxy]phenyl]-3-pyridinyl]propane-2-sulfonamide;hydrochloride | 495033: Displacement of [3H]epibatidine from alpha3beta4 nicotinic receptor expressed in human HEK293 cells | ki | 0.0001 | uM |
| (1R,2R,4S)-2-(6-chloro-3-pyridinyl)-7-azabicyclo[2.2.1]heptane | 1563867: Displacement of [3H]epibatidine from human alpha3beta4 nAChR transfected in HEK243 cell membrane | ki | 0.0001 | uM |
| 3-[(1R,6R,9S,12S,15S,21S,24S,27S,30S,33R,36S,39S,45S,48S,53R)-53-[(2-aminoacetyl)amino]-24-(3-carbamimidamidopropyl)-6-carbamoyl-48-(hydroxymethyl)-21,30,45-tris(1H-imidazol-5-ylmethyl)-9-(2-methylpropyl)-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 | 1753051: Inhibition of human alpha6/alpha3beta4 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced current response measured after 5 min by two-electrode voltage-clamp method | ic50 | 0.0002 | 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 | 1753051: Inhibition of human alpha6/alpha3beta4 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced current response measured after 5 min by two-electrode voltage-clamp method | ic50 | 0.0002 | uM |
| 7-(6-chloro-3-pyridinyl)-2-azabicyclo[2.2.1]heptane | 276250: Displacement of [3H]epibatidine from human recombinant alpha-3-beta-4 nAChR in HEK293 cells by SPA assay | ki | 0.0002 | uM |
| 3-(6-chloro-3-pyridinyl)-3,6-diazabicyclo[3.1.1]heptane | 1252850: Displacement of [3H]-Epibatidine from human aplha3beta4 nAChR expressed in HEK293 cells pre-incubated for 5 mins followed by overnight incubation by radioligand liquid scintillation counter analysis | ki | 0.0002 | uM |
| (2S)-N-[3-[4-(3-aminopropylamino)butylamino]propyl]-3-cyclohexyl-2-[(2-naphthalen-1-ylacetyl)amino]propanamide | 1563140: Antagonist activity at alpha3beta4 nAChR (unknown origin) expressed in Xenopus laevis oocytes assessed as inhibition of Ach-induced channel activation at -100 mV holding potential treated for 1 min by two electrode voltage-clamp assay | ic50 | 0.0002 | uM |
| 5-[2-[[(1R,5R,6S)-3-azabicyclo[3.2.1]octan-6-yl]oxy]phenyl]pyridin-3-ol;hydrochloride | 495033: Displacement of [3H]epibatidine from alpha3beta4 nicotinic receptor expressed in human HEK293 cells | ki | 0.0002 | uM |
| N-[5-[2-[[(1R,5R,6S)-3-azabicyclo[3.2.1]octan-6-yl]oxy]phenyl]-3-pyridinyl]methanesulfonamide;hydrochloride | 495033: Displacement of [3H]epibatidine from alpha3beta4 nicotinic receptor expressed in human HEK293 cells | ki | 0.0002 | uM |
| (2S)-N-[3-[4-(3-aminopropylamino)butylamino]propyl]-3-cyclohexyl-2-[[(E)-3-phenylprop-2-enoyl]amino]propanamide | 1563140: Antagonist activity at alpha3beta4 nAChR (unknown origin) expressed in Xenopus laevis oocytes assessed as inhibition of Ach-induced channel activation at -100 mV holding potential treated for 1 min by two electrode voltage-clamp assay | ic50 | 0.0003 | uM |
| 3-[(1R,6R,9S,12S,15S,21S,24S,27S,30S,33R,36S,39S,45S,48S,53R)-53-[(2-aminoacetyl)amino]-30-(2-amino-2-oxoethyl)-24-(3-carbamimidamidopropyl)-6-carbamoyl-48-(hydroxymethyl)-21,45-bis(1H-imidazol-5-ylmethyl)-9-(2-methylpropyl)-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 | 1753051: Inhibition of human alpha6/alpha3beta4 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced current response measured after 5 min by two-electrode voltage-clamp method | ic50 | 0.0003 | uM |
| (3S)-3-[[(2S)-5-amino-2-[[(2S)-4-amino-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2R)-2-[[2-[(2-aminoacetyl)amino]acetyl]amino]-3-sulfanylpropanoyl]amino]-3-sulfanylpropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]pyrrolidine-2-carbonyl]amino]propanoyl]amino]-3-sulfanylpropanoyl]amino]propanoyl]amino]propanoyl]amino]-4-oxobutanoyl]amino]-4-oxobutanoyl]amino]-5-oxopentanoyl]amino]-4-[[(2S)-1-[[(2R)-1-amino-1-oxo-3-sulfanylpropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-4-oxobutanoic acid | 241633: Inhibitory concentration against Nicotinic acetylcholine receptor alpha3-beta4 | ic50 | 0.0003 | uM |
| N-[(2S)-1-[3-[4-(3-aminopropylamino)butylamino]propylamino]-3-cyclohexyl-1-oxopropan-2-yl]benzamide | 1563140: Antagonist activity at alpha3beta4 nAChR (unknown origin) expressed in Xenopus laevis oocytes assessed as inhibition of Ach-induced channel activation at -100 mV holding potential treated for 1 min by two electrode voltage-clamp assay | ic50 | 0.0004 | uM |
| 3-[(1R,6R,9S,12S,15S,21S,24S,27S,30S,33R,36S,39S,45S,48S,53R)-53-[(2-aminoacetyl)amino]-9-[(2S)-butan-2-yl]-24-(3-carbamimidamidopropyl)-6-carbamoyl-48-(hydroxymethyl)-21,30,45-tris(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 | 1753051: Inhibition of human alpha6/alpha3beta4 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced current response measured after 5 min by two-electrode voltage-clamp method | ic50 | 0.0004 | uM |
| N-[3-[2-[[(1R,5R,6S)-3-azabicyclo[3.2.1]octan-6-yl]oxy]phenyl]-4-pyridinyl]methanesulfonamide;hydrochloride | 495033: Displacement of [3H]epibatidine from alpha3beta4 nicotinic receptor expressed in human HEK293 cells | ki | 0.0004 | uM |
| N-[(2S)-1-[3-[4-(3-aminopropylamino)butylamino]propylamino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]cyclohexanecarboxamide | 1563140: Antagonist activity at alpha3beta4 nAChR (unknown origin) expressed in Xenopus laevis oocytes assessed as inhibition of Ach-induced channel activation at -100 mV holding potential treated for 1 min by two electrode voltage-clamp assay | ic50 | 0.0005 | uM |
| 6-(6-chloro-3-pyridinyl)-8-azabicyclo[3.2.1]octane | 276250: Displacement of [3H]epibatidine from human recombinant alpha-3-beta-4 nAChR in HEK293 cells by SPA assay | ki | 0.0005 | uM |
| 2-(tert-butylamino)-1-(3,4-dichlorophenyl)butan-1-one | 459714: Antagonist activity at alpha3beta4 nAChR receptor in human SH-SY5Y cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting | ic50 | 0.0005 | uM |
| N-[(2S)-1-[3-[4-(3-aminopropylamino)butylamino]propylamino]-3-cyclohexyl-1-oxopropan-2-yl]cycloheptanecarboxamide | 1563140: Antagonist activity at alpha3beta4 nAChR (unknown origin) expressed in Xenopus laevis oocytes assessed as inhibition of Ach-induced channel activation at -100 mV holding potential treated for 1 min by two electrode voltage-clamp assay | ic50 | 0.0006 | uM |
| N-[(2S)-1-[3-[4-(3-aminopropylamino)butylamino]propylamino]-3-cyclohexyl-1-oxopropan-2-yl]cyclopentanecarboxamide | 1563140: Antagonist activity at alpha3beta4 nAChR (unknown origin) expressed in Xenopus laevis oocytes assessed as inhibition of Ach-induced channel activation at -100 mV holding potential treated for 1 min by two electrode voltage-clamp assay | ic50 | 0.0006 | uM |
| N-[(2S)-1-[3-[4-(3-aminopropylamino)butylamino]propylamino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]cyclopentanecarboxamide | 1563140: Antagonist activity at alpha3beta4 nAChR (unknown origin) expressed in Xenopus laevis oocytes assessed as inhibition of Ach-induced channel activation at -100 mV holding potential treated for 1 min by two electrode voltage-clamp assay | ic50 | 0.0006 | uM |
| 2-(tert-butylamino)-1-(3-chlorophenyl)butan-1-one | 459714: Antagonist activity at alpha3beta4 nAChR receptor in human SH-SY5Y cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting | ic50 | 0.0006 | uM |
| 2-(tert-butylamino)-1-(3-chloro-4-methylphenyl)propan-1-one | 459714: Antagonist activity at alpha3beta4 nAChR receptor in human SH-SY5Y cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting | ic50 | 0.0006 | uM |
| 2-(tert-butylamino)-1-(3,4-dichlorophenyl)pentan-1-one | 459714: Antagonist activity at alpha3beta4 nAChR receptor in human SH-SY5Y cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting | ic50 | 0.0006 | uM |
| 5-(3,6-diazabicyclo[3.1.1]heptan-3-yl)-N-(4-nitrophenyl)pyridin-3-amine | 1359525: Displacement of [3H]epibatidine from human alpha3beta4 nAChR expressed in HEK293 cell membranes | ki | 0.0007 | uM |
| 2-(tert-butylamino)-1-(3-chlorophenyl)pentan-1-one | 459714: Antagonist activity at alpha3beta4 nAChR receptor in human SH-SY5Y cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting | ic50 | 0.0007 | uM |
| 5-(3,6-diazabicyclo[3.1.1]heptan-3-yl)-N-phenylpyridin-3-amine | 1359525: Displacement of [3H]epibatidine from human alpha3beta4 nAChR expressed in HEK293 cell membranes | ki | 0.0008 | uM |
| 5-(3,6-diazabicyclo[3.1.1]heptan-3-yl)-N-[4-(trifluoromethyl)phenyl]pyridin-2-amine | 1359525: Displacement of [3H]epibatidine from human alpha3beta4 nAChR expressed in HEK293 cell membranes | ki | 0.0008 | uM |
| (3S)-3-[[(2S)-1-[(2S)-4-amino-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-1-[(2S)-1-[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2R)-2-[(2-aminoacetyl)amino]-3-sulfanylpropanoyl]amino]-3-sulfanylpropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carbonyl]amino]-3-sulfanylpropanoyl]amino]-3-phenylpropanoyl]amino]propanoyl]amino]-3-hydroxybutanoyl]amino]-4-oxobutanoyl]pyrrolidine-2-carbonyl]amino]-4-oxo-4-[[(2R)-1-oxo-3-sulfanylpropan-2-yl]amino]butanoic acid | 242203: Inhibitory concentration against Nicotinic acetylcholine receptor alpha2-beta4; Range is 0.3-1.5 nM | ic50 | 0.0008 | uM |
| 5-(6-chloro-3-pyridinyl)-2-azabicyclo[2.2.1]heptane | 276250: Displacement of [3H]epibatidine from human recombinant alpha-3-beta-4 nAChR in HEK293 cells by SPA assay | ki | 0.0009 | uM |
| N-[(2S)-1-[3-[4-(3-aminopropylamino)butylamino]propylamino]-1-oxo-3-phenylpropan-2-yl]butanamide | 1563140: Antagonist activity at alpha3beta4 nAChR (unknown origin) expressed in Xenopus laevis oocytes assessed as inhibition of Ach-induced channel activation at -100 mV holding potential treated for 1 min by two electrode voltage-clamp assay | ic50 | 0.0009 | uM |
| (2S)-N-[3-[4-(3-aminopropylamino)butylamino]propyl]-2-[[2-(2-bicyclo[2.2.1]heptanyl)acetyl]amino]-3-cyclohexylpropanamide | 1563140: Antagonist activity at alpha3beta4 nAChR (unknown origin) expressed in Xenopus laevis oocytes assessed as inhibition of Ach-induced channel activation at -100 mV holding potential treated for 1 min by two electrode voltage-clamp assay | ic50 | 0.0009 | uM |
| N-[(2S)-1-[3-[[(1R,2R)-2-[(3-aminopropylamino)methyl]cyclopropyl]methylamino]propylamino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]butanamide | 1563140: Antagonist activity at alpha3beta4 nAChR (unknown origin) expressed in Xenopus laevis oocytes assessed as inhibition of Ach-induced channel activation at -100 mV holding potential treated for 1 min by two electrode voltage-clamp assay | ic50 | 0.0009 | uM |
| (1R,5R,6S)-6-[2-(4-methoxy-3-pyridinyl)phenoxy]-3-azabicyclo[3.2.1]octane;hydrochloride | 495033: Displacement of [3H]epibatidine from alpha3beta4 nicotinic receptor expressed in human HEK293 cells | ki | 0.0009 | uM |
| (1R,5R,6S)-6-[2-(4-fluoro-3-pyridinyl)phenoxy]-3-azabicyclo[3.2.1]octane;hydrochloride | 495033: Displacement of [3H]epibatidine from alpha3beta4 nicotinic receptor expressed in human HEK293 cells | ki | 0.0009 | uM |
| 4-[[5-(3,6-diazabicyclo[3.1.1]heptan-3-yl)-3-pyridinyl]amino]phenol | 1359525: Displacement of [3H]epibatidine from human alpha3beta4 nAChR expressed in HEK293 cell membranes | ki | 0.0010 | uM |
| 5-(3,6-diazabicyclo[3.1.1]heptan-3-yl)-N-[4-(trifluoromethyl)phenyl]pyridin-3-amine | 1359525: Displacement of [3H]epibatidine from human alpha3beta4 nAChR expressed in HEK293 cell membranes | ki | 0.0010 | uM |
| (1R,15R,17S,18S)-17-ethyl-7-methoxy-3,13-diazapentacyclo[13.3.1.02,10.04,9.013,18]nonadeca-2(10),4(9),5,7-tetraene | 1973135: Displacement of [3H]Ibogaine from human alpha3beta4 nAChRs expressed in HEK293 cells assessed as inhibition constant incubated for 2 hrs by scintillation counter analysis | ki | 0.0010 | 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 | 242122: Inhibitory concentration against Nicotinic acetylcholine receptor alpha3-beta4; Range is 0.7-1 nM | ic50 | 0.0010 | uM |
| 3-[2-[[(1R,5R,6S)-3-azabicyclo[3.2.1]octan-6-yl]oxy]phenyl]pyridin-4-amine;hydrochloride | 495033: Displacement of [3H]epibatidine from alpha3beta4 nicotinic receptor expressed in human HEK293 cells | ki | 0.0010 | uM |
| N-[(2S)-1-[3-[4-(3-aminopropylamino)butylamino]propylamino]-3-cyclohexyl-1-oxopropan-2-yl]cyclobutanecarboxamide | 1563140: Antagonist activity at alpha3beta4 nAChR (unknown origin) expressed in Xenopus laevis oocytes assessed as inhibition of Ach-induced channel activation at -100 mV holding potential treated for 1 min by two electrode voltage-clamp assay | ic50 | 0.0011 | uM |
| N-(4-chlorophenyl)-5-(3,6-diazabicyclo[3.1.1]heptan-3-yl)pyridin-3-amine | 1359525: Displacement of [3H]epibatidine from human alpha3beta4 nAChR expressed in HEK293 cell membranes | ki | 0.0012 | uM |
| 2-[tert-butyl(methyl)amino]-1-(3-chlorophenyl)propan-1-one | 459714: Antagonist activity at alpha3beta4 nAChR receptor in human SH-SY5Y cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting | ic50 | 0.0012 | uM |
| (1R,5R,6S)-6-(2-pyridin-3-ylphenoxy)-3-azabicyclo[3.2.1]octane;hydrochloride | 495033: Displacement of [3H]epibatidine from alpha3beta4 nicotinic receptor expressed in human HEK293 cells | ki | 0.0012 | uM |
| 5-(3,6-diazabicyclo[3.1.1]heptan-3-yl)-N-(4-fluorophenyl)pyridin-3-amine | 1359525: Displacement of [3H]epibatidine from human alpha3beta4 nAChR expressed in HEK293 cell membranes | ki | 0.0013 | uM |
| 1-(3-bromophenyl)-2-(tert-butylamino)propan-1-one | 459714: Antagonist activity at alpha3beta4 nAChR receptor in human SH-SY5Y cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting | ic50 | 0.0013 | uM |
| N-[5-[2-[[(1S,5S,6R)-3-azabicyclo[3.2.1]octan-6-yl]oxy]phenyl]-3-pyridinyl]methanesulfonamide;hydrochloride | 495033: Displacement of [3H]epibatidine from alpha3beta4 nicotinic receptor expressed in human HEK293 cells | ki | 0.0013 | uM |
| 5-(3,6-diazabicyclo[3.1.1]heptan-3-yl)-N-(4-methylphenyl)pyridin-3-amine | 1359525: Displacement of [3H]epibatidine from human alpha3beta4 nAChR expressed in HEK293 cell membranes | ki | 0.0014 | uM |
CTD chemical–gene interactions
58 total (human), top 30 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| Acetylcholine | decreases reaction, increases activity, affects binding, affects reaction, increases reaction (+2 more) | 6 |
| epibatidine | decreases reaction, increases activity, affects binding | 3 |
| bisphenol A | decreases methylation, affects activity, affects binding, decreases reaction, increases reaction | 2 |
| entinostat | increases expression, affects cotreatment | 2 |
| Estradiol | affects cotreatment, increases expression, affects activity, affects binding, decreases reaction (+1 more) | 2 |
| Nicotine | affects binding, increases activity | 2 |
| Tubocurarine | affects binding, decreases reaction, increases activity | 2 |
| triptolide | affects binding, decreases reaction, increases activity | 1 |
| cytisine | affects binding, increases activity | 1 |
| propionaldehyde | decreases expression | 1 |
| crotonyl alcohol | increases reaction, increases transport, affects binding, decreases reaction | 1 |
| N’-nitrosonornicotine | affects binding | 1 |
| decabromobiphenyl ether | increases expression | 1 |
| tetrabromobisphenol A | increases expression | 1 |
| n-pentanol | decreases reaction, increases reaction, increases transport, affects binding | 1 |
| coumarin | decreases phosphorylation | 1 |
| isobutyl alcohol | affects binding, affects reaction, increases reaction, increases transport | 1 |
| tetrachlorodian | increases expression | 1 |
| 4-nonylphenol | decreases reaction, increases reaction, affects activity, affects binding | 1 |
| 2-butanol | affects reaction, increases reaction, increases transport, affects binding | 1 |
| celastrol | increases activity, affects binding, decreases reaction | 1 |
| 4-octylphenol | affects activity, affects binding, decreases reaction | 1 |
| imidacloprid | affects binding, increases activity | 1 |
| CGP 52608 | affects binding, increases reaction | 1 |
| cisatracurium | affects binding, decreases reaction, increases activity | 1 |
| 4-((2-(1-methyl-2-pyrrolidinyl)ethyl)thio)phenol hydrochloride | affects binding, increases activity | 1 |
| 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide | affects cotreatment, increases expression | 1 |
| 1,2-bis-N-cytisinylethane | affects binding, increases reaction, increases localization | 1 |
| 2,2’,4,4’-tetrabromodiphenyl ether | increases expression | 1 |
| dorsomorphin | increases expression, affects cotreatment | 1 |
ChEMBL screening assays
407 unique, capped per target: 309 binding, 96 functional, 2 admet
Representative assays (with source publication via chembl_document):
| Assay ID | Type | Description | Source paper |
|---|---|---|---|
| CHEMBL1020768 | Binding | Displacement of [3H]epibatidine from alpha4beta4 nAChR expressed in HEK293 cells | Carbamoylcholine analogs as nicotinic acetylcholine receptor agonists–structural modifications of 3-(dimethylamino)butyl dimethylcarbamate (DMABC). — Bioorg Med Chem Lett |
| CHEMBL1068091 | Functional | Antagonist activity at human alpha4beta4 nAChR receptor expressed in human SH-SY5Y cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting | Synthesis and biological evaluation of bupropion analogues as potential pharmacotherapies for smoking cessation. — J Med Chem |
| CHEMBL4603065 | ADMET | Inhibition of human alpha3beta4 nAChR assessed as increase in acetylcholine-induced normalized current at 2 uM (Rvb = 78.5 +/- 10 uM) | Differentiating the Pharmacodynamics and Toxicology of Macrolide and Ketolide Antibiotics. — J Med Chem |
Cellosaurus cell lines
1 cell lines: 1 transformed cell line
First 10 cell lines (id-ordered, not curated):
| Cellosaurus | Name | Category | Sex |
|---|---|---|---|
| CVCL_D1KF | PrecisION hnAChR alpha3/beta4-HEK | Transformed cell line | Female |
Clinical trials (associated diseases)
455 trials via MONDO — disease-level, not drug-specific.
| Trial | Phase | Status | Title |
|---|---|---|---|
| NCT00158041 | PHASE4 | COMPLETED | Subcutaneous Amifostine Safety Study |
| NCT00277160 | PHASE4 | COMPLETED | A Study of Primary Prophylaxis With Neulasta (Pegfilgrastim) Versus Secondary Prophylaxis After Chemotherapy in Elderly Subjects (>/= 65 Years Old) With Cancer |
| NCT00365508 | PHASE4 | COMPLETED | Counseling and Nicotine Replacement Therapy in Helping Adult Smokers Quit Smoking |
| NCT00440960 | PHASE4 | COMPLETED | Anesthesia in Flexible Bronchoscopy for Lung Cancer Diagnostic |
| NCT00492843 | PHASE4 | TERMINATED | Loading Dose or Standard Dose of Intravenous Ibandronate in Treating Patients With Lung Cancer and Skeletal Metastasis |
| NCT00666978 | PHASE4 | COMPLETED | Health Education Counseling With or Without Bupropion in Helping African Americans Stop Smoking |
| NCT00675168 | PHASE4 | UNKNOWN | Positron Emission Tomography (PET)/Computed Tomography (CT) and Roentgen in Lung Cancer: Evaluation of Patients in General Practice |
| NCT00712647 | PHASE4 | COMPLETED | Carotene and Retinol Efficacy Trial |
| NCT00747773 | PHASE4 | COMPLETED | Cryospray Ablation of Surgical Resection Specimens To Determine Safety And Histological Effect In The Lung |
| NCT01060137 | PHASE4 | COMPLETED | Fentanyl Matrix in Lung Cancer Pain |
| NCT01381627 | PHASE4 | UNKNOWN | Safety Evaluation of Dexmedetomidine for EBUS-TBNA |
| NCT01741506 | PHASE4 | COMPLETED | Coagulation Profile in Patients Undergoing Video Assisted Thorascopic Surgery (VATS) for Lung Cancer |
| NCT02246023 | PHASE4 | COMPLETED | Fractionated Versus Target-controlled Propofol Administration in Bronchoscopy |
| NCT02275702 | PHASE4 | COMPLETED | Randomized Study of Preoperative Dexamethasone for Quality of Recovery in VATS Lung Resection Patients |
| NCT02346318 | PHASE4 | UNKNOWN | The Randomized Controlled Clinical Trial of Kushen Injection |
| NCT02476526 | PHASE4 | COMPLETED | Safety of Low Dose IV Contrast CT Scanning in Chronic Kidney Disease |
| NCT02490059 | PHASE4 | COMPLETED | Ultrathin Bronchoscopy for Solitary Pulmonary Nodules |
| NCT02504801 | PHASE4 | UNKNOWN | Efficacy of Nebulized Pulmicort Respules in Primary Lung Cancer Patients With COPD |
| NCT02869789 | PHASE4 | COMPLETED | An Investigational Immuno-therapy Study for Safety of Nivolumab in Combination With Ipilimumab to Treat Advanced Cancers |
| NCT03302221 | PHASE4 | WITHDRAWN | Regional Haemodynamic Changes in Radial Artery Assessment With Continuous Pulsed-wave Doppler Ultrasound |
| NCT03313544 | PHASE4 | UNKNOWN | Evolution of the Heart Function When Monitoring Immunotherapies Anti-cancerous Inhibiting PD-1 |
| NCT03394222 | PHASE4 | COMPLETED | Effect of Preoperative Budesonide Inhalation on Arterial Blood Oxygenation and Intrapulmonary Shunt During OLV |
| NCT03570645 | PHASE4 | COMPLETED | Comparison of the Duration of Ropivacaine Combined With Dexmedetomidine or Dexamethasone on Paravertebral Block |
| NCT03571126 | PHASE4 | UNKNOWN | Olanzapine for the Prevention and Treatment of Nausea and Vomiting Induced by Chemotherapy of Lung Cancer |
| NCT03642457 | PHASE4 | TERMINATED | Efficacy Between Serratus Plane Block And Local Infiltration In Vats |
| NCT04145570 | PHASE4 | COMPLETED | A Single-Dose,ComparativeBioavailability Study ofTwo Formulations ofErlotinib150mgTabletsunderFastingConditions |
| NCT04155008 | PHASE4 | TERMINATED | Nutrition and Pharmacological Algorithm for Oncology Patients Study |
| NCT04613284 | PHASE4 | UNKNOWN | Rh-Endostatin Combined With CCRT(50 Gy) Followed by Durvalumab Maintenance for the Treatment of Specific Phase III NSCLC |
| NCT05463913 | PHASE4 | RECRUITING | Lung Nodule Detection Using Ultra-long FOV PET/CT |
| NCT05521789 | PHASE4 | RECRUITING | Erector Spinae Block for Thoracic Surgery |
| NCT05525338 | PHASE4 | RECRUITING | Comparison of Standard Dose Alectinib to Alectinib in Adjusted Dose Based on Alectinib Bloodlevels |
| NCT05663242 | PHASE4 | RECRUITING | The Effects of Using Different Anesthetics on the Prognosis of Primary Lung Tumors and Its Mechanism of Action |
| NCT05926336 | PHASE4 | RECRUITING | The Effects of Using Different Anesthetics on the Prognosis of Primary Tumors and Its Mechanism of Action |
| NCT06105801 | PHASE4 | RECRUITING | EBUS-TBNA vs Transbronchial Mediastinal Cryobiopsy for Adequacy of Next Generation Sequencing |
| NCT06276933 | PHASE4 | NOT_YET_RECRUITING | A Study of Camrelizumab Combined With Chemotherapy ± Thalidomide in First-line Treatment of Patients With Advanced Non-small Cell Lung Cancer (NSCLC) |
| NCT06646471 | PHASE4 | RECRUITING | PROspective Master-protocol for Evaluation of Systemic THErapeutics in Elderly With Thoracic Malignancies |
| NCT07405086 | PHASE4 | RECRUITING | Morning Versus Afternoon Administration of Immunotherapy for the Treatment of Advanced or Metastatic Solid Tumors, The Knight SHIFT Study |
| NCT00376051 | PHASE4 | COMPLETED | Serotonergic Function and Behavioural and Psychological Symptoms of Frontotemporal Dementia |
| NCT00950430 | PHASE4 | ENROLLING_BY_INVITATION | Imaging of Brain Amyloid Plaques in the Aging Population |
| NCT06093126 | PHASE4 | RECRUITING | Lemborexant for Insomnia in a Patient With Dementia: An N-of-1 Trial |
Related Atlas pages
- Associated diseases: lung carcinoma
- Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): chronic obstructive pulmonary disease, frontotemporal dementia, lung adenocarcinoma, lung cancer, nicotine dependence, small cell lung carcinoma