CHRM1

Summary

CHRM1 (cholinergic receptor muscarinic 1, HGNC:1950) is a protein-coding gene on chromosome 11q12.3, encoding Muscarinic acetylcholine receptor M1 (P11229). The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins.

The muscarinic cholinergic receptors belong to a larger family of G protein-coupled receptors. The functional diversity of these receptors is defined by the binding of acetylcholine and includes cellular responses such as adenylate cyclase inhibition, phosphoinositide degeneration, and potassium channel mediation. Muscarinic receptors influence many effects of acetylcholine in the central and peripheral nervous system. The muscarinic cholinergic receptor 1 is involved in mediation of vagally-induced bronchoconstriction and in the acid secretion of the gastrointestinal tract. The gene encoding this receptor is localized to 11q13.

Source: NCBI Gene 1128 — RefSeq curated summary.

At a glance

• Gene–disease (curated): intellectual disability (Limited, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 51 total — 1 likely-pathogenic
• Druggable target: yes — 421 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000738

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1950
Approved symbol	CHRM1
Name	cholinergic receptor muscarinic 1
Location	11q12.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000168539
Ensembl biotype	protein_coding
OMIM	118510
Entrez	1128

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000306960, ENST00000536524, ENST00000543973, ENST00000856787, ENST00000856788

RefSeq mRNA: 1 — MANE Select: NM_000738 NM_000738

CCDS: CCDS8040

Canonical transcript exons

ENST00000306960 — 2 exons

Exon	Start	End
ENSE00001141432	62908679	62911178
ENSE00001368899	62921218	62921363

Expression profiles

Bgee: expression breadth ubiquitous, 132 present calls, max score 92.90.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 2.3650 / max 144.7892, expressed in 169 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
120262	1.8533	112
120263	0.2795	96
120261	0.1644	53
120260	0.0438	34
120264	0.0240	14

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
prefrontal cortex	UBERON:0000451	92.90	gold quality
frontal cortex	UBERON:0001870	90.92	gold quality
middle temporal gyrus	UBERON:0002771	90.58	gold quality
Brodmann (1909) area 9	UBERON:0013540	90.55	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	90.35	gold quality
right frontal lobe	UBERON:0002810	89.81	gold quality
superior frontal gyrus	UBERON:0002661	89.66	gold quality
neocortex	UBERON:0001950	89.19	gold quality
nucleus accumbens	UBERON:0001882	88.93	gold quality
postcentral gyrus	UBERON:0002581	88.66	gold quality
parietal lobe	UBERON:0001872	88.27	gold quality
anterior cingulate cortex	UBERON:0009835	88.06	gold quality
cerebral cortex	UBERON:0000956	87.79	gold quality
putamen	UBERON:0001874	87.37	gold quality
entorhinal cortex	UBERON:0002728	87.28	gold quality
telencephalon	UBERON:0001893	86.76	gold quality
caudate nucleus	UBERON:0001873	86.55	gold quality
primary visual cortex	UBERON:0002436	86.14	gold quality
temporal lobe	UBERON:0001871	85.41	gold quality
occipital lobe	UBERON:0002021	84.91	gold quality
Ammon’s horn	UBERON:0001954	84.78	gold quality
amygdala	UBERON:0001876	84.41	gold quality
Brodmann (1909) area 46	UBERON:0006483	82.64	gold quality
forebrain	UBERON:0001890	80.31	gold quality
Brodmann (1909) area 23	UBERON:0013554	80.02	gold quality
parotid gland	UBERON:0001831	78.23	gold quality
prostate gland	UBERON:0002367	78.09	gold quality
cortical plate	UBERON:0005343	75.94	gold quality
saliva-secreting gland	UBERON:0001044	75.86	gold quality
brain	UBERON:0000955	73.92	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-84465	yes	7.00
E-ANND-3	no	2.25

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR

miRNA regulators (miRDB)

96 targeting CHRM1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-3156-3P	99.76	66.72	939
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-4470	99.66	69.35	1767
HSA-MIR-4690-5P	99.65	66.24	813
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-4663	99.62	65.33	957

Literature-anchored findings (GeneRIF, showing 40)

• Fifteen single nucleotide polymorphisms (SNPs) of CHRM1 have been discovered, 9 of which are located in the coding region of the receptor; of these, 8 represent synonymous SNPs, indicating that CHRM1 is highly conserved in humans. (PMID:12049494)
• Evidence that there are decreased levels of CHRM1, but not CHRM4, protein and mRNA in the dorsolateral prefrontal cortex from subjects with schizophenia. (PMID:12476323)
• 28% decrease in post-mortem levels of steady-state cortical muscarinic 1 receptor cDNA in schizophrenia patient samples relative to controls (PMID:12707929)
• role of M1 and M2 muscarinic receptors expressed by human L cells in the control of GLP-1 secretion. (PMID:12810581)
• In conclusion, autoantibodies to CHRM1 were detected in a large number of CFS patients and were related to CFS symptoms. (PMID:12851722)
• mRNA of muscarinic acetylcholine receptor-1 is expressed in human scleral fibroblasts. (PMID:16318751)
• All three of the Kir2 channels are similarly inhibited by m1 muscarinic receptor stimulation through calcium-dependent activation of the small GTPase Rho. (PMID:16328454)
• Increased phosphorylation of M1 and M2 mAChRs underlies sequestration of these receptors after transient hypoxia. Distinct pathways involving CK1alpha and GRK2 mediated sequestration of M1 and M2 mAChRs after transient hypoxic-induced oxidative stress. (PMID:16336219)
• Data demonstrate that M(1), M(2), and M(3) muscarinic acetylcholine receptors (mAChR)can form homo- and heterodimers in living cells, and suggest that heterodimerization plays a role in the mechanism of mAChR long term regulation. (PMID:16368694)
• Data show that intracellular zinc uptake in SK-SH-SY5Y cells is controlled by M1-mAChR mediated signalling pathways and that zinc may act as a cofactor for transcriptional regulation of zinc finger genes such as PNUTS. (PMID:16406470)
• MT7 toxin interacts with hM1 receptor at a specific allosteric site, which may partially overlap those identified previously for “classic” or “atypical” allosteric agents. (PMID:16439611)
• Association of the nicotinic acetylcholine receptor beta1 subunit (CHRNB1) and M1 muscarinic acetylcholine receptor (CHRM1) with vulnerability for nicotine dependence. (PMID:16874522)
• mAChR subtypes (m1 to m5) presents in human scleral fibroblasts at both mRNA and protein levels. (PMID:16877267)
• This study provides the structural insight for improved understanding of M1 receptor and its binding sites. (PMID:16902941)
• Gene Coding the human cholinergic receptor muscarinic-1 is an important susceptibility locus for asthma at chromosome 11q13. (PMID:16931638)
• results demonstrate the ability of beta-arrestins to recruit diacylglycerol kinases to ligand-activated M1 muscarinic receptors (PMID:17272726)
• M1 receptor plays an important role in the maintenance of function of retinal pigment epithelium. (PMID:17415969)
• M1r-IR in cholinergic and nitrergic neurons and nerve fibres indicate that M1rs have a role in both cholinergic and nitrergic transmission. (PMID:17462859)
• The observations suggest that Cysteine pairs Cys259/Cys260 and Cys262/Cys263 in the 3rd intracellular loop play an important role in the agonist-induced internalization of muscarinic M1 receptors. (PMID:17540859)
• M1 muscarinic and alpha7 nicotinic receptors have roles in inhibition of pemphigus acantholysis (PMID:18073210)
• Certain Sjogren’s syndrome individuals may have antibodies against M1R, M2R and M3R. (PMID:18249005)
• The observed effect of tau protein on neurons (in neuroblastomas and primary cultures of hippocampal and cortical neurons) is through M1 and M3 muscarinic receptors. (PMID:18272392)
• In progressive supranuclear palsy: there were no changes in M1 muscarinic receptor density or M1 coupling (PMID:18282687)
• This study demonistred that in subgroup of subjects with schizophrenia decreased cortical muscarinic acetylcholine receptor M1. (PMID:18317461)
• The M(1) receptor is the predominant mAChR subtype coupling to the Galpha(q/11) G protein in the cerebral cortex. (PMID:18322150)
• Results demonstrate that the actions of pilocarpine and carbachol in salivary cells are mediated through two distinct signaling mechanisms via M3/M1 receptors. (PMID:18385290)
• Data suggest that 77-LH-28-1 is a potent and selective agonist at recombinant human M1 mAChRs. (PMID:18454168)
• analysis of a molecular that simultaneously utilizes both an allosteric and the orthosteric site on the M(2) mAChR (PMID:18723515)
• This study shows a decrease in levels of CHRM1 in BA 6 from subjects with schizophrenia (PMID:18790604)
• data indicate that despite marked declines in CHRM1 expression in some patients with schizophrenia, the ability of this receptor to initiate signal transduction through Gq/11 proteins is undiminished (PMID:19404243)
• Data showed that EGFP-fused muscarinic M1 receptors predominate as monomers in the absence of ligand and dimerize upon pirenzepine binding. (PMID:19451648)
• The S2 and S4 polymorphisms of CHRM1 are associated with susceptibility for developing high myopia. (PMID:19753311)
• increased inattention scores (Conners’ teacher-rating scale) and lower l-MR associated with increased score for oppositional-defiant disorder. (PMID:19863190)
• Muscarinic cholinoceptor activation by pilocarpine triggers apoptosis in human skin fibroblast cells. (PMID:19927300)
• Data show that two-color TIRFM established the dynamic nature of dimer formation with M(1) receptors undergoing interconversion between monomers and dimers on the timescale of seconds. (PMID:20133736)
• Distribution of M1 receptors in human colon. (PMID:20146726)
• analysis of the long-term effects of xanomeline on the M(1) muscarinic acetylcholine receptor (PMID:21203415)
• docking calculations structurally support the high affinity and selectivity of the MT7-human M1 muscarinic receptor interaction and highlight the atypical mode of interaction of this allosteric ligand on its G protein-coupled receptor target. (PMID:21685390)
• Binding properties of human muscarinic M1 receptor in stably transfected Chinese hamster ovary cells is significantly enhanced after supplementation, probably by facilitating receptor-mediated G protein activation. (PMID:22146060)
• Decreased muscarinic M1 receptor radioligand binding is found in the cerebral cortex of schizophrenic patients. (PMID:22338582)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	chrm1a	ENSDARG00000037292
mus_musculus	Chrm1	ENSMUSG00000032773
rattus_norvegicus	Chrm1	ENSRNOG00000074156

Paralogs (25): DRD4 (ENSG00000069696), HRH3 (ENSG00000101180), HRH2 (ENSG00000113749), CHRM3 (ENSG00000133019), HRH4 (ENSG00000134489), TAAR5 (ENSG00000135569), GPR84 (ENSG00000139572), GPR161 (ENSG00000143147), TAAR2 (ENSG00000146378), TAAR6 (ENSG00000146383), TAAR8 (ENSG00000146385), TAAR1 (ENSG00000146399), DRD3 (ENSG00000151577), HTR4 (ENSG00000164270), DRD5 (ENSG00000169676), HTR1A (ENSG00000178394), HTR1D (ENSG00000179546), CHRM4 (ENSG00000180720), CHRM2 (ENSG00000181072), DRD1 (ENSG00000184845), CHRM5 (ENSG00000184984), GPR21 (ENSG00000188394), HRH1 (ENSG00000196639), GPR52 (ENSG00000203737), TAAR9 (ENSG00000237110)

Protein

Protein identifiers

Muscarinic acetylcholine receptor M1 — P11229 (reviewed: P11229)

All UniProt accessions (3): P11229, F5GZF8, Q53XZ3

UniProt curated annotations — full annotation on UniProt →

Function. The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover.

Subunit / interactions. Interacts with GPRASP2. Interacts with TMEM147.

Subcellular location. Cell membrane. Postsynaptic cell membrane.

Similarity. Belongs to the G-protein coupled receptor 1 family. Muscarinic acetylcholine receptor subfamily. CHRM1 sub-subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P11229-1	1	yes
P11229-2	2

RefSeq proteins (1): NP_000729* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000995	Musac_Ach_rcpt	Family
IPR002228	Musac_Ach_M1_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (53 total): helix 15, topological domain 8, transmembrane region 7, site 5, modified residue 5, region of interest 3, compositionally biased region 2, glycosylation site 2, chain 1, disulfide bond 1, splice variant 1, sequence conflict 1, turn 1, strand 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
6ZFZ	X-RAY DIFFRACTION	2.17
6ZG4	X-RAY DIFFRACTION	2.33
6ZG9	X-RAY DIFFRACTION	2.5
6WJC	X-RAY DIFFRACTION	2.55
5CXV	X-RAY DIFFRACTION	2.7
6OIJ	ELECTRON MICROSCOPY	3.3
9JEA	ELECTRON MICROSCOPY	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P11229-F1	75.51	0.53

Antibody-complex structures (SAbDab): 1 — 6OIJ

Functional residue map

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

Catalytic / active sites (5): 170 (subtype-specific residue that binds to snake venom muscarinic toxin 7); 172 (binds to snake venom muscarinic toxin 7); 174 (subtype-specific residue that binds to snake venom muscarinic toxin 7); 397 (subtype-specific residue that binds to snake venom muscarinic toxin 7); 401 (subtype-specific residue that binds to snake venom muscarinic toxin 7)

Post-translational modifications (5): 230, 428, 451, 455, 457

Disulfide bonds (1): 98–178

Glycosylation sites (2): 2, 12

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-390648	Muscarinic acetylcholine receptors
R-HSA-416476	G alpha (q) signalling events
R-HSA-162582	Signal Transduction
R-HSA-372790	Signaling by GPCR
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)
R-HSA-375280	Amine ligand-binding receptors
R-HSA-388396	GPCR downstream signalling
R-HSA-500792	GPCR ligand binding

MSigDB gene sets: 232 (showing top): RNGTGGGC_UNKNOWN, GOBP_DIGESTION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_COGNITION, MODULE_274, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_PROTEIN_TRANSPORT, AREB6_03, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, AREB6_01, GOBP_NEUROGENESIS, GGGTGGRR_PAX4_03, AAAYRNCTG_UNKNOWN, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, USF_C

GO Biological Process (19): signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186), G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger (GO:0007187), adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway (GO:0007197), phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), phospholipase C-activating G protein-coupled acetylcholine receptor signaling pathway (GO:0007207), G protein-coupled acetylcholine receptor signaling pathway (GO:0007213), chemical synaptic transmission (GO:0007268), neuromuscular synaptic transmission (GO:0007274), nervous system development (GO:0007399), regulation of locomotion (GO:0040012), positive regulation of monoatomic ion transport (GO:0043270), saliva secretion (GO:0046541), cognition (GO:0050890), regulation of postsynaptic membrane potential (GO:0060078), regulation of glial cell proliferation (GO:0060251), positive regulation of intracellular protein transport (GO:0090316), postsynaptic modulation of chemical synaptic transmission (GO:0099170), acetylcholine receptor signaling pathway (GO:0095500)

GO Molecular Function (4): phosphatidylinositol-4,5-bisphosphate phospholipase C activity (GO:0004435), G protein-coupled acetylcholine receptor activity (GO:0016907), G protein-coupled receptor activity (GO:0004930), protein binding (GO:0005515)

GO Cellular Component (13): plasma membrane (GO:0005886), membrane (GO:0016020), dendrite (GO:0030425), presynaptic membrane (GO:0042734), axon terminus (GO:0043679), synapse (GO:0045202), Schaffer collateral - CA1 synapse (GO:0098685), postsynaptic density membrane (GO:0098839), glutamatergic synapse (GO:0098978), cholinergic synapse (GO:0098981), cell junction (GO:0030054), asymmetric synapse (GO:0032279), postsynaptic membrane (GO:0045211)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Signaling by GPCR	2
Amine ligand-binding receptors	1
GPCR downstream signalling	1
Signal Transduction	1
GPCR ligand binding	1
Class A/1 (Rhodopsin-like receptors)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor signaling pathway	4
G protein-coupled acetylcholine receptor signaling pathway	3
synapse	3
postsynapse	2
acetylcholine receptor activity	2
cellular anatomical structure	2
synaptic membrane	2
presynapse	2
postsynaptic density	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
G protein-coupled receptor activity	1
signal transduction	1
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	1
phospholipase C activator activity	1
phospholipase C-activating G protein-coupled receptor signaling pathway	1
G protein-coupled acetylcholine receptor activity	1
acetylcholine receptor signaling pathway	1
anterograde trans-synaptic signaling	1
chemical synaptic transmission	1
system development	1
locomotion	1
regulation of biological process	1
monoatomic ion transport	1
regulation of monoatomic ion transport	1
positive regulation of transport	1
body fluid secretion	1
digestive system process	1
secretion by tissue	1
nervous system process	1
regulation of membrane potential	1
glial cell proliferation	1
regulation of cell population proliferation	1
intracellular protein transport	1
positive regulation of intracellular transport	1
regulation of intracellular protein transport	1
positive regulation of protein transport	1

Protein interactions and networks

STRING

1658 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHRM1	PLCB3	Q01970	796
CHRM1	CAPN1	P07384	768
CHRM1	COX8A	P10176	766
CHRM1	FKBP2	P26885	766
CHRM1	AHNAK	Q09666	766
CHRM1	SF1	Q15637	766
CHRM1	FTH1	P02794	765
CHRM1	ROM1	Q03395	764
CHRM1	FOSL1	P15407	764
CHRM1	MAP3K11	Q16584	764
CHRM1	PYGM	P11217	763
CHRM1	SCGB1A1	P11684	762
CHRM1	MARK2	Q7KZI7	762
CHRM1	ARRB1	P49407	731
CHRM1	ARRB2	P32121	715

IntAct

9 interactions, top by confidence:

A	B	Type	Score
GPRASP1	CHRM1	psi-mi:“MI:0407”(direct interaction)	0.440
GPRASP2	CHRM1	psi-mi:“MI:0407”(direct interaction)	0.440
CHRM1	Dlg4	psi-mi:“MI:0407”(direct interaction)	0.440
	CHRM1	psi-mi:“MI:0915”(physical association)	0.400
CHRM1	RAMP2	psi-mi:“MI:0915”(physical association)	0.400
CHRM1	RAMP3	psi-mi:“MI:0915”(physical association)	0.400
CHRM1	ARRB2	psi-mi:“MI:0914”(association)	0.350

BioGRID (4): RGS7 (Reconstituted Complex), GPRASP1 (Reconstituted Complex), GPRASP2 (Reconstituted Complex), CHRM1 (Biochemical Activity)

ESM2 similar proteins: O42490, P04761, P08173, P08482, P08485, P08911, P08912, P08913, P11229, P11617, P12657, P15823, P17200, P18089, P18841, P22909, P29274, P30543, P30546, P30729, P31389, P32211, P35368, P41984, P43140, P46616, P47901, P48974, P56489, P56490, P70174, Q01338, Q28838, Q5IS53, Q5IS98, Q5R949, Q5XXP2, Q5YKK9, Q60474, Q60475

Diamond homologs: A0A287A2K5, C8YUV0, O00155, O02836, O08786, O15973, O18935, O19012, O19014, O19025, O19032, O19054, O19091, O62729, O77408, O77700, O77721, O77830, O97665, O97772, P04761, P08482, P0C5I1, P11229, P12657, P17200, P18089, P19328, P22270, P25021, P30545, P30551, P30552, P30553, P30796, P32211, P32238, P32239, P32302, P46627

SIGNOR signaling

23 interactions.

A	Effect	B	Mechanism
CHRM1	“up-regulates activity”	GNAI1	binding
CHRM1	“up-regulates activity”	GNAI3	binding
CHRM1	“up-regulates activity”	GNAQ	binding
CHRM1	“up-regulates activity”	GNA14	binding
acetylcholine	“up-regulates activity”	CHRM1	“chemical activation”
aclidinium	“down-regulates activity”	CHRM1	“chemical inhibition”
sabcomeline	“up-regulates activity”	CHRM1	“chemical activation”
solifenacin	“down-regulates activity”	CHRM1	“chemical inhibition”
oxybutynin	“down-regulates activity”	CHRM1	“chemical inhibition”
pirenzepine	“down-regulates activity”	CHRM1	“chemical inhibition”
tiotropium	“down-regulates activity”	CHRM1	“chemical inhibition”
carbachol	“up-regulates activity”	CHRM1	“chemical activation”
bethanechol	“up-regulates activity”	CHRM1	“chemical activation”
(+)-pilocarpine	“up-regulates activity”	CHRM1	“chemical activation”
“1-methyl-3,6-dihydro-2H-pyridine-5-carboxylic acid prop-2-ynyl ester”	“up-regulates activity”	CHRM1	“chemical activation”
arecoline	“up-regulates activity”	CHRM1	“chemical activation”
furtrethonium	“up-regulates activity”	CHRM1	“chemical activation”
trimethyl-[(5-methyl-2-furanyl)methyl]ammonium	“up-regulates activity”	CHRM1	“chemical activation”
Oxotremorine	“up-regulates activity”	CHRM1	“chemical activation”
“oxotremorine M”	“up-regulates activity”	CHRM1	“chemical activation”
dothiepin	“down-regulates activity”	CHRM1	“chemical inhibition”
amitriptyline	“down-regulates activity”	CHRM1	“chemical inhibition”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	45
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1098339	NM_000738.3(CHRM1):c.1274T>C (p.Phe425Ser)	Likely pathogenic

SpliceAI

261 predictions. Top by Δscore:

Variant	Effect	Δscore
11:62911175:TCAC:T	acceptor_gain	0.9900
11:62911176:CACC:C	acceptor_gain	0.9900
11:62911179:C:G	acceptor_loss	0.9900
11:62911180:T:A	acceptor_loss	0.9900
11:62921214:TCACC:T	donor_loss	0.9900
11:62921215:CAC:C	donor_loss	0.9900
11:62921216:A:AC	donor_gain	0.9900
11:62921216:A:C	donor_loss	0.9900
11:62921217:C:CC	donor_gain	0.9900
11:62921217:C:G	donor_loss	0.9900
11:62921217:CCA:C	donor_gain	0.9900
11:62911176:CAC:C	acceptor_gain	0.9800
11:62911177:AC:A	acceptor_gain	0.9800
11:62911178:CC:C	acceptor_gain	0.9800
11:62911179:C:CC	acceptor_gain	0.9800
11:62921212:ACTC:A	donor_loss	0.9800
11:62921216:AC:A	donor_gain	0.9800
11:62921217:CC:C	donor_gain	0.9800
11:62921217:CCACG:C	donor_gain	0.9800
11:62911174:ATCAC:A	acceptor_gain	0.9700
11:62921214:TCAC:T	donor_gain	0.9700
11:62921215:CACC:C	donor_gain	0.9700
11:62921216:ACCA:A	donor_gain	0.9700
11:62921217:CCAC:C	donor_gain	0.9700
11:62921210:GTAC:G	donor_loss	0.9300
11:62921211:TACT:T	donor_loss	0.9300
11:62911807:CT:C	donor_gain	0.9200
11:62911806:ACTCT:A	donor_gain	0.8200
11:62911807:CTCTC:C	donor_gain	0.8200
11:62911179:C:T	acceptor_gain	0.8000

AlphaMissense

2949 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:62909826:G:C	F425L	1.000
11:62909826:G:T	F425L	1.000
11:62909827:A:G	F425S	1.000
11:62909828:A:G	F425L	1.000
11:62909849:A:G	Y418H	1.000
11:62909852:A:G	C417R	1.000
11:62909857:G:A	P415L	1.000
11:62909857:G:C	P415R	1.000
11:62909857:G:T	P415H	1.000
11:62909858:G:A	P415S	1.000
11:62909859:G:C	N414K	1.000
11:62909859:G:T	N414K	1.000
11:62909861:T:C	N414D	1.000
11:62909868:G:C	S411R	1.000
11:62909868:G:T	S411R	1.000
11:62909870:T:G	S411R	1.000
11:62909871:G:C	N410K	1.000
11:62909871:G:T	N410K	1.000
11:62909880:G:C	C407W	1.000
11:62909881:C:T	C407Y	1.000
11:62909894:C:G	G403R	1.000
11:62909955:G:C	N382K	1.000
11:62909955:G:T	N382K	1.000
11:62909962:G:C	P380R	1.000
11:62909962:G:T	P380Q	1.000
11:62909969:A:G	W378R	1.000
11:62909969:A:T	W378R	1.000
11:62909979:G:C	F374L	1.000
11:62909979:G:T	F374L	1.000
11:62909980:A:G	F374S	1.000

dbSNP variants (sampled 300 via entrez): RS1000186941 (11:62923090 G>A), RS1000363905 (11:62918907 G>C), RS1000740533 (11:62916532 C>G,T), RS1000887215 (11:62911719 A>G), RS1000889852 (11:62923724 G>T), RS1001485787 (11:62918504 G>T), RS1001497220 (11:62918820 G>T), RS1001519936 (11:62917291 C>A), RS1001637247 (11:62923691 C>T), RS1002084089 (11:62911963 C>T), RS1002189616 (11:62917627 G>A), RS1002488450 (11:62917159 A>G), RS1002488776 (11:62923468 C>T), RS1002674503 (11:62911794 G>A,T), RS1002742073 (11:62919172 C>T)

Disease associations

OMIM: gene MIM:118510 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual disability	Limited	Autosomal dominant

Mondo (1): intellectual disability (MONDO:0001071)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008972_106	Urate levels	9.000000e-27

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (5): CHEMBL2094109 (PROTEIN FAMILY), CHEMBL2095219 (SELECTIVITY GROUP), CHEMBL2111417 (CHIMERIC PROTEIN), CHEMBL2111418 (SELECTIVITY GROUP), CHEMBL216 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

421 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 805,623 (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
CHEMBL14	CARBACHOL	4	21,785
CHEMBL1482	BETHANECHOL	4	4,165
CHEMBL42	CLOZAPINE	4	37,581
CHEMBL517712	ATROPINE	4	53,874
CHEMBL54	HALOPERIDOL	4	60,883
CHEMBL715	OLANZAPINE	4	40,057
CHEMBL716	QUETIAPINE	4	26,465
CHEMBL85	RISPERIDONE	4	41,869
CHEMBL965	CARBAMOYLCHOLINE	4	22,580
CHEMBL9967	PIRENZEPINE	4	11,458
CHEMBL21536	XANOMELINE	4	3,299
CHEMBL1008	BEPRIDIL	4	11,776
CHEMBL1017	TELMISARTAN	4	27,457
CHEMBL1023	BEXAROTENE	4	40,951
CHEMBL103	PROGESTERONE	4	162,141
CHEMBL104	CLOTRIMAZOLE	4	56,325
CHEMBL1064	SIMVASTATIN	4	123,163
CHEMBL1071	OXAPROZIN	4	51,044
CHEMBL1075	MORICIZINE	4	3,860
CHEMBL1078261	PROPIVERINE	4	4,890
CHEMBL109	VALPROIC ACID	4
CHEMBL1091	HYDROCORTISONE ACETATE	4
CHEMBL1092	TRIHEXYPHENIDYL HYDROCHLORIDE	4
CHEMBL1094636	NIRAPARIB	4
CHEMBL11	IMIPRAMINE	4
CHEMBL1101	BIPERIDEN	4
CHEMBL110691	CHLORMADINONE ACETATE	4
CHEMBL1112	ARIPIPRAZOLE	4
CHEMBL1113	AMOXAPINE	4
CHEMBL1117	IDARUBICIN	4

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

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2075748	CHRM1		0.00	0
rs1942499	CHRM1		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Acetylcholine receptors (muscarinic)

Most potent curated ligand interactions (108 total), top 25:

Ligand	Action	Affinity	Parameter
muscarinic toxin 7	Negative	11.1	pKi
[3H]QNB	Antagonist	10.8	pKd
tiotropium	Antagonist	10.7	pKi
Cy3B-telenzepine	Antagonist	10.5	pKd
[3H]N-methyl scopolamine	Antagonist	10.3	pKd
aclidinium	Antagonist	10.2	pIC50
glycopyrrolate	Antagonist	10.1	pIC50
NNC 11-1585	Full agonist	9.9	pKi
N-methyl scopolamine	Antagonist	9.9	pKi
ipratropium	Antagonist	9.8	pKi
umeclidinium	Antagonist	9.8	pKi
propantheline	Antagonist	9.7	pKi
atropine	Antagonist	9.6	pKi
3Htelenzepine	Antagonist	9.4	pKi
revefenacin	Antagonist	9.38	pKi
biperiden	Antagonist	9.32	pKd
4-DAMP	Antagonist	9.3	pKi
Alexa-488-telenzepine	Antagonist	9.3	pKd
darifenacin	Antagonist	9.1	pKi
dicyclomine	Antagonist	9.08	pKi
benzatropine	Antagonist	9.02	pKi
scopolamine	Antagonist	9.0	pKi
trihexyphenidyl	Antagonist	8.87	pKi
[3H]darifenacin	Antagonist	8.8	pKd
tripitramine	Antagonist	8.8	pKi

Binding affinities (BindingDB)

687 measured of 726 human assays (759 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-acetoxypropyl(trimethyl)ammonium;chloride	EC50	0.0062 nM
(3-endo)-3-(2-Cyano-2,2-diphenylethyl)-8,8-dimethyl-8-azoniabicyclo[3.2.1]octane Bromide	KI	0.05 nM
CHEMBL2023764	KI	0.12 nM
NNC 11-1585	KI	0.129 nM
(2S,4aR,6aR,7R,9S,10aS,10bR)-9-(acetyloxy)-2-(furan-3-yl)dodecahydro-6a,10b-dimethyl-4,10-dioxo-2H-naphtho-[2,1-c]pyran-7-carboxylic acid methyl ester	EC50	0.3 nM
1-[(2R)-3-[(1R,5S)-3-(cyclopropylmethoxy)-8-azabicyclo[3.2.1]octan-8-yl]-2-methylpropyl]-6-fluoroindazole	EC50	0.32 nM	US-9670209: Muscarinic agonists
(3-endo)-3-(2,2-Di-2-thienylethenyl)-8,8-dimethyl-8-azoniabicyclo[3.2.1]octane Bromide	KI	0.38 nM
6-fluoro-1-[(2R)-3-[(1R,5S)-3-(2-methoxyethyl)-8-azabicyclo[3.2.1]octan-8-yl]-2-methylpropyl]indazole	EC50	0.4 nM	US-9670209: Muscarinic agonists
1-(bicyclo[2.2.1]hept-5-en-2-yl)-1-phenyl-3-(piperidin-1-yl)propan-1-ol	KI	0.48 nM
NSC_3746	KI	0.49 nM
1-[(2R)-3-[(1R,5S)-3-(2-methoxyethyl)-8-azabicyclo[3.2.1]octan-8-yl]-2-methylpropyl]-6-methylindazole	EC50	0.5 nM	US-9670209: Muscarinic agonists
2-Chlor-11-(2-dimethylaminoaethoxy)-dibenzo(b,f)-thiepin	KI	0.5 nM
4-Diphenylacetoxy-1,1-dimethyl-piperidinium; iodide	KI	0.58 nM
3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-N-methylpropan-1-amine	KI	0.6 nM
1-[(2R)-3-[(1R,5S)-3-(2-ethoxyethyl)-8-azabicyclo[3.2.1]octan-8-yl]-2-methylpropyl]indazole	EC50	0.79 nM	US-9670209: Muscarinic agonists
1-[(2R)-3-[(1R,5S)-3-(2-ethoxyethyl)-8-azabicyclo[3.2.1]octan-8-yl]-2-methylpropyl]-6-methylindazole	EC50	0.79 nM	US-9670209: Muscarinic agonists
tert-butyl (5S)-3-hydroxy-8-azabicyclo[3.2.1]octane-8-carboxylate	EC50	1 nM	US-9670209: Muscarinic agonists
1-[(2R)-3-[(1R,5S)-3-(cyclopropylmethoxy)-8-azabicyclo[3.2.1]octan-8-yl]-2-methylpropyl]indazole	EC50	1.3 nM	US-9670209: Muscarinic agonists
1-[(2R)-3-[(1R,5S)-3-(cyclopropylmethoxy)-8-azabicyclo[3.2.1]octan-8-yl]-2-methylpropyl]-6-methylindazole	EC50	1.3 nM	US-9670209: Muscarinic agonists
6-fluoro-1-[(2R)-2-methyl-3-[(1R,5S)-3-prop-2-enoxy-8-azabicyclo[3.2.1]octan-8-yl]propyl]indazole	EC50	1.3 nM	US-9670209: Muscarinic agonists
CAS_62865	KI	1.5 nM
NSC_132947	KI	1.58 nM
CHEMBL195011	EC50	1.74 nM
5-[2-(4-Benzo[d]isothiazol-3-yl-piperazin-1-yl)-ethyl]-6-chloro-1,3-dihydro-indol-2-one	KI	1.9 nM
1-fluoro-N- ((3RS,4SR)-3- hydroxytetrahydro- 2H-pyran-4-yl)-4- ((6-(1-methyl-1H- pyrazol-4-yl)pyridin- 3-yl)methyl)-2- naphthamide	EC50	2 nM	US-9708302: Flouro-naphthyl derivatives
NNC 11-1607	KI	2.4 nM
OXO-M	KI	2.5 nM
3-(benzyl-thiophen-2-yl-carbamoyloxy)-8,8-dimethyl-8-azonia-bicyclo[3.2.1]octane; bromide	IC50	2.7 nM
4-[4-(4-Chloro-phenyl)-4-hydroxy-piperidin-1-yl]-1-(4-fluoro-phenyl)-butan-1-one;propionate(HCl)	KI	2.92 nM
ATR	IC50	3.2 nM	US-9333195: Quinuclidine derivatives and medicinal compositions containing the same
1-[(2R)-3-[(1R,5S)-3-(2-methoxyethyl)-8-azabicyclo[3.2.1]octan-8-yl]-2-methylpropyl]indazole	EC50	4 nM	US-9670209: Muscarinic agonists
1-[(2R)-3-[(1R,5S)-3-cyclopentyloxy-8-azabicyclo[3.2.1]octan-8-yl]-2-methylpropyl]indazole	EC50	4 nM	US-9670209: Muscarinic agonists
cid_9301	KI	4.1 nM
1-Cyclohexyl-1-phenyl-3-pyrrolidin-1-yl-propan-1-ol	KI	4.6 nM
CHEMBL196218	EC50	4.79 nM
Enablex	KI	5.5 nM
6-methoxy-1-[(2R)-3-[(1R,5S)-3-(2-methoxyethyl)-8-azabicyclo[3.2.1]octan-8-yl]-2-methylpropyl]indazole	EC50	6.3 nM	US-9670209: Muscarinic agonists
1-[(2R)-3-[(1R,5S)-3-(2-methoxyethylidene)-8-azabicyclo[3.2.1]octan-8-yl]-2-methylpropyl]indazole	EC50	6.3 nM	US-9670209: Muscarinic agonists
CHEMBL194008	EC50	6.46 nM
3-(3-Hexylsulfanyl-pyrazin-2-yloxy)-1-aza-bicyclo[2.2.1]heptane	KI	7 nM
1-[(2R)-2-methyl-3-[(1R,5S)-3-prop-2-enoxy-8-azabicyclo[3.2.1]octan-8-yl]propyl]indazole	EC50	7.9 nM	US-9670209: Muscarinic agonists
1-[(2R)-3-[(1R,5S)-3-(cyclobutylmethoxy)-8-azabicyclo[3.2.1]octan-8-yl]-2-methylpropyl]indazole	EC50	7.9 nM	US-9670209: Muscarinic agonists
1-[(2R)-2-methyl-3-[(1R,5S)-3-propoxy-8-azabicyclo[3.2.1]octan-8-yl]propyl]indazole	EC50	7.9 nM	US-9670209: Muscarinic agonists
CHEMBL4784357	IC50	7.9 nM
McN-A-343	KI	8.2 nM
1-[(2R)-3-[(1R,5S)-3-(cyclopropylmethoxy)-8-azabicyclo[3.2.1]octan-8-yl]-2-methylpropyl]-6-methoxyindazole	EC50	10 nM	US-9670209: Muscarinic agonists
1-[(2R)-2-methyl-3-[(1R,5S)-3-prop-2-ynoxy-8-azabicyclo[3.2.1]octan-8-yl]propyl]indazole	EC50	10 nM	US-9670209: Muscarinic agonists
6-methoxy-1-[(2R)-2-methyl-3-[(1R,5S)-3-prop-2-ynoxy-8-azabicyclo[3.2.1]octan-8-yl]propyl]indazole	EC50	10 nM	US-9670209: Muscarinic agonists
1-Fluoro-N-((1S,2S)-2-hydroxycyclohexyl)-4-((6-(1-methyl-1H-pyrazol-4-yl) pyridin-3-yl)methyl)-2-naphthamide	EC50	10 nM	US-9708302: Flouro-naphthyl derivatives
N-[(1S,2S)-2-hydroxycyclohexyl]-1-[[4-(1-methylimidazol-4-yl)phenyl]methyl]pyrrolo[3,2-b]pyridine-3-carboxamide	EC50	10 nM	US-10072005: 4-azaindole derivatives

ChEMBL bioactivities

4499 potent at pChembl≥5 of 4954 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.92	Kd	0.01202	nM	CHEMBL318812
10.89	Ki	0.013	nM	TIOTROPIUM BROMIDE
10.89	Ki	0.01288	nM	CHEMBL112297
10.80	Kd	0.01585	nM	CHEMBL3084650
10.52	Kd	0.03	nM	CHEMBL112297
10.50	Ki	0.03162	nM	CHEMBL4634333
10.50	IC50	0.03162	nM	TIOTROPIUM BROMIDE
10.46	Kd	0.03467	nM	CHEMBL320611
10.40	Ki	0.03981	nM	CHEMBL4634333
10.40	Kd	0.04	nM	CHEMBL115078
10.35	Ki	0.045	nM	QUINUCLIDINYL BENZILATE
10.30	Ki	0.05012	nM	CHEMBL2103803
10.30	Ki	0.05	nM	CHEMBL2103803
10.30	ED50	0.05	nM	ATROPINE
10.29	Ki	0.051	nM	QUINUCLIDINYL BENZILATE
10.27	Ki	0.054	nM	CHEMBL320611
10.10	Ki	0.08	nM	CHEMBL564057
10.10	Ki	0.08	nM	ACLIDINIUM BROMIDE
10.06	Ki	0.088	nM	AZAPROPHEN
10.05	Ki	0.09	nM	CHEMBL556635
10.02	Ki	0.0955	nM	METHSCOPOLAMINE
10.00	IC50	0.1	nM	TIOTROPIUM BROMIDE
10.00	Ki	0.1	nM	CHEMBL335542
10.00	Ki	0.1	nM	CHEMBL3084650
10.00	IC50	0.1	nM	ACLIDINIUM BROMIDE
9.96	Ki	0.11	nM	CHEMBL4647437
9.94	Ki	0.115	nM	PF-03635659
9.93	Ki	0.1175	nM	CHEMBL219786
9.92	Ki	0.12	nM	CHEMBL2023764
9.92	Ki	0.12	nM	CHEMBL4633816
9.92	Ki	0.12	nM	TIOTROPIUM BROMIDE
9.92	Ki	0.12	nM	CHEMBL335542
9.90	Kd	0.1259	nM	CHEMBL540359
9.90	IC50	0.1259	nM	GLYCOPYRRONIUM BROMIDE
9.88	Ki	0.131	nM	BENZTROPINE
9.85	Ki	0.14	nM	CHEMBL4790083
9.85	IC50	0.14	nM	CHEMBL564057
9.85	IC50	0.14	nM	ACLIDINIUM BROMIDE
9.82	IC50	0.15	nM	CHEMBL556635
9.82	ED50	0.15	nM	ATROPINE
9.80	Ki	0.16	nM	CHEMBL3629360
9.80	Ki	0.16	nM	UMECLIDINIUM BROMIDE
9.80	IC50	0.16	nM	CHEMBL556222
9.77	Ki	0.1698	nM	METHSCOPOLAMINE
9.77	Kd	0.17	nM	CHEMBL4860528
9.77	Kd	0.17	nM	CHEMBL5207281
9.77	Kd	0.17	nM	CHEMBL5206565
9.77	Kd	0.17	nM	CHEMBL5201074
9.72	IC50	0.19	nM	CHEMBL562642
9.72	Ki	0.19	nM	CHEMBL141452

PubChem BioAssay actives

1967 with measured affinity, of 6100 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
3-(1-methyl-3,6-dihydro-2H-pyridin-5-yl)-4-pentylsulfanyl-1,2,5-thiadiazole	167809: Efficacy at muscarinic acetylcholine receptor M1 measured by the ability to inhibit the electrically stimulated twitch of the rabbit vas deferens	ic50	<0.0001	uM
[(2S)-3-oxo-3-phenylmethoxy-2-[[2-(tetradecanoylamino)acetyl]amino]propyl] hexadecanoate	141239: Binding of [3H]QNB to HM1 receptor was evaluated by saturation binding assay	kd	<0.0001	uM
benzyl (2S)-3-hydroxy-2-[[2-(tetradecanoylamino)acetyl]amino]propanoate	141239: Binding of [3H]QNB to HM1 receptor was evaluated by saturation binding assay	kd	<0.0001	uM
Tiotropium Bromide Monohydrate	539980: Displacement of [3H]NMS from human muscarinic M1 receptor expressed in CHO-K1 cells after 16 hrs by scintillation proximity assay	ic50	<0.0001	uM
3-hexylsulfanyl-4-(1-methyl-3,6-dihydro-2H-pyridin-5-yl)-1,2,5-thiadiazole	167809: Efficacy at muscarinic acetylcholine receptor M1 measured by the ability to inhibit the electrically stimulated twitch of the rabbit vas deferens	ic50	<0.0001	uM
[(3S)-6-methyl-6-azabicyclo[3.2.1]octan-3-yl] 2,2-diphenylpropanoate	73701: Inhibition of methacholine induced phasic contraction of guinea pig ileum	kd	<0.0001	uM
[(3S)-6-methyl-6-azabicyclo[3.2.1]octan-3-yl] 2-hydroxy-2,2-diphenylacetate	73701: Inhibition of methacholine induced phasic contraction of guinea pig ileum	kd	<0.0001	uM
5,5,27,27-tetramethyl-24-[2-[10-[4-[2-(1-methyl-4-oxo-5H-thieno[3,4-b][1,5]benzodiazepin-10-yl)-2-oxoethyl]piperazin-1-yl]decylamino]-2-oxoethyl]-16-oxa-20-aza-12-azoniaheptacyclo[15.11.0.03,15.04,12.06,11.020,28.021,26]octacosa-1(28),2,4(12),6(11),7,9,21(26),22,24-nonaene-8-sulfonate	1710657: Displacement of [3H]NMS from human recombinant muscarinic receptor M1 expressed in CHO-K9 cell membranes measured after 3 hrs by radioligand competition binding assay	ki	<0.0001	uM
3-(1-methyl-3,6-dihydro-2H-pyridin-5-yl)-4-pentoxy-1,2,5-thiadiazole	167809: Efficacy at muscarinic acetylcholine receptor M1 measured by the ability to inhibit the electrically stimulated twitch of the rabbit vas deferens	ic50	<0.0001	uM
1-azabicyclo[2.2.2]octan-3-yl 2-hydroxy-2,2-diphenylacetate	141150: Ability of compound to displace (-)-[3H]3-Quinuclidinyl benzilate (-)-[3H]-QNB from Muscarinic acetylcholine receptors in the heart from Guinea Pig.	ki	<0.0001	uM
[(3R)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] (2S)-2-cyclopentyl-2-hydroxy-2-thiophen-2-ylacetate bromide	430616: Displacement of [3H]NMS from human muscarinic M1 receptor expressed in CHOK1 cells by microplate scintillation counting	ic50	0.0001	uM
3-(8-hex-5-enyl-8-methyl-8-azoniabicyclo[3.2.1]octan-3-yl)-2,2-diphenylpropanenitrile bromide	658773: Displacement of [3H]-N-methyl scopolamine from muscarinic acetylcholine M1 receptor expressed in CHO cell membrane	ki	0.0001	uM
Aclidinium Bromide	430616: Displacement of [3H]NMS from human muscarinic M1 receptor expressed in CHOK1 cells by microplate scintillation counting	ic50	0.0001	uM
Glycopyrrolate	539980: Displacement of [3H]NMS from human muscarinic M1 receptor expressed in CHO-K1 cells after 16 hrs by scintillation proximity assay	ic50	0.0001	uM
(6-methyl-6-azabicyclo[3.2.1]octan-3-yl) 2,2-diphenylpropanoate	140902: Inhibition of [3H]QNB binding to CHO cells bearing transfected muscarinic acetylcholine receptor M1	ki	0.0001	uM
6-[3-[3-(1,3-benzothiazol-7-ylsulfonyl)propanoyl]-3,8-diazabicyclo[3.2.1]octan-8-yl]pyridine-3-carbonitrile	1685152: Displacement of [3H]NMS from human recombinant muscarinic receptor M1 expressed in CHO-K1 cell membranes assessed as inhibition constant incubated for 1 hr by Radioligand binding assay	ki	0.0001	uM
[(3R)-1-methyl-1-azoniabicyclo[2.2.2]octan-3-yl] N-[2-(3-chloro-4-fluorophenyl)-4-fluorophenyl]carbamate formate	1648375: Displacement of [3H]N-methylscopolamine from human muscarinic M1 receptor transiently expressed in HEK293T cell membranes incubated for 1 hr by scintillation counting method	ki	0.0001	uM
[(3R)-1-methyl-1-azoniabicyclo[2.2.2]octan-3-yl] N-[2-(3-chlorophenyl)-4-fluorophenyl]carbamate formate	1648375: Displacement of [3H]N-methylscopolamine from human muscarinic M1 receptor transiently expressed in HEK293T cell membranes incubated for 1 hr by scintillation counting method	ki	0.0001	uM
5-[3-(3-hydroxyphenoxy)azetidin-1-yl]-5-methyl-2,2-diphenylhexanamide	627077: Displacement of [3H]-NMS from human recombinant M1 receptor expressed in CHO cells after 24 hrs by filter binding assay	ki	0.0001	uM
(2S)-2-[(2R,5S)-2-cyclohexyl-2-phenyl-1,3-oxathiolan-5-yl]-1,1-dimethylpyrrolidin-1-ium iodide	280351: Binding affinity to human cloned muscarinic receptor M1 expressed in CHO cells	ki	0.0001	uM
3-(1-methyl-3,6-dihydro-2H-pyridin-5-yl)-4-[8-[[4-(1-methyl-3,6-dihydro-2H-pyridin-5-yl)-1,2,5-thiadiazol-3-yl]oxy]octoxy]-1,2,5-thiadiazole	141171: Binding affinity towards M1 muscarinic receptor expressed in A9 L cells by displacing 3H-QNB radioligand.	ki	0.0002	uM
N-[[4-fluoro-3-[3-[[(3S)-3-methylpiperazin-1-yl]methyl]phenyl]phenyl]methyl]-3-(piperidin-4-ylmethyl)benzamide	414362: Antagonist activity at human recombinant muscarinic M1 receptor expressed in CHO cells assessed as inhibition of acetylcholine-induced calcium mobilization by FLIPR assay	kd	0.0002	uM
diphenyl-[1-(2-phenylmethoxyethyl)-1-azoniabicyclo[2.2.2]octan-4-yl]methanol bromide	414942: Displacement of [3H]N-methyl scopolamine from human cloned muscarinic M1 receptor expressed in CHO cells coexpressing Gqi5 by scintillation proximity assay	ki	0.0002	uM
piperidin-4-ylmethyl N-[2-(3-chloro-4-fluorophenyl)-4-fluorophenyl]carbamate	1936433: Displacement of [3H]N-methylscopolamine from human muscarinic M1 receptor expressed in human HEK293T cell membranes by radioligand competition binding based analysis	ki	0.0002	uM
2-[3-(dimethylamino)-6-dimethylazaniumylidenexanthen-9-yl]-5-[2-[4-[4-[1-[2-oxo-2-(6-oxo-5H-benzo[b][1,4]benzodiazepin-11-yl)ethyl]piperidin-4-yl]butyl]piperazin-1-yl]ethylcarbamoyl]benzoate;tris(2,2,2-trifluoroacetic acid)	1710658: Displacement of [3H]NMS from human recombinant muscarinic receptor M2 expressed in CHO-K9 cell membranes measured after 3 hrs by radioligand competition binding assay	ki	0.0002	uM
1-[N’-[3-(2-amino-4-methyl-1,3-thiazol-5-yl)propyl]carbamimidoyl]-3-pentylurea	1895227: Displacement of [3H]N-methylscopolamine from human muscarinic acetylcholine M1 receptor stably expressed in CHO cells by radioligand competition binding based analysis	kd	0.0002	uM
1-[(1R)-1-phenylethyl]-3-[N’-[3-(1H-1,2,4-triazol-5-yl)propyl]carbamimidoyl]urea;dihydrochloride	1895227: Displacement of [3H]N-methylscopolamine from human muscarinic acetylcholine M1 receptor stably expressed in CHO cells by radioligand competition binding based analysis	kd	0.0002	uM
1-[N’-[3-(5-amino-1,3,4-thiadiazol-2-yl)propyl]carbamimidoyl]-3-pentylurea;bis(2,2,2-trifluoroacetic acid)	1895227: Displacement of [3H]N-methylscopolamine from human muscarinic acetylcholine M1 receptor stably expressed in CHO cells by radioligand competition binding based analysis	kd	0.0002	uM
1-[N’-[3-(5-amino-1,3,4-thiadiazol-2-yl)propyl]carbamimidoyl]-3-benzylurea;bis(2,2,2-trifluoroacetic acid)	1895227: Displacement of [3H]N-methylscopolamine from human muscarinic acetylcholine M1 receptor stably expressed in CHO cells by radioligand competition binding based analysis	kd	0.0002	uM
3-[2-(1-azabicyclo[2.2.2]oct-2-en-3-yl)furan-3-yl]phenol	141149: Ability of compound to displace (-)-[3H]3-Quinuclidinyl benzilate (-)-[3H]-QNB from Muscarinic acetylcholine receptors in cerebral cortex from Guinea Pig.	ki	0.0003	uM
3-(1-methyl-3,6-dihydro-2H-pyridin-5-yl)-4-[10-[[4-(1-methyl-3,6-dihydro-2H-pyridin-5-yl)-1,2,5-thiadiazol-3-yl]sulfanyl]decylsulfanyl]-1,2,5-thiadiazole	141171: Binding affinity towards M1 muscarinic receptor expressed in A9 L cells by displacing 3H-QNB radioligand.	ki	0.0003	uM
[(1R,5S)-8-methyl-8-azabicyclo[3.2.1]octan-3-yl] (2S)-3-hydroxy-2-phenylpropanoate	1063776: Displacement of [3H]QNB from muscarinic M1 receptor (unknown origin)	ki	0.0003	uM
piperidin-4-ylmethyl N-[2-(3-chlorophenyl)-4-fluorophenyl]carbamate	1648375: Displacement of [3H]N-methylscopolamine from human muscarinic M1 receptor transiently expressed in HEK293T cell membranes incubated for 1 hr by scintillation counting method	ki	0.0003	uM
(2R)-2-[(2S,5R)-2-cyclohexyl-2-phenyl-1,3-oxathiolan-5-yl]-1-methylpyrrolidine	280351: Binding affinity to human cloned muscarinic receptor M1 expressed in CHO cells	ki	0.0003	uM
(2S)-2-[(2S,5S)-2-cyclohexyl-2-phenyl-1,3-oxathiolan-5-yl]-1,1-dimethylpyrrolidin-1-ium iodide	280351: Binding affinity to human cloned muscarinic receptor M1 expressed in CHO cells	ki	0.0003	uM
(2S)-2-[(5S)-2,2-diphenyl-1,3-oxathiolan-5-yl]-1,1-dimethylpyrrolidin-1-ium iodide	280351: Binding affinity to human cloned muscarinic receptor M1 expressed in CHO cells	ki	0.0003	uM
[1-(8-aminooctyl)piperidin-4-yl]methyl N-[2-(3-chloro-4-fluorophenyl)-4-fluorophenyl]carbamate	1936433: Displacement of [3H]N-methylscopolamine from human muscarinic M1 receptor expressed in human HEK293T cell membranes by radioligand competition binding based analysis	ki	0.0003	uM
[1-(8-aminooctyl)piperidin-4-yl] N-[2-(3-chloro-4-fluorophenyl)-4-fluorophenyl]carbamate	1936433: Displacement of [3H]N-methylscopolamine from human muscarinic M1 receptor expressed in human HEK293T cell membranes by radioligand competition binding based analysis	ki	0.0003	uM
[(1S,5R)-8-methyl-8-azabicyclo[3.2.1]octan-3-yl] 3-hydroxy-2-phenylpropanoate	140903: Inhibition of [3H]QNB binding to CHO cells bearing transfected muscarinic acetylcholine receptor M3	ki	0.0003	uM
11-[2-[4-[4-(diethylamino)butyl]piperidin-1-yl]acetyl]-5H-benzo[b][1,4]benzodiazepin-6-one	1710665: Displacement of [3H]-NMS from muscarinic M2 receptor (unknown origin) expressed in A9 cells by scintillation counting analysis	ki	0.0003	uM
[(3R)-1-(2-phenoxyethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] N-phenyl-N-(thiophen-2-ylmethyl)carbamate bromide	598151: Displacement of [3H]NMS from human muscarinic M1 receptor expressed in CHO-K1 cells after 1 hr by scintillation counting	ic50	0.0004	uM
[(3R)-1-(2-phenoxyethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] N-phenyl-N-(thiophen-3-ylmethyl)carbamate bromide	598151: Displacement of [3H]NMS from human muscarinic M1 receptor expressed in CHO-K1 cells after 1 hr by scintillation counting	ic50	0.0004	uM
(2S)-N-[(3R)-1-azabicyclo[2.2.2]octan-3-yl]-2-cyclopentyl-2-hydroxy-2-thiophen-2-ylacetamide	1194252: Displacement of [3H]NMS from human M1 receptor expressed in CHOK1 cell membranes after 4 hrs by scintillation counting method	ic50	0.0004	uM
(1S,5R)-3-(2,2-dithiophen-2-ylethenyl)-8,8-dimethyl-8-azoniabicyclo[3.2.1]octane bromide	600363: Displacement of [3H]N-methyl Scopolamine from human muscarinic M1 receptor expressed in CHO cells by scintillation proximity assay	ki	0.0004	uM
[(3R)-1-heptyl-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate bromide	430616: Displacement of [3H]NMS from human muscarinic M1 receptor expressed in CHOK1 cells by microplate scintillation counting	ic50	0.0004	uM
[(3R)-1-(2-phenylethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 9H-xanthene-9-carboxylate bromide	430616: Displacement of [3H]NMS from human muscarinic M1 receptor expressed in CHOK1 cells by microplate scintillation counting	ic50	0.0004	uM
[(3R)-1-azabicyclo[2.2.2]octan-3-yl] N-[2-(3-chloro-4-fluorophenyl)-4-fluorophenyl]carbamate	1648375: Displacement of [3H]N-methylscopolamine from human muscarinic M1 receptor transiently expressed in HEK293T cell membranes incubated for 1 hr by scintillation counting method	ki	0.0004	uM
[(3R)-1-methyl-1-azoniabicyclo[2.2.2]octan-3-yl] N-(2-phenylphenyl)carbamate;2,2,2-trifluoroacetate	1648375: Displacement of [3H]N-methylscopolamine from human muscarinic M1 receptor transiently expressed in HEK293T cell membranes incubated for 1 hr by scintillation counting method	ki	0.0004	uM
[1-(6-aminohexyl)piperidin-4-yl]methyl N-[2-(3-chloro-4-fluorophenyl)-4-fluorophenyl]carbamate	1936433: Displacement of [3H]N-methylscopolamine from human muscarinic M1 receptor expressed in human HEK293T cell membranes by radioligand competition binding based analysis	ki	0.0004	uM
6-fluoro-5-methyl-3-[1-(1-methyl-4-propoxycyclohexyl)piperidin-4-yl]-1H-benzimidazol-2-one	502823: Agonist activity at human muscarinic M1 receptor expressed in CHO cells assessed as effect on calcium mobilization by FLIPR assay	ec50	0.0004	uM

CTD chemical–gene interactions

61 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Acetylcholine	increases reaction, decreases reaction, affects binding, increases activity, increases abundance (+1 more)	8
N-Methylscopolamine	affects binding, affects reaction, increases reaction, decreases reaction	8
brucine	decreases reaction, affects binding, affects reaction, increases reaction, increases activity	6
Carbachol	affects binding, increases reaction, increases activity, increases abundance, increases expression	3
Gallamine Triethiodide	affects binding, affects reaction, decreases reaction	3
Pilocarpine	increases reaction, increases activity, increases abundance, increases expression, affects binding	3
Pirenzepine	affects binding, affects reaction, decreases reaction	3
Quinuclidinyl Benzilate	affects binding, decreases reaction, increases activity, increases reaction	3
KT 5720	affects binding, affects reaction, increases reaction	2
Atropine	affects binding, affects reaction, decreases activity	2
Calcium	increases abundance, increases activity, increases reaction	2
Clozapine	affects binding	2
Scopolamine Derivatives	decreases reaction, affects binding	2
Staurosporine	affects binding, affects reaction, increases reaction	2
5-methylfurtrethonium	affects binding, increases reaction	1
arsenite	increases methylation	1
acetylmonoethylcholine	increases activity	1
o,p’-DDT	increases expression	1
sodium arsenite	affects methylation	1
furtrethonium	affects binding, increases reaction	1
acetyldiethylcholine	increases activity	1
4-diphenylacetoxy-1,1-dimethylpiperidinium	affects binding, decreases reaction	1
oxotremorine M	affects binding, increases reaction	1
staurosporine aglycone	affects binding, increases reaction	1
methoctramine	affects binding, decreases reaction	1
taurolithocholic acid 3-sulfate	affects binding	1
KT 5823	affects binding, increases reaction	1
brucine N-oxide	affects binding, increases reaction	1
WIN 62577	affects binding, decreases reaction	1
WIN 51708	decreases reaction, affects binding	1

ChEMBL screening assays

1419 unique, capped per target: 979 binding, 412 functional, 27 admet, 1 unclassified

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1691873	Binding	Inhibition of human non-selective muscarinic receptor at up to 10 uM	Lersivirine, a nonnucleoside reverse transcriptase inhibitor with activity against drug-resistant human immunodeficiency virus type 1. — Antimicrob Agents Chemother
CHEMBL4144311	ADMET	Antagonist activity at mAChR in human CCRF-CEM cells assessed as inhibition of acetylcholine-stimulated Ca2+ flux pretreated for 25 mins followed by acetylacholine addition measured for 90 secs by calcium dye-based fluorescence assay	Synthesis and SAR of 1,2,3,4-Tetrahydroisoquinoline-Based CXCR4 Antagonists. — ACS Med Chem Lett
CHEMBL4149800	Functional	Antagonist activity at mAChR in human CCRF-CEM cells assessed as inhibition of acetylcholine-induced calcium flux pretreated for 25 mins followed by acetylcholine addition measured for 90 secs by calcium-dye based assay	Discovery of N-Alkyl Piperazine Side Chain Based CXCR4 Antagonists with Improved Drug-like Properties. — ACS Med Chem Lett

Cellosaurus cell lines

12 cell lines: 6 spontaneously immortalized cell line, 5 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_F2AT	CHO-K1 hm1	Spontaneously immortalized cell line	Female
CVCL_H454	CHO-K1/M1	Spontaneously immortalized cell line	Female
CVCL_KW67	PathHunter CHO-K1 CHRM1 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_LA00	PathHunter U2OS CHRM1 Activated GPCR Internalization	Cancer cell line	Female
CVCL_LA01	PathHunter U2OS CHRM1 beta-arrestin	Cancer cell line	Female
CVCL_RQ16	ValiScreen human CHRM1	Spontaneously immortalized cell line	Female
CVCL_U002	CHO-CHRM1	Spontaneously immortalized cell line	Female
CVCL_YK07	HEK293 CHRM1 HiTSeeker	Transformed cell line	Female
CVCL_YK37	U2OS CHRM1 HiTSeeker	Cancer cell line	Female
CVCL_ZI71	GeneBLAzer M1-NFAT-bla CHO-K1	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study
NCT02561754	Not specified	COMPLETED	Weight Management for Adolescents With IDD
NCT02591446	Not specified	COMPLETED	Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders
NCT02714868	Not specified	COMPLETED	Evaluation of Project TEAM (Teens Making Environmental and Activity Modifications)
NCT02721394	Not specified	UNKNOWN	FCT With Young Children With ID in the UK: A Feasibility Project V.1
NCT02746614	Not specified	COMPLETED	Psychomotor Therapy Effects in Adaptive Behavior and Motor Proficiency in Intellectual Disability
NCT02836405	Not specified	COMPLETED	TMS for the Investigation of Brain Plasticity in Autism Spectrum Disorders