CHRNA1

Summary

CHRNA1 (cholinergic receptor nicotinic alpha 1 subunit, HGNC:1955) is a protein-coding gene on chromosome 2q31.1, encoding Acetylcholine receptor subunit alpha (P02708). Upon acetylcholine binding, 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 consiststs of 5 subunits of 4 different types: 2 alpha subunits and 1 each of the beta, gamma, and delta subunits. This gene encodes an alpha subunit that plays a role in acetlycholine binding/channel gating. Alternatively spliced transcript variants encoding different isoforms have been identified.

Source: NCBI Gene 1134 — RefSeq curated summary.

At a glance

• Gene–disease (curated): myasthenic syndrome, congenital, 1B, fast-channel (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 590 total — 32 pathogenic, 15 likely-pathogenic
• Phenotypes (HPO): 97
• Druggable target: yes — 12 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000079

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1955
Approved symbol	CHRNA1
Name	cholinergic receptor nicotinic alpha 1 subunit
Location	2q31.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000138435
Ensembl biotype	protein_coding
OMIM	100690
Entrez	1134

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000261007, ENST00000348749, ENST00000409219, ENST00000409323, ENST00000409542, ENST00000416004, ENST00000435083, ENST00000636168, ENST00000672640

RefSeq mRNA: 2 — MANE Select: NM_000079 NM_000079, NM_001039523

CCDS: CCDS2261, CCDS33331

Canonical transcript exons

ENST00000348749 — 9 exons

Exon	Start	End
ENSE00001016397	174759488	174759633
ENSE00001424185	174747592	174748255
ENSE00001693622	174759331	174759375
ENSE00001708702	174764352	174764472
ENSE00002067241	174757566	174757675
ENSE00003512176	174754219	174754414
ENSE00003576436	174749946	174750169
ENSE00003606940	174748580	174748819
ENSE00003632767	174753503	174753740

Expression profiles

Bgee: expression breadth ubiquitous, 149 present calls, max score 93.95.

FANTOM5 (CAGE): breadth broad, TPM avg 5.9372 / max 1093.7955, expressed in 335 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
31894	4.9730	317
31893	0.5943	129
31892	0.3163	96
31897	0.0344	16
31896	0.0122	1
31895	0.0070	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	93.95	gold quality
gluteal muscle	UBERON:0002000	93.36	gold quality
muscle of leg	UBERON:0001383	91.28	gold quality
tibialis anterior	UBERON:0001385	90.61	gold quality
deltoid	UBERON:0001476	88.10	silver quality
muscle organ	UBERON:0001630	87.41	gold quality
hindlimb stylopod muscle	UBERON:0004252	87.01	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.06	gold quality
triceps brachii	UBERON:0001509	84.05	silver quality
quadriceps femoris	UBERON:0001377	78.21	gold quality
skeletal muscle tissue	UBERON:0001134	76.97	gold quality
vastus lateralis	UBERON:0001379	76.39	silver quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	75.56	silver quality
biceps brachii	UBERON:0001507	74.30	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	74.08	silver quality
muscle tissue	UBERON:0002385	72.40	gold quality
adenohypophysis	UBERON:0002196	65.56	gold quality
pituitary gland	UBERON:0000007	64.83	gold quality
Brodmann (1909) area 10	UBERON:0013541	63.71	gold quality
endometrium epithelium	UBERON:0004811	61.78	gold quality
diaphragm	UBERON:0001103	61.15	gold quality
rectum	UBERON:0001052	60.01	gold quality
Ammon’s horn	UBERON:0001954	59.77	gold quality
lymph node	UBERON:0000029	58.34	gold quality
pancreatic ductal cell	CL:0002079	57.82	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	56.83	gold quality
transverse colon	UBERON:0001157	56.12	gold quality
prefrontal cortex	UBERON:0000451	55.43	gold quality
mucosa of transverse colon	UBERON:0004991	54.47	gold quality
apex of heart	UBERON:0002098	54.34	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	14.27

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AIRE, ATOH1, IRF8, MYOD1

miRNA regulators (miRDB)

39 targeting CHRNA1, 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-1277-5P	100.00	73.95	5056
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-8062	99.88	68.43	995
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-548M	99.70	68.87	1749
HSA-MIR-105-5P	99.54	69.24	2060
HSA-MIR-7853-5P	99.54	69.30	2055
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-410-3P	99.27	69.98	2457
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-6760-5P	98.87	66.73	1515
HSA-MIR-3922-5P	98.77	66.53	1059
HSA-MIR-6794-3P	98.76	66.99	894
HSA-MIR-3161	98.71	67.14	816
HSA-MIR-6728-3P	98.63	67.63	1534
HSA-MIR-6754-5P	98.60	65.54	1627
HSA-MIR-7843-5P	98.12	65.26	1421
HSA-MIR-193B-5P	97.91	65.88	837
HSA-MIR-4632-5P	97.82	65.38	1470
HSA-MIR-7111-3P	97.80	66.75	1467

Literature-anchored findings (GeneRIF, showing 26)

• expression of extracellular domain of human muscle acetylcholine receptor alpha subunit in yeast Pichia pastoris (PMID:12015305)
• DNA analysis of a father and son with dominant fast channel congenital myasthenic syndrome revealed an AChR alpha-subunit F256L missense mutation affecting channel gating (PMID:15079006)
• A good correlation was found between the expression of PAX3/7-FKHR and AChR, while MyoD1 was more sensitive but less specific. (PMID:16435141)
• the interaction between alpha AChR M1 and M2 domains plays a key role in channel gating (PMID:17028140)
• growth factor-induced HMVEC migration, a key angiogenesis event, requires nAChR activation–an effect mediated in part by nAChR-dependent regulation of thioredoxin activity. (PMID:17082486)
• Here we describe a mechanism controlling thymic transcription of a prototypic tissue-restricted human auto-antigen gene, CHRNA1 (PMID:17687331)
• 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)
• study reports homozygous nonsense mutations in CHRNA1 and CHRND and shows that they were lethal (PMID:18252226)
• Presence of heterogeneous nuclear ribonucleoprotein H-binding motif in CHRNA1 close to the 3’ end of an intron is an essential but underestimated splicing regulator of the downstream exon. (PMID:18806275)
• Studies suggest that the receptor nAChRalpha1 is an important regulator of calpain-1 activation and inflammation in the chronic hypercholesterolemic nephropathy. (PMID:20661225)
• V188 is functionally linked to Y190 in the C-loop and to D200 in beta-strand 10 of the acetylcholine receptor alpha subunit, which connects to the M1 transmembrane domain (PMID:22728938)
• Findings identify a novel lung cancer risk locus on 2q31.1 which correlates with CHRNA1 expression and replicate previous associations on 15q25.1 in African-Americans. (PMID:23232035)
• No mutations were found in CHRNG, CHRND and CHRNA1 genes of Indian families with Escobar syndrome. (PMID:23448903)
• High expression of CHRNA1 is associated with lung adenocarcinoma after complete resection. (PMID:23775407)
• HnRNP L and hnRNP LL antagonistically modulate PTB-mediated splicing suppression of CHRNA1 pre-mRNA. (PMID:24121633)
• The CHRNA1 extracellular domain is an improved protein for use in antigen-specific Myasthenia Gravis therapeutic strategies. (PMID:24376846)
• ChRnA1 gene variants did not affect the pharmacodynamics of rocuronium. (PMID:25279974)
• nicotine contributes to the progression and erlotinib-resistance of the NSCLC xenograft model via the cooperation between nAChR and EGFR. (PMID:25670150)
• show that AON complementary to the 5’ splice site of the exon was the most effective at exon skipping of the minigene with causative mutations, as well as endogenous wild-type CHRNA1 (PMID:25888793)
• Cholesterol and CAV-1 modulate the function and dynamics of the slow channel congenital myasthenia syndrome alphaC418W nicotinic acetylcholine receptor mutation. (PMID:26354438)
• Study indicated that nicotinic acetylcholine receptor alpha 1-subunit peptides may act as receptor decoy molecules and inhibit the binding of virus to the native host cell receptors and hence may reduce viral infection. (PMID:26656837)
• Data suggest that the mutations made the cholinergic receptor nicotinic alpha 1 subunit channel (CHRNA1) resistant to the antagonists, not by impairing antagonist binding, but rather by producing a gain-of-function phenotype, e.g. increased agonist sensitivity. (PMID:27649498)
• In our analysis, we found one pair of SNPs in CHRNA1 and CHRNA7, plus one pair of SNPs in CHRNA2 and CHRNA3 reached corrected significance in tests for GxG interaction. Our study suggested evidence of interactions between CHRNs in controlling the risk of NSCL/P. (PMID:29688589)
• Serum AChR alpha1 subunit protein concentrations were higher in patients with ant-AChR antibody-positive myasthenia gravis than those in controls. (PMID:31855720)
• CHRNA1 promotes the pathogenesis of primary focal hyperhidrosis. (PMID:33476802)
• Point Mutations of Nicotinic Receptor alpha1 Subunit Reveal New Molecular Features of G153S Slow-Channel Myasthenia. (PMID:33652901)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	chrna1	ENSDARG00000009021
mus_musculus	Chrna1	ENSMUSG00000027107
rattus_norvegicus	Chrna1	ENSRNOG00000018286

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), 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

Acetylcholine receptor subunit alpha — P02708 (reviewed: P02708)

All UniProt accessions (7): P02708, A0A1B0GV17, B8ZZD3, E7ENE5, F8WDS3, G5E9G9, Q53SH4

UniProt curated annotations — full annotation on UniProt →

Function. Upon acetylcholine binding, 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. Non functional acetylcholine receptor alpha subunit which is not integrated into functional acetylcholine-gated cation-selective channels.

Subunit / interactions. One of the alpha chains that assemble within the acetylcholine receptor, a pentamer of two alpha chains, a beta, a delta, and a 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. Is able to interact with other subunits of the acetylcholine receptor but is not assembled into functional acetylcholine-gated cation-selective channels.

Subcellular location. Postsynaptic cell membrane. Cell membrane.

Tissue specificity. Isoform 1 is only expressed in skeletal muscle. Isoform 2 is constitutively expressed in skeletal muscle, brain, heart, kidney, liver, lung and thymus.

Disease relevance. Multiple pterygium syndrome, lethal type (LMPS) [MIM:253290] Multiple pterygia are found infrequently in children with arthrogryposis and in fetuses with fetal akinesia syndrome. In lethal multiple pterygium syndrome there is intrauterine growth retardation, multiple pterygia, and flexion contractures causing severe arthrogryposis and fetal akinesia. Subcutaneous edema can be severe, causing fetal hydrops with cystic hygroma and lung hypoplasia. Oligohydramnios and facial anomalies are frequent. The disease is caused by variants affecting the gene represented in this entry. The alpha subunit is the main focus for antibody binding in myasthenia gravis. Myasthenia gravis is characterized by sporadic muscular fatigability and weakness, occurring chiefly in muscles innervated by cranial nerves, and characteristically improved by cholinesterase-inhibiting drugs. Myasthenic syndrome, congenital, 1A, slow-channel (CMS1A) [MIM:601462] A common congenital myasthenic syndrome. Congenital myasthenic syndromes are characterized by 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. CMS1A 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, 1B, fast-channel (CMS1B) [MIM:608930] 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. CMS1B is a fast-channel myasthenic syndrome. It is caused by kinetic abnormalities of the AChR, resulting in brief opening and activity of the channel, with a rapid decay in endplate current, failure to achieve threshold depolarization of the endplate and consequent failure to fire an action potential. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. Acetylcholine receptors incorporating that alpha subunit do not bind alpha-bungarotoxin.

Similarity. Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Alpha-1/CHRNA1 sub-subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P02708-2	1	yes
P02708-1	2, P3A(+), alpha+

RefSeq proteins (2): NP_000070, NP_001034612 (=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 (49 total): sequence variant 13, strand 13, topological domain 5, transmembrane region 4, helix 3, disulfide bond 2, mutagenesis site 2, turn 2, signal peptide 1, chain 1, glycosylation site 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

15 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
4ZJS	X-RAY DIFFRACTION	2.23
9DML	ELECTRON MICROSCOPY	2.24
9DMK	ELECTRON MICROSCOPY	2.46
9GU1	ELECTRON MICROSCOPY	2.48
5HBT	X-RAY DIFFRACTION	2.61
9GU3	ELECTRON MICROSCOPY	2.64
9GU2	ELECTRON MICROSCOPY	2.73
9GU0	ELECTRON MICROSCOPY	2.96

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P02708-F1	84.34	0.56

Antibody-complex structures (SAbDab): 11 — 5HBT, 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.

Disulfide bonds (2): 148–162, 212–213

Glycosylation sites (1): 161

Mutagenesis-validated functional residues (2):

Position	Phenotype
261	changed acetylcholine-gated cation-selective channel activity.
275	increased length of channel opening.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

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

MSigDB gene sets: 350 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, GOBP_NEUROMUSCULAR_JUNCTION_DEVELOPMENT, GOBP_MEMBRANE_DEPOLARIZATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, HORIUCHI_WTAP_TARGETS_DN, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_GROWTH, GOBP_SYNAPTIC_TRANSMISSION_CHOLINERGIC, GOCC_CELL_SURFACE, GOBP_MULTICELLULAR_ORGANISMAL_MOVEMENT, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_SKELETAL_MUSCLE_CONTRACTION, CAGCTG_AP4_Q5, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_CELL_CELL_SIGNALING

GO Biological Process (20): skeletal muscle contraction (GO:0003009), synaptic transmission, cholinergic (GO:0007271), neuromuscular synaptic transmission (GO:0007274), neuromuscular junction development (GO:0007528), neuronal action potential (GO:0019228), monoatomic ion transmembrane transport (GO:0034220), response to nicotine (GO:0035094), regulation of membrane potential (GO:0042391), muscle cell cellular homeostasis (GO:0046716), skeletal muscle tissue growth (GO:0048630), musculoskeletal movement (GO:0050881), neuromuscular process (GO:0050905), membrane depolarization (GO:0051899), neuron cellular homeostasis (GO:0070050), acetylcholine receptor signaling pathway (GO:0095500), presynaptic modulation of chemical synaptic transmission (GO:0099171), monoatomic ion transport (GO:0006811), monoatomic cation transport (GO:0006812), regulation of postsynaptic membrane potential (GO:0060078), excitatory postsynaptic potential (GO:0060079)

GO Molecular Function (7): acetylcholine receptor activity (GO:0015464), 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), transmembrane signaling receptor activity (GO:0004888), monoatomic ion channel activity (GO:0005216), extracellular ligand-gated monoatomic ion channel activity (GO:0005230)

GO Cellular Component (11): plasma membrane (GO:0005886), acetylcholine-gated channel complex (GO:0005892), cell surface (GO:0009986), neuromuscular junction (GO:0031594), neuron projection (GO:0043005), synapse (GO:0045202), postsynaptic membrane (GO:0045211), presynapse (GO:0098793), postsynaptic specialization membrane (GO:0099634), membrane (GO:0016020), synaptic membrane (GO:0097060)

Reactome top-level categories

Rollup of top-6 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
synapse	3
chemical synaptic transmission	2
monoatomic ion transport	2
cellular homeostasis	2
regulation of membrane potential	2
regulation of postsynaptic membrane potential	2
postsynaptic neurotransmitter receptor activity	2
synaptic membrane	2
striated muscle contraction	1
musculoskeletal movement	1
synapse organization	1
action potential	1
transmission of nerve impulse	1
transmembrane transport	1
response to chemical	1
monoatomic ion transmembrane transport	1
regulation of biological quality	1
skeletal muscle tissue development	1
developmental growth	1
multicellular organismal movement	1
neuromuscular process	1
nervous system process	1
acetylcholine receptor activity	1
postsynaptic signal transduction	1
cellular response to acetylcholine	1
modulation of chemical synaptic transmission	1
presynapse	1
transport	1
chemical synaptic transmission, postsynaptic	1
transmembrane signaling receptor activity	1
synaptic transmission, cholinergic	1
acetylcholine binding	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
signaling receptor activity	1
monoatomic ion transmembrane transporter activity	1

Protein interactions and networks

STRING

1012 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHRNA1	RAPSN	Q13702	864
CHRNA1	AIRE	O43918	764
CHRNA1	DOK7	Q18PE1	751
CHRNA1	COLQ	Q9Y215	741
CHRNA1	CHRNE	Q04844	707
CHRNA1	CHRND	Q07001	682
CHRNA1	MUSK	O15146	682
CHRNA1	CHRNB1	P11230	673
CHRNA1	LYNX1	P0DP58	629
CHRNA1	IRF8	Q02556	602
CHRNA1	CHRNG	P07510	580
CHRNA1	GFPT1	Q06210	549
CHRNA1	ALG14	Q96F25	543
CHRNA1	DPAGT1	Q9H3H5	538
CHRNA1	CXCL9	Q07325	497

IntAct

3 interactions, top by confidence:

A	B	Type	Score
CHRNA1	CHRNB1	psi-mi:“MI:0915”(physical association)	0.400
CHRNA1	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (43): CHRNA1 (Synthetic Lethality), LILRB3 (Two-hybrid), CHRNA1 (Reconstituted Complex), CHRNG (Co-fractionation), CHRND (Co-fractionation), CHRNA1 (Reconstituted Complex), CHRNA1 (Affinity Capture-Western), TBL2 (Affinity Capture-MS), GOLM1 (Affinity Capture-MS), DST (Affinity Capture-MS), SLC27A2 (Affinity Capture-MS), ITPRIPL2 (Affinity Capture-MS), PREB (Affinity Capture-MS), SCNN1A (Affinity Capture-MS), GBF1 (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

6 interactions.

A	Effect	B	Mechanism
WNT11	up-regulates	CHRNA1
WNT16	up-regulates	CHRNA1
WNT9A	up-regulates	CHRNA1	binding
WNT9B	up-regulates	CHRNA1	binding
CHRNA1	“form complex”	“Muscle-type nicotinic acetylcholine receptor complex, alpha1-beta1-delta-epsilon”	binding
CHRNA1	“form complex”	“Muscle-type nicotinic acetylcholine receptor complex, alpha1-beta1-delta-gamma”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	32
Likely pathogenic	15
Uncertain significance	273
Likely benign	173
Benign	44

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1071880	NM_000079.4(CHRNA1):c.292dup (p.Ile98fs)	Pathogenic
1076455	NC_000002.11:g.(?175612832)(175619162_?)del	Pathogenic
135654	NM_000079.4(CHRNA1):c.737C>A (p.Ser246Tyr)	Pathogenic
1438291	NM_000079.4(CHRNA1):c.249C>A (p.Tyr83Ter)	Pathogenic
1454489	NC_000002.11:g.(?175612852)(175629122_?)del	Pathogenic
18376	NM_000079.4(CHRNA1):c.711C>G (p.Asn237Lys)	Pathogenic
18378	NM_000079.4(CHRNA1):c.821C>T (p.Thr274Ile)	Pathogenic
18380	NM_000079.4(CHRNA1):c.866G>T (p.Ser289Ile)	Pathogenic
18382	NM_000079.4(CHRNA1):c.913G>A (p.Val305Ile)	Pathogenic
18384	NM_000079.4(CHRNA1):c.826T>C (p.Phe276Leu)	Pathogenic
18385	NM_000079.4(CHRNA1):c.454G>C (p.Val152Leu)	Pathogenic
18386	NM_000079.4(CHRNA1):c.441del (p.Cys148fs)	Pathogenic
18387	NM_000079.4(CHRNA1):c.1314C>G (p.Cys438Trp)	Pathogenic
18389	NM_000079.4(CHRNA1):c.117_133dup (p.His45fs)	Pathogenic
2125739	NM_000079.4(CHRNA1):c.345-63_403del	Pathogenic
2415180	NM_000079.4(CHRNA1):c.222del (p.Arg75fs)	Pathogenic
2710165	NM_000079.4(CHRNA1):c.1079dup (p.Ile361fs)	Pathogenic
2739921	NM_000079.4(CHRNA1):c.1079del (p.Lys360fs)	Pathogenic
29581	NM_000079.4(CHRNA1):c.235-353G>A	Pathogenic
3247274	NC_000002.11:g.(?175612852)(175619162_?)del	Pathogenic
3639584	NM_000079.4(CHRNA1):c.379A>T (p.Lys127Ter)	Pathogenic
429993	NM_000079.4(CHRNA1):c.175C>T (p.Gln59Ter)	Pathogenic
466174	NC_000002.12:g.(?174747592)(174754414_?)del	Pathogenic
466184	NM_000079.4(CHRNA1):c.711C>A (p.Asn237Lys)	Pathogenic
4696884	NM_000079.4(CHRNA1):c.613A>T (p.Lys205Ter)	Pathogenic
4715243	NM_000079.4(CHRNA1):c.639C>A (p.Cys213Ter)	Pathogenic
4773557	NM_000079.4(CHRNA1):c.587G>A (p.Trp196Ter)	Pathogenic
4801085	NM_000079.4(CHRNA1):c.1171G>T (p.Glu391Ter)	Pathogenic
687895	GRCh37/hg19 2q31.1(chr2:175578577-175617380)x1	Pathogenic
688740	GRCh37/hg19 2q31.1(chr2:175578577-175617380)x1	Pathogenic

SpliceAI

1555 predictions. Top by Δscore:

Variant	Effect	Δscore
2:174748252:CCGC:C	acceptor_gain	1.0000
2:174748253:CGC:C	acceptor_gain	1.0000
2:174748253:CGCC:C	acceptor_gain	1.0000
2:174748254:GCC:G	acceptor_loss	1.0000
2:174748256:C:CC	acceptor_gain	1.0000
2:174748256:CTG:C	acceptor_loss	1.0000
2:174748257:T:A	acceptor_loss	1.0000
2:174748573:AGCTT:A	donor_loss	1.0000
2:174748574:GCTT:G	donor_loss	1.0000
2:174748575:CTTA:C	donor_loss	1.0000
2:174748576:TTACA:T	donor_loss	1.0000
2:174748577:TACA:T	donor_loss	1.0000
2:174748578:A:AC	donor_gain	1.0000
2:174748578:A:C	donor_loss	1.0000
2:174748579:C:CA	donor_loss	1.0000
2:174748579:C:CC	donor_gain	1.0000
2:174748579:CA:C	donor_gain	1.0000
2:174748603:T:TA	donor_gain	1.0000
2:174748775:CAT:C	acceptor_gain	1.0000
2:174748777:T:C	acceptor_gain	1.0000
2:174748777:T:TC	acceptor_gain	1.0000
2:174749942:TCA:T	donor_loss	1.0000
2:174749943:CACC:C	donor_loss	1.0000
2:174749945:C:CA	donor_loss	1.0000
2:174750114:C:CT	acceptor_gain	1.0000
2:174750115:A:T	acceptor_gain	1.0000
2:174750123:C:CT	acceptor_gain	1.0000
2:174750126:A:T	acceptor_gain	1.0000
2:174750129:C:CT	acceptor_gain	1.0000
2:174750170:C:CC	acceptor_gain	1.0000

AlphaMissense

3030 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:174750136:A:G	L296P	1.000
2:174750154:A:G	L290P	1.000
2:174753693:C:A	W221C	1.000
2:174753693:C:G	W221C	1.000
2:174753695:A:G	W221R	1.000
2:174753695:A:T	W221R	1.000
2:174754295:A:C	F180C	1.000
2:174754316:C:T	C173Y	1.000
2:174748177:C:G	G466R	0.999
2:174748177:C:T	G466R	0.999
2:174748218:T:A	D452V	0.999
2:174748218:T:G	D452A	0.999
2:174748219:C:G	D452H	0.999
2:174748241:C:A	W444C	0.999
2:174748241:C:G	W444C	0.999
2:174748243:A:G	W444R	0.999
2:174748243:A:T	W444R	0.999
2:174749986:C:G	R346P	0.999
2:174750073:G:C	P317R	0.999
2:174750094:G:T	P310H	0.999
2:174750115:A:G	L303P	0.999
2:174750118:A:G	L302P	0.999
2:174750120:G:C	F301L	0.999
2:174750120:G:T	F301L	0.999
2:174750122:A:G	F301L	0.999
2:174750136:A:T	L296Q	0.999
2:174750150:G:C	S291R	0.999
2:174750150:G:T	S291R	0.999
2:174750152:T:G	S291R	0.999
2:174753517:A:G	L280P	0.999

dbSNP variants (sampled 300 via entrez): RS1000407106 (2:174759727 C>T), RS1000736621 (2:174757084 C>T), RS1000783998 (2:174749462 C>T), RS1001086389 (2:174750769 C>T), RS1001117823 (2:174761405 C>T), RS1001684620 (2:174754822 A>G), RS1001734101 (2:174761668 C>T), RS1001739788 (2:174765677 C>A,T), RS1002415377 (2:174756374 A>G), RS1002523790 (2:174747449 C>T), RS1002661060 (2:174747244 A>G), RS1002666279 (2:174751631 T>A), RS1002743562 (2:174760154 T>A), RS1002820589 (2:174753150 T>A), RS1003007036 (2:174764180 A>G)

Disease associations

OMIM: gene MIM:100690 | disease phenotypes: MIM:253290, MIM:601462, MIM:608930, MIM:117000, MIM:236750, MIM:277970, MIM:614493, MIM:254770, MIM:606904, MIM:209850, MIM:160150

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital myasthenic syndrome 1A	Strong	Autosomal dominant
myasthenic syndrome, congenital, 1B, fast-channel	Strong	Autosomal dominant
lethal multiple pterygium syndrome	Strong	Autosomal recessive
postsynaptic congenital myasthenic syndrome	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
myasthenic syndrome, congenital, 1B, fast-channel	Definitive	AR

Mondo (13): lethal multiple pterygium syndrome (MONDO:0009668), congenital myasthenic syndrome 1A (MONDO:0011088), congenital myasthenic syndrome (MONDO:0018940), myasthenic syndrome, congenital, 1B, fast-channel (MONDO:0012156), congenital myopathy (MONDO:0019952), non-immune hydrops fetalis (MONDO:0009369), Wiskott-Aldrich syndrome 2 (MONDO:0013779), juvenile myoclonic epilepsy (MONDO:0009696), epilepsy (MONDO:0005027), autism (MONDO:0005260), centronuclear myopathy (MONDO:0018947), hydrops fetalis (MONDO:0015193), postsynaptic congenital myasthenic syndrome (MONDO:0020344)

Orphanet (8): Lethal multiple pterygium syndrome (Orphanet:33108), Congenital myasthenic syndrome (Orphanet:590), Congenital myopathy (Orphanet:97245), Non-immune hydrops fetalis (Orphanet:363999), Wiskott-Aldrich syndrome (Orphanet:906), Juvenile myoclonic epilepsy (Orphanet:307), Centronuclear myopathy (Orphanet:595), Hydrops fetalis (Orphanet:1041)

HPO phenotypes

97 total (30 of 97 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000175	Cleft palate
HP:0000218	High palate
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000347	Micrognathia
HP:0000369	Low-set ears
HP:0000400	Macrotia
HP:0000457	Depressed nasal ridge
HP:0000467	Neck muscle weakness
HP:0000476	Cystic hygroma
HP:0000496	Abnormality of eye movement
HP:0000508	Ptosis
HP:0000597	Ophthalmoparesis
HP:0000602	Ophthalmoplegia
HP:0000651	Diplopia
HP:0000883	Thin ribs
HP:0000961	Cyanosis
HP:0000969	Edema
HP:0001040	Multiple pterygia
HP:0001252	Hypotonia
HP:0001260	Dysarthria
HP:0001270	Motor delay
HP:0001283	Bulbar palsy
HP:0001315	Reduced tendon reflexes
HP:0001319	Neonatal hypotonia
HP:0001324	Muscle weakness
HP:0001371	Flexion contracture
HP:0001373	Joint dislocation

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST006061_94	Atrial fibrillation	2.000000e-19
GCST006061_95	Atrial fibrillation	6.000000e-20

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D004827	Epilepsy	C10.228.140.490
D015160	Hydrops Fetalis	C12.050.703.277.060.480; C15.378.295.480; C15.378.420.826.100.350; C16.300.060.480; C16.320.365.826.100.350; C20.306.480; C23.888.277.395
D020294	Myasthenic Syndromes, Congenital	C10.668.758.800; C16.320.590
D020190	Myoclonic Epilepsy, Juvenile	C10.228.140.490.375.130.670; C10.228.140.490.493.063.670

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (8): CHEMBL1907588 (PROTEIN COMPLEX), CHEMBL2362997 (PROTEIN COMPLEX GROUP), CHEMBL3038458 (PROTEIN COMPLEX), CHEMBL3038459 (PROTEIN COMPLEX), CHEMBL3885508 (PROTEIN COMPLEX), CHEMBL4106145 (PROTEIN COMPLEX), CHEMBL4524133 (PROTEIN COMPLEX GROUP), CHEMBL4808 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

12 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 258,524 (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
CHEMBL111659	ALTINICLINE	2	129
CHEMBL1232461	MOLIBRESIB	2	1,538
CHEMBL504652	TC-2216	1	32

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs137852808	CHRNA1		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: lgic — Nicotinic acetylcholine receptors (nACh)

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
atracurium	Antagonist	7.01	pIC50
gallamine	Channel blocker	6.0	pIC50
mecamylamine	Channel blocker	5.82	pIC50

Binding affinities (BindingDB)

2 measured of 9 human assays (10 total across all organisms); most potent 2 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
SSR591813	KI	6000 nM

ChEMBL bioactivities

115 potent at pChembl≥5 of 184 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
6.80	IC50	160	nM	EPIBATIDINE
6.60	Ki	250	nM	CYTISINICLINE
6.54	Ki	292	nM	CHEMBL3235483
6.54	EC50	286	nM	CHEMBL4228846
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
6.25	Ki	562	nM	CHEMBL3235484
6.24	Ki	580	nM	CHEMBL2057714
6.22	IC50	600	nM	DEXMECAMYLAMINE
6.19	Ki	650	nM	CHEMBL194204
6.18	EC50	660	nM	CHEMBL4228846
6.11	Ki	784	nM	CHEMBL3235488

PubChem BioAssay actives

114 with measured affinity, of 795 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
7-bromo-N-[(3R)-piperidin-3-yl]-1-benzothiophene-2-carboxamide	1387984: Positive allosteric modulation of human alpha2beta4 nAChR expressed in HEK cells preincubated for 15 mins followed by dihydro-beta-erythroidine hydrobromide addition by fluorometric analysis	ec50	0.2860	uM
3-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-4-fluorodibenzothiophene 5,5-dioxide	1127759: Displacement of [3H]epibatidine from alpha2beta2-nAChR (unknown origin) expressed in HEK293 cells after 2 hrs by liquid scintillation counting analysis	ki	0.2920	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-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-4-fluorodibenzothiophene 5,5-dioxide	1127758: Displacement of [3H]epibatidine from alpha2beta4-nAChR (unknown origin) expressed in HEK293 cells after 2 hrs by liquid scintillation counting analysis	ki	0.5620	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
7-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-2-iododibenzothiophene 5,5-dioxide	1127759: Displacement of [3H]epibatidine from alpha2beta2-nAChR (unknown origin) expressed in HEK293 cells after 2 hrs by liquid scintillation counting analysis	ki	0.7840	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
2-[3-cyclohexyl-5-(furan-2-ylmethyl)-6-oxopyridazin-1-yl]-N-(2,3-dihydro-1H-inden-2-yl)acetamide	493529: Antagonist activity at human alpha1 nAChR in human TE671 cells	ic50	0.7943	uM

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Acetylcholine	affects binding, increases activity	2
Valproic Acid	affects cotreatment, increases expression, decreases methylation	2
o,p’-DDT	increases expression	1
CGP 52608	affects binding, increases reaction	1
incobotulinumtoxinA	decreases expression	1
Persistent Organic Pollutants	increases abundance, increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	increases methylation	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
DDT	increases expression	1
Hydralazine	affects cotreatment, increases expression	1
Oxygen	increases expression	1
Pesticides	increases expression, increases abundance	1
Smoke	increases expression	1

ChEMBL screening assays

157 unique, capped per target: 107 binding, 47 functional, 2 admet, 1 toxicity

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
CHEMBL4373190	ADMET	Displacement of [125I] alpha-Bungarotoxin from human alpha1 nAChR expressed in human RD cell membranes at 1 uM after 120 mins by scintillation counting method relative to control	Improvement of Aqueous Solubility of Lapatinib-Derived Analogues: Identification of a Quinolinimine Lead for Human African Trypanosomiasis Drug Development. — 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_D1KE	PrecisION hnAChR alpha1/beta1/delta/epsilon-HEK	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00004637	PHASE4	COMPLETED	Double-Blind, Placebo-Controlled Trial of Vitamin E as Add-on Therapy for Children With Epilepsy
NCT00043914	PHASE4	COMPLETED	Measurement Of Serum Levels Of Two Antiepileptic Drugs During Conversion In Patients With Epilepsy
NCT00132223	PHASE4	UNKNOWN	Effects on the Diagnostic Accuracy of Magnetic Imaging Angiographies of the Supra-Aortic Vessels by Three Different Magnetic Resonance Contrast Agents in Patients
NCT00133081	PHASE4	UNKNOWN	Study to Improve the Treatment of Epilepsy (SITE)
NCT00137709	PHASE4	UNKNOWN	Hormone Profiles in Adults With Newly Diagnosed Epilepsy
NCT00154076	PHASE4	COMPLETED	A Multicenter Comparative Trial of Zonisamide and Topiramate as Initial Monotherapy in Untreated Epilepsies
NCT00165828	PHASE4	TERMINATED	Efficacy and Safety of an add-on Treatment With Zonisamide in Adults With Focal Epileptic Seizures With or Without Secondary Generalization
NCT00181116	PHASE4	COMPLETED	Levetiracetam for Benign Rolandic Epilepsy
NCT00207935	PHASE4	COMPLETED	Use of Sustained Release Antiepileptic Medication (Depakote® ER) for Pediatric Epilepsy in a Mental Retardation/Developmental Disorder Population
NCT00215592	PHASE4	COMPLETED	Open Label, Zonegran (Zonisamide) In Partial Onset Seizures
NCT00266604	PHASE4	COMPLETED	A Study to Evaluate the Dosing, Effectiveness and Safety of Topiramate for the Treatment of Epilepsy
NCT00288639	PHASE4	COMPLETED	Lyrica (Pregabalin) Administered as an Add-on Therapy for Partial Seizures (LEADER).
NCT00312676	PHASE4	UNKNOWN	Compare Tolerability of an Overnight Switch to Gradual Switch Between Two Different Forms of Depakote
NCT00323947	PHASE4	COMPLETED	Methylphenidate for Treating Attention Deficit Hyperactivity Disorder in Children With Both ADHD and Epilepsy
NCT00385411	PHASE4	COMPLETED	Study of Valproate in Young Patients Suffering From Epilepsy
NCT00522418	PHASE4	TERMINATED	Study Comparing Best Medical Practice With or Without VNS Therapy in Pharmacoresistant Partial Epilepsy Patients
NCT00537940	PHASE4	COMPLETED	Comparative Study Of Pregabalin And Gabapentin As Adjunctive Therapy In Subjects With Partial Seizures
NCT00552526	PHASE4	UNKNOWN	Ketogenic Diet vs.Antiepileptic Drug Treatment in Drug Resistant Epilepsy
NCT00564915	PHASE4	COMPLETED	RCT of the Efficacy of the Ketogenic Diet in the Treatment of Epilepsy
NCT00571155	PHASE4	COMPLETED	Trial of Levetiracetam in Patients With Primary Brain Tumors and Symptomatic Seizures Who Undergo Surgery
NCT00572195	PHASE4	COMPLETED	RNS® System LTT Study
NCT00610532	PHASE4	TERMINATED	Evaluating the Transporter Protein Inhibitor Probenecid In Patients With Epilepsy
NCT00630357	PHASE4	COMPLETED	Trial to Evaluate the Safety and Efficacy of Keppra After Conversion to Mono-therapy in Subjects With Partial Epilepsy
NCT00630630	PHASE4	COMPLETED	Study on Safety and Efficacy of Levetiracetam in the Adjunctive Treatment of Female Subjects With C1 Catamenial Epilepsy
NCT00630968	PHASE4	COMPLETED	S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00631150	PHASE4	COMPLETED	A Phase IV-Pharmacovigilance Study of Keppra Greece - S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00659958	PHASE4	COMPLETED	ZAGAL Study: Evaluating Effectiveness and Tolerability of Zonisamide as Adjunctive Therapy in Patients With Partial Onset Seizures Treated With Two Antiepileptic Drugs
NCT00713622	PHASE4	COMPLETED	Comparing The Effect On Cognition Of Adjunctive Therapy With Zonisamide Versus Sodium Valproate
NCT00807989	PHASE4	COMPLETED	The Efficacy and Safety of Low Dose Combination of LTG and VPA Compared to CBZ Monotherapy
NCT00832884	PHASE4	COMPLETED	The Safety of Intravenous Lacosamide
NCT00869622	PHASE4	COMPLETED	Antiepileptic Drugs and Osteoporotic Prevention Trial
NCT00896987	PHASE4	COMPLETED	Lamotrigine Cognitive Function Study in Adult Untreated Epilepsies
NCT00952081	PHASE4	COMPLETED	A Pilot Study to Evaluate Efficacy and Safety of Clevidipine in Neurosurgical Patients
NCT01118455	PHASE4	TERMINATED	Trial to Assess Vagus Nerve Stimulation Therapy vs. Anti-Epileptic Drug (AED) Treatment in Children With Refractory Seizures
NCT01127165	PHASE4	COMPLETED	Low and High Dose Zonisamide in Children as Monotherapy
NCT01127256	PHASE4	COMPLETED	Comparative Study of Zonisamide and Carbamazepine as an Initial Monotherapy: Efficacy and Safety Evaluation
NCT01140867	PHASE4	COMPLETED	Open-label, Multi-center Trial of Zonisamide as Adjunctive Therapy in Patients With Uncontrolled Partial Epilepsy
NCT01175954	PHASE4	COMPLETED	Cognitive and Behavioral Effects of Lacosamide
NCT01229735	PHASE4	COMPLETED	Levetiracetam Versus Topiramate as Adjunctive Therapy to Evaluate Efficacy and Safety in Subjects With Refractory Partial Onset Seizures
NCT01244724	PHASE4	TERMINATED	Lexapro for Major Depression in Patients With Epilepsy