CHRNE

Summary

CHRNE (cholinergic receptor nicotinic epsilon subunit, HGNC:1966) is a protein-coding gene on chromosome 17p13.2, encoding Acetylcholine receptor subunit epsilon (Q04844). 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.

Acetylcholine receptors at mature mammalian neuromuscular junctions are pentameric protein complexes composed of four subunits in the ratio of two alpha subunits to one beta, one epsilon, and one delta subunit. The acetylcholine receptor changes subunit composition shortly after birth when the epsilon subunit replaces the gamma subunit seen in embryonic receptors. Mutations in the epsilon subunit are associated with congenital myasthenic syndrome.

Source: NCBI Gene 1145 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital myasthenic syndrome (Definitive, GenCC) — +4 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 694 total — 45 pathogenic, 43 likely-pathogenic
• Phenotypes (HPO): 80
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000080

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1966
Approved symbol	CHRNE
Name	cholinergic receptor nicotinic epsilon subunit
Location	17p13.2
Locus type	gene with protein product
Status	Approved
Aliases	ACHRE
Ensembl gene	ENSG00000108556
Ensembl biotype	protein_coding
OMIM	100725
Entrez	1145

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 2 retained_intron, 2 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000572438, ENST00000575637, ENST00000649488, ENST00000649830, ENST00000652550

RefSeq mRNA: 1 — MANE Select: NM_000080 NM_000080

CCDS: CCDS11058

Canonical transcript exons

ENST00000649488 — 12 exons

Exon	Start	End
ENSE00000678330	4901932	4902087
ENSE00000678337	4902621	4902763
ENSE00003462086	4902450	4902494
ENSE00003476565	4899001	4899107
ENSE00003485951	4902217	4902326
ENSE00003491017	4899198	4899384
ENSE00003538214	4900793	4900907
ENSE00003549733	4899468	4899582
ENSE00003552899	4901525	4901625
ENSE00003588085	4900990	4901190
ENSE00003841001	4903018	4903098
ENSE00003842762	4897771	4898891

Expression profiles

Bgee: expression breadth ubiquitous, 162 present calls, max score 95.23.

FANTOM5 (CAGE): breadth broad, TPM avg 1.1906 / max 179.8787, expressed in 288 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
163970	0.8927	252
163971	0.2979	61

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right atrium auricular region	UBERON:0006631	95.23	gold quality
cardiac atrium	UBERON:0002081	93.66	gold quality
adenohypophysis	UBERON:0002196	92.74	gold quality
pituitary gland	UBERON:0000007	86.71	gold quality
cardiac muscle of right atrium	UBERON:0003379	78.99	gold quality
granulocyte	CL:0000094	75.06	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	74.91	gold quality
right lobe of liver	UBERON:0001114	73.70	gold quality
myocardium	UBERON:0002349	70.71	gold quality
skin of leg	UBERON:0001511	69.68	gold quality
body of pancreas	UBERON:0001150	68.60	gold quality
stromal cell of endometrium	CL:0002255	68.35	gold quality
blood	UBERON:0000178	68.01	gold quality
heart	UBERON:0000948	67.98	gold quality
skin of abdomen	UBERON:0001416	67.87	gold quality
gall bladder	UBERON:0002110	67.65	gold quality
left ventricle myocardium	UBERON:0006566	67.46	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	66.35	gold quality
zone of skin	UBERON:0000014	65.88	gold quality
omental fat pad	UBERON:0010414	65.83	gold quality
peritoneum	UBERON:0002358	65.79	gold quality
vena cava	UBERON:0004087	64.93	gold quality
periodontal ligament	UBERON:0008266	64.88	gold quality
buccal mucosa cell	CL:0002336	64.76	gold quality
parotid gland	UBERON:0001831	64.60	gold quality
adipose tissue of abdominal region	UBERON:0007808	64.52	gold quality
liver	UBERON:0002107	64.04	gold quality
pancreas	UBERON:0001264	63.92	gold quality
spleen	UBERON:0002106	63.52	gold quality
tibial nerve	UBERON:0001323	62.95	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.49

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EGR1, ELK3, ETS2, GABPA, HNF4A, NRG1

miRNA regulators (miRDB)

36 targeting CHRNE, 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-8068	99.98	73.85	2376
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-7161-5P	99.68	68.92	1592
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-548U	99.65	67.78	1463
HSA-MIR-3685	99.62	68.83	1621
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-2053	99.57	69.15	1635
HSA-MIR-6716-5P	99.56	68.62	1244
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-3160-5P	99.28	69.07	1938
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-4478	99.07	65.16	2320
HSA-MIR-502-5P	98.77	66.51	906
HSA-MIR-1183	98.75	67.10	1116
HSA-MIR-3929	98.32	65.58	1026
HSA-MIR-4483	98.09	64.12	1642
HSA-MIR-4468	98.01	66.85	1187
HSA-MIR-7113-5P	97.88	67.33	1735
HSA-MIR-4327	97.21	67.71	676

Literature-anchored findings (GeneRIF, showing 26)

• two binding sites differ by roughly 10-fold in the affinity of the shut receptor for ACh in the wild type, and that in the epsilonL221F mutation the lower affinity is increased so the sites become more similar. (PMID:12562900)
• There was deletion in exon 7 of CHRNE. We cloned the entire CHRNE spanning 12 exons and 11 introns and expressed it in COS cells (PMID:14532324)
• It was found that mutations within muscle AChRs are the most common cause of CMS. The majority are located within the epsilon-subunit gene and result in AChR deficiency. (PMID:14592868)
• AChR epsilon-chain peptides are tested for their in vitro ability to activate peripheral blood mononuclear leukocytes of myasthenia gravis (MG) patients; MG patient cells are stimulated, whereas cells from nonmyasthenic subjects do not respond. (PMID:15652413)
• Reported is a patient with a congenital myasthenic syndrome due to two compound heterozygous mutations of the CHRNE gene. T (PMID:16087917)
• a patient with a slow-channel congenital myasthenic syndrome who carries a novel slow-channel mutation(novel valine to phenylalanine mutation ) in the epsilon subunit of the acetylcholine receptor. (PMID:16198106)
• the intrinsically high Ca2+ permeability of human AChRs probably predisposes to development of the endplate myopathy when opening events of the AChR channel are prolonged by altered AChR-channel kinetics (PMID:16527851)
• enhanced Ca2+ permeability of the mutant receptors overrides the protective effect of desensitization and, together with the prolonged opening events of the AChR channel, is important in slow channel syndromes (PMID:17272341)
• Upon activation of AChR, GABP recruits the histone acetyl transferase (HAT) p300 on the AChR epsilon subunit promoter, whereas it rather recruits the histone deacetylase HDAC1 when the promoter is not activated. (PMID:17304221)
• This is the first synonymous mutation in CHRNE known to generate a cryptic splice site, and mRNA quantification strongly suggests that it is the disease-causing mutation. (PMID:17363247)
• The greater abundance of mRNA for AChR epsilon-subunit than for other subunits suggests that the AChR epsilon-subunit may play a distinctive role in autosensitization in MG-associated thymomas, particularly those of type A or AB. (PMID:18657869)
• These results strongly support the hypothesis that epsilon1293insG mutations in a myasthenic syndrome derives from an ancient single founder event in the North African population. (PMID:19064877)
• We have identified mutations within the acetylcholine receptor (AChR) epsilon-subunit gene underlying congenital myasthenic syndromes in nine patients (seven kinships) of Dutch origin. (PMID:19544078)
• analysis of symmetry at the extracellular domain-transmembrane domain interface in acetylcholine receptor channel gating (PMID:20864527)
• Three siblings have a clinical history and examination findings typical of homozygous CHRNE mutations; clinical presentation of congenital myasthenia subtypes is variable, and accurate genotyping is essential in choosing appropriate treatment. (PMID:21150643)
• mutational analysis of CHRNE revealed a homozygous 1293insG, which is a well-known low-expressor receptor mutation in patients with epidermolysis bullosa simplex and congenital myasthenic syndrome. (PMID:21175599)
• The mutations in the varepsilon subunit altered Ca(2+) permeability of AChR-channels, with varepsilon(L269F) increasing P(f) and varepsilon(I257F) decreasing it. (PMID:21470676)
• Targeting nAChR could offer a strategy for reducing neurodegeneration secondary to hyperphosphorylation of protein tau. (PMID:21715663)
• This study provied that new mouse model for the slow-channel congenital myasthenic syndrome induced by the AChR epsilonL221F mutation. (PMID:22178625)
• 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)
• Specific mutations in COLQ, RAPSN, and CHRNE occur in specific ethnic populations in Israel and should be taken into account when the diagnosis of congenital myasthenic syndrome is suspected.. (PMID:28024842)
• Study identified 2 potentially novel homozygous mutations in the AChR epsilon-subunit, epsilonR218W at a position equivalent to alphaR209, and E184K at a position equivalent to alphaE175, in 3 unrelated congenital myasthenic patients. (PMID:29367459)
• Study found a pretest probability of CHRNE c.130dupG mutation of 31.9% in at least one allele of CMS patients, and when considering only homozygous patients the percentage is still high (26.4%); percentages notably increase ifonly patients with impaired eye movement and improvement of symptoms with pyridostigmine are considered. (PMID:29383513)
• This study report a family with progressive proximal and distal weakness in which an accurate electrophysiological and CHRNE mutation led to a final diagnosis of congenital myasthenic syndromes. (PMID:30542963)
• Delineation of molecular characteristics of congenital myasthenic syndromes in Indian families and review of literature. (PMID:37646703)
• Characterization of Clinical Phenotypes in Congenital Myasthenic Syndrome Associated with the c.1327delG Frameshift Mutation in CHRNE Encoding the Acetylcholine Receptor Epsilon Subunit. (PMID:38995797)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	chrne	ENSDARG00000034307
mus_musculus	Chrne	ENSMUSG00000014609
rattus_norvegicus	Chrne	ENSRNOG00000003777

Paralogs (45): GABRA3 (ENSG00000011677), GABRA1 (ENSG00000022355), CHRNA3 (ENSG00000080644), GABRP (ENSG00000094755), CHRNA4 (ENSG00000101204), GLRA2 (ENSG00000101958), GABRE (ENSG00000102287), 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), CHRNB1 (ENSG00000170175), CHRNA9 (ENSG00000174343), CHRNA7 (ENSG00000175344), HTR3C (ENSG00000178084), GABRG3 (ENSG00000182256), GABRR3 (ENSG00000183185), HTR3E (ENSG00000186038), HTR3D (ENSG00000186090)

Protein

Protein identifiers

Acetylcholine receptor subunit epsilon — Q04844 (reviewed: Q04844)

All UniProt accessions (2): Q04844, A0A3B3IRM1

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. The muscle AChR is the major target antigen in the autoimmune disease 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, 4A, slow-channel (CMS4A) [MIM:605809] 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. CMS4A 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, 4B, fast-channel (CMS4B) [MIM:616324] 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. CMS4B 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. Myasthenic syndrome, congenital, 4C, associated with acetylcholine receptor deficiency (CMS4C) [MIM:608931] 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. CMS4C 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. 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. Epsilon/CHRNE sub-subfamily.

RefSeq proteins (1): NP_000071* (*=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 (28 total): sequence variant 14, topological domain 5, transmembrane region 4, glycosylation site 2, signal peptide 1, chain 1, disulfide bond 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-Q04844-F1	81.32	0.32

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.

Disulfide bonds (1): 148–162

Glycosylation sites (2): 86, 161

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-629587	Highly sodium permeable postsynaptic acetylcholine nicotinic 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: 281 (showing top): MODULE_92, GOBP_MEMBRANE_DEPOLARIZATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, MYOGENIN_Q6, MODULE_274, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GCANCTGNY_MYOD_Q6, MODULE_64, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GOBP_SYNAPTIC_TRANSMISSION_CHOLINERGIC, GOBP_MULTICELLULAR_ORGANISMAL_MOVEMENT, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_SKELETAL_MUSCLE_CONTRACTION, CAGCTG_AP4_Q5, GOBP_MONOATOMIC_CATION_TRANSPORT

GO Biological Process (13): skeletal muscle contraction (GO:0003009), muscle contraction (GO:0006936), signal transduction (GO:0007165), chemical synaptic transmission (GO:0007268), synaptic transmission, cholinergic (GO:0007271), monoatomic ion transmembrane transport (GO:0034220), membrane depolarization (GO:0051899), acetylcholine receptor signaling pathway (GO:0095500), monoatomic ion transport (GO:0006811), regulation of membrane potential (GO:0042391), regulation of postsynaptic membrane potential (GO:0060078), excitatory postsynaptic potential (GO:0060079), monoatomic cation transmembrane transport (GO:0098655)

GO Molecular Function (7): monoatomic cation transmembrane transporter activity (GO:0008324), acetylcholine receptor activity (GO:0015464), acetylcholine-gated monoatomic cation-selective channel activity (GO:0022848), 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 (7): plasma membrane (GO:0005886), acetylcholine-gated channel complex (GO:0005892), neuromuscular junction (GO:0031594), neuron projection (GO:0043005), synapse (GO:0045202), postsynaptic membrane (GO:0045211), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Acetylcholine binding and downstream events	2
Presynaptic nicotinic acetylcholine receptors	1
Postsynaptic 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
regulation of membrane potential	2
monoatomic ion transmembrane transport	2
regulation of postsynaptic membrane potential	2
monoatomic ion transmembrane transporter activity	2
postsynaptic neurotransmitter receptor activity	2
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
anterograde trans-synaptic signaling	1
chemical synaptic transmission	1
monoatomic ion transport	1
transmembrane transport	1
acetylcholine receptor activity	1
postsynaptic signal transduction	1
cellular response to acetylcholine	1
transport	1
regulation of biological quality	1
chemical synaptic transmission, postsynaptic	1
monoatomic cation transport	1
monoatomic cation transmembrane transport	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
transmitter-gated monoatomic ion channel activity	1
signaling receptor activity	1
channel activity	1
ligand-gated monoatomic ion channel activity	1
membrane	1
cell periphery	1
monoatomic ion channel complex	1
plasma membrane signaling receptor complex	1
synapse	1

Protein interactions and networks

STRING

860 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHRNE	RAPSN	Q13702	903
CHRNE	COLQ	Q9Y215	867
CHRNE	DOK7	Q18PE1	858
CHRNE	MUSK	O15146	842
CHRNE	MINK1	Q8N4C8	825
CHRNE	CHRNA1	P02708	707
CHRNE	GFPT1	Q06210	623
CHRNE	BCHE	P06276	619
CHRNE	GP1BA	P07359	610
CHRNE	ALG14	Q96F25	607
CHRNE	DPAGT1	Q9H3H5	593
CHRNE	SCN4A	P35499	582
CHRNE	GMPPB	Q9Y5P6	572
CHRNE	CAPN3	P20807	562
CHRNE	UTRN	P46939	560

IntAct

7 interactions, top by confidence:

A	B	Type	Score
COLQ	PLOD3	psi-mi:“MI:0914”(association)	0.530
LGALS1	PODXL	psi-mi:“MI:0914”(association)	0.530
CHRNE	PODXL	psi-mi:“MI:0914”(association)	0.350
C1orf54	QSOX1	psi-mi:“MI:0914”(association)	0.350
C1QTNF9B	DNASE2	psi-mi:“MI:0914”(association)	0.350
CLGN	TMEM131L	psi-mi:“MI:0914”(association)	0.350

BioGRID (29): CHRNE (Affinity Capture-MS), CHRNA1 (Reconstituted Complex), FAM69A (Affinity Capture-MS), TMEM59L (Affinity Capture-MS), TTC17 (Affinity Capture-MS), ITGA6 (Affinity Capture-MS), SPPL2B (Affinity Capture-MS), ST3GAL4 (Affinity Capture-MS), TMEM131 (Affinity Capture-MS), TMUB2 (Affinity Capture-MS), CYB5R1 (Affinity Capture-MS), LTBP1 (Affinity Capture-MS), CNNM1 (Affinity Capture-MS), PXYLP1 (Affinity Capture-MS), SEC11C (Affinity Capture-MS)

ESM2 similar proteins: A2A259, A5X5Y0, H2Q5A1, O46547, O70212, O95264, O97741, P01906, P01909, P02713, P02715, P02716, P04758, P04759, P04760, P07510, P09660, P09690, P11230, P13536, P18916, P20782, P23979, P25109, P25110, P35563, P37088, P37089, P46098, P55270, P78334, Q04844, Q07001, Q14246, Q5Y4N8, Q60HE8, Q61180, Q61549, Q70Z44, Q7Z418

Diamond homologs: A8WQK3, O70174, P02708, P02709, P02710, P02711, P02712, P02713, P02714, P02715, P02716, P02717, P02718, P04755, P04756, P04757, P04758, P04759, P04760, P05376, P05377, P07510, P09478, P09479, P09480, P09481, P09482, P09483, P09484, P09628, P09660, P09690, P11230, P12389, P12390, P12391, P12392, P13536, P13908, P17644

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CHRNE	“form complex”	“Muscle-type nicotinic acetylcholine receptor complex, alpha1-beta1-delta-epsilon”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	45
Likely pathogenic	43
Uncertain significance	228
Likely benign	275
Benign	24

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1069090	NM_000080.4(CHRNE):c.1076_1115del (p.Pro359fs)	Pathogenic
1071548	NM_000080.4(CHRNE):c.1158dup (p.Lys387fs)	Pathogenic
1074055	NM_000080.4(CHRNE):c.1214G>A (p.Trp405Ter)	Pathogenic
1075354	NM_000080.4(CHRNE):c.439_440insGAGGTCA (p.Val147fs)	Pathogenic
1399255	NM_000080.4(CHRNE):c.1012del (p.Met338fs)	Pathogenic
1399349	NM_000080.4(CHRNE):c.295C>T (p.Arg99Ter)	Pathogenic
1424525	NM_000080.4(CHRNE):c.985_986del (p.Ser329fs)	Pathogenic
1454210	NM_000080.4(CHRNE):c.105T>A (p.Tyr35Ter)	Pathogenic
1454490	NC_000017.10:g.(?4802021)(4802196_?)del	Pathogenic
1455044	NM_000080.4(CHRNE):c.1326+2T>C	Pathogenic
1456370	NM_000080.4(CHRNE):c.1271_1290del (p.Val424fs)	Pathogenic
1458892	NM_000080.4(CHRNE):c.1219+2T>G	Pathogenic
1687321	NM_000080.4(CHRNE):c.1064del (p.Gly355fs)	Pathogenic
1694812	NM_000080.4(CHRNE):c.1255G>T (p.Glu419Ter)	Pathogenic
1810265	NM_000080.4(CHRNE):c.967_968insCTCACAGGGGCATGGGAGACAGTGGTGGGCCTCTGCCTCGCTCCACCCGCCTCTGGCTCCTGTCCCACCTCGCCGGTGGCCTCCTGATCTCTCGTGCTCTCAG (p.Val323fs)	Pathogenic
18346	NM_000080.4(CHRNE):c.422C>T (p.Pro141Leu)	Pathogenic
18349	NM_000080.4(CHRNE):c.344+1G>A	Pathogenic
18350	NM_000080.4(CHRNE):c.1030del (p.His344fs)	Pathogenic
1959021	NM_000080.4(CHRNE):c.1248_1266dup (p.Cys423fs)	Pathogenic
2010867	NM_000080.4(CHRNE):c.1238dup (p.Ala415fs)	Pathogenic
2033252	NM_000080.4(CHRNE):c.1332del (p.Ser445fs)	Pathogenic
2090933	NM_000080.4(CHRNE):c.1002_1008dup (p.Ala337fs)	Pathogenic
2102390	NM_000080.4(CHRNE):c.1219+1G>C	Pathogenic
243030	NM_000080.4(CHRNE):c.130dup (p.Glu44fs)	Pathogenic
243032	NM_000080.4(CHRNE):c.1353dup (p.Asn452fs)	Pathogenic
2498162	NM_000080.4(CHRNE):c.1032+1G>C	Pathogenic
2680791	NM_000080.4(CHRNE):c.1090del (p.Arg364fs)	Pathogenic
2680797	NM_000080.4(CHRNE):c.1204C>T (p.Gln402Ter)	Pathogenic
2736401	NM_000080.4(CHRNE):c.569dup (p.Asn190fs)	Pathogenic
2753928	NM_000080.4(CHRNE):c.477G>A (p.Trp159Ter)	Pathogenic

SpliceAI

2119 predictions. Top by Δscore:

Variant	Effect	Δscore
17:4898888:CTTC:C	acceptor_gain	1.0000
17:4899014:T:TA	donor_gain	1.0000
17:4899104:GCAG:G	acceptor_gain	1.0000
17:4899105:CAG:C	acceptor_gain	1.0000
17:4899105:CAGC:C	acceptor_gain	1.0000
17:4899106:AG:A	acceptor_gain	1.0000
17:4899107:GCTGG:G	acceptor_loss	1.0000
17:4899108:C:CA	acceptor_loss	1.0000
17:4899108:C:CC	acceptor_gain	1.0000
17:4899109:T:A	acceptor_loss	1.0000
17:4899192:GCTCA:G	donor_loss	1.0000
17:4899193:CTCAC:C	donor_loss	1.0000
17:4899194:TCAC:T	donor_loss	1.0000
17:4899195:CACCC:C	donor_loss	1.0000
17:4899196:A:AC	donor_gain	1.0000
17:4899196:AC:A	donor_gain	1.0000
17:4899197:C:CC	donor_gain	1.0000
17:4899197:CC:C	donor_gain	1.0000
17:4899197:CCCGT:C	donor_gain	1.0000
17:4899462:GCTTA:G	donor_loss	1.0000
17:4899463:CTTA:C	donor_loss	1.0000
17:4899464:TTA:T	donor_loss	1.0000
17:4899465:TACGT:T	donor_loss	1.0000
17:4899466:A:AC	donor_gain	1.0000
17:4899466:A:AT	donor_loss	1.0000
17:4899467:C:CT	donor_gain	1.0000
17:4899467:CG:C	donor_gain	1.0000
17:4899467:CGTGG:C	donor_gain	1.0000
17:4899564:C:CT	acceptor_gain	1.0000
17:4899581:ACC:A	acceptor_loss	1.0000

AlphaMissense

3191 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:4901177:C:A	W205C	1.000
17:4901177:C:G	W205C	1.000
17:4901179:A:G	W205R	0.999
17:4901179:A:T	W205R	0.999
17:4901946:A:C	C162W	0.999
17:4901988:G:C	C148W	0.999
17:4901989:C:T	C148Y	0.999
17:4901990:A:G	C148R	0.999
17:4901947:C:T	C162Y	0.998
17:4901989:C:G	C148S	0.998
17:4901990:A:T	C148S	0.998
17:4902245:A:G	W106R	0.998
17:4902245:A:T	W106R	0.998
17:4902475:A:G	L70P	0.998
17:4901079:C:G	R238P	0.997
17:4901935:A:G	F166S	0.997
17:4901941:A:G	L164P	0.997
17:4901947:C:G	C162S	0.997
17:4901948:A:G	C162R	0.997
17:4901948:A:T	C162S	0.997
17:4901968:A:C	F155C	0.997
17:4901994:G:C	S146R	0.997
17:4901994:G:T	S146R	0.997
17:4901996:T:G	S146R	0.997
17:4902243:C:A	W106C	0.997
17:4902243:C:G	W106C	0.997
17:4902323:A:G	W80R	0.997
17:4902323:A:T	W80R	0.997
17:4901066:G:C	F242L	0.996
17:4901066:G:T	F242L	0.996

dbSNP variants (sampled 300 via entrez): RS1000043550 (17:4900519 C>T), RS1000414132 (17:4909974 C>A,G,T), RS1000680432 (17:4905410 A>C,T), RS1000874985 (17:4897733 G>T), RS1001048941 (17:4901270 G>A), RS1001291717 (17:4897702 G>A,T), RS1001557880 (17:4897520 G>A), RS1002050065 (17:4910346 C>T), RS1002588557 (17:4907290 G>A), RS1002660849 (17:4905867 C>CA), RS1002861575 (17:4908591 G>A), RS1003018187 (17:4903383 T>C), RS1003180884 (17:4908422 C>T), RS1003183195 (17:4908252 G>C), RS1003252479 (17:4899198 C>A,T)

Disease associations

OMIM: gene MIM:100725 | disease phenotypes: MIM:605809, MIM:601462, MIM:616324, MIM:608931, MIM:613688

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital myasthenic syndrome	Definitive	Autosomal recessive
congenital myasthenic syndrome 4A	Strong	Autosomal dominant
congenital myasthenic syndrome 4C	Strong	Autosomal recessive
congenital myasthenic syndrome 4B	Strong	Autosomal recessive
postsynaptic congenital myasthenic syndrome	Supportive	Autosomal recessive

Mondo (8): congenital myasthenic syndrome 4A (MONDO:0011600), congenital myasthenic syndrome (MONDO:0018940), congenital myasthenic syndrome 4B (MONDO:0014586), congenital myasthenic syndrome 4C (MONDO:0012157), congenital myasthenic syndrome 4 (MONDO:1040021), long QT syndrome 2 (MONDO:0013367), ptosis (MONDO:0000728), postsynaptic congenital myasthenic syndrome (MONDO:0020344)

Orphanet (3): Congenital myasthenic syndrome (Orphanet:590), Romano-Ward syndrome (Orphanet:101016), Congenital long QT syndrome (Orphanet:768)

HPO phenotypes

80 total (30 of 80 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000218	High palate
HP:0000276	Long face
HP:0000303	Mandibular prognathia
HP:0000467	Neck muscle weakness
HP:0000486	Strabismus
HP:0000496	Abnormality of eye movement
HP:0000508	Ptosis
HP:0000597	Ophthalmoparesis
HP:0000602	Ophthalmoplegia
HP:0000651	Diplopia
HP:0000689	Dental malocclusion
HP:0000961	Cyanosis
HP:0001252	Hypotonia
HP:0001260	Dysarthria
HP:0001270	Motor delay
HP:0001283	Bulbar palsy
HP:0001290	Generalized hypotonia
HP:0001315	Reduced tendon reflexes
HP:0001319	Neonatal hypotonia
HP:0001324	Muscle weakness
HP:0001446	Abnormality of the musculature of the upper limbs
HP:0001558	Decreased fetal movement
HP:0001612	Weak cry
HP:0002015	Dysphagia
HP:0002033	Poor suck
HP:0002091	Restrictive ventilatory defect
HP:0002093	Respiratory insufficiency
HP:0002098	Respiratory distress

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST005991_41	Platelet count	5.000000e-60
GCST012182_10	Alzheimer’s disease	2.000000e-10
GCST90013442_27	Keratoconus	2.000000e-14

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D001763	Blepharoptosis	C11.338.204
D020294	Myasthenic Syndromes, Congenital	C10.668.758.800; C16.320.590
C563614	Long Qt Syndrome 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2362997 (PROTEIN COMPLEX GROUP), CHEMBL2484 (SINGLE PROTEIN), CHEMBL4106145 (PROTEIN COMPLEX), CHEMBL4524133 (PROTEIN COMPLEX GROUP)

Molecules with ChEMBL bioactivity

4 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 269,445 (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
CHEMBL267936	MECAMYLAMINE	4	5,623
CHEMBL3	NICOTINE	4	184,969
CHEMBL502	DONEPEZIL	4	43,493
CHEMBL95	TACRINE	4	35,360

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: lgic — Nicotinic acetylcholine receptors (nACh)

ChEMBL bioactivities

30 potent at pChembl≥5 of 32 total, top 30 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.64	IC50	2.291	nM	CHEMBL5179810
8.51	Ki	3.07	nM	CHEMBL4473371
8.22	IC50	6	nM	CHEMBL4435544
7.92	IC50	12.02	nM	CHEMBL5204683
7.57	IC50	27	nM	CHEMBL4471876
7.49	IC50	32.36	nM	DONEPEZIL
7.49	IC50	32.36	nM	CHEMBL5181578
7.44	IC50	36.31	nM	CHEMBL5176418
7.36	IC50	44	nM	TACRINE
7.36	IC50	43.65	nM	CHEMBL5173121
7.33	IC50	46.5	nM	CHEMBL4518438
7.30	IC50	50	nM	CHEMBL4228909
7.24	IC50	57.4	nM	CHEMBL4516351
7.24	IC50	57.7	nM	CHEMBL4518992
7.24	IC50	57.54	nM	CHEMBL5207035
7.21	IC50	62.3	nM	CHEMBL4514263
7.15	IC50	70.79	nM	CHEMBL5190924
7.09	IC50	81.82	nM	CHEMBL2376519
7.08	IC50	83.18	nM	CHEMBL5188135
7.06	IC50	87.7	nM	CHEMBL4447626
7.06	IC50	87.1	nM	CHEMBL5200573
7.04	IC50	91.2	nM	CHEMBL5179648
7.01	IC50	96.6	nM	CHEMBL4544630
6.92	Ki	120	nM	CHEMBL5176418
6.90	IC50	125	nM	CHEMBL224906
6.88	IC50	131	nM	CHEMBL4872191
6.82	Ki	152.3	nM	TACRINE
6.39	IC50	407.4	nM	CHEMBL5196896
6.17	IC50	676.1	nM	CHEMBL5206933
5.72	IC50	1900	nM	CHEMBL4456791

PubChem BioAssay actives

30 with measured affinity, of 131 total; 28 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
N-[3-[1-[6-[[2-(dimethylamino)phenyl]methyl-ethylamino]hexyl]-6-oxopyridazin-3-yl]-4-hydroxyphenyl]acetamide	1877965: Inhibition of human AChE by Ellman’s method	ic50	0.0023	uM
4-(3-methoxyphenyl)-3-[6-[4-(3-methoxyphenyl)-5-sulfanylidene-1H-1,2,4-triazol-3-yl]-3-pyridinyl]-1H-1,2,4-triazole-5-thione	1570273: Inhibition of AChE (unknown origin) by spectrophotometric analysis	ki	0.0031	uM
7-[7-[4-[(1,2,3,4-tetrahydroacridin-9-ylamino)methyl]triazol-1-yl]heptoxy]chromen-2-one	1570255: Inhibition of AChE (unknown origin) after 2 mins	ic50	0.0060	uM
N-[3-[1-[6-[ethyl-[(2-methoxyphenyl)methyl]amino]hexyl]-6-oxopyridazin-3-yl]-4-hydroxyphenyl]acetamide	1877965: Inhibition of human AChE by Ellman’s method	ic50	0.0120	uM
7-[5-[4-[[(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]methyl]triazol-1-yl]pentoxy]-4-methylchromen-2-one	1570255: Inhibition of AChE (unknown origin) after 2 mins	ic50	0.0270	uM
2-[6-[[2-(dimethylamino)phenyl]methyl-ethylamino]hexyl]-6-(5-fluoro-2-hydroxyphenyl)pyridazin-3-one	1877965: Inhibition of human AChE by Ellman’s method	ic50	0.0324	uM
Donepezil	1877965: Inhibition of human AChE by Ellman’s method	ic50	0.0324	uM
6-[5-(dimethylamino)-2-hydroxyphenyl]-2-[6-[[2-(dimethylamino)phenyl]methyl-ethylamino]hexyl]pyridazin-3-one	1877965: Inhibition of human AChE by Ellman’s method	ic50	0.0363	uM
2-[6-[[2-(dimethylamino)phenyl]methyl-ethylamino]hexyl]-6-(2-hydroxy-5-nitrophenyl)pyridazin-3-one	1877965: Inhibition of human AChE by Ellman’s method	ic50	0.0437	uM
1,2,3,4-tetrahydroacridin-9-amine	283051: Inhibition of acetylcholinesterase	ic50	0.0440	uM
N-[(E)-benzylideneamino]-4-[1-[2-[(2E)-2-benzylidenehydrazinyl]-2-oxoethyl]-3-methyl-5-oxo-1,2,4-triazol-4-yl]benzamide	1570274: Inhibition of AChE (unknown origin) by Ellman’s method	ic50	0.0465	uM
(2S)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-1-[(2S)-2-[[(2S)-1-[(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(3S,9S,12R,17R,20S)-12-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-6-amino-2-[[2-[(2-aminoacetyl)amino]acetyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-3-carboxypropanoyl]amino]-4-methylpentanoyl]amino]-5-carbamimidamidopentanoyl]pyrrolidine-2-carbonyl]amino]-9-(1H-imidazol-5-ylmethyl)-2,8,11,19-tetraoxo-14,15-dithia-1,7,10,18-tetrazatricyclo[18.3.0.03,7]tricosane-17-carbonyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbonyl]amino]-5-carbamimidamidopentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-5-carbamimidamidopentanoic acid	1388451: Inhibition of nAChR epsilon (unknown origin)	ic50	0.0500	uM
N-[(E)-(4-chlorophenyl)methylideneamino]-4-[1-[2-[(2E)-2-[(4-chlorophenyl)methylidene]hydrazinyl]-2-oxoethyl]-3-methyl-5-oxo-1,2,4-triazol-4-yl]benzamide	1570274: Inhibition of AChE (unknown origin) by Ellman’s method	ic50	0.0574	uM
2-[6-[ethyl-[(2-methoxyphenyl)methyl]amino]hexyl]-6-(5-fluoro-2-hydroxyphenyl)pyridazin-3-one	1877965: Inhibition of human AChE by Ellman’s method	ic50	0.0575	uM
N-[(E)-(4-bromo-2-hydroxyphenyl)methylideneamino]-4-[1-[2-[(2E)-2-[(4-bromo-2-hydroxyphenyl)methylidene]hydrazinyl]-2-oxoethyl]-3-methyl-5-oxo-1,2,4-triazol-4-yl]benzamide	1570274: Inhibition of AChE (unknown origin) by Ellman’s method	ic50	0.0577	uM
N-[(E)-(4-methoxyphenyl)methylideneamino]-4-[1-[2-[(2E)-2-[(4-methoxyphenyl)methylidene]hydrazinyl]-2-oxoethyl]-3-methyl-5-oxo-1,2,4-triazol-4-yl]benzamide	1570274: Inhibition of AChE (unknown origin) by Ellman’s method	ic50	0.0623	uM
N-[3-[1-[6-[ethyl-[(3-fluorophenyl)methyl]amino]hexyl]-6-oxopyridazin-3-yl]-4-hydroxyphenyl]acetamide	1877965: Inhibition of human AChE by Ellman’s method	ic50	0.0708	uM
4-phenyl-3-thiophen-2-yl-1H-1,2,4-triazole-5-thione	1570262: Inhibition of AChE (unknown origin)	ic50	0.0818	uM
2-[6-[ethyl-[(3-fluorophenyl)methyl]amino]hexyl]-6-(2-hydroxy-5-nitrophenyl)pyridazin-3-one	1877965: Inhibition of human AChE by Ellman’s method	ic50	0.0832	uM
6-[5-(dimethylamino)-2-hydroxyphenyl]-2-[6-[ethyl-[(2-methoxyphenyl)methyl]amino]hexyl]pyridazin-3-one	1877965: Inhibition of human AChE by Ellman’s method	ic50	0.0871	uM
N-[(E)-(4-bromophenyl)methylideneamino]-4-[1-[2-[(2E)-2-[(4-bromophenyl)methylidene]hydrazinyl]-2-oxoethyl]-3-methyl-5-oxo-1,2,4-triazol-4-yl]benzamide	1570274: Inhibition of AChE (unknown origin) by Ellman’s method	ic50	0.0877	uM
2-[6-[ethyl-[(2-methoxyphenyl)methyl]amino]hexyl]-6-(2-hydroxy-5-nitrophenyl)pyridazin-3-one	1877965: Inhibition of human AChE by Ellman’s method	ic50	0.0912	uM
N-[(E)-(3-bromophenyl)methylideneamino]-4-[1-[2-[(2E)-2-[(3-bromophenyl)methylidene]hydrazinyl]-2-oxoethyl]-3-methyl-5-oxo-1,2,4-triazol-4-yl]benzamide	1570274: Inhibition of AChE (unknown origin) by Ellman’s method	ic50	0.0966	uM
(9-amino-5,6,7,8-tetrahydroacridin-4-yl)methanol	283051: Inhibition of acetylcholinesterase	ic50	0.1250	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
2-[6-[ethyl-[(3-fluorophenyl)methyl]amino]hexyl]-6-(5-fluoro-2-hydroxyphenyl)pyridazin-3-one	1877965: Inhibition of human AChE by Ellman’s method	ic50	0.4074	uM
6-[5-(dimethylamino)-2-hydroxyphenyl]-2-[6-[ethyl-[(3-fluorophenyl)methyl]amino]hexyl]pyridazin-3-one	1877965: Inhibition of human AChE by Ellman’s method	ic50	0.6761	uM
9-[[1-[(2-methylphenyl)methyl]triazol-4-yl]methyl]carbazole	1570266: Inhibition of human AChE using acetylthiocholine iodide as substrate after 10 secs measured at 30 s intervals for two minutes by Ellman’s method	ic50	1.9000	uM

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Acetylcholine	affects binding, increases activity	2
Air Pollutants	affects expression, increases abundance, increases expression	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation, decreases methylation	1
candoxin	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Atrazine	increases expression	1
Benzo(a)pyrene	affects methylation	1
Calcitriol	increases expression, affects cotreatment	1
Catechin	affects cotreatment, increases expression	1
Cisplatin	increases expression, affects cotreatment	1
Methotrexate	decreases expression	1
Ozone	affects expression, increases abundance	1
Progesterone	decreases expression	1
Sarin	increases expression	1
Selenium	increases expression	1
Testosterone	affects cotreatment, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	increases expression	1
Valproic Acid	increases methylation	1
Lactic Acid	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

ChEMBL screening assays

28 unique, capped per target: 26 binding, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL745041	Functional	The compound was tested on recombinant human alpha-1-beta-1-gamma-delta cell lines of human embryonic kidney for nicotinic acetylcholine receptor agonist functional potency; nd=not determined.	(S)-(-)-5-ethynyl-3-(1-methyl-2-pyrrolidinyl)pyridine maleate (SIB-1508Y): a novel anti-parkinsonian agent with selectivity for neuronal nicotinic acetylcholine receptors. — J Med Chem
CHEMBL750567	Binding	Compound was evaluated for functional potencies and efficacies at human muscle type Nicotinic acetylcholine receptor in TE671 cells	Neuronal nicotinic acetylcholine receptors as targets for drug discovery. — J Med Chem

Cellosaurus cell lines

6 cell lines: 3 transformed cell line, 3 induced pluripotent stem cell

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_VT77	HEK-293-AChE	Transformed cell line	Female
CVCL_VT78	HEK-293-AChE-ST	Transformed cell line	Female
CVCL_ZZ62	JUCTCi007-A	Induced pluripotent stem cell	Female
CVCL_ZZ63	JUCTCi007-B	Induced pluripotent stem cell	Female
CVCL_ZZ64	JUCTCi007-C	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00793988	PHASE4	COMPLETED	Vibration-Assisted Anaesthesia
NCT01239498	PHASE4	UNKNOWN	Saline Injection - Assisted Anesthesia in Eyelid Surgery
NCT02761083	PHASE4	WITHDRAWN	PMCF-study Using Novosyn® Quick Suture Material in Ophthalmic Surgery
NCT04007276	PHASE4	NOT_YET_RECRUITING	The Effect of Lumify™ on Ocular Redness, Intraocular Pressure, and Eyelid Position in Glaucoma Patients
NCT07390578	PHASE4	NOT_YET_RECRUITING	Upneeq vs. Lumify Ptosis
NCT02436759	PHASE3	COMPLETED	Study of the Safety and Efficacy of RVL-1201 in the Treatment of Acquired Blepharoptosis
NCT03536949	PHASE3	COMPLETED	Study of Safety of RVL-1201 in Treatment of Blepharoptosis
NCT03565887	PHASE3	COMPLETED	Study of Safety and Efficacy of RVL-1201 in the Treatment of Blepharoptosis
NCT05945615	PHASE3	COMPLETED	Oxymetazoline Drops for Acquired Blepharoptosis From Synkinesis
NCT06683651	PHASE3	RECRUITING	A Study in Chinese Patients With Acquired Blepharoptosis
NCT03266081	PHASE2	WITHDRAWN	Bupivacaine Epiphora Trial
NCT01203592	PHASE1	COMPLETED	Efficacy of Albuterol in the Treatment of Congenital Myasthenic Syndromes
NCT06436742	PHASE1	RECRUITING	A Phase 1b Study to Investigate Safety and Tolerability of ARGX-119 in Adult Participants With DOK7-Congenital Myasthenic Syndromes (CMS)
NCT07226726	PHASE1	RECRUITING	Patients With Congenital Myasthenic Syndrome Will be Treated With Mesenchymal Stem Cell Exosome Solution
NCT00872950	Not specified	APPROVED_FOR_MARKETING	3,4-Diaminopyridine Use in Lambert-Eaton Myasthenic Syndrome(LEMS) and Congenital Myasthenic Syndromes (CMS)
NCT01403402	Not specified	RECRUITING	Congenital Muscle Disease Study of Patient and Family Reported Medical Information
NCT01474980	Not specified	COMPLETED	Pregnancy Outcomes in Congenital Myasthenie Syndrome
NCT02012933	Not specified	NO_LONGER_AVAILABLE	3,4-Diaminopyridine for Lambert-Eaton Myasthenic Syndrome (LEMS) and Congenital Myasthenia (CM)
NCT02189720	Not specified	APPROVED_FOR_MARKETING	Expanded Access Study Amifampridine Phosphate in Lambert-Eaton Myasthenic Syndrome (LEMS),Congenital Myasthenic Syndrome
NCT03062631	Not specified	NO_LONGER_AVAILABLE	Treatment Use of 3,4 Diaminopyridine in Congenital Myasthenia
NCT05408702	Not specified	COMPLETED	Exercise in Autoimmune Myasthenia Gravis and Myasthenic Syndromes
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening
NCT06078553	Not specified	RECRUITING	A Natural History Study in Participants With Congenital Myasthenic Syndromes (CMS) Due to Mutations in DOK7, MUSK, AGRN, or LRP4
NCT07277582	PHASE2/PHASE3	RECRUITING	Evaluation of Efficacy and Safety of THRV-1268 in Long QT Syndrome Type 2 (LQTS 2)
NCT07075445	Not specified	RECRUITING	Observational Study to Describe Health-Related Quality of Life and Measure Disease Burden Among Patients With Long QT Syndrome Types (LQTS) 2 and 3
NCT02878694	PHASE2/PHASE3	TERMINATED	Treatment of Ptosis to Muscular Dystrophy Oculopharyngeal by Myoblast Autologous Graft
NCT05358977	PHASE2/PHASE3	UNKNOWN	Fibrin Sealant in Eyelid Surgery
NCT01848041	PHASE1/PHASE2	COMPLETED	Safety and Efficacy Study of RVL-1201 in Acquired Blepharoptosis
NCT05715346	PHASE1/PHASE2	COMPLETED	LEV102 Topical Gel in Acquired Blepharoptosis
NCT04807855	EARLY_PHASE1	COMPLETED	Custom Print Megnetic Levator Prosthesis Pilot Comparison
NCT06911216	EARLY_PHASE1	COMPLETED	A Pharmacokinetics (PK) Study in Healthy Adults
NCT00816270	Not specified	TERMINATED	Liquid Bandage (2-Octyl-Cyanoacrylate) in Upper Lid Blepharoplasty
NCT00864656	Not specified	COMPLETED	Eyelid Position Interdependence in Involutional Ptosis Patients Submitted to 10% Phenylephrine
NCT01350024	Not specified	COMPLETED	Comparison of Postoperative Pain With Two Different Types of Local Anesthesia in Surgery for a Drooping Eyelid
NCT01430247	Not specified	COMPLETED	Vision Screening for the Detection of Amblyopia
NCT01968174	Not specified	UNKNOWN	Astigmatic Changes Secondary to Eyelid Surgeries
NCT02201979	Not specified	COMPLETED	Laser Fluorescent Imaging of Nipple and Areola During Breast Lift
NCT02226016	Not specified	UNKNOWN	Levator Muscle Strength Evaluation
NCT02367677	Not specified	COMPLETED	Digital Photographs to Evaluate Blepharoptosis
NCT02376556	Not specified	COMPLETED	The Effect of Eyelid Surgery on Dry Eye - a Prospective Study