CHRND

Summary

CHRND (cholinergic receptor nicotinic delta subunit, HGNC:1965) is a protein-coding gene on chromosome 2q37.1, encoding Acetylcholine receptor subunit delta (Q07001). After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.

The acetylcholine receptor of muscle has 5 subunits of 4 different types: 2 alpha and 1 each of beta, gamma and delta subunits. After acetylcholine binding, the receptor undergoes an extensive conformation change that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane. Defects in this gene are a cause of multiple pterygium syndrome lethal type (MUPSL), congenital myasthenic syndrome slow-channel type (SCCMS), and congenital myasthenic syndrome fast-channel type (FCCMS). Several transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 1144 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital myasthenic syndrome 3A (Strong, GenCC) — +4 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 636 total — 20 pathogenic, 20 likely-pathogenic
• Phenotypes (HPO): 87
• Druggable target: yes — 10 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000751

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1965
Approved symbol	CHRND
Name	cholinergic receptor nicotinic delta subunit
Location	2q37.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000135902
Ensembl biotype	protein_coding
OMIM	100720
Entrez	1144

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding, 3 nonsense_mediated_decay

ENST00000258385, ENST00000412233, ENST00000441621, ENST00000446616, ENST00000449596, ENST00000543200, ENST00000955151

RefSeq mRNA: 4 — MANE Select: NM_000751 NM_000751, NM_001256657, NM_001311195, NM_001311196

CCDS: CCDS2494, CCDS58754

Canonical transcript exons

ENST00000258385 — 12 exons

Exon	Start	End
ENSE00001613412	232535130	232536664
ENSE00001767101	232526160	232526267
ENSE00003479678	232528501	232528656
ENSE00003485995	232533931	232534135
ENSE00003490844	232534224	232534342
ENSE00003498530	232531352	232531463
ENSE00003510274	232526529	232526674
ENSE00003555045	232527401	232527445
ENSE00003577889	232529939	232530139
ENSE00003652311	232531542	232531656
ENSE00003670174	232528262	232528371
ENSE00003688442	232528862	232528971

Expression profiles

Bgee: expression breadth broad, 86 present calls, max score 92.57.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3471 / max 82.6729, expressed in 60 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
25990	0.1374	33
25988	0.1318	41
25989	0.0779	28

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	92.57	gold quality
muscle of leg	UBERON:0001383	89.74	gold quality
hindlimb stylopod muscle	UBERON:0004252	88.96	gold quality
muscle organ	UBERON:0001630	80.86	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.23	silver quality
gluteal muscle	UBERON:0002000	68.18	gold quality
endometrium epithelium	UBERON:0004811	62.97	gold quality
skeletal muscle tissue	UBERON:0001134	62.38	gold quality
parotid gland	UBERON:0001831	60.48	gold quality
triceps brachii	UBERON:0001509	60.25	gold quality
tibialis anterior	UBERON:0001385	59.98	silver quality
Brodmann (1909) area 10	UBERON:0013541	59.53	gold quality
muscle tissue	UBERON:0002385	59.29	gold quality
buccal mucosa cell	CL:0002336	57.82	gold quality
tendon of biceps brachii	UBERON:0008188	57.42	gold quality
nasal cavity epithelium	UBERON:0005384	57.05	gold quality
bone marrow cell	CL:0002092	55.49	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	54.62	gold quality
endothelial cell	CL:0000115	54.52	silver quality
pancreatic ductal cell	CL:0002079	54.35	silver quality
inferior olivary complex	UBERON:0002127	54.21	gold quality
cranial nerve II	UBERON:0000941	54.18	silver quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	53.93	gold quality
cerebellar vermis	UBERON:0004720	53.52	gold quality
paraflocculus	UBERON:0005351	53.13	gold quality
heart right ventricle	UBERON:0002080	51.77	gold quality
stromal cell of endometrium	CL:0002255	50.45	silver quality
frontal pole	UBERON:0002795	50.41	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
thymus	UBERON:0002370	50.23	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.46

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GABPA

miRNA regulators (miRDB)

48 targeting CHRND, 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-4455	100.00	65.48	1587
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-377-5P	99.70	65.28	712
HSA-MIR-6086	99.70	65.38	699
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-12131	99.48	68.72	1673
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-6513-5P	99.43	67.81	1071
HSA-MIR-4721	99.26	66.05	818
HSA-MIR-296-3P	99.21	66.56	474
HSA-MIR-6829-5P	98.86	65.12	1480
HSA-MIR-502-5P	98.77	66.51	906
HSA-MIR-876-3P	98.76	68.23	945
HSA-MIR-423-5P	98.69	67.48	1522
HSA-MIR-7155-5P	98.65	66.14	1290
HSA-MIR-3184-5P	98.56	67.13	1491

Literature-anchored findings (GeneRIF, showing 9)

• No CHRNA1, CHRNB1, or CHRND mutations were detected, but a homozygous RAPSN frameshift mutation, c.1177-1178delAA, was identified in a family with three children affected with lethal fetal akinesia sequence. (PMID:18179903)
• study reports homozygous nonsense mutations in CHRNA1 and CHRND and shows that they were lethal (PMID:18252226)
• Results describe the effects of a point mutation in the AChR delta subunit from a congenital myasthenia patient. (PMID:18398509)
• No mutations were found in CHRNG, CHRND and CHRNA1 genes of Indian families with Escobar syndrome. (PMID:23448903)
• These findings identify novel Golgi retention signals in the beta and delta subunit loops that regulate surface trafficking of assembled AChR and may help prevent surface expression of unassembled subunits. (PMID:24240098)
• This study showed that a single mutation of the delta subunit, L332P, allows the synapse in slow muscles to function but renders those in fast muscles almost nonfunctional. (PMID:25080583)
• Data suggest mutation in invariant Cys-loop of CHRND (D140N) observed in muscle of one patient (11 y/o girl) with congenital myasthenia (w/ severe muscle weakness) alters conformation of ligand/acetylcholine binding site and receptor functionality. (PMID:26698174)
• child was diagnosed with slow-channel congenital myasthenic syndrome (SCCMS) type 3A caused by heterozygous variant of the CHRND gene (PMID:32335884)
• CHRND variant in a paternally inherited esophageal atresia and tracheoesophgageal fistula: Report of a case. (PMID:38087897)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	chrnd	ENSDARG00000019342
mus_musculus	Chrnd	ENSMUSG00000026251
rattus_norvegicus	Chrnd	ENSRNOG00000019527

Paralogs (45): GABRA3 (ENSG00000011677), GABRA1 (ENSG00000022355), CHRNA3 (ENSG00000080644), GABRP (ENSG00000094755), CHRNA4 (ENSG00000101204), GLRA2 (ENSG00000101958), GABRE (ENSG00000102287), CHRNE (ENSG00000108556), GABRA4 (ENSG00000109158), GLRB (ENSG00000109738), GABRR2 (ENSG00000111886), GABRG2 (ENSG00000113327), CHRNB4 (ENSG00000117971), CHRNA2 (ENSG00000120903), CHRNA10 (ENSG00000129749), 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 delta — Q07001 (reviewed: Q07001)

All UniProt accessions (5): B4DKT6, C9JJV8, Q07001, F8WB46, F8WBS0

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. Multiple pterygium syndrome, lethal type (LMPS) [MIM:253290] Multiple pterygia are found infrequently in children with arthrogryposis and in fetuses with fetal akinesia syndrome. In lethal multiple pterygium syndrome there is intrauterine growth retardation, multiple pterygia, and flexion contractures causing severe arthrogryposis and fetal akinesia. Subcutaneous edema can be severe, causing fetal hydrops with cystic hygroma and lung hypoplasia. Oligohydramnios and facial anomalies are frequent. The disease is caused by variants affecting the gene represented in this entry. Myasthenic syndrome, congenital, 3A, slow-channel (CMS3A) [MIM:616321] 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. CMS3A 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, 3B, fast-channel (CMS3B) [MIM:616322] 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. CMS3B 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, 3C, associated with acetylcholine receptor deficiency (CMS3C) [MIM:616323] 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. CMS3C 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. Delta/CHRND sub-subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q07001-1	1	yes
Q07001-2	2

RefSeq proteins (4): NP_000742, NP_001243586, NP_001298124, NP_001298125 (=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 (24 total): sequence variant 10, transmembrane region 4, glycosylation site 2, topological domain 2, signal peptide 1, chain 1, disulfide bond 1, splice variant 1, mutagenesis site 1, modified residue 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-Q07001-F1	84.21	0.51

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

Functional residue map

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

Post-translational modifications (1): 390

Disulfide bonds (1): 151–165

Glycosylation sites (2): 164, 97

Mutagenesis-validated functional residues (1):

Position	Phenotype
290	increased length of channel opening.

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: 303 (showing top): GOBP_MEMBRANE_DEPOLARIZATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, YAATNRNNNYNATT_UNKNOWN, GOBP_MUSCLE_TISSUE_DEVELOPMENT, MODULE_274, MODULE_64, GOBP_GROWTH, GOBP_SYNAPTIC_TRANSMISSION_CHOLINERGIC, GOBP_MULTICELLULAR_ORGANISMAL_MOVEMENT, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_SKELETAL_MUSCLE_CONTRACTION, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_CELL_CELL_SIGNALING, MARTINEZ_RB1_TARGETS_UP, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT

GO Biological Process (16): skeletal muscle contraction (GO:0003009), muscle contraction (GO:0006936), signal transduction (GO:0007165), chemical synaptic transmission (GO:0007268), monoatomic ion transmembrane transport (GO:0034220), skeletal muscle tissue growth (GO:0048630), musculoskeletal movement (GO:0050881), neuromuscular process (GO:0050905), membrane depolarization (GO:0051899), acetylcholine receptor signaling pathway (GO:0095500), monoatomic ion transport (GO:0006811), monoatomic cation transport (GO:0006812), synaptic transmission, cholinergic (GO:0007271), regulation of membrane potential (GO:0042391), regulation of postsynaptic membrane potential (GO:0060078), excitatory postsynaptic potential (GO:0060079)

GO Molecular Function (8): acetylcholine receptor activity (GO:0015464), acetylcholine-gated monoatomic cation-selective channel activity (GO:0022848), acetylcholine binding (GO:0042166), transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential (GO:1904315), transmembrane signaling receptor activity (GO:0004888), monoatomic ion channel activity (GO:0005216), extracellular ligand-gated monoatomic ion channel activity (GO:0005230), ligand-gated monoatomic ion channel activity (GO:0015276)

GO Cellular Component (8): plasma membrane (GO:0005886), acetylcholine-gated channel complex (GO:0005892), neuromuscular junction (GO:0031594), neuron projection (GO:0043005), synapse (GO:0045202), postsynaptic membrane (GO:0045211), postsynaptic specialization membrane (GO:0099634), 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
monoatomic ion transport	2
regulation of membrane potential	2
regulation of postsynaptic membrane potential	2
postsynaptic neurotransmitter receptor activity	2
synaptic membrane	2
striated muscle contraction	1
musculoskeletal movement	1
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
transmembrane transport	1
skeletal muscle tissue development	1
developmental growth	1
multicellular organismal movement	1
neuromuscular process	1
nervous system process	1
acetylcholine receptor activity	1
postsynaptic signal transduction	1
cellular response to acetylcholine	1
transport	1
chemical synaptic transmission	1
monoatomic ion transmembrane transport	1
regulation of biological quality	1
chemical synaptic transmission, postsynaptic	1
transmembrane signaling receptor activity	1
synaptic transmission, cholinergic	1
acetylcholine binding	1
excitatory extracellular ligand-gated monoatomic ion channel activity	1
ligand-gated monoatomic cation channel activity	1
transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential	1
cation binding	1
transmitter-gated monoatomic ion channel activity	1
signaling receptor activity	1
monoatomic ion transmembrane transporter activity	1
channel activity	1
ligand-gated monoatomic ion channel activity	1

Protein interactions and networks

STRING

924 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHRND	RAPSN	Q13702	915
CHRND	ALPI	P09923	780
CHRND	DOK7	Q18PE1	763
CHRND	MUSK	O15146	759
CHRND	COL4A3	Q01955	719
CHRND	COLQ	Q9Y215	701
CHRND	ALPP	P05187	692
CHRND	CHRNA1	P02708	682
CHRND	CHRNB1	P11230	654
CHRND	AGRN	O00468	647
CHRND	PAX3	P23760	617
CHRND	ECEL1	O95672	616
CHRND	ALG14	Q96F25	586
CHRND	GFPT1	Q06210	572
CHRND	VIL1	P09327	551

IntAct

6 interactions, top by confidence:

A	B	Type	Score
CHRND	TPST2	psi-mi:“MI:0914”(association)	0.530
CHRND	EXTL3	psi-mi:“MI:0914”(association)	0.350
CHRND	EPHX1	psi-mi:“MI:0914”(association)	0.350
CHRND	CHRNB1	psi-mi:“MI:0914”(association)	0.350
LPCAT4	PDE2A	psi-mi:“MI:0914”(association)	0.350

BioGRID (111): LPPR3 (Affinity Capture-MS), DNAJC18 (Affinity Capture-MS), SEC11C (Affinity Capture-MS), SIDT2 (Affinity Capture-MS), PKD2 (Affinity Capture-MS), OCA2 (Affinity Capture-MS), ST7L (Affinity Capture-MS), EIF2AK3 (Affinity Capture-MS), CNNM1 (Affinity Capture-MS), DPY19L4 (Affinity Capture-MS), SPPL2B (Affinity Capture-MS), SPPL3 (Affinity Capture-MS), TPST2 (Affinity Capture-MS), SLC12A4 (Affinity Capture-MS), BTN2A2 (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, O16926, O70174, P02708, P02709, P02710, P02711, P02712, P02713, P02716, P02717, P04755, P04756, P04757, P04758, P04759, P05377, P09478, P09479, P09480, P09481, P09482, P09483, P09484, P09628, P09690, P11230, P12389, P12390, P12391, P12392, P13908, P17644, P17787, P18257, P18845, P19370, P20420, P22456, P22770

SIGNOR signaling

2 interactions.

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

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	20
Likely pathogenic	20
Uncertain significance	326
Likely benign	177
Benign	25

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1075530	NM_000751.3(CHRND):c.88del (p.Arg30fs)	Pathogenic
1492568	NM_000751.3(CHRND):c.2T>C (p.Met1Thr)	Pathogenic
18366	NM_000751.3(CHRND):c.238G>A (p.Glu80Lys)	Pathogenic
18367	NM_000751.3(CHRND):c.820_820+1del	Pathogenic
18368	NM_000751.3(CHRND):c.234G>A (p.Trp78Ter)	Pathogenic
18369	NM_000751.3(CHRND):c.283T>C (p.Phe95Leu)	Pathogenic
18371	NM_000751.3(CHRND):c.188T>C (p.Leu63Pro)	Pathogenic
189818	NM_000751.3(CHRND):c.901_1048-282del	Pathogenic
1923533	NM_000751.3(CHRND):c.249del (p.Gly82_Trp83insTer)	Pathogenic
2014916	NM_000751.3(CHRND):c.677_766delinsGGGT (p.Ala226fs)	Pathogenic
2097009	NM_000751.3(CHRND):c.316dup (p.Asp106fs)	Pathogenic
2144350	NM_000751.3(CHRND):c.628G>T (p.Glu210Ter)	Pathogenic
2169508	NM_000751.3(CHRND):c.59G>A (p.Trp20Ter)	Pathogenic
2191909	NM_000751.3(CHRND):c.211del (p.Glu71fs)	Pathogenic
2423390	NC_000002.11:g.(?233390926)(233400022_?)del	Pathogenic
2843903	NM_000751.3(CHRND):c.36del (p.Ala13fs)	Pathogenic
3650417	NM_000751.3(CHRND):c.247_251dup (p.Asp85fs)	Pathogenic
3725432	NM_000751.3(CHRND):c.95del (p.Leu32fs)	Pathogenic
4713749	NM_000751.3(CHRND):c.600_603del (p.Asp201fs)	Pathogenic
657502	NM_000751.3(CHRND):c.521_524dup (p.Ala176fs)	Pathogenic
1324076	NM_000751.3(CHRND):c.269G>A (p.Trp90Ter)	Likely pathogenic
1477166	NM_000751.3(CHRND):c.1252+1G>A	Likely pathogenic
1506763	NM_000751.3(CHRND):c.243+1G>A	Likely pathogenic
1512971	NC_000002.11:g.(?233396141)(233398358_?)del	Likely pathogenic
1687227	NM_000751.3(CHRND):c.52+1G>A	Likely pathogenic
18363	NM_000751.3(CHRND):c.866C>T (p.Ser289Phe)	Likely pathogenic
18364	NM_000751.3(CHRND):c.812C>A (p.Pro271Gln)	Likely pathogenic
1956161	NM_000751.3(CHRND):c.932+2T>A	Likely pathogenic
2127503	NM_000751.3(CHRND):c.423G>C (p.Trp141Cys)	Likely pathogenic
3653271	NM_000751.3(CHRND):c.510-1G>T	Likely pathogenic

SpliceAI

1726 predictions. Top by Δscore:

Variant	Effect	Δscore
2:232526625:A:T	donor_gain	1.0000
2:232526671:CCTGG:C	donor_loss	1.0000
2:232526673:TGGTG:T	donor_loss	1.0000
2:232526674:GGTGA:G	donor_loss	1.0000
2:232526675:G:GA	donor_loss	1.0000
2:232526675:G:GG	donor_gain	1.0000
2:232526676:T:A	donor_loss	1.0000
2:232528499:A:AG	acceptor_gain	1.0000
2:232528500:G:GT	acceptor_gain	1.0000
2:232528500:GC:G	acceptor_gain	1.0000
2:232528500:GCA:G	acceptor_gain	1.0000
2:232528500:GCAAT:G	acceptor_gain	1.0000
2:232528858:CCA:C	acceptor_loss	1.0000
2:232528860:A:AG	acceptor_gain	1.0000
2:232528861:G:GA	acceptor_gain	1.0000
2:232528861:GTT:G	acceptor_gain	1.0000
2:232530136:GACA:G	donor_gain	1.0000
2:232530140:G:GG	donor_gain	1.0000
2:232531460:GCAA:G	donor_gain	1.0000
2:232531464:G:GG	donor_gain	1.0000
2:232531652:AGAAG:A	donor_gain	1.0000
2:232531653:GAAG:G	donor_gain	1.0000
2:232531653:GAAGG:G	donor_gain	1.0000
2:232531655:AG:A	donor_gain	1.0000
2:232531655:AGGTG:A	donor_loss	1.0000
2:232531656:GG:G	donor_gain	1.0000
2:232531657:G:GA	donor_loss	1.0000
2:232531657:G:GG	donor_gain	1.0000
2:232531658:T:A	donor_loss	1.0000
2:232534095:G:GG	donor_gain	1.0000

AlphaMissense

3387 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:232528343:T:A	W109R	0.999
2:232528343:T:C	W109R	0.999
2:232528642:C:G	C165W	0.999
2:232529950:T:A	W211R	0.999
2:232529950:T:C	W211R	0.999
2:232529952:G:C	W211C	0.999
2:232529952:G:T	W211C	0.999
2:232530049:C:A	R244S	0.999
2:232528265:T:A	W83R	0.998
2:232528265:T:C	W83R	0.998
2:232528267:G:C	W83C	0.998
2:232528267:G:T	W83C	0.998
2:232528345:G:C	W109C	0.998
2:232528345:G:T	W109C	0.998
2:232528598:T:C	C151R	0.998
2:232528599:G:A	C151Y	0.998
2:232528600:C:G	C151W	0.998
2:232528640:T:C	C165R	0.998
2:232528641:G:A	C165Y	0.998
2:232527420:T:C	L73P	0.997
2:232528286:T:A	W90R	0.997
2:232528286:T:C	W90R	0.997
2:232528288:G:C	W90C	0.997
2:232528288:G:T	W90C	0.997
2:232528619:T:C	F158L	0.997
2:232528620:T:G	F158C	0.997
2:232528621:C:A	F158L	0.997
2:232528621:C:G	F158L	0.997
2:232528623:C:A	P159H	0.997
2:232528640:T:A	C165S	0.997

dbSNP variants (sampled 300 via entrez): RS1000343674 (2:232533201 A>C), RS1000384330 (2:232524283 T>G), RS1000543140 (2:232526928 C>A), RS1000680070 (2:232532052 G>A), RS1000857869 (2:232529256 C>G), RS1000879519 (2:232531753 A>G), RS1000973038 (2:232535082 T>C), RS1001165106 (2:232526628 G>A), RS1001667340 (2:232528167 C>A,G), RS1002052746 (2:232527172 G>A), RS1002190775 (2:232530114 C>A,T), RS1002204599 (2:232524363 G>A), RS1002229081 (2:232532382 C>T), RS1002574618 (2:232531243 A>C,G), RS1002677016 (2:232526979 C>T)

Disease associations

OMIM: gene MIM:100720 | disease phenotypes: MIM:253290, MIM:616321, MIM:601462, MIM:616322, MIM:616323, MIM:617468, MIM:208150, MIM:160150

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital myasthenic syndrome 3A	Strong	Autosomal dominant
congenital myasthenic syndrome 3B	Strong	Autosomal recessive
congenital myasthenic syndrome 3C	Strong	Autosomal recessive
lethal multiple pterygium syndrome	Strong	Autosomal recessive
postsynaptic congenital myasthenic syndrome	Supportive	Autosomal recessive

Mondo (10): lethal multiple pterygium syndrome (MONDO:0009668), congenital myasthenic syndrome 3A (MONDO:0014583), congenital myasthenic syndrome (MONDO:0018940), congenital myasthenic syndrome 3B (MONDO:0014584), congenital myasthenic syndrome 3C (MONDO:0014585), ptosis (MONDO:0000728), arthrogryposis multiplex congenita (MONDO:0015168), fetal akinesia deformation sequence 1 (MONDO:0100101), centronuclear myopathy (MONDO:0018947), postsynaptic congenital myasthenic syndrome (MONDO:0020344)

Orphanet (5): Lethal multiple pterygium syndrome (Orphanet:33108), Congenital myasthenic syndrome (Orphanet:590), Arthrogryposis multiplex congenita (Orphanet:1037), Fetal akinesia deformation sequence (Orphanet:994), Centronuclear myopathy (Orphanet:595)

HPO phenotypes

87 total (30 of 87 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000175	Cleft palate
HP:0000218	High palate
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000347	Micrognathia
HP:0000369	Low-set ears
HP:0000457	Depressed nasal ridge
HP:0000467	Neck muscle weakness
HP:0000476	Cystic hygroma
HP:0000496	Abnormality of eye movement
HP:0000508	Ptosis
HP:0000597	Ophthalmoparesis
HP:0000602	Ophthalmoplegia
HP:0000651	Diplopia
HP:0000883	Thin ribs
HP:0000961	Cyanosis
HP:0000969	Edema
HP:0001040	Multiple pterygia
HP:0001252	Hypotonia
HP:0001270	Motor delay
HP:0001315	Reduced tendon reflexes
HP:0001319	Neonatal hypotonia
HP:0001324	Muscle weakness
HP:0001371	Flexion contracture
HP:0001373	Joint dislocation
HP:0001446	Abnormality of the musculature of the upper limbs
HP:0001511	Intrauterine growth retardation
HP:0001558	Decreased fetal movement

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST000265_4	Brain lesion load	4.000000e-06
GCST010002_411	Refractive error	1.000000e-123

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D001763	Blepharoptosis	C11.338.204
D020294	Myasthenic Syndromes, Congenital	C10.668.758.800; C16.320.590

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (5): CHEMBL1907588 (PROTEIN COMPLEX), CHEMBL2362997 (PROTEIN COMPLEX GROUP), CHEMBL3011 (SINGLE PROTEIN), CHEMBL4106145 (PROTEIN COMPLEX), CHEMBL4524133 (PROTEIN COMPLEX GROUP)

Molecules with ChEMBL bioactivity

10 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 256,857 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1076903	VARENICLINE	4	5,807
CHEMBL3	NICOTINE	4	184,969
CHEMBL56564	TROPISETRON	4	19,312
CHEMBL894	BUPROPION	4	36,982
CHEMBL267936	MECAMYLAMINE	4	5,623
CHEMBL2103881	DEXMECAMYLAMINE	3	18
CHEMBL497939	CYTISINICLINE	3	2,766
CHEMBL1172928	RADAFAXINE	2	1,079
CHEMBL134713	GTS-21	2	269
CHEMBL504652	TC-2216	1	32

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: lgic — Nicotinic acetylcholine receptors (nACh)

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
PhTX-11	Antagonist	6.34	pIC50

Binding affinities (BindingDB)

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

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

ChEMBL bioactivities

92 potent at pChembl≥5 of 146 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.28	EC50	0.053	nM	EPIBATIDINE
8.82	IC50	1.5	nM	CHEMBL566050
8.70	IC50	2	nM	CHEMBL569465
8.57	IC50	2.7	nM	CHEMBL566208
8.41	IC50	3.9	nM	CHEMBL566886
8.24	IC50	5.7	nM	CHEMBL565844
8.24	IC50	5.8	nM	CHEMBL592854
8.19	IC50	6.5	nM	CHEMBL599846
8.12	IC50	7.6	nM	CHEMBL566001
8.04	IC50	9.2	nM	CHEMBL589250
8.01	IC50	9.8	nM	CHEMBL568140
8.00	IC50	10	nM	CHEMBL565396
7.96	EC50	11	nM	CYTISINICLINE
7.96	IC50	11	nM	CHEMBL566832
7.92	IC50	12	nM	CHEMBL566207
7.92	IC50	12	nM	CHEMBL565845
7.85	IC50	14	nM	CHEMBL566000
7.80	IC50	16	nM	CHEMBL603620
7.80	IC50	16	nM	CHEMBL578612
7.80	IC50	16	nM	CHEMBL567481
7.77	IC50	17	nM	CHEMBL578611
7.72	IC50	19	nM	CHEMBL596775
7.72	IC50	19	nM	CHEMBL599230
7.62	IC50	24	nM	CHEMBL578610
7.58	IC50	26	nM	CHEMBL605501
7.55	EC50	28	nM	CHEMBL64496
7.55	IC50	28	nM	CHEMBL566420
7.51	EC50	31	nM	CHEMBL305106
7.50	IC50	32	nM	CHEMBL576063
7.43	EC50	37	nM	CHEMBL181840
7.39	IC50	41	nM	CHEMBL598026
7.35	EC50	45	nM	CHEMBL62858
7.28	IC50	53	nM	CHEMBL589494
7.16	IC50	69	nM	CHEMBL565386
7.06	IC50	87	nM	CHEMBL580143
6.88	IC50	131	nM	CHEMBL4872191
6.60	Ki	250	nM	CYTISINICLINE
6.52	IC50	300	nM	2(R)-MECAMYLAMINE
6.50	Ki	314	nM	CHEMBL59986
6.34	IC50	460	nM	CHEMBL16044
6.28	Ki	520	nM	CHEMBL196626
6.28	Ki	530	nM	CHEMBL1209305
6.24	Ki	580	nM	CHEMBL2057714
6.24	IC50	580	nM	CHEMBL16044
6.22	IC50	600	nM	DEXMECAMYLAMINE
6.19	Ki	650	nM	CHEMBL194204
6.10	IC50	790	nM	CHEMBL15998
6.03	IC50	930	nM	CHEMBL15998
5.99	Ki	1020	nM	CHEMBL1209070
5.83	Ki	1480	nM	NICOTINE

PubChem BioAssay actives

92 with measured affinity, of 552 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-(6-chloro-3-pyridinyl)-7-azabicyclo[2.2.1]heptane	246397: Change in membrane potential in TE-671 cells expressing acetylcholine neuromuscular receptors	ec50	0.0001	uM
2-(tert-butylamino)-1-(3,4-dichlorophenyl)pentan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0015	uM
2-(tert-butylamino)-1-(3-chlorophenyl)pentan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0020	uM
2-(tert-butylamino)-1-(3,4-dichlorophenyl)butan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0027	uM
2-(tert-butylamino)-1-(3-chlorophenyl)butan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0039	uM
2-(tert-butylamino)-1-(3-chloro-4-methylphenyl)propan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0057	uM
2-(cyclopentylamino)-1-(3-methylphenyl)propan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0058	uM
1-(3-bromophenyl)-2-(cyclopentylamino)propan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0065	uM
1-(4-bromophenyl)-2-(tert-butylamino)propan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0076	uM
Bupropion	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0079	uM
2-(cyclopentylamino)-1-(3-methoxyphenyl)propan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0092	uM
2-(tert-butylamino)-1-(3,4-dichlorophenyl)propan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0098	uM
1-(3-bromophenyl)-2-(tert-butylamino)propan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0100	uM
cytisinicline	246397: Change in membrane potential in TE-671 cells expressing acetylcholine neuromuscular receptors	ec50	0.0110	uM
2-(tert-butylamino)-1-(3-methylphenyl)propan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0110	uM
1-(4-bromo-3-methylphenyl)-2-(tert-butylamino)propan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0120	uM
2-(tert-butylamino)-1-(4-methylphenyl)propan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0120	uM
2-(tert-butylamino)-1-(4-chlorophenyl)propan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0140	uM
2-[tert-butyl(methyl)amino]-1-(3-chlorophenyl)propan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0160	uM
3-(tert-butylamino)-1-(3-chlorophenyl)-2-methylpropan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0160	uM
2-(tert-butylamino)-1-(3-methoxyphenyl)propan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0160	uM
2-(tert-butylamino)-1-(3,5-dichlorophenyl)propan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0170	uM
2-(cyclopentylamino)-1-(3-nitrophenyl)propan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0190	uM
1-(3-bromophenyl)-2-piperidin-1-ylpropan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0190	uM
2-(tert-butylamino)-1-(3,4-difluorophenyl)propan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0240	uM
2-(cyclopentylamino)-1-(3-fluorophenyl)propan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0260	uM
1-(3-chlorophenyl)-2-piperidin-1-ylpropan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0280	uM
5-chloro-7,11-diazatricyclo[7.3.1.02,7]trideca-2,4-dien-6-one	246397: Change in membrane potential in TE-671 cells expressing acetylcholine neuromuscular receptors	ec50	0.0280	uM
5-bromo-7,11-diazatricyclo[7.3.1.02,7]trideca-2,4-dien-6-one	246397: Change in membrane potential in TE-671 cells expressing acetylcholine neuromuscular receptors	ec50	0.0310	uM
2-(tert-butylamino)-1-(3-fluorophenyl)propan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0320	uM
11,11-dimethyl-7-aza-11-azoniatricyclo[7.3.1.02,7]trideca-2,4-dien-6-one iodide	246397: Change in membrane potential in TE-671 cells expressing acetylcholine neuromuscular receptors	ec50	0.0370	uM
2-(tert-butylamino)-1-(3-nitrophenyl)propan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0410	uM
5-iodo-7,11-diazatricyclo[7.3.1.02,7]trideca-2,4-dien-6-one	246397: Change in membrane potential in TE-671 cells expressing acetylcholine neuromuscular receptors	ec50	0.0450	uM
1-(3-methylphenyl)-2-piperidin-1-ylpropan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0530	uM
2-(tert-butylamino)-1-thiophen-2-ylpropan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0690	uM
1-(3-methoxyphenyl)-2-piperidin-1-ylpropan-1-one	459717: Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0870	uM
(1R,6R,9S,12S,15S,18S,21S,24S,27S,30R,33S,36S,42S,45S,50R)-50-[(2-aminoacetyl)amino]-15,21,27-tris(3-carbamimidamidopropyl)-45-(hydroxymethyl)-18,42-bis(1H-imidazol-5-ylmethyl)-12,24-dimethyl-9-(2-methylpropyl)-8,11,14,17,20,23,26,29,32,35,41,44,47,49-tetradecaoxo-33-propan-2-yl-3,4,52,53-tetrathia-7,10,13,16,19,22,25,28,31,34,40,43,46,48-tetradecazatricyclo[28.17.7.036,40]tetrapentacontane-6-carboxamide	1753063: Inhibition of human alpha1beta1deltaepsilon nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced current response by two-electrode voltage-clamp method	ic50	0.1310	uM
(1R,2R,4S)-N,2,3,3-tetramethylbicyclo[2.2.1]heptan-2-amine	1179333: Antagonist activity at human alpha1beta1gammadelta nAChR	ic50	0.3000	uM
3-[[(2S)-azetidin-2-yl]methoxy]pyridine	1179333: Antagonist activity at human alpha1beta1gammadelta nAChR	ki	0.3140	uM
N-[(2S)-1-(11-aminoundecylamino)-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]butanamide	145352: Compound was evaluated for inhibitory activity against human embryonic muscle type Nicotinic acetylcholine receptor specifically delta-subunit expressed in TE-671 cell (at holding potential -100 mV)	ic50	0.4600	uM
10-azatricyclo[6.3.1.02,7]dodeca-2(7),3,5-triene-4-carbonitrile	254522: Binding affinity to human Nicotinic acetylcholine receptor alpha-1-beta-gamma-delta expressed in HEK 293 cells using [3H]alpha-bungarotoxin	ki	0.5200	uM
N-[5-[2-[[(1R,5R,6S)-3-azabicyclo[3.2.1]octan-6-yl]oxy]phenyl]-3-pyridinyl]acetamide;hydrochloride	495032: Binding affinity to alpha-1-beta-gamma-delta nicotinic receptor	ki	0.5300	uM
1’-pyridin-3-ylspiro[1-azabicyclo[2.2.1]heptane-7,3’-pyrrolidine]	673332: Binding affinity to human muscle nAChR alpha1beta1gammadelta expressed in human TE-671 cells	ki	0.5800	uM
(1R,2S,4S)-N,2,3,3-tetramethylbicyclo[2.2.1]heptan-2-amine	1179333: Antagonist activity at human alpha1beta1gammadelta nAChR	ic50	0.6000	uM
1-(10-azatricyclo[6.3.1.02,7]dodeca-2(7),3,5-trien-4-yl)ethanone	254522: Binding affinity to human Nicotinic acetylcholine receptor alpha-1-beta-gamma-delta expressed in HEK 293 cells using [3H]alpha-bungarotoxin	ki	0.6500	uM
N-[(2S)-1-(12-aminododecylamino)-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]butanamide	225872: Antagonist activity at human muscle-type nAChR (embryonic muscle) expressed in TE671 cells; (end value).	ic50	0.7900	uM
(1R,5R,6S)-6-(2-pyridin-3-ylphenoxy)-3-azabicyclo[3.2.1]octane;hydrochloride	495032: Binding affinity to alpha-1-beta-gamma-delta nicotinic receptor	ki	1.0200	uM
Nicotine	495032: Binding affinity to alpha-1-beta-gamma-delta nicotinic receptor	ki	1.4800	uM
5-[2-[[(1R,5R,6S)-3-azabicyclo[3.2.1]octan-6-yl]oxy]phenyl]pyridin-3-ol;hydrochloride	495032: Binding affinity to alpha-1-beta-gamma-delta nicotinic receptor	ki	1.6800	uM
N-[(2S)-1-(12-aminododecylamino)-3-(3-hydroxyphenyl)-1-oxopropan-2-yl]butanamide	225872: Antagonist activity at human muscle-type nAChR (embryonic muscle) expressed in TE671 cells; (end value).	ic50	2.4300	uM

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	increases expression, decreases expression	2
Acetylcholine	affects binding, increases activity	2
bisphenol F	decreases expression	1
aminomethylphosphonic acid (AMPA)	decreases expression	1
bisphenol A	decreases methylation	1
tris(2-butoxyethyl) phosphate	affects expression	1
beta-lapachone	decreases expression	1
licochalcone B	decreases expression	1
bisphenol S	decreases expression	1
incobotulinumtoxinA	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	affects methylation	1
Diazinon	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression, increases expression	1
Valproic Acid	increases methylation	1
2,4-Dichlorophenoxyacetic Acid	decreases expression	1
1-Methyl-4-phenylpyridinium	increases expression	1
Cyclosporine	decreases methylation	1
Particulate Matter	affects expression	1

ChEMBL screening assays

75 unique, capped per target: 44 binding, 31 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1039312	Binding	Activity at alpha-1-beta-1-gamma-delta nAChR in human TE671 cells assessed as effect on membrane potential by FLIPR assay	SAR and biological evaluation of SEN12333/WAY-317538: Novel alpha 7 nicotinic acetylcholine receptor agonist. — Bioorg Med Chem
CHEMBL1068092	Functional	Antagonist activity at alpha-1-beta-1-gamma-delta nAChR receptor expressed in human TE671/RD cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	Synthesis and biological evaluation of bupropion analogues as potential pharmacotherapies for smoking cessation. — J Med Chem

Cellosaurus cell lines

2 cell lines: 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1KE	PrecisION hnAChR alpha1/beta1/delta/epsilon-HEK	Transformed cell line	Female
CVCL_YA37	IDG-HEK293T-CHRND-V5-OE	Transformed cell line	Female

Clinical trials (associated diseases)

72 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
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
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