CHRNB1

Summary

CHRNB1 (cholinergic receptor nicotinic beta 1 subunit, HGNC:1961) is a protein-coding gene on chromosome 17p13.1, encoding Acetylcholine receptor subunit beta (P11230). After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.

The muscle acetylcholine receptor is composed of five subunits: two alpha subunits and one beta, one gamma, and one delta subunit. This gene encodes the beta subunit of the acetylcholine receptor. The acetylcholine receptor changes conformation upon acetylcholine binding leading to the opening of an ion-conducting channel across the plasma membrane. Mutations in this gene are associated with slow-channel congenital myasthenic syndrome.

Source: NCBI Gene 1140 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital myasthenic syndrome 2C (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 6
• Clinical variants (ClinVar): 599 total — 18 pathogenic, 15 likely-pathogenic
• Phenotypes (HPO): 60
• Druggable target: yes — 10 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000747

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1961
Approved symbol	CHRNB1
Name	cholinergic receptor nicotinic beta 1 subunit
Location	17p13.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000170175
Ensembl biotype	protein_coding
OMIM	100710
Entrez	1140

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 2 retained_intron

ENST00000306071, ENST00000536404, ENST00000570557, ENST00000572857, ENST00000573209, ENST00000574054, ENST00000575379, ENST00000576360

RefSeq mRNA: 1 — MANE Select: NM_000747 NM_000747

CCDS: CCDS11106

Canonical transcript exons

ENST00000306071 — 11 exons

Exon	Start	End
ENSE00001147886	7455284	7455456
ENSE00001147902	7447503	7447650
ENSE00001147910	7447043	7447151
ENSE00001147919	7446833	7446942
ENSE00001147940	7445270	7445409
ENSE00001147955	7445061	7445185
ENSE00001202416	7455794	7455941
ENSE00001202452	7456583	7457710
ENSE00003504077	7446069	7446113
ENSE00003537244	7454297	7454520
ENSE00003655520	7448579	7448788

Expression profiles

Bgee: expression breadth ubiquitous, 137 present calls, max score 97.36.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.8745 / max 294.6666, expressed in 1655 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
159198	4.1037	593
159202	2.1929	1228
159201	0.6477	397
159200	0.5107	274
159199	0.4194	272

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	97.36	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.60	gold quality
muscle of leg	UBERON:0001383	96.47	gold quality
muscle organ	UBERON:0001630	96.44	gold quality
skeletal muscle tissue	UBERON:0001134	95.65	gold quality
right adrenal gland cortex	UBERON:0035827	91.42	gold quality
right adrenal gland	UBERON:0001233	91.35	gold quality
muscle tissue	UBERON:0002385	90.54	gold quality
left adrenal gland	UBERON:0001234	90.52	gold quality
left adrenal gland cortex	UBERON:0035825	90.47	gold quality
adrenal gland	UBERON:0002369	88.79	gold quality
placenta	UBERON:0001987	87.05	gold quality
right lobe of liver	UBERON:0001114	84.41	gold quality
amygdala	UBERON:0001876	83.34	gold quality
granulocyte	CL:0000094	83.33	gold quality
temporal lobe	UBERON:0001871	83.33	gold quality
prefrontal cortex	UBERON:0000451	83.26	gold quality
islet of Langerhans	UBERON:0000006	83.25	gold quality
pancreas	UBERON:0001264	83.14	gold quality
body of pancreas	UBERON:0001150	83.05	gold quality
monocyte	CL:0000576	82.93	gold quality
leukocyte	CL:0000738	82.91	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	82.87	gold quality
apex of heart	UBERON:0002098	82.60	gold quality
putamen	UBERON:0001874	82.44	gold quality
substantia nigra	UBERON:0002038	82.35	gold quality
caudate nucleus	UBERON:0001873	82.26	gold quality
Ammon’s horn	UBERON:0001954	82.17	gold quality
cortical plate	UBERON:0005343	82.08	gold quality
anterior cingulate cortex	UBERON:0009835	81.94	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.60

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC, TEF

miRNA regulators (miRDB)

30 targeting CHRNB1, 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-4482-3P	99.98	72.50	3147
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-217-5P	99.49	69.93	1419
HSA-MIR-4999-5P	99.35	69.15	926
HSA-MIR-504-3P	99.30	67.18	1745
HSA-MIR-6807-3P	99.15	69.23	1275
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-6506-5P	99.04	65.66	1386
HSA-MIR-6770-5P	98.97	66.76	1853
HSA-MIR-455-3P	98.94	67.68	878
HSA-MIR-2355-5P	98.83	65.51	1589
HSA-MIR-4272	98.76	68.74	1810
HSA-MIR-619-5P	98.57	64.97	1988
HSA-MIR-5089-5P	98.45	66.06	1388
HSA-MIR-302F	98.44	69.02	1776
HSA-MIR-5008-5P	98.42	65.87	1019
HSA-MIR-6792-5P	98.39	68.16	1330
HSA-MIR-653-3P	98.31	67.71	1542
HSA-MIR-744-3P	97.99	67.76	637
HSA-MIR-4733-5P	97.75	67.44	866
HSA-MIR-4653-3P	96.26	67.03	725

Literature-anchored findings (GeneRIF, showing 10)

• Association of the nicotinic acetylcholine receptor beta1 subunit (CHRNB1) and M1 muscarinic acetylcholine receptor (CHRM1) with vulnerability for nicotine dependence. (PMID:16874522)
• the beta1 subunit showed significantly increased expression in lung tumors as compared to non-tumor bronchial tissue (PMID:17015027)
• No CHRNA1, CHRNB1, or CHRND mutations were detected, but a homozygous RAPSN frameshift mutation, c.1177-1178delAA, was identified in a family with three children affected with lethal fetal akinesia sequence. (PMID:18179903)
• Extracellular beta1-beta2 and cysteine-loops bridge the pre-M1 transmembrane domain and M2-M3 linker to transduce agonist binding into channel gating. (PMID:19279256)
• Single nucleotide polymorphisms , rs55633891 (alpha9, C>T) and rs17856697 (beta1, A>G), did not exhibit a significant trend to be associated with cervical lesions. (PMID:22406075)
• These findings identify novel Golgi retention signals in the beta and delta subunit loops that regulate surface trafficking of assembled AChR and may help prevent surface expression of unassembled subunits. (PMID:24240098)
• Study traced the cause of congenital myasthenia syndrome in unrelated patients with dominant missense mutations in the M2 domain of AChR. A valine residue is replaced by a smaller alanine either in the epsilon subunit or an equivalent position in the beta one. Also, each valine in the valine ring was found to contribute to channel kinetics equally, and the valine ring has bee optimized during evolution to govern channe… (PMID:27375219)
• This study reports on the presence of the CHRNB1 at the cellular level in human skeletal muscle and placenta and that mRNA expression mirrors that of protein within cell types. (PMID:28153524)
• CHRNB1-associated congenital myasthenia syndrome: Expanding the clinical spectrum. (PMID:33296147)
• Reply to Zhu et al.: Implications of CHRNB1 and ERBB2 in the pathobiology of myasthenia gravis. (PMID:35969799)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	chrnb1l	ENSDARG00000022532
danio_rerio	chrnb1	ENSDARG00000069660
mus_musculus	Chrnb1	ENSMUSG00000041189
rattus_norvegicus	Chrnb1	ENSRNOG00000014698

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), CHRNB3 (ENSG00000147432), CHRNA6 (ENSG00000147434), HTR3B (ENSG00000149305), GABRA2 (ENSG00000151834), CHRNB2 (ENSG00000160716), GABRG1 (ENSG00000163285), GABRB1 (ENSG00000163288), GABRB3 (ENSG00000166206), CHRFAM7A (ENSG00000166664), HTR3A (ENSG00000166736), CHRNA5 (ENSG00000169684), CHRNA9 (ENSG00000174343), CHRNA7 (ENSG00000175344), HTR3C (ENSG00000178084), GABRG3 (ENSG00000182256), GABRR3 (ENSG00000183185), HTR3E (ENSG00000186038), HTR3D (ENSG00000186090)

Protein

Protein identifiers

Acetylcholine receptor subunit beta — P11230 (reviewed: P11230)

All UniProt accessions (5): P11230, I3L1T7, I3L3Q9, I3L4N5, I3L535

UniProt curated annotations — full annotation on UniProt →

Function. After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.

Subunit / interactions. Pentamer of two alpha chains, and one each of the beta, delta, and gamma (in immature muscle) or epsilon (in mature muscle) chains. The muscle heteropentamer composed of alpha-1, beta-1, delta, epsilon subunits interacts with the alpha-conotoxin ImII.

Subcellular location. Postsynaptic cell membrane. Cell membrane.

Disease relevance. Myasthenic syndrome, congenital, 2A, slow-channel (CMS2A) [MIM:616313] A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. CMS2A is a slow-channel myasthenic syndrome. It is caused by kinetic abnormalities of the AChR, resulting in prolonged AChR channel opening episodes, prolonged endplate currents, and depolarization block. This is associated with calcium overload, which may contribute to subsequent degeneration of the endplate and postsynaptic membrane. The disease is caused by variants affecting the gene represented in this entry. Myasthenic syndrome, congenital, 2C, associated with acetylcholine receptor deficiency (CMS2C) [MIM:616314] A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. CMS2C is an autosomal recessive disorder of postsynaptic neuromuscular transmission, due to deficiency of AChR at the endplate that results in low amplitude of the miniature endplate potential and current. CMS2C is clinically characterized by early-onset muscle weakness with variable severity. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Beta-1/CHRNB1 sub-subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P11230-1	1	yes
P11230-2	2

RefSeq proteins (1): NP_000738* (*=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), 2 shown:

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

UniProt features (20 total): sequence variant 6, transmembrane region 4, sequence conflict 2, topological domain 2, signal peptide 1, chain 1, disulfide bond 1, splice variant 1, modified residue 1, glycosylation site 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
9DMS	ELECTRON MICROSCOPY	1.92
9DMG	ELECTRON MICROSCOPY	2.05
9DMH	ELECTRON MICROSCOPY	2.06
9DMQ	ELECTRON MICROSCOPY	2.06
9DMV	ELECTRON MICROSCOPY	2.13
9DMT	ELECTRON MICROSCOPY	2.18
9DMJ	ELECTRON MICROSCOPY	2.19
9DML	ELECTRON MICROSCOPY	2.24
9DMK	ELECTRON MICROSCOPY	2.46
9GU1	ELECTRON MICROSCOPY	2.48
9GU3	ELECTRON MICROSCOPY	2.64
9GU2	ELECTRON MICROSCOPY	2.73
9GU0	ELECTRON MICROSCOPY	2.96

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P11230-F1	80.01	0.45

Antibody-complex structures (SAbDab): 10 — 9DMJ, 9DMK, 9DMQ, 9DMS, 9DMT, 9DMV, 9GU0, 9GU1, 9GU2, 9GU3

Functional residue map

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

Post-translational modifications (1): 390

Disulfide bonds (1): 151–165

Glycosylation sites (1): 164

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 331 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_DN, MODULE_92, GOBP_MEMBRANE_DEPOLARIZATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, MODULE_328, MODULE_274, GOBP_BEHAVIOR, ENK_UV_RESPONSE_KERATINOCYTE_UP, GCANCTGNY_MYOD_Q6, GOBP_ADULT_BEHAVIOR, MODULE_64, AREB6_03, GOBP_SYNAPTIC_TRANSMISSION_CHOLINERGIC, GOBP_MULTICELLULAR_ORGANISMAL_MOVEMENT, MODULE_329

GO Biological Process (17): postsynaptic membrane organization (GO:0001941), skeletal muscle contraction (GO:0003009), monoatomic cation transport (GO:0006812), muscle contraction (GO:0006936), signal transduction (GO:0007165), synaptic transmission, cholinergic (GO:0007271), neuromuscular synaptic transmission (GO:0007274), monoatomic ion transmembrane transport (GO:0034220), behavioral response to nicotine (GO:0035095), regulation of membrane potential (GO:0042391), nervous system process (GO:0050877), membrane depolarization (GO:0051899), muscle cell development (GO:0055001), acetylcholine receptor signaling pathway (GO:0095500), monoatomic ion transport (GO:0006811), regulation of postsynaptic membrane potential (GO:0060078), excitatory postsynaptic potential (GO:0060079)

GO Molecular Function (10): transmembrane signaling receptor activity (GO:0004888), channel activity (GO:0015267), ligand-gated monoatomic ion channel activity (GO:0015276), acetylcholine-gated monoatomic cation-selective channel activity (GO:0022848), acetylcholine binding (GO:0042166), transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential (GO:1904315), monoatomic ion channel activity (GO:0005216), extracellular ligand-gated monoatomic ion channel activity (GO:0005230), protein binding (GO:0005515), acetylcholine receptor activity (GO:0015464)

GO Cellular Component (8): plasma membrane (GO:0005886), acetylcholine-gated channel complex (GO:0005892), neuromuscular junction (GO:0031594), neuron projection (GO:0043005), synapse (GO:0045202), postsynaptic specialization membrane (GO:0099634), membrane (GO:0016020), postsynaptic membrane (GO:0045211)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
monoatomic ion transport	2
chemical synaptic transmission	2
regulation of membrane potential	2
regulation of postsynaptic membrane potential	2
postsynaptic neurotransmitter receptor activity	2
synaptic membrane	2
membrane organization	1
postsynapse organization	1
striated muscle contraction	1
musculoskeletal movement	1
muscle system process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
transmembrane transport	1
adult behavior	1
response to nicotine	1
monoatomic ion transmembrane transport	1
regulation of biological quality	1
system process	1
muscle cell differentiation	1
cell development	1
acetylcholine receptor activity	1
postsynaptic signal transduction	1
cellular response to acetylcholine	1
transport	1
chemical synaptic transmission, postsynaptic	1
signaling receptor activity	1
passive transmembrane transporter activity	1
monoatomic ion channel activity	1
ligand-gated channel 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
transmitter-gated monoatomic ion channel activity	1
monoatomic ion transmembrane transporter activity	1
channel activity	1

Protein interactions and networks

STRING

666 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHRNB1	RAPSN	Q13702	910
CHRNB1	COLQ	Q9Y215	796
CHRNB1	MUSK	O15146	793
CHRNB1	DOK7	Q18PE1	786
CHRNB1	CHRNA1	P02708	673
CHRNB1	CHRND	Q07001	654
CHRNB1	ALG14	Q96F25	547
CHRNB1	DPAGT1	Q9H3H5	527
CHRNB1	GFPT1	Q06210	518
CHRNB1	SCN4A	P35499	511
CHRNB1	AGRN	O00468	490
CHRNB1	CHRM5	P08912	460
CHRNB1	CHRNE	Q04844	454
CHRNB1	CHRNG	P07510	438
CHRNB1	FGA	P02671	428

IntAct

17 interactions, top by confidence:

A	B	Type	Score
NEMP1	RGPD8	psi-mi:“MI:0914”(association)	0.640
CHRNB1	ASB6	psi-mi:“MI:0915”(physical association)	0.560
WLS	CHRNB1	psi-mi:“MI:0914”(association)	0.530
CHRNA4	FZD6	psi-mi:“MI:0914”(association)	0.530
EVA1B	NRP1	psi-mi:“MI:0914”(association)	0.530
CHRNB1	BET1	psi-mi:“MI:0914”(association)	0.350
BSCL2	QSOX1	psi-mi:“MI:0914”(association)	0.350
CHRNA3	ENTPD6	psi-mi:“MI:0914”(association)	0.350
CHRNB1	CLGN	psi-mi:“MI:0914”(association)	0.350
CHRND	CHRNB1	psi-mi:“MI:0914”(association)	0.350
DUOXA2	CHRNB1	psi-mi:“MI:0914”(association)	0.350
HTR3A	ZZEF1	psi-mi:“MI:0914”(association)	0.350
TMEM9B	FANCG	psi-mi:“MI:0914”(association)	0.350
CHRNB1	ASB6	psi-mi:“MI:0915”(physical association)	0.000
CHRNB1	COPS6	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (28): CHRNB1 (Two-hybrid), EDA (Affinity Capture-MS), SARAF (Affinity Capture-MS), GHDC (Affinity Capture-MS), RHBDD1 (Affinity Capture-MS), LRRC8A (Affinity Capture-MS), C1orf43 (Affinity Capture-MS), APOL2 (Affinity Capture-MS), DNAJC30 (Affinity Capture-MS), SPPL2B (Affinity Capture-MS), PDZD8 (Affinity Capture-MS), LEMD2 (Affinity Capture-MS), ZBTB33 (Affinity Capture-MS), DNAJC18 (Affinity Capture-MS), CISD2 (Affinity Capture-MS)

ESM2 similar proteins: A1A5B4, A2A259, A2AIR5, E9PTA2, F6RG56, H2Q5A1, O35245, O62826, O70212, O94759, P02715, P04758, P09690, P11230, P13536, P23979, P25109, P35563, P37088, Q04671, Q13507, Q13563, Q4GZT3, Q60HE8, Q6IVV8, Q7Z403, Q86V40, Q8BWC0, Q8MIQ9, Q8R4F0, Q8TCT7, Q8TCU5, Q8TDD5, Q91YD4, Q96BD0, Q99J21, Q9EQJ0, Q9GZU1, Q9HA82, Q9JJH7

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
CHRNB1	“form complex”	“Muscle-type nicotinic acetylcholine receptor complex, alpha1-beta1-delta-epsilon”	binding
CHRNB1	“form complex”	“Muscle-type nicotinic acetylcholine receptor complex, alpha1-beta1-delta-gamma”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	18
Likely pathogenic	15
Uncertain significance	305
Likely benign	159
Benign	50

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1068934	NM_000747.3(CHRNB1):c.759dup (p.Ala254fs)	Pathogenic
1723268	NC_000017.10:g.(7352108_7357615)_(7357840_7358602)del	Pathogenic
18372	NM_000747.3(CHRNB1):c.865G>A (p.Val289Met)	Pathogenic
18373	NM_000747.3(CHRNB1):c.853C>A (p.Leu285Met)	Pathogenic
18374	NM_000747.3(CHRNB1):c.1347_1355del (p.Glu449_Glu451del)	Pathogenic
18375	NM_000747.3(CHRNB1):c.821_1044del p.Gly274Aspfs	Pathogenic
2023085	NM_000747.3(CHRNB1):c.1072_1073del (p.Leu358fs)	Pathogenic
2118016	NM_000747.3(CHRNB1):c.1102_1103del (p.Asp368fs)	Pathogenic
2579228	GRCh38/hg38 17p13.1(chr17:7454200-7454618)x0	Pathogenic
280253	NM_000747.3(CHRNB1):c.919del (p.Ile307fs)	Pathogenic
3703779	NM_000747.3(CHRNB1):c.270G>A (p.Trp90Ter)	Pathogenic
430426	NM_000747.3(CHRNB1):c.295_299delinsACG (p.Asp99fs)	Pathogenic
451505	NM_000747.3(CHRNB1):c.645_646del (p.Arg216fs)	Pathogenic
4702847	NM_000747.3(CHRNB1):c.863del (p.Thr288fs)	Pathogenic
584314	NC_000017.11:g.(?7454277)(7454540_?)del	Pathogenic
631787	NM_000747.3(CHRNB1):c.605dup (p.Ile203fs)	Pathogenic
651814	NC_000017.11:g.(?7454287)(7454530_?)del	Pathogenic
860460	NM_000747.3(CHRNB1):c.866T>C (p.Val289Ala)	Pathogenic
1321823	NM_000747.3(CHRNB1):c.42_44delinsAA (p.Ala15fs)	Likely pathogenic
1324074	NM_000747.3(CHRNB1):c.353+2T>C	Likely pathogenic
1324075	NM_000747.3(CHRNB1):c.403_407delinsGTGCGTGGTGTC (p.Ser135fs)	Likely pathogenic
1349189	NM_000747.3(CHRNB1):c.854T>C (p.Leu285Pro)	Likely pathogenic
2144433	NM_000747.3(CHRNB1):c.611-1G>C	Likely pathogenic
2663945	NM_000747.3(CHRNB1):c.353+1del	Likely pathogenic
2701345	NM_000747.3(CHRNB1):c.757_820+135del	Likely pathogenic
3066140	NM_000747.3(CHRNB1):c.1071C>A (p.Tyr357Ter)	Likely pathogenic
3377480	NM_000747.3(CHRNB1):c.1435del (p.Thr479fs)	Likely pathogenic
3582827	NM_000747.3(CHRNB1):c.544C>T (p.Gln182Ter)	Likely pathogenic
3715131	NM_000747.3(CHRNB1):c.610+1G>A	Likely pathogenic
4081247	NM_000747.3(CHRNB1):c.434dup (p.Ile146fs)	Likely pathogenic

SpliceAI

1817 predictions. Top by Δscore:

Variant	Effect	Δscore
17:7445186:G:GA	donor_loss	1.0000
17:7445405:GCCTG:G	donor_gain	1.0000
17:7446178:GCCCA:G	donor_gain	1.0000
17:7446943:G:GG	donor_gain	1.0000
17:7446966:G:T	donor_gain	1.0000
17:7447171:G:GT	donor_gain	1.0000
17:7447171:G:T	donor_gain	1.0000
17:7447175:C:G	donor_gain	1.0000
17:7447177:G:GT	donor_gain	1.0000
17:7447180:G:GT	donor_gain	1.0000
17:7447181:G:GT	donor_gain	1.0000
17:7447182:A:T	donor_gain	1.0000
17:7447620:G:GT	donor_gain	1.0000
17:7447650:GGTG:G	donor_loss	1.0000
17:7447651:GT:G	donor_loss	1.0000
17:7447652:T:G	donor_loss	1.0000
17:7447655:G:GG	donor_gain	1.0000
17:7448566:T:TA	acceptor_gain	1.0000
17:7448577:A:AG	acceptor_gain	1.0000
17:7448578:G:GG	acceptor_gain	1.0000
17:7448578:GA:G	acceptor_gain	1.0000
17:7448578:GAGA:G	acceptor_gain	1.0000
17:7448789:GT:G	donor_loss	1.0000
17:7448790:T:G	donor_loss	1.0000
17:7454286:T:TA	acceptor_gain	1.0000
17:7454295:A:G	acceptor_gain	1.0000
17:7455378:G:GT	donor_gain	1.0000
17:7455418:G:GT	donor_gain	1.0000
17:7455545:G:GT	donor_gain	1.0000
17:7455558:T:G	donor_gain	1.0000

AlphaMissense

3263 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:7448592:G:C	W208C	0.999
17:7448592:G:T	W208C	0.999
17:7448695:C:A	R243S	0.999
17:7446836:T:A	W83R	0.998
17:7446836:T:C	W83R	0.998
17:7446838:G:C	W83C	0.998
17:7446838:G:T	W83C	0.998
17:7446914:T:A	W109R	0.998
17:7446914:T:C	W109R	0.998
17:7446916:G:C	W109C	0.998
17:7446916:G:T	W109C	0.998
17:7447141:G:A	C151Y	0.998
17:7447512:T:C	F158L	0.998
17:7447513:T:G	F158C	0.998
17:7447514:C:A	F158L	0.998
17:7447514:C:G	F158L	0.998
17:7447534:G:A	C165Y	0.998
17:7447535:C:G	C165W	0.998
17:7448590:T:A	W208R	0.998
17:7448590:T:C	W208R	0.998
17:7448767:T:C	F267L	0.998
17:7448769:C:A	F267L	0.998
17:7448769:C:G	F267L	0.998
17:7454452:A:C	S326R	0.998
17:7454454:T:A	S326R	0.998
17:7454454:T:G	S326R	0.998
17:7446859:G:C	W90C	0.997
17:7446859:G:T	W90C	0.997
17:7447134:A:C	S149R	0.997
17:7447136:C:A	S149R	0.997

dbSNP variants (sampled 300 via entrez): RS1000133499 (17:7451407 G>A,C), RS1000241010 (17:7444971 C>T), RS1000896955 (17:7445648 A>G), RS1001211203 (17:7443810 C>A), RS1001242391 (17:7443505 C>T), RS1001271364 (17:7445330 G>C,T), RS1001543159 (17:7449780 C>G,T), RS1001581401 (17:7455192 G>A,C), RS1001717072 (17:7454906 G>A), RS1001872905 (17:7446413 G>A), RS1001918497 (17:7453463 C>T), RS1001964095 (17:7455048 C>G,T), RS1002146344 (17:7448501 TG>T), RS1002535718 (17:7449197 G>A), RS1002690714 (17:7455953 G>A,T)

Disease associations

OMIM: gene MIM:100710 | disease phenotypes: MIM:616313, MIM:608931, MIM:616314, MIM:201475

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital myasthenic syndrome 2C	Definitive	Autosomal dominant
congenital myasthenic syndrome 2A	Strong	Autosomal dominant
postsynaptic congenital myasthenic syndrome	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
congenital myasthenic syndrome 2A	Moderate	AD
congenital myasthenic syndrome 2C	Definitive	AR

Mondo (5): congenital myasthenic syndrome 2A (MONDO:0014581), congenital myasthenic syndrome 4C (MONDO:0012157), congenital myasthenic syndrome 2C (MONDO:0014582), very long chain acyl-CoA dehydrogenase deficiency (MONDO:0008723), postsynaptic congenital myasthenic syndrome (MONDO:0020344)

Orphanet (2): Congenital myasthenic syndrome (Orphanet:590), Very long chain acyl-CoA dehydrogenase deficiency (Orphanet:26793)

HPO phenotypes

60 total (30 of 60 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000218	High palate
HP:0000275	Narrow face
HP:0000276	Long face
HP:0000496	Abnormality of eye movement
HP:0000508	Ptosis
HP:0000597	Ophthalmoparesis
HP:0000602	Ophthalmoplegia
HP:0000651	Diplopia
HP:0000961	Cyanosis
HP:0001252	Hypotonia
HP:0001315	Reduced tendon reflexes
HP:0001319	Neonatal hypotonia
HP:0001324	Muscle weakness
HP:0001371	Flexion contracture
HP:0001446	Abnormality of the musculature of the upper limbs
HP:0001620	Abnormally high-pitched voice
HP:0002033	Poor suck
HP:0002091	Restrictive ventilatory defect
HP:0002093	Respiratory insufficiency
HP:0002194	Delayed gross motor development
HP:0002329	Drowsiness
HP:0002421	Poor head control
HP:0002650	Scoliosis
HP:0002792	Reduced vital capacity
HP:0002875	Exertional dyspnea
HP:0002878	Respiratory failure
HP:0003198	Myopathy
HP:0003202	Skeletal muscle atrophy

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST009308_1	Emotional recognition	1.000000e-06
GCST009325_52	Parkinson’s disease or first degree relation to individual with Parkinson’s disease	1.000000e-08
GCST010002_119	Refractive error	3.000000e-22
GCST010703_158	Brain morphology (MOSTest)	3.000000e-09
GCST012226_395	Waist circumference adjusted for body mass index	3.000000e-08
GCST90020029_817	Waist circumference adjusted for body mass index	4.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0008354	cognitive function measurement
EFO:0004346	neuroimaging measurement
EFO:0007789	BMI-adjusted waist circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (6): CHEMBL1907588 (PROTEIN COMPLEX), CHEMBL2111384 (PROTEIN COMPLEX GROUP), CHEMBL2362997 (PROTEIN COMPLEX GROUP), CHEMBL3885508 (PROTEIN COMPLEX), CHEMBL4106145 (PROTEIN COMPLEX), CHEMBL4524133 (PROTEIN COMPLEX GROUP)

Molecules with ChEMBL bioactivity

10 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 256,857 (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
CHEMBL56564	TROPISETRON	4	19,312
CHEMBL894	BUPROPION	4	36,982
CHEMBL267936	MECAMYLAMINE	4	5,623
CHEMBL2103881	DEXMECAMYLAMINE	3	18
CHEMBL497939	CYTISINICLINE	3	2,766
CHEMBL1172928	RADAFAXINE	2	1,079
CHEMBL134713	GTS-21	2	269
CHEMBL504652	TC-2216	1	32

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2302764	CHRNB1, ZBTB4		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: lgic — Nicotinic acetylcholine receptors (nACh)

Binding affinities (BindingDB)

1 measured of 6 human assays (6 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
9-Iodo-1,2,3,4,5,6-hexahydro-1,5-methano-pyrido[1,2-a][1,5]diazocin-8-one	EC50	45 nM

ChEMBL bioactivities

115 potent at pChembl≥5 of 176 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.28	EC50	0.053	nM	EPIBATIDINE
8.82	IC50	1.5	nM	CHEMBL566050
8.70	IC50	2	nM	CHEMBL569465
8.57	IC50	2.7	nM	CHEMBL566208
8.41	IC50	3.9	nM	CHEMBL566886
8.24	IC50	5.7	nM	CHEMBL565844
8.24	IC50	5.8	nM	CHEMBL592854
8.19	IC50	6.5	nM	CHEMBL599846
8.12	IC50	7.6	nM	CHEMBL566001
8.04	IC50	9.2	nM	CHEMBL589250
8.01	IC50	9.8	nM	CHEMBL568140
8.00	IC50	10	nM	CHEMBL565396
7.96	EC50	11	nM	CYTISINICLINE
7.96	IC50	11	nM	CHEMBL566832
7.92	IC50	12	nM	CHEMBL566207
7.92	IC50	12	nM	CHEMBL565845
7.85	IC50	14	nM	CHEMBL566000
7.80	IC50	16	nM	CHEMBL603620
7.80	IC50	16	nM	CHEMBL578612
7.80	IC50	16	nM	CHEMBL567481
7.77	IC50	17	nM	CHEMBL578611
7.72	IC50	19	nM	CHEMBL596775
7.72	IC50	19	nM	CHEMBL599230
7.62	IC50	24	nM	CHEMBL578610
7.58	IC50	26	nM	CHEMBL605501
7.55	EC50	28	nM	CHEMBL64496
7.55	IC50	28	nM	CHEMBL566420
7.51	EC50	31	nM	CHEMBL305106
7.50	IC50	32	nM	CHEMBL576063
7.43	EC50	37	nM	CHEMBL181840
7.39	IC50	41	nM	CHEMBL598026
7.35	EC50	45	nM	CHEMBL62858
7.28	IC50	53	nM	CHEMBL589494
7.16	IC50	69	nM	CHEMBL565386
7.06	IC50	87	nM	CHEMBL580143
6.88	IC50	131	nM	CHEMBL4872191
6.60	Ki	250	nM	CYTISINICLINE
6.52	IC50	300	nM	2(R)-MECAMYLAMINE
6.50	Ki	314	nM	CHEMBL59986
6.28	Ki	520	nM	CHEMBL196626
6.28	Ki	530	nM	CHEMBL1209305
6.24	Ki	580	nM	CHEMBL2057714
6.22	IC50	600	nM	DEXMECAMYLAMINE
6.19	Ki	650	nM	CHEMBL194204
6.16	IC50	690	nM	CHEMBL160950
6.10	IC50	790	nM	CHEMBL346301
6.10	IC50	800	nM	CHEMBL156204
6.10	IC50	790	nM	CHEMBL15998
6.05	IC50	890	nM	CHEMBL157250
5.99	Ki	1020	nM	CHEMBL1209070

PubChem BioAssay actives

115 with measured affinity, of 591 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	246397: Change in membrane potential in TE-671 cells expressing acetylcholine neuromuscular receptors	ec50	0.0001	uM
2-(tert-butylamino)-1-(3,4-dichlorophenyl)pentan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0015	uM
2-(tert-butylamino)-1-(3-chlorophenyl)pentan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0020	uM
2-(tert-butylamino)-1-(3,4-dichlorophenyl)butan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0027	uM
2-(tert-butylamino)-1-(3-chlorophenyl)butan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0039	uM
2-(tert-butylamino)-1-(3-chloro-4-methylphenyl)propan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0057	uM
2-(cyclopentylamino)-1-(3-methylphenyl)propan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0058	uM
1-(3-bromophenyl)-2-(cyclopentylamino)propan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0065	uM
1-(4-bromophenyl)-2-(tert-butylamino)propan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0076	uM
Bupropion	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0079	uM
2-(cyclopentylamino)-1-(3-methoxyphenyl)propan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0092	uM
2-(tert-butylamino)-1-(3,4-dichlorophenyl)propan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0098	uM
1-(3-bromophenyl)-2-(tert-butylamino)propan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0100	uM
cytisinicline	246397: Change in membrane potential in TE-671 cells expressing acetylcholine neuromuscular receptors	ec50	0.0110	uM
2-(tert-butylamino)-1-(3-methylphenyl)propan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0110	uM
1-(4-bromo-3-methylphenyl)-2-(tert-butylamino)propan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0120	uM
2-(tert-butylamino)-1-(4-methylphenyl)propan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0120	uM
2-(tert-butylamino)-1-(4-chlorophenyl)propan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0140	uM
2-[tert-butyl(methyl)amino]-1-(3-chlorophenyl)propan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0160	uM
3-(tert-butylamino)-1-(3-chlorophenyl)-2-methylpropan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0160	uM
2-(tert-butylamino)-1-(3-methoxyphenyl)propan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0160	uM
2-(tert-butylamino)-1-(3,5-dichlorophenyl)propan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0170	uM
2-(cyclopentylamino)-1-(3-nitrophenyl)propan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0190	uM
1-(3-bromophenyl)-2-piperidin-1-ylpropan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0190	uM
2-(tert-butylamino)-1-(3,4-difluorophenyl)propan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0240	uM
2-(cyclopentylamino)-1-(3-fluorophenyl)propan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0260	uM
1-(3-chlorophenyl)-2-piperidin-1-ylpropan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0280	uM
5-chloro-7,11-diazatricyclo[7.3.1.02,7]trideca-2,4-dien-6-one	246397: Change in membrane potential in TE-671 cells expressing acetylcholine neuromuscular receptors	ec50	0.0280	uM
5-bromo-7,11-diazatricyclo[7.3.1.02,7]trideca-2,4-dien-6-one	246397: Change in membrane potential in TE-671 cells expressing acetylcholine neuromuscular receptors	ec50	0.0310	uM
2-(tert-butylamino)-1-(3-fluorophenyl)propan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0320	uM
11,11-dimethyl-7-aza-11-azoniatricyclo[7.3.1.02,7]trideca-2,4-dien-6-one iodide	246397: Change in membrane potential in TE-671 cells expressing acetylcholine neuromuscular receptors	ec50	0.0370	uM
2-(tert-butylamino)-1-(3-nitrophenyl)propan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0410	uM
5-iodo-7,11-diazatricyclo[7.3.1.02,7]trideca-2,4-dien-6-one	246397: Change in membrane potential in TE-671 cells expressing acetylcholine neuromuscular receptors	ec50	0.0450	uM
1-(3-methylphenyl)-2-piperidin-1-ylpropan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0530	uM
2-(tert-butylamino)-1-thiophen-2-ylpropan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0690	uM
1-(3-methoxyphenyl)-2-piperidin-1-ylpropan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0870	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	1753063: Inhibition of human alpha1beta1deltaepsilon nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced current response by two-electrode voltage-clamp method	ic50	0.1310	uM
(1R,2R,4S)-N,2,3,3-tetramethylbicyclo[2.2.1]heptan-2-amine	1179333: Antagonist activity at human alpha1beta1gammadelta nAChR	ic50	0.3000	uM
3-[[(2S)-azetidin-2-yl]methoxy]pyridine	1179333: Antagonist activity at human alpha1beta1gammadelta nAChR	ki	0.3140	uM
10-azatricyclo[6.3.1.02,7]dodeca-2(7),3,5-triene-4-carbonitrile	254522: Binding affinity to human Nicotinic acetylcholine receptor alpha-1-beta-gamma-delta expressed in HEK 293 cells using [3H]alpha-bungarotoxin	ki	0.5200	uM
N-[5-[2-[[(1R,5R,6S)-3-azabicyclo[3.2.1]octan-6-yl]oxy]phenyl]-3-pyridinyl]acetamide;hydrochloride	495032: Binding affinity to alpha-1-beta-gamma-delta nicotinic receptor	ki	0.5300	uM
1’-pyridin-3-ylspiro[1-azabicyclo[2.2.1]heptane-7,3’-pyrrolidine]	673332: Binding affinity to human muscle nAChR alpha1beta1gammadelta expressed in human TE-671 cells	ki	0.5800	uM
(1R,2S,4S)-N,2,3,3-tetramethylbicyclo[2.2.1]heptan-2-amine	1179333: Antagonist activity at human alpha1beta1gammadelta nAChR	ic50	0.6000	uM
1-(10-azatricyclo[6.3.1.02,7]dodeca-2(7),3,5-trien-4-yl)ethanone	254522: Binding affinity to human Nicotinic acetylcholine receptor alpha-1-beta-gamma-delta expressed in HEK 293 cells using [3H]alpha-bungarotoxin	ki	0.6500	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-[[(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
N-[(2S)-1-(12-aminododecylamino)-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]butanamide	225872: Antagonist activity at human muscle-type nAChR (embryonic muscle) expressed in TE671 cells; (end value).	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
(1R,5R,6S)-6-(2-pyridin-3-ylphenoxy)-3-azabicyclo[3.2.1]octane;hydrochloride	495032: Binding affinity to alpha-1-beta-gamma-delta nicotinic receptor	ki	1.0200	uM

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Resveratrol	affects cotreatment, decreases expression	2
Acetylcholine	affects binding, increases activity	2
Benzo(a)pyrene	decreases expression, decreases methylation, affects methylation	2
Particulate Matter	affects expression, increases methylation	2
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
gaboxadol	increases activity, affects binding, affects cotreatment	1
sulforaphane	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
entinostat	increases expression	1
abrine	decreases expression	1
jinfukang	increases expression	1
incobotulinumtoxinA	decreases expression	1
Sunitinib	decreases expression	1
Ethanol	decreases expression	1
Doxorubicin	decreases expression	1
gamma-Aminobutyric Acid	affects binding, affects cotreatment, increases activity	1
Muscimol	increases activity, affects binding, affects cotreatment	1
Niclosamide	increases expression	1
Oxygen	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Sarin	decreases expression	1
Vanadates	decreases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1
Acrylamide	increases expression	1

ChEMBL screening assays

87 unique, capped per target: 51 binding, 36 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1039312	Binding	Activity at alpha-1-beta-1-gamma-delta nAChR in human TE671 cells assessed as effect on membrane potential by FLIPR assay	SAR and biological evaluation of SEN12333/WAY-317538: Novel alpha 7 nicotinic acetylcholine receptor agonist. — Bioorg Med Chem
CHEMBL1068092	Functional	Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD 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

Cellosaurus cell lines

2 cell lines: 2 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D1KE	PrecisION hnAChR alpha1/beta1/delta/epsilon-HEK	Transformed cell line	Female
CVCL_YA36	IDG-HEK293T-CHRNB1-V5-OE	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00983788	PHASE2	COMPLETED	Effect of Bezafibrate on Muscle Metabolism in Patients With Fatty Acid Oxidation Defects
NCT01886378	PHASE2	COMPLETED	A Study of UX007 (Triheptanoin) in Participants With Long-Chain Fatty Acid Oxidation Disorders (LC-FAOD)
NCT02214160	PHASE2	COMPLETED	Long-Chain Fatty Acid Oxidation Disorders (LC-FAOD) Extension Study for Subjects Previously Enrolled in Triheptanoin Studies
NCT01494051	PHASE1/PHASE2	COMPLETED	High Protein Diet in Patients With Long-chain Fatty Acid Oxidation Disorders
NCT05411835	EARLY_PHASE1	COMPLETED	Oral Ketones and Exercise Among Patients With Long-chain Fatty Acid Oxidation Disorders
NCT02517307	Not specified	COMPLETED	Fatty Acid Oxidation Defects and Insulin Sensitivity
NCT02635269	Not specified	UNKNOWN	Fat and Sugar Metabolism During Exercise in Patients With Metabolic Myopathy
NCT03531554	Not specified	COMPLETED	Acute Nutritional Ketosis in VLCAD Deficiency
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns
NCT05910151	Not specified	UNKNOWN	Selective Screening of Children for Hereditary Metabolic Diseases by Tandem Mass Spectrometry in Kazakhstan