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) — +3 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 643 total — 20 pathogenic, 21 likely-pathogenic (top 5% of genes corpus-wide)
• GTEx eGene: eQTL in 6 tissues, sQTL in 1 (q < 0.05)
• Phenotypes (HPO): 57
• Drug target: yes — 14 via a complex or family; 10 molecules with ChEMBL bioactivity (top 3% of genes corpus-wide)
• 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 0.85 (unconstrained)
• 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: 8 — 5 protein_coding, 3 nonsense_mediated_decay

MANE Select: ENST00000258385

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 1, TSL 3: 1, TSL 4: 2, TSL 5: 1

ENST00000258385, ENST00000412233, ENST00000441621, ENST00000446616, ENST00000449596, ENST00000543200, ENST00000955151, ENST00001142977

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.

Highest expression (Bgee): gastrocnemius, muscle of leg, hindlimb stylopod muscle, muscle organ, male germ line stem cell (sensu Vertebrata) in testis.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CHRND is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 6 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

7 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Muscle Skeletal	eqtl	8.7e-24	+0.29	2:232526227:A:G
Muscle Skeletal	sqtl	2.3e-07	+0.27	2:232546212:A:G
Brain Nucleus accumbens basal ganglia	eqtl	1.5e-04	-0.42	2:232536197:T:C
Pituitary	eqtl	9.6e-04	-0.43	2:231851527:C:G
Testis	eqtl	1.1e-03	-0.24	2:232524616:C:T
Spleen	eqtl	1.3e-02	+0.48	2:232456931:C:T
Brain Cortex	eqtl	4.2e-02	-0.37	2:232510758:G:A

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

showing 100 of 256 tissues 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
epithelial cell of pancreas	CL:0000083	50.22	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.89	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
hair follicle	UBERON:0002073	49.18	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
choroid plexus epithelium	UBERON:0003911	48.89	gold quality
myocardium	UBERON:0002349	48.87	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
oviduct epithelium	UBERON:0004804	48.62	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
metanephric glomerulus	UBERON:0004736	48.44	gold quality
left ventricle myocardium	UBERON:0006566	48.24	gold quality
orbitofrontal cortex	UBERON:0004167	48.20	gold quality
renal glomerulus	UBERON:0000074	48.16	gold quality
nasal cavity mucosa	UBERON:0001826	48.11	silver quality
upper arm skin	UBERON:0004263	48.06	gold quality
cervix epithelium	UBERON:0004801	48.04	gold quality
tongue squamous epithelium	UBERON:0006919	47.92	gold quality
lower lobe of lung	UBERON:0008949	47.89	silver quality
mucosa of urinary bladder	UBERON:0001259	47.80	gold quality
kidney epithelium	UBERON:0004819	47.60	gold quality
biceps brachii	UBERON:0001507	47.54	gold quality
periodontal ligament	UBERON:0008266	47.14	gold quality
diaphragm	UBERON:0001103	47.05	gold quality
nephron tubule	UBERON:0001231	46.88	gold quality
mammalian vulva	UBERON:0000997	46.07	gold quality
layer of synovial tissue	UBERON:0007616	45.76	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	45.68	gold quality
granulocyte	CL:0000094	45.33	silver quality
ileal mucosa	UBERON:0000331	45.32	silver quality
bone marrow	UBERON:0002371	45.17	gold quality
hypothalamus	UBERON:0001898	44.96	silver quality
blood	UBERON:0000178	44.83	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	44.29	silver quality
apex of heart	UBERON:0002098	44.20	silver quality
metanephros	UBERON:0000081	43.66	gold quality
epithelium of bronchus	UBERON:0002031	43.62	gold quality
bronchus	UBERON:0002185	43.47	gold quality
squamous epithelium	UBERON:0006914	43.42	gold quality
medulla oblongata	UBERON:0001896	43.36	gold quality
substantia nigra	UBERON:0002038	43.29	silver quality
midbrain	UBERON:0001891	42.90	silver quality
cardiac ventricle	UBERON:0002082	42.90	gold quality
epithelium of esophagus	UBERON:0001976	42.87	gold quality
heart left ventricle	UBERON:0002084	42.74	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
primary visual cortex	UBERON:0002436	42.33	gold quality
tendon	UBERON:0000043	42.23	silver quality
putamen	UBERON:0001874	42.16	gold quality
saliva-secreting gland	UBERON:0001044	42.08	gold quality
occipital lobe	UBERON:0002021	42.08	gold quality
colonic epithelium	UBERON:0000397	42.05	gold quality
cartilage tissue	UBERON:0002418	42.04	gold quality
gingiva	UBERON:0001828	41.88	gold quality
cardiac atrium	UBERON:0002081	41.87	gold quality
nucleus accumbens	UBERON:0001882	41.68	silver quality
frontal cortex	UBERON:0001870	41.50	silver quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
epithelium of mammary gland	UBERON:0003244	41.33	gold quality
colonic mucosa	UBERON:0000317	41.29	gold quality
dorsal plus ventral thalamus	UBERON:0001897	41.27	gold quality
middle temporal gyrus	UBERON:0002771	41.19	gold quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality
right atrium auricular region	UBERON:0006631	41.09	gold quality
prefrontal cortex	UBERON:0000451	41.04	silver quality
trachea	UBERON:0003126	41.02	gold quality
right adrenal gland cortex	UBERON:0035827	41.00	silver quality
mucosa of paranasal sinus	UBERON:0005030	40.98	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

HPA expression

RNA tissue specificity: Tissue enriched

40 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Skeletal muscle	tissue	29.1
Tongue	tissue	5.9
Retina	tissue	5.8
Olfactory bulb	tissue	3.5
Cerebral cortex	tissue	2.9
Temporal cortex	tissue	2.9
Cerebellum	tissue	2.7
Hippocampal formation	tissue	2.7
Entorhinal cortex	tissue	2.7
Retrosplenial and cingulate cortex	tissue	2.6
Retrosplenial cortex	tissue	2.6
Occipital cortex	tissue	2.6
Prefrontal cortex	tissue	2.5
Amygdala	tissue	2.5
Somatosensory cortex	tissue	2.4
Insular cortex	tissue	2.4
Motor cortex	tissue	2.2
Putamen	tissue	2.1
Basal ganglia	tissue	2.0
Corpus callosum	tissue	2.0
Ventral forebrain	tissue	1.9
Periaqueductal gray	tissue	1.6
Septum	tissue	1.6
Medulla oblongata	tissue	1.4
Hypothalamus	tissue	1.4
Midbrain	tissue	1.3
Substantia nigra	tissue	1.3
Pons	tissue	1.2
Thalamus	tissue	1.2
Spinal cord	tissue	1.2
Superior colliculi	tissue	1.1
Prostate	tissue	0.5
Nucleus accumbens	tissue	0.2
Hippocampus	tissue	0.2
Thymus	tissue	0.2
Postcentral gyrus	tissue	0.2
Testis	tissue	0.1
Esophagus	tissue	0.1
Choroid plexus	tissue	0.1
Locus coeruleus	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 185; highest nTPM — White matter (2.0), Subiculum (1.8), Ventral hippocampus (1.8), Dorsal hippocampus (1.4), Dorsal spinal cord (1.2).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GABPA

miRNA regulators (miRDB)

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

showing 30 of 48 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 4.97e-09, LOEUF 0.848, missense Z 1.02 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000258385 — one region, missense o/e 0.94.

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

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:87893) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 13 distinct phenotype terms.

Mouse phenotype (MP)	Records
microphthalmia	1
abnormal retina morphology	1
abnormal placenta morphology	1
abnormal skin morphology	1
abnormal kidney morphology	1
abnormal vitreous body morphology	1
abnormal PNS synaptic transmission	1
abnormal endplate potential	1
small kidney	1
embryonic growth retardation	1
abnormal miniature endplate potential	1
abnormal action potential	1
preweaning lethality, complete penetrance	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
Tetronarce californica	P02710	99.1%	Diamond
Torpedo marmorata	P02711	99.1%	Diamond
Macaca mulatta	Q866A2	99.0%	Diamond
Naja naja	P14143	98.1%	Diamond
Natrix tessellata	P14144	98.1%	Diamond
Felis catus	P54250	97.6%	Diamond
Bos taurus	P02709	96.7%	Diamond
Caenorhabditis briggsae	A8WQK3	95.6%	Diamond
Caenorhabditis elegans	P48180	95.6%	Diamond
Crocidura russula	P54248	94.0%	Diamond
Erinaceus concolor	P54249	94.0%	Diamond
Gallus gallus	P22770	91.7%	Diamond
Herpestes ichneumon	P54251	91.7%	Diamond
Cavia porcellus	O70212	85.3%	Diamond
Xenopus laevis	P05377	82.6%	Diamond
Electrophorus electricus	P09691	82.6%	Diamond
Carassius auratus	P13908	82.6%	Diamond
Mustela putorius furo	Q19AE6	80.0%	Diamond
Drosophila melanogaster	P17644	79.7%	Diamond
Schistocerca gregaria	P23414	79.7%	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
CHRNG	protein-coding	1146
TIGD1	protein-coding	200765
EFHD1	protein-coding	80303
EIF4E2	protein-coding	9470
MIR5001	ncRNA	100847037
PRSS56	protein-coding	646960
ALPI	protein-coding	248
ECEL1	protein-coding	9427

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)

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

UniProt features (67 total): strand 19, helix 18, sequence variant 10, turn 6, 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)

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-Q07001-F1	84.21	0.51

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, Congenital malformations, Other congenital malformations

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): plasma membrane

Antibody reliability (HPA): IF supported

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)

Type	Positions
Phosphotyrosine	390

Disulfide bonds (1)

Type	Positions
Disulfide bond	151–165

Glycosylation sites (2)

Type	Positions
N-linked (glcnac…) asparagine	164, 97

Mutagenesis-validated functional residues (1)

Position	Phenotype
290	increased length of channel opening.

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: 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), calcium ion transport (GO:0006816), synaptic transmission, cholinergic (GO:0007271), 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

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

52 GO namespaces:

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
metal ion transport	1
chemical synaptic transmission	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
monoatomic ion channel activity	1
ligand-gated 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
postsynapse	1
postsynaptic membrane	1
postsynaptic specialization	1
cellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 5 of 32 annotations. The rest are phylogenetic / computational / electronic (IEA).

5 experimentally-supported GO terms:

GO term	NS	Evidence
musculoskeletal movement	BP	mutant phenotype
skeletal muscle tissue growth	BP	mutant phenotype
neuromuscular junction	CC	direct assay
plasma membrane	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 784 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHRND	RAPSN	Q13702	913
CHRND	DOK7	Q18PE1	787
CHRND	MUSK	O15146	772
CHRND	ALPI	P09923	772
CHRND	COLQ	Q9Y215	718
CHRND	COL4A3	Q01955	716
CHRND	ALPP	P05187	685
CHRND	AGRN	O00468	651
CHRND	PAX3	P23760	628
CHRND	ALG14	Q96F25	601
CHRND	COL6A3	P12111	557
CHRND	COMMD6	Q7Z4G1	552
CHRND	GFPT1	Q06210	547
CHRND	DPAGT1	Q9H3H5	546
CHRND	SCN4A	P35499	523

IntAct

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

4 partners by confidence:

Partner	Interaction type	MIscore	Records
TPST2	association	0.530	1
CHRNB1	association	0.350	1
EPHX1	association	0.350	1
EXTL3	association	0.350	1

BioGRID (112 interactions; top human partners by supporting records): ABCA3 (Affinity Capture-MS; 2 records), ABCC10 (Affinity Capture-MS; 2 records), ALG9 (Affinity Capture-MS; 2 records), APOL2 (Affinity Capture-MS; 2 records), ATG9A (Affinity Capture-MS; 2 records), BNIP1 (Affinity Capture-MS; 2 records), BTN2A2 (Affinity Capture-MS; 2 records), C1orf43 (Affinity Capture-MS; 2 records), CHRNA1 (Co-fractionation; 2 records), CISD2 (Affinity Capture-MS; 2 records), CNNM1 (Affinity Capture-MS; 2 records), DHRS7 (Affinity Capture-MS; 2 records), DNAJC18 (Affinity Capture-MS; 2 records), DPY19L4 (Affinity Capture-MS; 2 records), EIF2AK3 (Affinity Capture-MS; 2 records)

SIGNOR signaling

2 signaling 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

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) (2)

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

2 ligand–receptor pairs:

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

Disease & clinical

Genetic variants

Variant evidence for CHRND: 643 ClinVar records (41 pathogenic / likely pathogenic); 2 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	20
Likely pathogenic	21
Uncertain significance	329
Likely benign	178
Benign	22

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 41 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
18368	NM_000751.3(CHRND):c.234G>A (p.Trp78Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	6
657502	NM_000751.3(CHRND):c.521_524dup (p.Ala176fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
801910	NM_000751.3(CHRND):c.1007G>A (p.Arg336Gln)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3
422341	NM_000751.3(CHRND):c.933-2A>G	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
18367	NM_000751.3(CHRND):c.820_820+1del	Pathogenic	criteria provided, single submitter	2
1075530	NM_000751.3(CHRND):c.88del (p.Arg30fs)	Pathogenic	criteria provided, single submitter	1
1492568	NM_000751.3(CHRND):c.2T>C (p.Met1Thr)	Pathogenic	criteria provided, single submitter	1
1923533	NM_000751.3(CHRND):c.249del (p.Gly82_Trp83insTer)	Pathogenic	criteria provided, single submitter	1
2014916	NM_000751.3(CHRND):c.677_766delinsGGGT (p.Ala226fs)	Pathogenic	criteria provided, single submitter	1
2097009	NM_000751.3(CHRND):c.316dup (p.Asp106fs)	Pathogenic	criteria provided, single submitter	1
2144350	NM_000751.3(CHRND):c.628G>T (p.Glu210Ter)	Pathogenic	criteria provided, single submitter	1
2169508	NM_000751.3(CHRND):c.59G>A (p.Trp20Ter)	Pathogenic	criteria provided, single submitter	1
2191909	NM_000751.3(CHRND):c.211del (p.Glu71fs)	Pathogenic	criteria provided, single submitter	1
2843903	NM_000751.3(CHRND):c.36del (p.Ala13fs)	Pathogenic	criteria provided, single submitter	1
3650417	NM_000751.3(CHRND):c.247_251dup (p.Asp85fs)	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore CHRND’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; 36 predictions of 998):

Position(s)	Effect	Δscore	Sites
2:232526625	donor_gain	1.0000
2:232526676	donor_loss	1.0000
2:232528860–232528861	acceptor_loss	1.0000	5
2:232531657–232531658	donor_loss	1.0000	4
2:232534343–232534344	donor_loss	1.0000	5
2:232535128–232535129	acceptor_loss	1.0000	5
2:232526675–232526676	donor_loss	0.9900	2
2:232528260–232528261	acceptor_loss	0.9900	6
2:232528373	donor_gain	0.9900
2:232528499–232528500	acceptor_loss	0.9900	6

AlphaMissense

1,221 missense substitutions predicted likely pathogenic (of 3,387 scored), across 336 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
D161	8	0.989	0.995
D85	8	0.978	0.994
F158	8	0.956	0.997
D470	8	0.948	0.980
F169	8	0.945	0.997
F291	8	0.944	0.992
F248	8	0.929	0.995
F160	8	0.917	0.986
N117	8	0.916	0.987
H341	8	0.869	0.938
F315	8	0.816	0.942
D201	8	0.762	0.928
C151	7	0.995	0.998
C165	7	0.995	0.999
W211	7	0.995	0.999
W83	7	0.992	0.998
W109	7	0.992	0.999
W90	7	0.988	0.997
W462	7	0.977	0.995
F205	7	0.975	0.994

HPA cancer prognostics

RNA cancer specificity: Cancer enriched (Head and Neck Squamous Cell Carcinoma)

Disease associations

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

GenCC curated gene-disease

4 curated gene-disease records:

Disease	Classification	Inheritance	Records
congenital myasthenic syndrome 3A	Strong	Autosomal dominant	2
congenital myasthenic syndrome 3B	Strong	Autosomal recessive
congenital myasthenic syndrome 3C	Strong	Autosomal recessive	2
lethal multiple pterygium syndrome	Strong	Autosomal recessive	2

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (6 panels, 6 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

6 panels:

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

Mondo (7): lethal multiple pterygium syndrome (MONDO:0009668), congenital myasthenic syndrome 3B (MONDO:0014584), congenital myasthenic syndrome 3A (MONDO:0014583), congenital myasthenic syndrome 3C (MONDO:0014585), ptosis (MONDO:0000728), arthrogryposis multiplex congenita (MONDO:0015168), fetal akinesia deformation sequence 1 (MONDO:0100101)

Orphanet (4): Lethal multiple pterygium syndrome (Orphanet:33108), Congenital myasthenic syndrome (Orphanet:590), Arthrogryposis multiplex congenita (Orphanet:1037), Fetal akinesia deformation sequence (Orphanet:994)

HPO phenotypes

57 phenotypes (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:0000508	Ptosis
HP:0000602	Ophthalmoplegia
HP:0000883	Thin ribs
HP:0000969	Edema
HP:0001040	Multiple pterygia
HP:0001252	Hypotonia
HP:0001270	Motor delay
HP:0001319	Neonatal hypotonia
HP:0001324	Muscle weakness
HP:0001371	Flexion contracture
HP:0001373	Joint dislocation
HP:0001511	Intrauterine growth retardation
HP:0001558	Decreased fetal movement
HP:0001561	Polyhydramnios
HP:0001612	Weak cry
HP:0001961	Hypoplastic ventricle
HP:0001989	Fetal akinesia sequence
HP:0001999	Abnormal facial shape
HP:0002015	Dysphagia
HP:0002033	Poor suck
HP:0002047	Malignant hyperthermia
HP:0002089	Pulmonary hypoplasia
HP:0002093	Respiratory insufficiency
HP:0002304	Akinesia
HP:0002421	Poor head control
HP:0002505	Loss of ambulation
HP:0002659	Increased susceptibility to fractures
HP:0002948	Vertebral fusion
HP:0003324	Generalized muscle weakness
HP:0003388	Easy fatigability
HP:0003402	Decreased miniature endplate potentials
HP:0003403	EMG: decremental response of compound muscle action potential to repetitive nerve stimulation
HP:0003436	Prolonged miniature endplate currents
HP:0003473	Fatigable weakness
HP:0003593	Infantile onset
HP:0003623	Neonatal onset
HP:0003634	Amyoplasia
HP:0003676	Progressive
HP:0003750	Increased muscle fatiguability
HP:0005905	Abnormal cervical curvature
HP:0009381	Short finger
HP:0010628	Facial palsy
HP:0011968	Feeding difficulties
HP:0025336	Delayed ability to sit
HP:0030208	Anti-neuromuscular Junction acetylcholine receptor antibody positivity
HP:0030319	Weakness of facial musculature

GWAS associations

2 associations:

Study	Trait	p-value
GCST010002_411	Refractive error	1e-123
GCST000265_4	Brain lesion load	4e-6

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
D001763	Blepharoptosis	C11.338.204

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)

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 CHRND — 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: 260,190 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

10 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL894	BUPROPION	4	37,410
CHEMBL267936	MECAMYLAMINE	4	5,654
CHEMBL3	NICOTINE	4	187,543
CHEMBL56564	TROPISETRON	4	19,468
CHEMBL1076903	VARENICLINE	4	5,898
CHEMBL497939	CYTISINICLINE	3	2,806
CHEMBL2103881	DEXMECAMYLAMINE	3	19
CHEMBL134713	GTS-21	2	275
CHEMBL1172928	RADAFAXINE	2	1,085
CHEMBL504652	TC-2216	1	32

PharmGKB: 1 entry (CPIC guideline: no)

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)

82 measured of 104 human assays (105 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL4098776	IC50	3.8 nM
(3-ENDO)-8-METHYL-8-AZABICYCLO[3.2.1]OCT-3-YL 1H-INDOLE-3-CARBOXYLATE	KI	5.3 nM
CHEMBL4095046	IC50	9 nM
(1R,9R)-7,11-diazatricyclo[7.3.1.02,7]trideca-2,4-dien-6-one	EC50	11 nM
CHEMBL3898922	IC50	15 nM
CHEMBL4074583	IC50	23 nM
CHEMBL4071859	IC50	23 nM
CHEMBL4084852	IC50	25 nM
CHEMBL4100355	IC50	27 nM
9-Chloro-1,2,3,4,5,6-hexahydro-1,5-methano-pyrido[1,2-a][1,5]diazocin-8-one	EC50	28 nM
CHEMBL4083246	IC50	29 nM
9-Bromo-1,2,3,4,5,6-hexahydro-1,5-methano-pyrido[1,2-a][1,5]diazocin-8-one	EC50	31 nM
11,11-dimethyl-6-oxo-7-aza-11-azoniatricyclo[7.3.1.02,7]trideca-2,4-diene iodide	EC50	37 nM
9-Iodo-1,2,3,4,5,6-hexahydro-1,5-methano-pyrido[1,2-a][1,5]diazocin-8-one	EC50	45 nM
CHEMBL4097654	IC50	100 nM
CHEMBL4089244	IC50	120 nM
CHEMBL4872191	IC50	131 nM
CHEMBL4075880	IC50	150 nM
CHEMBL4061082	IC50	150 nM
(2R,4S)-2-(6-Iodo-pyridin-3-yl)-7-aza-bicyclo[2.2.1]heptane	IC50	160 nM
CHEMBL4087500	IC50	170 nM
CHEMBL4102804	IC50	180 nM
N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-1-benzothiophene-6-carboxamide	IC50	188 nM
CHEMBL4098850	IC50	190 nM
2-(tert-butylamino)-1-(3-chlorophenyl)propan-1-one	IC50	330 nM
CHEMBL4077222	IC50	350 nM
CHEMBL4064914	IC50	440 nM
N-[(S)-1-(11-Amino-undecylcarbamoyl)-2-(4-hydroxy-phenyl)-ethyl]-butyramide	IC50	460 nM
CHEMBL3918431	IC50	480 nM
N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-1-benzofuran-5-carboxamide	IC50	580 nM
(R)-4-chloro-N-(quinuclidin-3-yl)benzamide	KI	930 nM
N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-1-benzofuran-6-carboxamide	IC50	962 nM
CHEMBL4063152	IC50	1700 nM
3-(1H-Indole-3-carbonyloxy)-8,8-dimethyl-8-azonia-bicyclo[3.2.1]octane	KI	3000 nM
N-[(S)-1-(8-Amino-octylcarbamoyl)-2-(4-hydroxy-phenyl)-ethyl]-butyramide	IC50	5030 nM
CHEMBL342235	IC50	5330 nM
(2S,3S)-2-Biphenyl-4-yl-3,5,5-trimethylmorpholin-2-ol	IC50	5900 nM
(2S,3S)-2-(Naphthalen-1-yl)-3,5,5-trimethylmorpholin-2-ol	IC50	6600 nM
CHEMBL4101249	IC50	6700 nM
(+/-)2-(3,5-Dichlorophenyl)-3,5,5-trimethylmorpholin-2-ol	IC50	7200 nM
(+/-)2-(3,4-Dichlorophenyl)-3,5,5-trimethylmorpholin-2-ol	IC50	7200 nM
(2S,3S)-2-(3-Chlorophenyl)-3,5,5-trimethylmorpholin-2-ol	IC50	7600 nM
N-[(S)-1-(10-Amino-decylcarbamoyl)-2-(4-hydroxy-phenyl)-ethyl]-butyramide	IC50	8660 nM
CHEMBL4102566	IC50	9200 nM
(2S,3S)-2-(3-Chlorophenyl)-5,5-dimethyl-3-propyl-morpholin-2-ol	IC50	10000 nM
CHEMBL140652	IC50	10100 nM
N-[(S)-1-(7-Amino-heptylcarbamoyl)-2-(4-hydroxy-phenyl)-ethyl]-butyramide	IC50	10500 nM
CHEMBL141954	IC50	10900 nM
(2S,3S)-2-(Naphthalen-2-yl)-3,5,5-trimethylmorpholin-2-ol	IC50	11000 nM
N-[1-{3-[4-(3-Amino-propylamino)-butylamino]-propylcarbamoyl}-2-(4-hydroxy-phenyl)-ethyl]-butyramide	IC50	11800 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 551 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	decreases expression, increases 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	decreases expression, affects cotreatment	1
Benzo(a)pyrene	affects methylation	1
Diazinon	increases methylation	1
Plant Extracts	decreases expression, affects cotreatment	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)

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

showing 60 of 74 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
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
NCT05393375	Not specified	COMPLETED	Arthrogryposis Multiplex Congenita in Pediatric Age: Correlation Between MUScular MRI and Functional Evaluation
NCT05673265	Not specified	UNKNOWN	Pediatric and Adult Registry for Patients With ARThrogryposis

Predicted chemistry — Sugi Predict

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