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) — +3 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 705 total — 42 pathogenic, 43 likely-pathogenic (top 5% of genes corpus-wide)
• GTEx eGene: eQTL in 48 tissues, sQTL in 21 (q < 0.05)
• Phenotypes (HPO): 53
• Drug target: yes — 14 via a complex or family; 4 molecules with ChEMBL bioactivity
• Approved drugs acting on a complex or family including it: 14 — Atracurium Besylate, Cisatracurium Besylate, Decamethonium Bromide, +11 more (Muscle-type nicotinic acetylcholine receptor)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.30 (unconstrained)
• 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: 9 — 4 protein_coding, 2 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000649488

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 3: 1, TSL 5: 1

ENST00000649488, ENST00000572438, ENST00000575637, ENST00000649830, ENST00000652550, ENST00001017166, ENST00001017167, ENST00001017168, ENST00001017169

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.

Highest expression (Bgee): atrium auricular region, cardiac atrium, adenohypophysis, pituitary gland, cardiac muscle of right atrium.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CHRNE is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 48 tissues and its splicing (sQTL) in 21 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 69 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	eqtl	6.5e-111	+1.54	17:4910284:C:T
Skin Sun Exposed Lower leg	eqtl	1.9e-97	+1.16	17:4901872:C:T
Artery Tibial	eqtl	7.3e-89	+1.56	17:4901872:C:T
Adipose Subcutaneous	eqtl	6.6e-85	+1.53	17:4901872:C:T
Skin Not Sun Exposed Suprapubic	eqtl	2.1e-81	+1.13	17:4901872:C:T
Thyroid	eqtl	5.5e-73	+1.40	17:4901872:C:T
Nerve Tibial	eqtl	6.4e-71	+1.59	17:4901872:C:T
Lung	eqtl	2.0e-65	+1.22	17:4901872:C:T
Adipose Visceral Omentum	eqtl	1.6e-59	+1.29	17:4901872:C:T
Esophagus Muscularis	eqtl	4.6e-57	+1.45	17:4901872:C:T
Esophagus Mucosa	eqtl	3.6e-52	+1.33	17:4901872:C:T
Artery Aorta	eqtl	9.2e-49	+1.40	17:4901872:C:T
Breast Mammary Tissue	eqtl	2.3e-46	+1.35	17:4905466:G:C
Colon Transverse	eqtl	2.9e-45	+1.36	17:4901872:C:T
Whole Blood	eqtl	3.2e-39	+0.77	17:4901872:C:T
Colon Sigmoid	eqtl	8.1e-37	+1.46	17:4901872:C:T
Heart Atrial Appendage	sqtl	2.0e-34	+1.25	17:4900778:G:C
Stomach	eqtl	4.1e-32	+1.17	17:4901872:C:T
Esophagus Gastroesophageal Junction	eqtl	1.5e-31	+1.32	17:4899022:T:C
Heart Left Ventricle	eqtl	2.0e-28	+1.07	17:4901872:C:T

FANTOM5 promoters

2 alternative TSS:

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

Top tissues by expression

showing 100 of 286 tissues 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
gastrocnemius	UBERON:0001388	62.47	gold quality
bone marrow cell	CL:0002092	62.44	silver quality
leukocyte	CL:0000738	62.32	gold quality
descending thoracic aorta	UBERON:0002345	62.22	gold quality
muscle of leg	UBERON:0001383	62.10	gold quality
monocyte	CL:0000576	61.90	gold quality
right ovary	UBERON:0002118	61.80	gold quality
mononuclear cell	CL:0000842	61.78	gold quality
prefrontal cortex	UBERON:0000451	61.67	gold quality
right lung	UBERON:0002167	61.58	gold quality
tibial artery	UBERON:0007610	61.57	gold quality
popliteal artery	UBERON:0002250	61.52	gold quality
bone marrow	UBERON:0002371	61.51	gold quality
pancreatic ductal cell	CL:0002079	61.32	silver quality
aorta	UBERON:0000947	61.05	gold quality
ascending aorta	UBERON:0001496	60.78	gold quality
oocyte	CL:0000023	60.77	gold quality
left ovary	UBERON:0002119	60.75	gold quality
left uterine tube	UBERON:0001303	60.74	gold quality
thoracic aorta	UBERON:0001515	60.70	gold quality
adrenal tissue	UBERON:0018303	60.53	gold quality
cerebellar cortex	UBERON:0002129	60.24	gold quality
metanephros cortex	UBERON:0010533	60.20	gold quality
type B pancreatic cell	CL:0000169	60.17	gold quality
cerebellar hemisphere	UBERON:0002245	60.04	gold quality
lower esophagus mucosa	UBERON:0035834	60.03	gold quality
adipose tissue	UBERON:0001013	59.86	gold quality
subcutaneous adipose tissue	UBERON:0002190	59.81	gold quality
connective tissue	UBERON:0002384	59.54	gold quality
cerebellum	UBERON:0002037	59.46	gold quality
muscle organ	UBERON:0001630	59.35	gold quality
right hemisphere of cerebellum	UBERON:0014890	59.20	gold quality
saliva-secreting gland	UBERON:0001044	59.05	gold quality
lymph node	UBERON:0000029	58.95	gold quality
right testis	UBERON:0004534	58.95	gold quality
gluteal muscle	UBERON:0002000	58.84	gold quality
hindlimb stylopod muscle	UBERON:0004252	58.81	gold quality
body of stomach	UBERON:0001161	58.63	gold quality
vermiform appendix	UBERON:0001154	58.47	gold quality
minor salivary gland	UBERON:0001830	58.41	gold quality
anatomical system	UBERON:0000467	58.02	gold quality
material anatomical entity	UBERON:0000465	57.93	gold quality
multicellular organism	UBERON:0000468	57.93	gold quality
ganglionic eminence	UBERON:0004023	57.93	gold quality
heart left ventricle	UBERON:0002084	57.91	gold quality
left adrenal gland cortex	UBERON:0035825	57.89	gold quality
left lobe of thyroid gland	UBERON:0001120	57.82	gold quality
cartilage tissue	UBERON:0002418	57.72	gold quality
cardiac ventricle	UBERON:0002082	57.67	gold quality
islet of Langerhans	UBERON:0000006	57.65	gold quality
right lobe of thyroid gland	UBERON:0001119	57.64	gold quality
colonic epithelium	UBERON:0000397	57.57	silver quality
ovary	UBERON:0000992	57.54	gold quality
upper lobe of left lung	UBERON:0008952	57.47	gold quality
left coronary artery	UBERON:0001626	57.40	gold quality
thyroid gland	UBERON:0002046	57.31	gold quality
right frontal lobe	UBERON:0002810	57.28	gold quality
left testis	UBERON:0004533	57.04	gold quality
frontal cortex	UBERON:0001870	57.01	gold quality
ectocervix	UBERON:0012249	56.86	gold quality
caecum	UBERON:0001153	56.80	gold quality
mouth mucosa	UBERON:0003729	56.74	gold quality
body of uterus	UBERON:0009853	56.65	gold quality
cortex of kidney	UBERON:0001225	56.51	gold quality
coronary artery	UBERON:0001621	56.41	gold quality
adult mammalian kidney	UBERON:0000082	56.40	gold quality
sural nerve	UBERON:0015488	56.39	silver quality
small intestine Peyer’s patch	UBERON:0003454	56.24	gold quality
testis	UBERON:0000473	56.21	gold quality
neocortex	UBERON:0001950	56.21	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

HPA expression

RNA tissue specificity: Group enriched

showing 60 of 70 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Heart muscle	tissue	49.1
Pituitary gland	tissue	27.7
Putamen	tissue	8.3
Basal ganglia	tissue	6.4
Retina	tissue	4.8
Ventral forebrain	tissue	2.5
Tongue	tissue	2.0
Liver	tissue	1.7
Pancreas	tissue	1.3
Skin 1	tissue	1.2
Epididymis	tissue	1.2
Hippocampus	tissue	1.1
Gallbladder	tissue	1.0
Septum	tissue	0.9
Salivary gland	tissue	0.8
Spleen	tissue	0.8
Ovary	tissue	0.7
Nucleus accumbens	tissue	0.7
Locus coeruleus	tissue	0.7
Bone marrow	tissue	0.7
Postcentral gyrus	tissue	0.7
Lymph node	tissue	0.5
Adipose tissue	tissue	0.5
Placenta	tissue	0.5
Substantia nigra	tissue	0.5
Vagina	tissue	0.4
Skeletal muscle	tissue	0.4
Choroid plexus	tissue	0.4
Hippocampal formation	tissue	0.4
Entorhinal cortex	tissue	0.4
Breast	tissue	0.3
Testis	tissue	0.3
Cerebral cortex	tissue	0.3
Esophagus	tissue	0.3
Urinary bladder	tissue	0.3
Duodenum	tissue	0.3
Retrosplenial and cingulate cortex	tissue	0.3
Appendix	tissue	0.3
Temporal cortex	tissue	0.3
Prefrontal cortex	tissue	0.2
Seminal vesicle	tissue	0.2
Parathyroid gland	tissue	0.2
Smooth muscle	tissue	0.2
Motor cortex	tissue	0.2
Amygdala	tissue	0.2
Small intestine	tissue	0.2
Kidney	tissue	0.2
Corpus callosum	tissue	0.2
Prostate	tissue	0.2
Tonsil	tissue	0.2
Fallopian tube	tissue	0.2
Somatosensory cortex	tissue	0.2
Retrosplenial cortex	tissue	0.2
Occipital cortex	tissue	0.2
Insular cortex	tissue	0.2
Cervix	tissue	0.1
Stomach 1	tissue	0.1
Pons	tissue	0.1
Colon	tissue	0.1
Endometrium 1	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Flocculonodular lobe (2.0), Area postrema (1.4), Vermis (1.4), Cerebellar cortex (1.3), Hippocampus, CA3 (1.3).

Regulation

Is transcription factor: no

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

miRNA regulators (miRDB)

Targeting CHRNE by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 36 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 8.82e-22, LOEUF 1.3, missense Z -1.45 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000649488 — one region, missense o/e 1.15.

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), GABRA5 (ENSG00000186297), ZACN (ENSG00000186919), GABRD (ENSG00000187730), CHRNG (ENSG00000196811), GABRQ (ENSG00000268089)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:87894) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 22 distinct phenotype terms.

Mouse phenotype (MP)	Records
premature death	3
weakness	2
abnormal neuromuscular synapse morphology	2
decreased body weight	2
decreased locomotor activity	2
abnormal PNS synaptic transmission	2
abnormal miniature endplate potential	2
skeletal muscle atrophy	2
muscle weakness	1
abnormal skeletal muscle morphology	1
impaired skeletal muscle contractility	1
abnormal endplate potential	1
abnormal skeletal muscle fiber morphology	1
decreased muscle weight	1
abnormal motor nerve collateral sprouting	1
abnormal action potential	1
increased pulmonary respiratory rate	1
slow postnatal weight gain	1
increased physiological sensitivity to xenobiotic	1
skeletal muscle fiber degeneration	1
decreased grip strength	1
neuromuscular synapse degeneration	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pan troglodytes	Q5IS75	100.0%	Diamond
Natrix tessellata	P14144	98.1%	Diamond
Bos taurus	P04758	92.1%	Diamond
Gallus gallus	P43679	85.3%	Diamond
Xenopus laevis	P05376	71.1%	Diamond
Carassius auratus	P19370	69.1%	Diamond
Tetronarce californica	P02714	66.3%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
GP1BA	protein-coding	2811
MINK1	protein-coding	50488
SLC25A11	protein-coding	8402
C17orf107	protein-coding	100130311
C17orf114	protein-coding	119139905
PLD2	protein-coding	5338
RNF167	protein-coding	26001
PFN1	protein-coding	5216

Protein

Protein identifiers

Acetylcholine receptor subunit epsilon — Q04844 (reviewed: Q04844)

All UniProt accessions (2): A0A3B3IRM1, Q04844

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)

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

UniProt features (67 total): helix 18, strand 15, sequence variant 14, turn 6, topological domain 5, transmembrane region 4, glycosylation site 2, signal peptide 1, chain 1, disulfide bond 1

Structure

Experimental structures (PDB)

25 structures by resolution:

PDB	Title	Method	Resolution (Å)
9DMS	Human muscle nAChR with fab6-bound	ELECTRON MICROSCOPY	1.92
9DMG	Human muscle nAChR apo state	ELECTRON MICROSCOPY	2.05
9DMH	Human muscle nAChR ACh-bound state	ELECTRON MICROSCOPY	2.06
9DMQ	Human muscle nAChR with fab3-bound	ELECTRON MICROSCOPY	2.06
9DMV	Human muscle nAChR with fab9-bound	ELECTRON MICROSCOPY	2.13
9DMT	Human muscle nAChR with fab7-bound	ELECTRON MICROSCOPY	2.18
9DMJ	Human muscle nAChR with two fab1b-bound	ELECTRON MICROSCOPY	2.19
9YER	Human muscle nAChR SCCMS eT264P ACh bound	ELECTRON MICROSCOPY	2.19
9YE8	Human muscle nAChR SCCMS eL269F ACh bound	ELECTRON MICROSCOPY	2.22
9DML	Human muscle nAChR with fab2-bound	ELECTRON MICROSCOPY	2.24
9YEI	Human muscle nAChR SCCMS eL269F ACh, Reboxetine bound (lower 1)	ELECTRON MICROSCOPY	2.36
9YET	Human muscle nAChR SCCMS eT264P ACh, Reboxetine bound	ELECTRON MICROSCOPY	2.36
9YEU	Human muscle nAChR SCCMS bV266M ACh bound	ELECTRON MICROSCOPY	2.39
9YE7	Human muscle nAChR FCCMS eP121L ACh, XG-590 bound	ELECTRON MICROSCOPY	2.44
9DMK	Human muscle nAChR with one fab1b-bound	ELECTRON MICROSCOPY	2.46
9YEH	Human muscle nAChR SCCMS eL269F ACh, Reboxetine bound (upper)	ELECTRON MICROSCOPY	2.46
9YE6	Human muscle nAChR FCCMS eP121L ACh-bound	ELECTRON MICROSCOPY	2.47
9YEX	Human muscle nAChR SCCMS bV266M ACh, Quinidine bound	ELECTRON MICROSCOPY	2.47
9GU1	Human adult muscle nAChR in resting state in nanodisc with alpha-bungarotoxin	ELECTRON MICROSCOPY	2.48
9YEL	Human muscle nAChR SCCMS eL269F ACh, Fluoxetine bound	ELECTRON MICROSCOPY	2.48
9GU3	Human adult muscle nAChR in desensitised state in nanodisc with 1 mM acetylcholine	ELECTRON MICROSCOPY	2.64
9YEK	Human muscle nAChR SCCMS eL269F ACh, Reboxetine bound (lower 2)	ELECTRON MICROSCOPY	2.68
9GU2	Human adult muscle nAChR in desensitised state in nanodisc with 100 uM acetylcholine	ELECTRON MICROSCOPY	2.73
9YF0	Human muscle nAChR SCCMS aV249F ACh, Fluoxetine bound	ELECTRON MICROSCOPY	2.79
9GU0	Human adult muscle nAChR in resting state in detergent with alpha-bungarotoxin	ELECTRON MICROSCOPY	2.96

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q04844-F1	81.32	0.32

Antibody-complex structures (SAbDab)

10 antibodies co-crystallized with this protein: 9DMJ, 9DMK, 9DMQ, 9DMS, 9DMT, 9DMV, 9GU0, 9GU1, 9GU2, 9GU3

Human Protein Atlas

Protein class: Transporters, Transporter channels and pores, Predicted membrane proteins, Predicted intracellular proteins, Disease related genes, Potential drug targets, Human disease related genes

Protein evidence: Evidence at protein level

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)

Type	Positions
Disulfide bond	148–162

Glycosylation sites (2)

Type	Positions
N-linked (glcnac…) asparagine	86, 161

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 7; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

7 pathways:

ID	Pathway	Evidence
R-HSA-629587	Highly sodium permeable postsynaptic acetylcholine nicotinic receptors	curated
R-HSA-181431	Acetylcholine binding and downstream events	—
R-HSA-112316	Neuronal System	—
R-HSA-112314	Neurotransmitter receptors and postsynaptic signal transmission	—
R-HSA-622327	Postsynaptic nicotinic acetylcholine receptors	—
R-HSA-622323	Presynaptic nicotinic acetylcholine receptors	—
R-HSA-112315	Transmission across Chemical Synapses	—

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 (14): 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), calcium ion transport (GO:0006816), 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

6 top-level categories:

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

46 GO namespaces:

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
metal ion 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
plasma membrane bounded cell projection	1
cell junction	1
synaptic membrane	1
postsynapse	1
cellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 2 of 28 annotations. The rest are phylogenetic / computational / electronic (IEA).

2 experimentally-supported GO terms:

GO term	NS	Evidence
neuromuscular junction	CC	direct assay
transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 670 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHRNE	RAPSN	Q13702	895
CHRNE	COLQ	Q9Y215	858
CHRNE	DOK7	Q18PE1	847
CHRNE	MUSK	O15146	843
CHRNE	MINK1	Q8N4C8	840
CHRNE	GFPT1	Q06210	620
CHRNE	GP1BA	P07359	602
CHRNE	BCHE	P06276	587
CHRNE	ALG14	Q96F25	583
CHRNE	CAPN3	P20807	583
CHRNE	DPAGT1	Q9H3H5	573
CHRNE	GMPPB	Q9Y5P6	570
CHRNE	SCN4A	P35499	557
CHRNE	CAST	P20810	552
CHRNE	ASPG	Q86U10	552

IntAct

Human interaction partners of CHRNE in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

1 partners by confidence:

Partner	Interaction type	MIscore	Records
PODXL	association	0.350	1

BioGRID (29 interactions; top human partners by supporting records): CHRNA1 (Reconstituted Complex), CNNM1 (Affinity Capture-MS), CYB5R1 (Affinity Capture-MS), DAG1 (Affinity Capture-MS), FAM69A (Affinity Capture-MS), ICAM4 (Affinity Capture-MS), ITGA6 (Affinity Capture-MS), ITPRIP (Affinity Capture-MS), LRP12 (Affinity Capture-MS), LTBP1 (Affinity Capture-MS), NMU (Affinity Capture-MS), NXPE3 (Affinity Capture-MS), PODXL (Affinity Capture-MS), POMT2 (Affinity Capture-MS), PXYLP1 (Affinity Capture-MS)

SIGNOR signaling

1 signaling interactions:

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

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
★ CHRNA1-CHRNB1-CHRND-CHRNE-CHRNA7 complex	5	CHRNA1, CHRNA7, CHRNB1, CHRND, CHRNE

Ligand–receptor pairs (CellPhoneDB) (1)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

1 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
CHRNA1;CHRNB1;CHRND;CHRNE		Signaling by Choline acetyltransferase

Disease & clinical

Genetic variants

Variant evidence for CHRNE: 705 ClinVar records (85 pathogenic / likely pathogenic); 3 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	42
Likely pathogenic	43
Uncertain significance	235
Likely benign	275
Benign	23

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 85 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
243032	NM_000080.4(CHRNE):c.1353dup (p.Asn452fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	12
1458892	NM_000080.4(CHRNE):c.1219+2T>G	Pathogenic	criteria provided, multiple submitters, no conflicts	5
973529	NM_000080.4(CHRNE):c.1364ACA[1] (p.Asn456del)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
2090933	NM_000080.4(CHRNE):c.1002_1008dup (p.Ala337fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
1071548	NM_000080.4(CHRNE):c.1158dup (p.Lys387fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
1694812	NM_000080.4(CHRNE):c.1255G>T (p.Glu419Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
1959021	NM_000080.4(CHRNE):c.1248_1266dup (p.Cys423fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
947210	NM_000080.4(CHRNE):c.447_459del (p.Val150fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
1399349	NM_000080.4(CHRNE):c.295C>T (p.Arg99Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
1687321	NM_000080.4(CHRNE):c.1064del (p.Gly355fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
2680791	NM_000080.4(CHRNE):c.1090del (p.Arg364fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
2680797	NM_000080.4(CHRNE):c.1204C>T (p.Gln402Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
2736401	NM_000080.4(CHRNE):c.569dup (p.Asn190fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
842325	NM_000080.4(CHRNE):c.1297_1314dup (p.Ser433_Glu438dup)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	4
1501328	NM_000080.4(CHRNE):c.1032+1G>A	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3

Per-variant reference — Sugi Variant

Explore CHRNE’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 27 predictions of 808):

Position(s)	Effect	Δscore	Sites
17:4899108–4899109	acceptor_loss	1.0000	6
17:4899196–4899197	donor_loss	1.0000	2
17:4899466	donor_loss	1.0000	2
17:4902185	donor_gain	1.0000
17:4902619–4902620	donor_loss	1.0000	4
17:4899106	acceptor_gain	0.9900
17:4899113	acceptor_gain	0.9900
17:4899196–4899197	donor_loss	0.9900	3
17:4899385–4899386	acceptor_loss	0.9900	5
17:4899467	donor_loss	0.9900	2

AlphaMissense

981 missense substitutions predicted likely pathogenic (of 3,191 scored), across 267 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D158	8	0.990	0.996
D82	8	0.982	0.995
F166	8	0.953	0.997
F155	8	0.949	0.997
F286	8	0.948	0.993
F242	8	0.936	0.996
N114	8	0.931	0.990
F157	8	0.924	0.988
D455	8	0.909	0.973
D117	8	0.851	0.933
F310	8	0.822	0.944
C148	7	0.996	0.999
C162	7	0.995	0.999
W205	7	0.995	1.000
W106	7	0.989	0.998
W80	7	0.987	0.997
W138	7	0.949	0.990
Q160	7	0.940	0.995
W75	7	0.939	0.982
F120	7	0.928	0.986

HPA cancer prognostics

RNA cancer specificity: Not detected

Disease associations

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

GenCC curated gene-disease

4 curated gene-disease records:

Disease	Classification	Inheritance	Records
congenital myasthenic syndrome 4A	Definitive	Autosomal dominant	4
congenital myasthenic syndrome 4C	Definitive	Autosomal recessive	2
congenital myasthenic syndrome 4B	Definitive	Autosomal recessive	3
congenital myasthenic syndrome	Definitive	Autosomal recessive

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (5 panels, 5 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

5 panels:

Panel	Rating
Arthrogryposis	green
Congenital myaesthenic syndrome	green
Fetal anomalies	green
Hypotonic infant	green
Other rare neuromuscular disorders	green

Mondo (6): congenital myasthenic syndrome 4A (MONDO:0011600), congenital myasthenic syndrome (MONDO:0018940), congenital myasthenic syndrome 4C (MONDO:0012157), congenital myasthenic syndrome 4B (MONDO:0014586), congenital myasthenic syndrome 4 (MONDO:1040021), long QT syndrome 2 (MONDO:0013367)

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

HPO phenotypes

53 phenotypes (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:0000508	Ptosis
HP:0000597	Ophthalmoparesis
HP:0000602	Ophthalmoplegia
HP:0000689	Dental malocclusion
HP:0001252	Hypotonia
HP:0001260	Dysarthria
HP:0001270	Motor delay
HP:0001283	Bulbar palsy
HP:0001290	Generalized hypotonia
HP:0001319	Neonatal hypotonia
HP:0001324	Muscle weakness
HP:0001558	Decreased fetal movement
HP:0001612	Weak cry
HP:0002015	Dysphagia
HP:0002033	Poor suck
HP:0002093	Respiratory insufficiency
HP:0002098	Respiratory distress
HP:0002747	Respiratory insufficiency due to muscle weakness
HP:0002804	Arthrogryposis multiplex congenita
HP:0002872	Apneic episodes precipitated by illness, fatigue, stress
HP:0002882	Sudden episodic apnea
HP:0003198	Myopathy
HP:0003199	Decreased muscle mass
HP:0003202	Skeletal muscle atrophy
HP:0003388	Easy fatigability
HP:0003391	Gowers sign
HP:0003394	Muscle spasm
HP:0003397	Generalized hypotonia due to defect at the neuromuscular junction
HP:0003402	Decreased miniature endplate potentials
HP:0003403	EMG: decremental response of compound muscle action potential to repetitive nerve stimulation
HP:0003443	Decreased size of nerve terminals
HP:0003473	Fatigable weakness
HP:0003554	Type 2 muscle fiber atrophy
HP:0003577	Congenital onset
HP:0003593	Infantile onset
HP:0003623	Neonatal onset
HP:0003680	Nonprogressive
HP:0003690	Limb muscle weakness
HP:0003828	Variable expressivity
HP:0008872	Feeding difficulties in infancy
HP:0010628	Facial palsy
HP:0011463	Childhood onset
HP:0011968	Feeding difficulties
HP:0030197	Fatigable weakness of skeletal muscles
HP:0030208	Anti-neuromuscular Junction acetylcholine receptor antibody positivity
HP:0030319	Weakness of facial musculature

GWAS associations

3 associations:

Study	Trait	p-value
GCST005991_41	Platelet count	5e-60
GCST90013442_27	Keratoconus	2e-14
GCST012182_10	Alzheimer’s disease	2e-10

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0004309	platelet count

MeSH disease descriptors

2 disease descriptors:

Descriptor	Name	Tree numbers
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)

Drugs acting on a complex or family that includes this protein

Curated ChEMBL mechanism-of-action drugs whose target is a protein complex or family of ≤10 members that includes CHRNE — the drug acts on the assembly or class, not necessarily on this subunit alone.

14 drugs via a complex or family:

Drug	Target (ChEMBL)	Members	Max phase
ATRACURIUM BESYLATE	Muscle-type nicotinic acetylcholine receptor	5	4
CISATRACURIUM BESYLATE	Muscle-type nicotinic acetylcholine receptor	5	4
DECAMETHONIUM BROMIDE	Muscle-type nicotinic acetylcholine receptor	5	4
DOXACURIUM CHLORIDE	Muscle-type nicotinic acetylcholine receptor	5	4
GALLAMINE TRIETHIODIDE	Muscle-type nicotinic acetylcholine receptor	5	4
METOCURINE IODIDE	Muscle-type nicotinic acetylcholine receptor	5	4
MIVACURIUM CHLORIDE	Muscle-type nicotinic acetylcholine receptor	5	4
PANCURONIUM BROMIDE	Muscle-type nicotinic acetylcholine receptor	5	4
PIPECURONIUM BROMIDE	Muscle-type nicotinic acetylcholine receptor	5	4
RAPACURONIUM BROMIDE	Muscle-type nicotinic acetylcholine receptor	5	4
ROCURONIUM BROMIDE	Muscle-type nicotinic acetylcholine receptor	5	4
SUCCINYLCHOLINE CHLORIDE	Muscle-type nicotinic acetylcholine receptor	5	4
TUBOCURARINE CHLORIDE	Muscle-type nicotinic acetylcholine receptor	5	4
VECURONIUM BROMIDE	Muscle-type nicotinic acetylcholine receptor	5	4

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 272,631 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

4 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL502	DONEPEZIL	4	43,884
CHEMBL267936	MECAMYLAMINE	4	5,654
CHEMBL3	NICOTINE	4	187,543
CHEMBL95	TACRINE	4	35,550

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

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

Target class: lgic — Nicotinic acetylcholine receptors (nACh)

Binding affinities (BindingDB)

61 measured of 69 human assays (69 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5179810	IC50	2.3 nM
CHEMBL4473371	KI	3.1 nM
CHEMBL4098776	IC50	3.8 nM
CHEMBL4435544	IC50	6 nM
CHEMBL4095046	IC50	9 nM
CHEMBL5204683	IC50	12 nM
CHEMBL3898922	IC50	15 nM
CHEMBL4074583	IC50	23 nM
CHEMBL4071859	IC50	23 nM
CHEMBL4084852	IC50	25 nM
CHEMBL4100355	IC50	27 nM
CHEMBL4471876	IC50	27 nM
CHEMBL4083246	IC50	29 nM
CHEMBL5181578	IC50	32 nM
CHEMBL5176418	IC50	36 nM
CHEMBL5173121	IC50	44 nM
CHEMBL4518438	IC50	47 nM
CHEMBL4228909	IC50	50 nM
CHEMBL4516351	IC50	57 nM
CHEMBL4518992	IC50	58 nM
CHEMBL5207035	IC50	58 nM
CHEMBL4514263	IC50	62 nM
CHEMBL5190924	IC50	71 nM
CHEMBL2376519	IC50	82 nM
CHEMBL5188135	IC50	83 nM
CHEMBL5200573	IC50	87 nM
CHEMBL4447626	IC50	88 nM
CHEMBL5179648	IC50	91 nM
CHEMBL4544630	IC50	97 nM
CHEMBL4097654	IC50	100 nM
CHEMBL4089244	IC50	120 nM
9-amino-5,6,7,8-tetrahydroacridin-4yl)methano	IC50	125 nM
CHEMBL4872191	IC50	131 nM
CHEMBL4075880	IC50	150 nM
CHEMBL4061082	IC50	150 nM
CHEMBL4087500	IC50	170 nM
CHEMBL4102804	IC50	180 nM
CHEMBL4098850	IC50	190 nM
CHEMBL4077222	IC50	350 nM
CHEMBL5196896	IC50	407 nM
CHEMBL4064914	IC50	440 nM
CHEMBL3918431	IC50	480 nM
CHEMBL5206933	IC50	676 nM
CHEMBL4063152	IC50	1700 nM
CHEMBL4456791	IC50	1900 nM
CHEMBL4544034	IC50	2100 nM
CHEMBL4452517	IC50	2720 nM
CHEMBL4458943	IC50	3060 nM
CHEMBL4573754	IC50	6370 nM
CHEMBL4101249	IC50	6700 nM

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	increases expression, affects expression, increases abundance	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	affects cotreatment, increases expression	1
Methotrexate	decreases expression	1
Ozone	affects expression, increases abundance	1
Progesterone	decreases expression	1
Sarin	increases expression	1
Selenium	increases expression	1
Testosterone	increases expression, affects cotreatment	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)

Via MONDO — disease-level, not drug-specific.

60 trials:

NCT	Phase	Status	Title
NCT00793988	Phase 4	COMPLETED	Vibration-Assisted Anaesthesia
NCT01239498	Phase 4	UNKNOWN	Saline Injection - Assisted Anesthesia in Eyelid Surgery
NCT02761083	Phase 4	WITHDRAWN	PMCF-study Using Novosyn® Quick Suture Material in Ophthalmic Surgery
NCT04007276	Phase 4	NOT_YET_RECRUITING	The Effect of Lumify™ on Ocular Redness, Intraocular Pressure, and Eyelid Position in Glaucoma Patients
NCT07390578	Phase 4	NOT_YET_RECRUITING	Upneeq vs. Lumify Ptosis
NCT07746089	Phase 3	NOT_YET_RECRUITING	A Study to Assess Efficacy and Safety of Adimanebart in Adult and Pediatric Participants With DOK7-,MUSK-, AGRN-, or LRP4- Congenital Myasthenic Syndromes (CMS)
NCT02436759	Phase 3	COMPLETED	Study of the Safety and Efficacy of RVL-1201 in the Treatment of Acquired Blepharoptosis
NCT03536949	Phase 3	COMPLETED	Study of Safety of RVL-1201 in Treatment of Blepharoptosis
NCT03565887	Phase 3	COMPLETED	Study of Safety and Efficacy of RVL-1201 in the Treatment of Blepharoptosis
NCT05945615	Phase 3	COMPLETED	Oxymetazoline Drops for Acquired Blepharoptosis From Synkinesis
NCT06683651	Phase 3	RECRUITING	A Study in Chinese Patients With Acquired Blepharoptosis
NCT03266081	Phase 2	WITHDRAWN	Bupivacaine Epiphora Trial
NCT01203592	Phase 1	COMPLETED	Efficacy of Albuterol in the Treatment of Congenital Myasthenic Syndromes
NCT06436742	Phase 1	ACTIVE_NOT_RECRUITING	A Phase 1b Study to Investigate Safety and Tolerability of ARGX-119 in Adult Participants With DOK7-Congenital Myasthenic Syndromes (CMS)
NCT07226726	Phase 1	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	Phase 2/3	RECRUITING	Evaluation of the Efficacy and Safety of THRV-1268 in Participants With Long QT Syndrome Type 2 (LQTS2) and Type 3 (LQTS3)
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	Phase 2/3	TERMINATED	Treatment of Ptosis to Muscular Dystrophy Oculopharyngeal by Myoblast Autologous Graft
NCT05358977	Phase 2/3	UNKNOWN	Fibrin Sealant in Eyelid Surgery
NCT01848041	Phase 1/2	COMPLETED	Safety and Efficacy Study of RVL-1201 in Acquired Blepharoptosis
NCT05715346	Phase 1/2	COMPLETED	LEV102 Topical Gel in Acquired Blepharoptosis
NCT04807855	Early Phase 1	COMPLETED	Custom Print Megnetic Levator Prosthesis Pilot Comparison
NCT06911216	Early Phase 1	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
NCT02501187	Not specified	UNKNOWN	Risk of Dry Eye Post Different Surgeries for Blepharoptosis Repair
NCT02638610	Not specified	UNKNOWN	Assessment of Changes of Periocular Skin Sensation Following Eyelid and Ocular Surface Surgeries
NCT02959697	Not specified	UNKNOWN	Subconjunctival Injection of Local Anesthetic in Anterior Blepharoptosis Repair
NCT02988856	Not specified	COMPLETED	Magnetic Correction of Eye Lid Paralysis
NCT03149367	Not specified	UNKNOWN	Surgical Management of Blepharoptosis
NCT03239418	Not specified	TERMINATED	NMES to Improve Eyelid Functions in Cranial Nerve (CN) III and VII Palsy
NCT03375879	Not specified	UNKNOWN	Bandage Contact Lens in Post Operative Ptosis Patients
NCT03812016	Not specified	RECRUITING	A Feedback-enabled Magnetic Device for Temporary Management of Blepharoptosis
NCT03818204	Not specified	COMPLETED	Clinical Trial to Improve the Magnetic Levator Prosthesis
NCT04214379	Not specified	COMPLETED	Management of Severe Congenital Blepharoptosis
NCT04235803	Not specified	COMPLETED	Telemedicine Follow-up for Routine, Low-Risk Oculoplastic Surgery
NCT04678115	Not specified	COMPLETED	Clinical Trial Comparing Two Non-Surgical Treatments for Severe Blepharoptosis
NCT04714424	Not specified	COMPLETED	Comparing Vision Tests in a Virtual Reality Headset to Existing Analogues
NCT04883853	Not specified	COMPLETED	A Newly Modified Technique for Levator Muscle Tucking in Blepharoptosis Surgery: An Egyptian Tertiary Center Study
NCT05746078	Not specified	RECRUITING	Performance and Safety Assessment of SPRING THREAD® Elastic Tensor Thread in Patients with Mild to Moderate Facial Ptosis.
NCT06047418	Not specified	COMPLETED	Blepharoptosis in Indonesia: A 5-Year Multicenter Study on Characteristics and Surgical Evaluation
NCT06292182	Not specified	UNKNOWN	Red Light Ptosis Proof-of-Concept
NCT07534436	Not specified	RECRUITING	A Prospective Cohort Study on Visual Function and Psychological Conditions Before and After Surgery for Congenital Ptosis
NCT07821450	Not specified	NOT_YET_RECRUITING	Blepharoptosis After Repeated Intravitreal Anti-VEGF Injections: A Prospective Study

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for CHRNE across ~30M SureChEMBL compounds — explore on Sugi Predict.