CHRNG

Summary

CHRNG (cholinergic receptor nicotinic gamma subunit, HGNC:1967) is a protein-coding gene on chromosome 2q37.1, encoding Acetylcholine receptor subunit gamma (P07510). 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 mammalian muscle-type acetylcholine receptor is a transmembrane pentameric glycoprotein with two alpha subunits, one beta, one delta, and one epsilon (in adult skeletal muscle) or gamma (in fetal and denervated muscle) subunit. This gene, which encodes the gamma subunit, is expressed prior to the thirty-third week of gestation in humans. The gamma subunit of the acetylcholine receptor plays a role in neuromuscular organogenesis and ligand binding and disruption of gamma subunit expression prevents the correct localization of the receptor in cell membranes. Mutations in this gene cause Escobar syndrome and a lethal form of multiple pterygium syndrome. Muscle-type acetylcholine receptor is the major antigen in the autoimmune disease myasthenia gravis.

Source: NCBI Gene 1146 — RefSeq curated summary.

At a glance

• Gene–disease (curated): CHRNG-associated hypo-akinesia disorder of prenatal onset (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 539 total — 37 pathogenic, 33 likely-pathogenic
• Phenotypes (HPO): 121
• Druggable target: yes — 10 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_005199

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1967
Approved symbol	CHRNG
Name	cholinergic receptor nicotinic gamma subunit
Location	2q37.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000196811
Ensembl biotype	protein_coding
OMIM	100730
Entrez	1146

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 retained_intron

ENST00000389492, ENST00000485094, ENST00000651502

RefSeq mRNA: 1 — MANE Select: NM_005199 NM_005199

CCDS: CCDS33400

Canonical transcript exons

ENST00000651502 — 12 exons

Exon	Start	End
ENSE00000922599	232541374	232541529
ENSE00000922600	232542423	232542520
ENSE00000922601	232542882	232543082
ENSE00000922602	232543275	232543389
ENSE00000922604	232544367	232544580
ENSE00000922605	232544772	232544902
ENSE00001506031	232543585	232543699
ENSE00003487420	232540602	232540711
ENSE00003524326	232539992	232540131
ENSE00003650506	232540381	232540425
ENSE00003843733	232539692	232539802
ENSE00003845666	232545543	232548115

Expression profiles

Bgee: expression breadth broad, 54 present calls, max score 86.22.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.0970 / max 178.8929, expressed in 109 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
25992	0.5045	67
25994	0.4026	86
25993	0.1899	58

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	86.22	silver quality
gastrocnemius	UBERON:0001388	84.84	gold quality
muscle of leg	UBERON:0001383	83.14	gold quality
hindlimb stylopod muscle	UBERON:0004252	78.28	gold quality
muscle organ	UBERON:0001630	77.57	gold quality
endothelial cell	CL:0000115	73.66	silver quality
epithelial cell of pancreas	CL:0000083	72.58	gold quality
cervix epithelium	UBERON:0004801	72.57	gold quality
cervix squamous epithelium	UBERON:0006922	72.32	gold quality
pharyngeal mucosa	UBERON:0000355	72.20	silver quality
body of tongue	UBERON:0011876	71.87	gold quality
cerebellar vermis	UBERON:0004720	70.62	silver quality
cardia of stomach	UBERON:0001162	70.43	gold quality
gluteal muscle	UBERON:0002000	70.41	silver quality
synovial joint	UBERON:0002217	70.39	silver quality
vena cava	UBERON:0004087	70.35	gold quality
subthalamic nucleus	UBERON:0001906	69.94	gold quality
inferior vagus X ganglion	UBERON:0005363	69.88	gold quality
pericardium	UBERON:0002407	69.80	gold quality
substantia nigra pars reticulata	UBERON:0001966	69.71	gold quality
ventral tegmental area	UBERON:0002691	69.65	gold quality
lateral globus pallidus	UBERON:0002476	69.60	gold quality
pons	UBERON:0000988	69.52	gold quality
lateral nuclear group of thalamus	UBERON:0002736	69.49	gold quality
dorsal plus ventral thalamus	UBERON:0001897	69.17	gold quality
penis	UBERON:0000989	68.87	silver quality
triceps brachii	UBERON:0001509	68.33	gold quality
periodontal ligament	UBERON:0008266	68.07	gold quality
mucosa of urinary bladder	UBERON:0001259	68.04	gold quality
skeletal muscle tissue	UBERON:0001134	66.87	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-5061	yes	243.54
E-ANND-3	yes	3.22

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYOD1, MYOG, TCF3

miRNA regulators (miRDB)

37 targeting CHRNG, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-1251-3P	99.64	67.21	1408
HSA-MIR-6861-3P	99.60	68.46	444
HSA-MIR-6716-5P	99.56	68.62	1244
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-4284	99.36	65.25	1293
HSA-MIR-5589-3P	99.29	68.30	1443
HSA-MIR-5693	99.24	66.67	1106
HSA-MIR-4758-3P	99.12	63.96	869
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-4774-3P	98.90	67.82	737
HSA-MIR-583	98.71	67.44	1791
HSA-MIR-6754-5P	98.60	65.54	1627
HSA-MIR-7114-3P	98.42	66.53	569
HSA-MIR-1262	98.17	66.52	757
HSA-MIR-1180-5P	98.16	65.32	460
HSA-MIR-4494	97.86	64.93	850
HSA-MIR-3664-3P	97.85	67.62	1452
HSA-MIR-4432	97.80	67.87	705
HSA-MIR-4741	97.69	64.14	883
HSA-MIR-4675	97.69	64.82	774
HSA-MIR-510-5P	97.66	65.82	916
HSA-MIR-4678	97.59	68.31	902
HSA-MIR-3189-5P	97.55	66.71	655
HSA-MIR-5699-5P	97.36	67.03	1014

Literature-anchored findings (GeneRIF, showing 13)

• A good correlation was found between the expression of PAX3/7-FKHR and AChR, while MyoD1 was more sensitive but less specific. (PMID:16435141)
• CHRNG mutations identified in families with Escobar syndrome show that the trait is a congenital dysmorphology caused by transient inactivation of the neuromuscular endplate. (PMID:16826520)
• Mutations cxause lethal and nonlethal forms of multiple pterygium syndrome. (PMID:16826531)
• constructed and characterized four AChR gamma extracellular domain variants (PMID:18502212)
• This study suggests for the first time in humans, a possible role for genetic variation in the neuromuscular nicotinic acetylcholine receptor, particularly the gamma subunit, in systolic blood pressure regulation (PMID:18625075)
• Detection of PAX3/7-FKHR fusion gene by one-step RT-PCR is useful in the diagnosis of rhabdomyosarcomas (RMS) and that AChR-gamma is overexpressed in Chinese RMS patients. (PMID:18988640)
• We did not identify a clear difference in mutation spectrum of the CHRNG gene between lethal form and non-lethal forms of multiple pterygium syndromes (PMID:22167768)
• No mutations were found in CHRNG, CHRND and CHRNA1 genes of Indian families with Escobar syndrome. (PMID:23448903)
• Two siblings with Escobar syndrome caused by homozygous mutations of the CHRNG gene were identified. (PMID:25411939)
• Rare cases of congenital arthrogryposis multiplex caused by novel recurrent CHRNG mutations. (PMID:25608830)
• CHRNG mutations associated with interfamilial variability of the severity of the Escobar variant of multiple pterygium syndrome (PMID:27245440)
• A homozygous nonsense CHRNG variant c.136C>T (p.R46*), predicted to produce a truncated protein that leads to acetylcholine receptor deficiency was detected in a consanguineous Pakistani family with Escobar syndrome. (PMID:30461311)
• Our study contributes to further define the phenotypic spectrum of CHRNG-related nonlethal MPS, including muscle imaging features, which may be useful in distinguishing it from other diffuse arthrogryposis entities. (PMID:30868735)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	chrng	ENSDARG00000086647
mus_musculus	Chrng	ENSMUSG00000026253
rattus_norvegicus	Chrng	ENSRNOG00000077483

Paralogs (45): GABRA3 (ENSG00000011677), GABRA1 (ENSG00000022355), CHRNA3 (ENSG00000080644), GABRP (ENSG00000094755), CHRNA4 (ENSG00000101204), GLRA2 (ENSG00000101958), GABRE (ENSG00000102287), CHRNE (ENSG00000108556), GABRA4 (ENSG00000109158), GLRB (ENSG00000109738), GABRR2 (ENSG00000111886), GABRG2 (ENSG00000113327), CHRNB4 (ENSG00000117971), CHRNA2 (ENSG00000120903), CHRNA10 (ENSG00000129749), CHRND (ENSG00000135902), 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)

Protein

Protein identifiers

Acetylcholine receptor subunit gamma — P07510 (reviewed: P07510)

All UniProt accessions (2): A0A6F7YAP6, P07510

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.

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. Multiple pterygium syndrome, Escobar variant (EVMPS) [MIM:265000] Non-lethal form of arthrogryposis multiplex congenita. It is an autosomal recessive condition characterized by excessive webbing (pterygia), congenital contractures (arthrogryposis), and scoliosis. Variable other features include intrauterine death, congenital respiratory distress, short stature, faciocranial dysmorphism, ptosis, low-set ears, arachnodactyly and cryptorchism in males. Congenital contractures are common and may be caused by reduced fetal movements at sensitive times of development. Possible causes of decreased fetal mobility include space constraints such as oligohydramnion, drugs, metabolic conditions or neuromuscular disorders including myasthenia gravis. 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. Gamma/CHRNG sub-subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P07510-1	1	yes
P07510-2	2

RefSeq proteins (1): NP_005190* (*=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 (16 total): transmembrane region 4, sequence variant 3, topological domain 2, glycosylation site 2, signal peptide 1, chain 1, disulfide bond 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P07510-F1	81.91	0.47

Functional residue map

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

Disulfide bonds (1): 150–164

Glycosylation sites (2): 52, 163

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: 380 (showing top): GOBP_MEMBRANE_DEPOLARIZATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_SYNAPTIC_TRANSMISSION_CHOLINERGIC, AP4_Q6, GOBP_MULTICELLULAR_ORGANISMAL_MOVEMENT, TAL1ALPHAE47_01, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_SKELETAL_MUSCLE_CONTRACTION, CAGCTG_AP4_Q5, GOBP_CELL_CELL_SIGNALING, MYOD_01, GOBP_MUSCLE_CONTRACTION, GOBP_REGULATION_OF_POSTSYNAPTIC_MEMBRANE_POTENTIAL, KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND

GO Biological Process (11): skeletal muscle contraction (GO:0003009), muscle contraction (GO:0006936), signal transduction (GO:0007165), chemical synaptic transmission (GO:0007268), monoatomic ion transmembrane transport (GO:0034220), membrane depolarization (GO:0051899), acetylcholine receptor signaling pathway (GO:0095500), monoatomic ion transport (GO:0006811), synaptic transmission, cholinergic (GO:0007271), regulation of postsynaptic membrane potential (GO:0060078), excitatory postsynaptic potential (GO:0060079)

GO Molecular Function (8): channel activity (GO:0015267), acetylcholine receptor activity (GO:0015464), acetylcholine-gated monoatomic cation-selective channel activity (GO:0022848), transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential (GO:1904315), transmembrane signaling receptor activity (GO:0004888), monoatomic ion channel activity (GO:0005216), extracellular ligand-gated monoatomic ion channel activity (GO:0005230), protein binding (GO:0005515)

GO Cellular Component (6): plasma membrane (GO:0005886), acetylcholine-gated channel complex (GO:0005892), neuron projection (GO:0043005), synapse (GO:0045202), postsynaptic membrane (GO:0045211), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-6 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of membrane potential	2
regulation of postsynaptic membrane potential	2
postsynaptic neurotransmitter receptor activity	2
striated muscle contraction	1
musculoskeletal movement	1
muscle system process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
anterograde trans-synaptic signaling	1
monoatomic ion transport	1
transmembrane transport	1
acetylcholine receptor activity	1
postsynaptic signal transduction	1
cellular response to acetylcholine	1
transport	1
chemical synaptic transmission	1
chemical synaptic transmission, postsynaptic	1
passive transmembrane transporter activity	1
transmembrane signaling receptor activity	1
synaptic transmission, cholinergic	1
acetylcholine binding	1
excitatory extracellular ligand-gated monoatomic ion channel activity	1
ligand-gated monoatomic cation channel activity	1
transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential	1
transmitter-gated monoatomic ion channel activity	1
signaling receptor activity	1
monoatomic ion transmembrane transporter activity	1
channel activity	1
ligand-gated monoatomic ion channel activity	1
binding	1
membrane	1
cell periphery	1
monoatomic ion channel complex	1
plasma membrane signaling receptor complex	1
plasma membrane bounded cell projection	1
cell junction	1
synaptic membrane	1

Protein interactions and networks

STRING

710 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHRNG	RAPSN	Q13702	882
CHRNG	MUSK	O15146	776
CHRNG	AGRN	O00468	668
CHRNG	COLQ	Q9Y215	652
CHRNG	DOK7	Q18PE1	650
CHRNG	TNNI2	P48788	617
CHRNG	CHRNA1	P02708	580
CHRNG	MYH2	Q9UKX2	575
CHRNG	TNNT3	P45378	563
CHRNG	COL6A3	P12111	533
CHRNG	TPM2	P06468	532
CHRNG	COMMD6	Q7Z4G1	512
CHRNG	CAST	P20810	494
CHRNG	CAPN3	P20807	486
CHRNG	VIL1	P09327	482

IntAct

27 interactions, top by confidence:

A	B	Type	Score
CHRNG	NOTCH2NLA	psi-mi:“MI:0915”(physical association)	0.740
NOTCH2NLA	CHRNG	psi-mi:“MI:0915”(physical association)	0.740
CHRNG	KRTAP10-7	psi-mi:“MI:0915”(physical association)	0.670
KRTAP10-8	CHRNG	psi-mi:“MI:0915”(physical association)	0.670
KRTAP10-9	CHRNG	psi-mi:“MI:0915”(physical association)	0.670
CHRNG	KRT31	psi-mi:“MI:0915”(physical association)	0.670
KRTAP10-7	CHRNG	psi-mi:“MI:0915”(physical association)	0.670
KRT31	CHRNG	psi-mi:“MI:0915”(physical association)	0.670
CHRNG	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.670
CHRNG	KRTAP10-9	psi-mi:“MI:0915”(physical association)	0.670
	CHRNG	psi-mi:“MI:0915”(physical association)	0.560
CHRNG	ACTL6B	psi-mi:“MI:0915”(physical association)	0.400
KRTAP10-3	CHRNG	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (41): KRT31 (Two-hybrid), KRTAP10-7 (Two-hybrid), KRTAP10-9 (Two-hybrid), KRTAP10-8 (Two-hybrid), KRTAP10-3 (Two-hybrid), NOTCH2NL (Two-hybrid), ACTL6B (Affinity Capture-MS), ADAMTSL4 (Two-hybrid), KRT31 (Two-hybrid), KRTAP10-3 (Two-hybrid), KRTAP10-7 (Two-hybrid), KRTAP10-8 (Two-hybrid), KRTAP10-9 (Two-hybrid), MDFI (Two-hybrid), MEOX2 (Two-hybrid)

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, O76554, P02708, P02709, P02710, P02711, P02713, P02716, P02717, P02718, P04755, P04756, P04757, P04759, P04760, P05377, P07510, P09478, P09479, P09480, P09481, P09482, P09483, P09484, P09628, P12389, P12390, P12391, P12392, P13536, P13908, P17644, P17787, P18257, P18845, P19370, P20420, P22456

SIGNOR signaling

1 interactions.

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

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	37
Likely pathogenic	33
Uncertain significance	110
Likely benign	273
Benign	30

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1322085	NM_005199.5(CHRNG):c.56-1G>A	Pathogenic
1679376	NM_005199.5(CHRNG):c.814del (p.Gln272fs)	Pathogenic
18337	NM_005199.5(CHRNG):c.715C>T (p.Arg239Cys)	Pathogenic
18341	NM_005199.5(CHRNG):c.136C>T (p.Arg46Ter)	Pathogenic
18342	NM_005199.5(CHRNG):c.753_754del (p.Val253fs)	Pathogenic
195239	NM_005199.5(CHRNG):c.117dup (p.Asn40fs)	Pathogenic
217751	NM_005199.5(CHRNG):c.428C>G (p.Pro143Arg)	Pathogenic
2506380	NM_005199.5(CHRNG):c.56-2A>G	Pathogenic
2506381	NM_005199.5(CHRNG):c.55+5G>A	Pathogenic
2506924	NM_005199.5(CHRNG):c.420G>A (p.Trp140Ter)	Pathogenic
2712908	NM_005199.5(CHRNG):c.458C>G (p.Ser153Ter)	Pathogenic
2724211	NM_005199.5(CHRNG):c.397_407del (p.Ser133fs)	Pathogenic
2724321	NM_005199.5(CHRNG):c.1010_1011dup (p.Ser338fs)	Pathogenic
2736962	NM_005199.5(CHRNG):c.1190_1208dup (p.Trp403Ter)	Pathogenic
2756541	NM_005199.5(CHRNG):c.670C>T (p.Gln224Ter)	Pathogenic
2769351	NM_005199.5(CHRNG):c.1292_1311del (p.Leu431fs)	Pathogenic
2850195	NM_005199.5(CHRNG):c.103C>T (p.Gln35Ter)	Pathogenic
2856826	NM_005199.5(CHRNG):c.1286_1289del (p.Gly429fs)	Pathogenic
2859850	NM_005199.5(CHRNG):c.807dup (p.Gly270fs)	Pathogenic
2862202	NM_005199.5(CHRNG):c.1123C>T (p.Gln375Ter)	Pathogenic
2890488	NM_005199.5(CHRNG):c.412_431dup (p.Ile145fs)	Pathogenic
2892868	NM_005199.5(CHRNG):c.534_537dup (p.Leu180Ter)	Pathogenic
2961828	NM_005199.5(CHRNG):c.562C>T (p.Gln188Ter)	Pathogenic
2962543	NM_005199.5(CHRNG):c.1021C>T (p.Arg341Ter)	Pathogenic
2989017	NM_005199.5(CHRNG):c.517_520del (p.Tyr173fs)	Pathogenic
2990760	NM_005199.5(CHRNG):c.617G>A (p.Trp206Ter)	Pathogenic
3247531	NC_000002.11:g.(?233402587)(233407600_?)del	Pathogenic
3247532	NC_000002.11:g.(?233404745)(233414968_?)del	Pathogenic
3586176	NM_005199.5(CHRNG):c.482G>A (p.Trp161Ter)	Pathogenic
3644334	NM_005199.5(CHRNG):c.488del (p.Asn163fs)	Pathogenic

SpliceAI

1917 predictions. Top by Δscore:

Variant	Effect	Δscore
2:232540131:GGT:G	donor_loss	1.0000
2:232540132:G:GG	donor_gain	1.0000
2:232540132:G:T	donor_loss	1.0000
2:232540601:GCA:G	acceptor_gain	1.0000
2:232540712:G:GG	donor_gain	1.0000
2:232541530:G:GG	donor_gain	1.0000
2:232542410:C:A	acceptor_gain	1.0000
2:232542411:G:A	acceptor_gain	1.0000
2:232542413:T:TA	acceptor_gain	1.0000
2:232542420:CAG:C	acceptor_loss	1.0000
2:232542421:A:AT	acceptor_loss	1.0000
2:232542422:G:GT	acceptor_loss	1.0000
2:232542516:CACAG:C	donor_loss	1.0000
2:232542517:ACAG:A	donor_loss	1.0000
2:232542518:CAG:C	donor_loss	1.0000
2:232542519:AG:A	donor_loss	1.0000
2:232542520:GGTAA:G	donor_loss	1.0000
2:232542521:G:C	donor_loss	1.0000
2:232542522:T:G	donor_loss	1.0000
2:232543081:GG:G	donor_gain	1.0000
2:232543082:GG:G	donor_gain	1.0000
2:232543100:G:GT	donor_gain	1.0000
2:232543100:G:T	donor_gain	1.0000
2:232543390:G:GG	donor_gain	1.0000
2:232544576:GCTAG:G	donor_gain	1.0000
2:232544577:C:G	donor_gain	1.0000
2:232544903:G:GG	donor_gain	1.0000
2:232540143:G:GT	donor_gain	0.9900
2:232540596:CTGCA:C	acceptor_loss	0.9900
2:232540597:TGCA:T	acceptor_loss	0.9900

AlphaMissense

3342 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:232542893:T:A	W206R	1.000
2:232542893:T:C	W206R	1.000
2:232542895:G:C	W206C	1.000
2:232542895:G:T	W206C	1.000
2:232540683:T:A	W108R	0.999
2:232540683:T:C	W108R	0.999
2:232540685:G:C	W108C	0.999
2:232540685:G:T	W108C	0.999
2:232541472:G:A	C150Y	0.999
2:232541473:C:G	C150W	0.999
2:232541514:G:A	C164Y	0.999
2:232541515:C:G	C164W	0.999
2:232540400:T:C	L72P	0.998
2:232540605:T:A	W82R	0.998
2:232540605:T:C	W82R	0.998
2:232540607:G:C	W82C	0.998
2:232540607:G:T	W82C	0.998
2:232540628:G:C	W89C	0.998
2:232540628:G:T	W89C	0.998
2:232541471:T:A	C150S	0.998
2:232541471:T:C	C150R	0.998
2:232541472:G:C	C150S	0.998
2:232541513:T:A	C164S	0.998
2:232541513:T:C	C164R	0.998
2:232541514:G:C	C164S	0.998
2:232541520:T:C	L166P	0.998
2:232541526:T:C	F168S	0.998
2:232542894:G:C	W206S	0.998
2:232540112:T:A	L59H	0.997
2:232540121:T:C	L62P	0.997

dbSNP variants (sampled 300 via entrez): RS1001023095 (2:232541084 C>G,T), RS1001054046 (2:232540847 G>A), RS1002421713 (2:232546745 T>C), RS1002460464 (2:232537999 A>C), RS1003410800 (2:232539240 C>T), RS1003627445 (2:232542150 T>C), RS1003654970 (2:232548247 A>G), RS1003728724 (2:232547948 A>G), RS1003960580 (2:232542446 A>AGATT), RS1004515576 (2:232548310 T>C), RS1004845693 (2:232537879 T>C), RS1005114717 (2:232548573 A>G), RS1005462691 (2:232542805 AG>A), RS1005469155 (2:232547670 G>A), RS1006021908 (2:232546329 A>C,G,T)

Disease associations

OMIM: gene MIM:100730 | disease phenotypes: MIM:265000, MIM:253290, MIM:617468, MIM:208150, MIM:601462, MIM:180300

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal recessive multiple pterygium syndrome	Definitive	Autosomal recessive
transient neonatal myasthenia gravis	Strong	Autosomal recessive
lethal multiple pterygium syndrome	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
CHRNG-associated hypo-akinesia disorder of prenatal onset	Definitive	AR

Mondo (11): autosomal recessive multiple pterygium syndrome (MONDO:0009926), lethal multiple pterygium syndrome (MONDO:0009668), multiple pterygium syndrome (MONDO:0017415), scoliosis (MONDO:0005392), CHRNG-associated hypo-akinesia disorder of prenatal onset (MONDO:0100158), peripheral neuropathy (MONDO:0005244), arthrogryposis multiplex congenita (MONDO:0015168), fetal akinesia deformation sequence 1 (MONDO:0100101), congenital myasthenic syndrome (MONDO:0018940), rheumatoid arthritis (MONDO:0008383), transient neonatal myasthenia gravis (MONDO:0018326)

Orphanet (7): Autosomal recessive multiple pterygium syndrome (Orphanet:2990), Lethal multiple pterygium syndrome (Orphanet:33108), Multiple pterygium syndrome (Orphanet:294060), Arthrogryposis multiplex congenita (Orphanet:1037), Fetal akinesia deformation sequence (Orphanet:994), Congenital myasthenic syndrome (Orphanet:590), NON RARE IN EUROPE: Rheumatoid arthritis (Orphanet:284130)

HPO phenotypes

121 total (30 of 121 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000046	Small scrotum
HP:0000047	Hypospadias
HP:0000135	Hypogonadism
HP:0000157	Abnormality of the tongue
HP:0000160	Narrow mouth
HP:0000175	Cleft palate
HP:0000202	Orofacial cleft
HP:0000207	Triangular mouth
HP:0000218	High palate
HP:0000252	Microcephaly
HP:0000268	Dolichocephaly
HP:0000276	Long face
HP:0000286	Epicanthus
HP:0000307	Pointed chin
HP:0000316	Hypertelorism
HP:0000324	Facial asymmetry
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000364	Hearing abnormality
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000405	Conductive hearing impairment
HP:0000457	Depressed nasal ridge
HP:0000465	Webbed neck
HP:0000470	Short neck
HP:0000476	Cystic hygroma
HP:0000486	Strabismus

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001858_8	Refractive error	5.000000e-11
GCST010002_411	Refractive error	1.000000e-123

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D001172	Arthritis, Rheumatoid	C05.550.114.154; C05.799.114; C17.300.775.099; C20.111.199
D020294	Myasthenic Syndromes, Congenital	C10.668.758.800; C16.320.590
D012600	Scoliosis	C05.116.900.800.875
C537377	Multiple pterygium syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL1907588 (PROTEIN COMPLEX), CHEMBL2362997 (PROTEIN COMPLEX GROUP), 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)

Binding affinities (BindingDB)

1 measured of 4 human assays (4 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

83 potent at pChembl≥5 of 133 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
6.60	Ki	250	nM	CYTISINICLINE
6.52	IC50	300	nM	2(R)-MECAMYLAMINE
6.50	Ki	314	nM	CHEMBL59986
6.28	Ki	520	nM	CHEMBL196626
6.28	Ki	530	nM	CHEMBL1209305
6.24	Ki	580	nM	CHEMBL2057714
6.22	IC50	600	nM	DEXMECAMYLAMINE
6.19	Ki	650	nM	CHEMBL194204
6.10	IC50	790	nM	CHEMBL15998
5.99	Ki	1020	nM	CHEMBL1209070
5.83	Ki	1480	nM	NICOTINE
5.78	Ki	1680	nM	CHEMBL1209124
5.61	IC50	2430	nM	CHEMBL342483
5.52	Ki	3000	nM	CHEMBL111583
5.52	IC50	3000	nM	CHEMBL1812748

PubChem BioAssay actives

83 with measured affinity, of 504 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,2R,4S)-N,2,3,3-tetramethylbicyclo[2.2.1]heptan-2-amine	1179333: Antagonist activity at human alpha1beta1gammadelta nAChR	ic50	0.3000	uM
3-[[(2S)-azetidin-2-yl]methoxy]pyridine	1179333: Antagonist activity at human alpha1beta1gammadelta nAChR	ki	0.3140	uM
10-azatricyclo[6.3.1.02,7]dodeca-2(7),3,5-triene-4-carbonitrile	254522: Binding affinity to human Nicotinic acetylcholine receptor alpha-1-beta-gamma-delta expressed in HEK 293 cells using [3H]alpha-bungarotoxin	ki	0.5200	uM
N-[5-[2-[[(1R,5R,6S)-3-azabicyclo[3.2.1]octan-6-yl]oxy]phenyl]-3-pyridinyl]acetamide;hydrochloride	495032: Binding affinity to alpha-1-beta-gamma-delta nicotinic receptor	ki	0.5300	uM
1’-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
(8,8-dimethyl-8-azoniabicyclo[3.2.1]octan-3-yl) 1H-indole-3-carboxylate	145855: In vitro Binding affinity towards alpha-1-beta-1-gamma-delta nAChR was determined	ki	3.0000	uM
5-[(1R,2S,3S,5S)-3-(4-chloro-3-methylphenyl)-8-methyl-8-azabicyclo[3.2.1]octan-2-yl]-3-phenyl-1,2-oxazole	610460: Antagonist activity against human muscle-type alpha1beta1gammadelta nAChR in TE671/RD cells assessed as inhibition of carbamylcholine induced 86Rb+ efflux	ic50	3.0000	uM

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, decreases methylation	2
aristolochic acid I	increases expression	1
CGP 52608	affects binding, increases reaction	1
licochalcone B	decreases expression	1
incobotulinumtoxinA	decreases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Persistent Organic Pollutants	increases abundance, increases expression	1
Acetylcholine	affects binding, increases activity	1
Carmustine	decreases expression	1
Estradiol	increases expression	1
Pesticides	increases abundance, increases expression	1
Phthalic Acids	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Thiram	decreases expression	1
Valproic Acid	increases methylation	1

ChEMBL screening assays

67 unique, capped per target: 36 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

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00508066	PHASE4	COMPLETED	Continuous Local Infusion of Anesthetic at the Incisional Site for Scoliosis Surgery
NCT00510575	PHASE4	COMPLETED	Surgical Outcomes Using Variable Rod Diameters in the Treatment of Idiopathic Scoliosis
NCT00768313	PHASE4	WITHDRAWN	Phase IV Comparing Rods of Yield Strengths to Correct Adolescent Idiopathic Scoliosis.
NCT00880607	PHASE4	COMPLETED	Intrathecal Morphine Versus Epidural Extended Release Morphine for Pediatric Patients Undergoing Spinal Fusion
NCT00958581	PHASE4	COMPLETED	Tranexamic Acid (TXA) Versus Epsilon Aminocaproic Acid (EACA) Versus Placebo for Spine Surgery
NCT01852747	PHASE4	TERMINATED	Comparison of Actifuse ABX and Local Bone in Spinal Surgery
NCT02464813	PHASE4	COMPLETED	Effect of Pregabalin on Immediate Post-operative and Longterm Pain
NCT02465099	PHASE4	TERMINATED	Posterior Spinal Fusion With Two Energy Dissection Techniques
NCT06540885	PHASE4	RECRUITING	A Comparison Between Palonosetron Versus Granisetron as PONV Prophylaxis in Scoliotic Patients Undergoing Spine Surgery
NCT06616220	PHASE4	COMPLETED	Dexamethasone for ESPB in Pain Management After Pediatric Idiopathic Scoliosis Surgery
NCT06789016	PHASE4	COMPLETED	Dexmedetomidine for ESPB in Pain Management After Pediatric Idiopathic Scoliosis Surgery
NCT00380965	PHASE4	COMPLETED	Evaluation of the Efficacy of Cesamet™ for the Treatment of Pain in Patients With Chemotherapy-Induced Neuropathy
NCT00487981	PHASE4	TERMINATED	Spinal Cord Stimulation for Painful Diabetic Neuropathy
NCT00904202	PHASE4	COMPLETED	A Study Of Lidocaine Patch 5% Alone, Gabapentin Alone, And Lidocaine Patch 5% And Gabapentin In Combination For The Relief Of Pain In Patients With Diverse Peripheral Neuropathic Pain Conditions
NCT01192113	PHASE4	COMPLETED	Safety and Efficacy of Mecobalamin Injection in Peripheral Neuropathies Patients (Study JGAZSY091109)
NCT01373983	PHASE4	COMPLETED	Intrathecal Bolus Doses of Ziconotide
NCT01458015	PHASE4	TERMINATED	Tapentadol Versus Oxycodone - a Mechanism-based Treatment Approach in Neuropathic Pain
NCT02074267	PHASE4	COMPLETED	Clinical Study for Assessment of the Efficacy of Gabapentin (Carbatin and Neurontin) in Patients With Neuropathy Pain
NCT02372149	PHASE4	UNKNOWN	IVIg for Demyelination in Diabetes Mellitus
NCT02670161	PHASE4	ENROLLING_BY_INVITATION	Quality Improvement and Practice Based Research in Neurology Using the EMR
NCT07022938	PHASE4	COMPLETED	Nutritional Supplement for Treating Chemotherapy Induced Neuropathy
NCT07025005	PHASE4	RECRUITING	Fenofibrate Role in the Prophylaxis From Peripheral Neuropathy Induced by Bortezomib, Lenalidomide and Dexamethasone (VRd) Protocol in the Treatment of Patients With Multiple Myeloma (MM)
NCT00323752	PHASE3	COMPLETED	Recombinant Human Erythropoietin Compared to Autologous Pre-Donation Prior to Scoliosis Surgery in Children.
NCT00684112	PHASE3	COMPLETED	Analgesic Effects of Gabapentin After Scoliosis Surgery in Children
NCT00737997	PHASE3	COMPLETED	Effect of Early Morphine Administration on the Development of Acute Opioid Tolerance During Pediatric Scoliosis Surgery
NCT01103115	PHASE3	COMPLETED	Calcium + Vitamin D Supplementation for Low Bone Mass in Adolescent Idiopathic Scoliosis (AIS)
NCT01108211	PHASE3	COMPLETED	Improving Low Bone Mass With Vibration Therapy in Adolescent Idiopathic Scoliosis (AIS)
NCT01205256	PHASE3	COMPLETED	IRB-HSR# 14145 R,S Methadone: Analgesia and Pharmacokinetics in Adolescents Undergoing Scoliosis Correction
NCT02558010	PHASE3	COMPLETED	Perioperative Methadone Use to Decrease Opioid Requirement in Pediatric Spinal Fusion Patients
NCT03537612	PHASE3	TERMINATED	Sensorial and Physiological Mechanism-based Assessments of Perioperative Pain
NCT00058071	PHASE3	COMPLETED	Amifostine in Treating Peripheral Neuropathy in Patients Who Have Received Chemotherapy for Cancer
NCT00125268	PHASE3	TERMINATED	Near Infrared Light for the Treatment of Painful Peripheral Neuropathy
NCT00195013	PHASE3	COMPLETED	Randomized Placebo-Controlled Trial of Glutamine for Breast Cancer Patients With Peripheral Neuropathy
NCT00232141	PHASE3	COMPLETED	Study of Pregabalin Versus Placebo in the Treatment of Nerve Pain Associated With HIV Neuropathy
NCT00264875	PHASE3	COMPLETED	Open Label Safety And Efficacy Study Of Pregabalin In Subjects With Nerve Pain Asociated With Human Immunodeficiency Virus (HIV) Neuropathy
NCT00369564	PHASE3	COMPLETED	Glutamic Acid in Reducing Nerve Damage Caused by Vincristine in Young Patients With Cancer
NCT00471445	PHASE3	COMPLETED	Topical Amitriptyline and Ketamine Cream in Treating Peripheral Neuropathy Caused by Chemotherapy in Cancer Patients
NCT00489411	PHASE3	COMPLETED	Duloxetine in Treating Peripheral Neuropathy Caused by Chemotherapy in Patients With Cancer
NCT00710554	PHASE3	COMPLETED	A Study of Sativex® for Pain Relief of Peripheral Neuropathic Pain, Associated With Allodynia
NCT00711880	PHASE3	COMPLETED	A Study of Sativex® for Relief of Peripheral Neuropathic Pain Associated With Allodynia.