CHRM5

Summary

CHRM5 (cholinergic receptor muscarinic 5, HGNC:1954) is a protein-coding gene on chromosome 15q14, encoding Muscarinic acetylcholine receptor M5 (P08912). 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 clinical implications of this receptor are unknown; however, stimulation of this receptor is known to increase cyclic AMP levels.

Source: NCBI Gene 1133 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Druggable target: yes — 111 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_012125

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1954
Approved symbol	CHRM5
Name	cholinergic receptor muscarinic 5
Location	15q14
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000184984
Ensembl biotype	protein_coding
OMIM	118496
Entrez	1133

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000383263, ENST00000557872, ENST00000560035

RefSeq mRNA: 2 — MANE Select: NM_012125 NM_001320917, NM_012125

CCDS: CCDS10031

Canonical transcript exons

ENST00000383263 — 3 exons

Exon	Start	End
ENSE00001495767	34046540	34046871
ENSE00001530083	33968497	33969150
ENSE00003730937	34062643	34067458

Expression profiles

Bgee: expression breadth ubiquitous, 102 present calls, max score 81.39.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3042 / max 54.2742, expressed in 75 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
145781	0.1722	39
145780	0.0474	29
145782	0.0344	17
145784	0.0281	9
207461	0.0221	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
diaphragm	UBERON:0001103	81.39	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.25	gold quality
type B pancreatic cell	CL:0000169	75.80	gold quality
olfactory bulb	UBERON:0002264	74.92	gold quality
hair follicle	UBERON:0002073	69.06	gold quality
left ventricle myocardium	UBERON:0006566	67.89	gold quality
tongue squamous epithelium	UBERON:0006919	67.67	gold quality
mucosa of paranasal sinus	UBERON:0005030	67.53	gold quality
cardiac muscle of right atrium	UBERON:0003379	67.38	gold quality
corpus callosum	UBERON:0002336	67.26	gold quality
cervix squamous epithelium	UBERON:0006922	67.06	gold quality
decidua	UBERON:0002450	67.01	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	66.05	gold quality
vastus lateralis	UBERON:0001379	65.98	gold quality
nasal cavity epithelium	UBERON:0005384	65.96	gold quality
epithelial cell of pancreas	CL:0000083	65.93	gold quality
quadriceps femoris	UBERON:0001377	65.49	gold quality
spinal cord	UBERON:0002240	65.15	gold quality
cervix epithelium	UBERON:0004801	64.94	gold quality
CA1 field of hippocampus	UBERON:0003881	64.35	gold quality
thymus	UBERON:0002370	64.08	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	63.93	gold quality
mucosa of urinary bladder	UBERON:0001259	63.27	gold quality
upper arm skin	UBERON:0004263	63.05	gold quality
pancreatic ductal cell	CL:0002079	62.71	silver quality
substantia nigra	UBERON:0002038	62.34	gold quality
hypothalamus	UBERON:0001898	62.23	gold quality
midbrain	UBERON:0001891	61.86	gold quality
orbitofrontal cortex	UBERON:0004167	61.82	gold quality
epithelium of nasopharynx	UBERON:0001951	60.60	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.90

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR

miRNA regulators (miRDB)

35 targeting CHRM5, 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-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-1208	99.70	68.28	1533
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-3685	99.62	68.83	1621
HSA-MIR-488-3P	99.61	68.79	1731
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-7159-3P	99.51	70.17	1920
HSA-MIR-6740-3P	99.48	68.49	1392
HSA-MIR-516A-3P	99.46	67.96	1378
HSA-MIR-516B-3P	99.46	67.96	1378
HSA-MIR-7162-5P	99.46	68.08	1368
HSA-MIR-4318	99.38	66.94	1505
HSA-MIR-2116-5P	99.32	69.34	1273
HSA-MIR-155-3P	99.03	67.99	924
HSA-MIR-6761-5P	98.71	68.03	1504
HSA-MIR-218-1-3P	98.63	67.97	832
HSA-MIR-3613-5P	98.40	68.91	604
HSA-MIR-6730-5P	98.03	68.12	1299
HSA-MIR-5681A	97.99	67.17	1658
HSA-MIR-5196-3P	97.57	65.98	979

Literature-anchored findings (GeneRIF, showing 6)

• Immunological stimulation leads to M5 mAChR gene expression in lymphocytes. (PMID:12675126)
• direct evidence suggesting that the M5 muscarinic receptor gene combined with the alpha7-nicotinic receptor gene may be linked to schizophrenia (PMID:15292665)
• mAChR subtypes (m1 to m5)presents in human scleral fibroblasts at both mRNA and protein levels. (PMID:16877267)
• the first study to show an association between CHRM5 and substance use in humans (PMID:17608938)
• the M(3)/M(5) subtypes appear to be the major contributor, leading to intracellular calcium mobilization from the internal store via an IP(3)-dependent pathway in the undifferentiated retinoblastoma cells. (PMID:17951979)
• Cigarette smoking may contribute to this imbalance by affecting the polarization and survival of Th/Tregs through the up-regulation of MR3 and MR5. (PMID:25375131)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	chrm5b	ENSDARG00000069598
danio_rerio	chrm5a	ENSDARG00000099928
mus_musculus	Chrm5	ENSMUSG00000074939
rattus_norvegicus	Chrm5	ENSRNOG00000006397

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), CHRM1 (ENSG00000168539), DRD5 (ENSG00000169676), HTR1A (ENSG00000178394), HTR1D (ENSG00000179546), CHRM4 (ENSG00000180720), CHRM2 (ENSG00000181072), DRD1 (ENSG00000184845), GPR21 (ENSG00000188394), HRH1 (ENSG00000196639), GPR52 (ENSG00000203737), TAAR9 (ENSG00000237110)

Protein

Protein identifiers

Muscarinic acetylcholine receptor M5 — P08912 (reviewed: P08912)

All UniProt accessions (2): P08912, H0YKC0

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.

Subcellular location. Cell membrane. Postsynaptic cell membrane.

Similarity. Belongs to the G-protein coupled receptor 1 family. Muscarinic acetylcholine receptor subfamily. CHRM5 sub-subfamily.

RefSeq proteins (2): NP_001307846, NP_036257* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000502	Musac_Ach_M5_rcpt	Family
IPR000995	Musac_Ach_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (39 total): helix 13, topological domain 8, transmembrane region 7, compositionally biased region 2, modified residue 2, chain 1, region of interest 1, glycosylation site 1, disulfide bond 1, sequence conflict 1, turn 1, strand 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6OL9	X-RAY DIFFRACTION	2.54
9EK0	ELECTRON MICROSCOPY	2.79

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P08912-F1	69.14	0.45

Functional residue map

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

Post-translational modifications (2): 501, 505

Disulfide bonds (1): 103–183

Glycosylation sites (1): 8

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: 127 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, GOBP_LIPID_MODIFICATION, GOBP_DIGESTION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, MULLIGHAN_NPM1_SIGNATURE_3_UP, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_ACID_SECRETION, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, GOBP_PHOSPHOLIPID_DEPHOSPHORYLATION, chr15q14, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_REGULATION_OF_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_CELL_CELL_SIGNALING, GOBP_ORGANIC_HYDROXY_COMPOUND_TRANSPORT

GO Biological Process (11): gastric acid secretion (GO:0001696), 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), G protein-coupled acetylcholine receptor signaling pathway (GO:0007213), chemical synaptic transmission (GO:0007268), obsolete dopamine transport (GO:0015872), transmission of nerve impulse (GO:0019226), regulation of phosphatidylinositol dephosphorylation (GO:0060304), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186), 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 (5): plasma membrane (GO:0005886), dendrite (GO:0030425), synapse (GO:0045202), postsynaptic membrane (GO:0045211), membrane (GO:0016020)

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	3
G protein-coupled acetylcholine receptor signaling pathway	2
cell communication	2
acetylcholine receptor activity	2
digestive system process	1
acid secretion	1
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	1
G protein-coupled acetylcholine receptor activity	1
acetylcholine receptor signaling pathway	1
anterograde trans-synaptic signaling	1
action potential	1
chemical synaptic transmission	1
nervous system process	1
regulation of lipid metabolic process	1
regulation of dephosphorylation	1
phosphatidylinositol dephosphorylation	1
regulation of phosphorus metabolic process	1
regulation of macromolecule metabolic process	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
postsynaptic signal transduction	1
cellular response to acetylcholine	1
C-type glycerophospholipase activity	1
G protein-coupled amine receptor activity	1
G protein-coupled neurotransmitter receptor activity	1
transmembrane signaling receptor activity	1
binding	1
membrane	1
cell periphery	1
neuron projection	1
dendritic tree	1
cell junction	1
synaptic membrane	1
postsynapse	1
cellular anatomical structure	1

Protein interactions and networks

STRING

594 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHRM5	CHRNB2	P17787	660
CHRM5	CHRNA4	P43681	633
CHRM5	GRIN2A	Q12879	497
CHRM5	CHRNA5	P30532	493
CHRM5	GRIA3	P42263	482
CHRM5	GRIK3	Q13003	474
CHRM5	GRM5	P41594	470
CHRM5	CHRNB4	P30926	464
CHRM5	CHRNA6	Q15825	463
CHRM5	CHRNA2	Q15822	463
CHRM5	GRIN2B	Q13224	462
CHRM5	CHRNB1	P11230	460
CHRM5	GRID1	Q9ULK0	460
CHRM5	SYDE2	Q5VT97	445
CHRM5	CHRNB3	Q05901	438

IntAct

50 interactions, top by confidence:

A	B	Type	Score
CHRM5	CHRM3	psi-mi:“MI:0915”(physical association)	0.590
CHRM5	CHRM3	psi-mi:“MI:0403”(colocalization)	0.590
CHRM5	CHRM3	psi-mi:“MI:2364”(proximity)	0.590
CHRM3	CHRM5	psi-mi:“MI:2364”(proximity)	0.590
	CHRM5	psi-mi:“MI:0915”(physical association)	0.400
CHRM5	RAMP1	psi-mi:“MI:0915”(physical association)	0.400
CHRM5	RAMP2	psi-mi:“MI:0915”(physical association)	0.400
RAMP2	CHRM5	psi-mi:“MI:0915”(physical association)	0.400
RAMP3	CHRM5	psi-mi:“MI:0915”(physical association)	0.400
CHRM5	RAMP3	psi-mi:“MI:0915”(physical association)	0.400
CHRM5	CHRM5	psi-mi:“MI:2364”(proximity)	0.380
CHRM5	CHRM5	psi-mi:“MI:0403”(colocalization)	0.380
USP33	CHRM5	psi-mi:“MI:0915”(physical association)	0.370
TMEM161A	CHRM5	psi-mi:“MI:0915”(physical association)	0.370
SNCA	CHRM5	psi-mi:“MI:0915”(physical association)	0.370
MSMO1	CHRM5	psi-mi:“MI:0915”(physical association)	0.370
STARD3NL	CHRM5	psi-mi:“MI:0915”(physical association)	0.370
SPNS1	CHRM5	psi-mi:“MI:0915”(physical association)	0.370
SLC6A8	CHRM5	psi-mi:“MI:0915”(physical association)	0.370
SLC5A6	CHRM5	psi-mi:“MI:0915”(physical association)	0.370
SLC2A6	CHRM5	psi-mi:“MI:0915”(physical association)	0.370
SMAD6	CHRM5	psi-mi:“MI:0915”(physical association)	0.370
RTN1	CHRM5	psi-mi:“MI:0915”(physical association)	0.370
REEP5	CHRM5	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (37): RGS7 (Reconstituted Complex), USP33 (Two-hybrid), TMEM161A (Two-hybrid), SNCA (Two-hybrid), MSMO1 (Two-hybrid), STARD3NL (Two-hybrid), SPNS1 (Two-hybrid), SLC6A8 (Two-hybrid), SLC5A6 (Two-hybrid), SLC2A6 (Two-hybrid), SMAD6 (Two-hybrid), RTN1 (Two-hybrid), REEP5 (Two-hybrid), PRSS16 (Two-hybrid), NLE1 (Two-hybrid)

ESM2 similar proteins: A0A2L0VBG2, A1ZAX0, O62169, O77408, P08483, P08911, P08912, P11483, P16395, P17970, P20309, P30974, P30994, P32240, P41595, P41984, P43114, P49578, P56490, Q09388, Q09502, Q18007, Q24352, Q24563, Q28691, Q29J90, Q2KNE5, Q4LBB9, Q4V622, Q5IS53, Q5IS98, Q7JQF1, Q7KVW5, Q868T3, Q8ITC7, Q8ITC9, Q8MJ08, Q920H4, Q9ERZ3, Q9N2A2

Diamond homologs: A1ZAX0, B2ZI34, E7F7V7, F1MV99, F1R332, O08726, O08786, O43603, O54798, O54799, O62709, O88626, O88854, O97666, O97772, O97967, P05363, P08911, P08912, P21451, P21729, P22270, P24053, P24530, P25101, P26684, P28088, P28336, P28646, P30550, P30551, P30552, P30553, P30796, P30872, P30873, P30937, P30974, P31391, P32238

SIGNOR signaling

12 interactions.

A	Effect	B	Mechanism
CHRM5	“up-regulates activity”	GNAI1	binding
CHRM5	“up-regulates activity”	GNAI3	binding
CHRM5	“up-regulates activity”	GNAO1	binding
CHRM5	“up-regulates activity”	GNAZ	binding
CHRM5	“up-regulates activity”	GNAQ	binding
CHRM5	“up-regulates activity”	GNA14	binding
CHRM5	“up-regulates activity”	GNA15	binding
acetylcholine	“up-regulates activity”	CHRM5	“chemical activation”
atropine	“down-regulates activity”	CHRM5	“chemical inhibition”
Hexocyclium	“down-regulates activity”	CHRM5	“chemical inhibition”
dothiepin	“down-regulates activity”	CHRM5	“chemical inhibition”
amitriptyline	“down-regulates activity”	CHRM5	“chemical inhibition”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 36 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
receptor internalization	5	46.3×	3e-05
protein transport	6	7.5×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	0
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1593 predictions. Top by Δscore:

Variant	Effect	Δscore
15:34003026:TCATA:T	donor_loss	1.0000
15:34003027:CATAC:C	donor_loss	1.0000
15:34003028:ATACC:A	donor_loss	1.0000
15:34003029:TACCT:T	donor_loss	1.0000
15:34003030:ACCT:A	donor_loss	1.0000
15:34003031:C:T	donor_loss	1.0000
15:34003031:CCTG:C	donor_gain	1.0000
15:34003205:TCAAC:T	acceptor_gain	1.0000
15:34003206:CAAC:C	acceptor_gain	1.0000
15:34003206:CAACC:C	acceptor_gain	1.0000
15:34003207:AAC:A	acceptor_gain	1.0000
15:34003208:AC:A	acceptor_gain	1.0000
15:34003209:CC:C	acceptor_gain	1.0000
15:34003210:C:CC	acceptor_gain	1.0000
15:34003213:C:CT	acceptor_gain	1.0000
15:34003217:C:CT	acceptor_gain	1.0000
15:34003218:A:C	acceptor_gain	1.0000
15:34003218:A:T	acceptor_gain	1.0000
15:34003219:T:C	acceptor_gain	1.0000
15:34003219:T:TC	acceptor_gain	1.0000
15:33987855:G:GT	donor_gain	0.9900
15:34003030:A:AC	donor_gain	0.9900
15:34003031:C:CC	donor_gain	0.9900
15:34003157:C:A	donor_gain	0.9900
15:34003214:A:T	acceptor_gain	0.9900
15:34003218:A:AC	acceptor_gain	0.9900
15:34038773:CTCTT:C	donor_loss	0.9900
15:34038774:TCTTA:T	donor_loss	0.9900
15:34038775:CTTA:C	donor_loss	0.9900
15:34038776:TTA:T	donor_loss	0.9900

AlphaMissense

3485 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:34062861:T:A	N48K	1.000
15:34062861:T:G	N48K	1.000
15:34062928:A:C	S71R	1.000
15:34062930:C:A	S71R	1.000
15:34062930:C:G	S71R	1.000
15:34062932:T:C	L72S	1.000
15:34062943:G:C	D76H	1.000
15:34062944:A:C	D76A	1.000
15:34062944:A:G	D76G	1.000
15:34062944:A:T	D76V	1.000
15:34063025:G:A	C103Y	1.000
15:34063046:A:T	D110V	1.000
15:34063079:T:C	L121P	1.000
15:34063090:A:C	S125R	1.000
15:34063092:T:A	S125R	1.000
15:34063092:T:G	S125R	1.000
15:34063100:G:C	R128P	1.000
15:34063180:T:A	W155R	1.000
15:34063180:T:C	W155R	1.000
15:34063201:T:A	W162R	1.000
15:34063201:T:C	W162R	1.000
15:34063321:T:C	F202L	1.000
15:34063323:C:A	F202L	1.000
15:34063323:C:G	F202L	1.000
15:34064068:T:C	F451L	1.000
15:34064070:C:A	F451L	1.000
15:34064070:C:G	F451L	1.000
15:34064080:T:A	W455R	1.000
15:34064080:T:C	W455R	1.000
15:34064178:T:A	N487K	1.000

dbSNP variants (sampled 300 via entrez): RS1000006925 (15:34053652 TCCTTATA>T), RS1000033054 (15:33979250 G>A,T), RS1000089211 (15:33996366 A>G), RS1000113118 (15:33974018 A>G), RS1000114881 (15:34003465 T>A,C), RS1000143686 (15:33969879 T>C), RS1000191887 (15:34066940 C>A), RS1000201618 (15:34066652 T>C), RS1000235063 (15:34001528 TCC>T), RS1000280892 (15:34046774 C>A,T), RS1000283140 (15:33994220 A>T), RS1000312545 (15:34007162 A>G), RS1000328079 (15:34010313 T>C), RS1000384685 (15:34016375 T>C), RS1000404451 (15:34040685 T>C)

Disease associations

OMIM: gene MIM:118496 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST010725_22	Malaria	3.000000e-06
GCST010725_37	Malaria	3.000000e-06
GCST010725_54	Malaria	5.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2035 (SINGLE PROTEIN), CHEMBL2094109 (PROTEIN FAMILY), CHEMBL2111352 (SELECTIVITY GROUP), CHEMBL2111417 (CHIMERIC PROTEIN)

Molecules with ChEMBL bioactivity

111 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 289,555 (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
CHEMBL1092	TRIHEXYPHENIDYL HYDROCHLORIDE	4	7,793
CHEMBL11	IMIPRAMINE	4	48,893
CHEMBL1108	DROPERIDOL	4	16,888
CHEMBL1113	AMOXAPINE	4	20,128
CHEMBL1123	DICYCLOMINE	4	8,691
CHEMBL1172	DESLORATADINE	4	19,720
CHEMBL1184	ACETYLCHOLINE CHLORIDE	4	3,851
CHEMBL1200406	DIMENHYDRINATE	4	26,424
CHEMBL1200604	TROPICAMIDE	4	14,498
CHEMBL1201027	GLYCOPYRRONIUM BROMIDE	4	14,355
CHEMBL1201203	BENZTROPINE	4	9,334
CHEMBL1201207	BETAMETHASONE PHOSPHORIC ACID	4	954
CHEMBL1201217	DYCLONINE	4	7,785
CHEMBL1201353	DEXCHLORPHENIRAMINE	4	8,566
CHEMBL1221	SULCONAZOLE	4	12,121
CHEMBL1231	OXYBUTYNIN	4	15,072
CHEMBL126224	IPRINDOLE	4	4,398
CHEMBL1263	SALMETEROL	4	40,383
CHEMBL1319362	HOMATROPINE HYDROBROMIDE	4	1,442
CHEMBL1346	DARIFENACIN	4	8,259
CHEMBL1354199	METHSCOPOLAMINE BROMIDE	4
CHEMBL1382	TOLTERODINE	4
CHEMBL14	CARBACHOL	4
CHEMBL1411979	METHAPYRILENE	4
CHEMBL1490	TRIHEXYPHENIDYL	4
CHEMBL1529	DIPHENIDOL HYDROCHLORIDE	4
CHEMBL1535	HYDROXYCHLOROQUINE	4
CHEMBL1621597	IPRATROPIUM	4
CHEMBL1626	CLEMASTINE	4
CHEMBL1628227	DOXEPIN	4

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Acetylcholine receptors (muscarinic)

Most potent curated ligand interactions (63 total), top 25:

Ligand	Action	Affinity	Parameter
[3H]QNB	Antagonist	10.7	pKd
tiotropium	Antagonist	10.2	pKi
umeclidinium	Antagonist	9.9	pKi
aclidinium	Antagonist	9.9	pKi
glycopyrrolate	Antagonist	9.9	pKi
[3H]N-methyl scopolamine	Antagonist	9.7	pKd
AE9C90CB	Antagonist	9.5	pKi
atropine	Antagonist	9.3	pKi
4-DAMP	Antagonist	9.0	pKi
ipratropium	Antagonist	8.8	pKi
tolterodine	Antagonist	8.8	pKi
silahexocyclium	Antagonist	8.7	pKi
scopolamine	Antagonist	8.7	pKi
darifenacin	Antagonist	8.6	pKi
hexocyclium	Antagonist	8.4	pKi
[3H]iperoxo	Agonist	8.3	pKd
UH-AH 37	Antagonist	8.3	pKi
NNC 11-1585	Full agonist	8.3	pKi
NNC 11-1607	Full agonist	8.2	pKi
revefenacin	Antagonist	8.2	pKi
biperiden	Antagonist	8.2	pKd
oxybutynin	Antagonist	7.9	pKi
amitriptyline	Antagonist	7.8	pKi
AQ-RA 741	Antagonist	7.8	pKi
NNC 11-1314	Full agonist	7.8	pKi

Binding affinities (BindingDB)

81 measured of 115 human assays (144 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
NSC_104911	KI	0.1 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-(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
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
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
NNC 11-1607	KI	2.4 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-Cyclohexyl-1-phenyl-3-pyrrolidin-1-yl-propan-1-ol	KI	4.6 nM
CHEMBL196218	EC50	4.79 nM
Enablex	KI	5.5 nM
CHEMBL194008	EC50	6.46 nM
HHSiD	KI	14 nM
Isoptpo Hyoscine	KI	18 nM
CAS_5311091	KI	22.4 nM
NSC_2054314	KI	26.3 nM
CHEMBL364454	EC50	26.9 nM
NSC_129989	KI	28.8 nM
NSC_119356	KI	30.9 nM
1-(4-{3-[4-(6-Fluoro-benzo[d]isoxazol-3-yl)-piperidin-1-yl]-propoxy}-3-methoxy-phenyl)-ethanone	KI	33 nM
Fluorocarazolol,(S)	KI	34 nM
NNC 11-1314	KI	41.7 nM
CHEMBL194793	EC50	44.7 nM
Dimethyl-[2-(phenyl-o-tolyl-methoxy)-ethyl]-amine	KI	48 nM
CHEMBL372536	EC50	50.1 nM
LY 246708	KI	50.1 nM
5-(1-methylpiperidylidene-4)-5H-dibenzo(a,d)cyclopheptene	KI	59 nM
CHEMBL197092	EC50	79.4 nM
NSC_40589	KI	85 nM
CHEMBL194196	EC50	89.1 nM
3-[4-(2-Methyl-1H-imidazol-1-yl)-2-butynyl]oxy-delta2-isoxazoline sesquifumarate	KI	91.2 nM
CHEMBL196151	EC50	93.3 nM
2-{3-[4-(3-chlorophenyl)piperazin-1-yl]propyl}[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one	KI	96 nM
CHEMBL373341	EC50	104 nM
HIMBACINE	KI	107 nM
NSC_0	KI	120 nM
METHOCTRAMINE	KI	150 nM
NSC_0	KI	229 nM
CHEMBL194847	EC50	263 nM
2-[4-(2,3-Dimethyl-1H-imidazolium-1-yl)-2-butynyl]isoxazolidin-3-one iodide	KI	275 nM
cis-doxepin	KI	276 nM
NORTRIPTYLINE	KI	294 nM
CAS_121029-35-4	KI	427 nM

ChEMBL bioactivities

1910 potent at pChembl≥5 of 2093 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
10.58	Ki	0.0266	nM	TIOTROPIUM BROMIDE
10.46	Kd	0.03467	nM	CHEMBL320611
10.35	Ki	0.045	nM	QUINUCLIDINYL BENZILATE
10.30	ED50	0.05	nM	ATROPINE
10.29	Ki	0.051	nM	QUINUCLIDINYL BENZILATE
10.27	Ki	0.054	nM	CHEMBL320611
10.00	IC50	0.1	nM	TIOTROPIUM BROMIDE
9.97	Ki	0.1072	nM	CHEMBL219786
9.85	Ki	0.14	nM	ENDO-ATROPINE
9.82	ED50	0.15	nM	ATROPINE
9.80	IC50	0.1585	nM	ACLIDINIUM BROMIDE
9.77	Ki	0.169	nM	PF-03635659
9.70	Ki	0.1995	nM	CHEMBL376057
9.70	Kd	0.2	nM	CHEMBL4860528
9.70	Kd	0.2	nM	CHEMBL5207281
9.70	Kd	0.2	nM	CHEMBL5206565
9.70	Kd	0.2	nM	CHEMBL5201074
9.70	Ki	0.2	nM	QUINUCLIDINYL BENZILATE
9.70	IC50	0.1995	nM	GLYCOPYRRONIUM BROMIDE
9.68	Ki	0.2089	nM	METHSCOPOLAMINE
9.68	Ki	0.21	nM	ATROPINE
9.66	Ki	0.22	nM	4-DAMP
9.62	Ki	0.24	nM	QUINUCLIDINYL BENZILATE
9.57	Ki	0.27	nM	CHEMBL331497
9.57	Ki	0.27	nM	AZAPROPHEN
9.55	Ki	0.279	nM	CHEMBL320611
9.52	Kd	0.302	nM	CHEMBL321214
9.49	IC50	0.32	nM	4-DAMP
9.49	Ki	0.32	nM	ATROPINE
9.49	Ki	0.32	nM	METHSCOPOLAMINE BROMIDE
9.47	Ki	0.3388	nM	ENDO-ATROPINE
9.47	Ki	0.34	nM	ENDO-ATROPINE
9.40	Ki	0.4	nM	ATROPINE
9.39	Ki	0.4074	nM	CHEMBL375969
9.38	Ki	0.42	nM	4-DAMP
9.35	IC50	0.45	nM	4-DAMP
9.35	Kd	0.4467	nM	CHEMBL321214
9.35	Ki	0.449	nM	CHEMBL318812
9.35	IC50	0.446	nM	METHSCOPOLAMINE BROMIDE
9.32	Ki	0.48	nM	4-DAMP
9.32	Ki	0.475	nM	CHEMBL321214
9.27	Ki	0.54	nM	ATROPINE
9.22	Ki	0.6	nM	ATROPINE
9.21	Ki	0.61	nM	CHEMBL331497
9.18	Ki	0.6607	nM	CHEMBL4645580
9.18	Ki	0.662	nM	ATROPINE
9.14	Ki	0.72	nM	CHEMBL331497
9.11	Ki	0.7762	nM	CHEMBL222259
9.10	IC50	0.8	nM	4-DAMP

PubChem BioAssay actives

1691 with measured affinity, of 3982 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
Tiotropium Bromide Monohydrate	627083: Displacement of [3H]-NMS from human recombinant M5 receptor expressed in CHO cells after 24 hrs by filter binding assay	ki	<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
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
[(1R,5S)-8-methyl-8-azabicyclo[3.2.1]octan-3-yl] (2S)-3-hydroxy-2-phenylpropanoate	757595: Antagonist activity at muscarinic M5 receptor (unknown origin) by PDSP assay	ki	0.0001	uM
(2S)-2-[(2R,5S)-2-cyclohexyl-2-phenyl-1,3-oxathiolan-5-yl]-1,1-dimethylpyrrolidin-1-ium iodide	280355: Binding affinity to human cloned muscarinic receptor M5 expressed in CHO cells	ki	0.0001	uM
Aclidinium Bromide	539983: Displacement of [3H]NMS from human muscarinic M5 receptor expressed in CHO-K1 cells after 16 hrs by scintillation proximity assay	ic50	0.0002	uM
Glycopyrrolate	539983: Displacement of [3H]NMS from human muscarinic M5 receptor expressed in CHO-K1 cells after 16 hrs by scintillation proximity assay	ic50	0.0002	uM
5-[3-(3-hydroxyphenoxy)azetidin-1-yl]-5-methyl-2,2-diphenylhexanamide	627083: Displacement of [3H]-NMS from human recombinant M5 receptor expressed in CHO cells after 24 hrs by filter binding assay	ki	0.0002	uM
(2S)-2-[(2S,5S)-2-cyclohexyl-2-phenyl-1,3-oxathiolan-5-yl]-1,1-dimethylpyrrolidin-1-ium iodide	280355: Binding affinity to human cloned muscarinic receptor M5 expressed in CHO cells	ki	0.0002	uM
1-[N’-[3-(2-amino-4-methyl-1,3-thiazol-5-yl)propyl]carbamimidoyl]-3-pentylurea	1895230: Displacement of [3H]N-methylscopolamine from human muscarinic acetylcholine M5 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	1895230: Displacement of [3H]N-methylscopolamine from human muscarinic acetylcholine M5 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)	1895230: Displacement of [3H]N-methylscopolamine from human muscarinic acetylcholine M5 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)	1895230: Displacement of [3H]N-methylscopolamine from human muscarinic acetylcholine M5 receptor stably expressed in CHO cells by radioligand competition binding based analysis	kd	0.0002	uM
[(1S,5R)-8-methyl-8-azabicyclo[3.2.1]octan-3-yl] 3-hydroxy-2-phenylpropanoate	371750: Activation of human muscarinic M5 receptor expressed in CHO cells coexpressing Gq protein assessed as increase in acetylcholine potency at 30 uM by calcium mobilization-based ACh concentration-response curve assay relative to control	ki	0.0002	uM
(1,1-dimethylpiperidin-1-ium-4-yl) 2,2-diphenylacetate iodide	751874: Binding affinity to human muscarinic M5 receptor by radioligand displacement assay	ki	0.0002	uM
[(1S,2S,4R,5R)-9,9-dimethyl-3-oxa-9-azoniatricyclo[3.3.1.02,4]nonan-7-yl] (2S)-3-hydroxy-2-phenylpropanoate	280355: Binding affinity to human cloned muscarinic receptor M5 expressed in CHO cells	ki	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
(6-methyl-6-azabicyclo[3.2.1]octan-3-yl) 2,2-diphenylpropanoate	141400: Inhibit the binding of [N-mnethyl-3H]-scopolamine [3H]-NMS) to Muscarinic acetylcholine receptor of human IRM-30 neuroblastoma cells	ki	0.0003	uM
[(3R)-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	0.0003	uM
(2S)-2-[(5S)-2,2-diphenyl-1,3-oxathiolan-5-yl]-1,1-dimethylpyrrolidin-1-ium iodide	280355: Binding affinity to human cloned muscarinic receptor M5 expressed in CHO cells	ki	0.0004	uM
[(2S,6S)-6-cyclohexyl-6-phenyl-1,4-dioxan-2-yl]methyl-trimethylazanium iodide	1654801: Displacement of [3H]NMS from human recombinant muscarinic receptor M5 expressed in CHO-K1 cell membranes incubated for 2 hrs by scintillation counting method	ki	0.0007	uM
4-[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	0.0008	uM
(2R)-2-[(2R,5R)-2-cyclohexyl-2-phenyl-1,3-oxathiolan-5-yl]-1,1-dimethylpyrrolidin-1-ium iodide	280355: Binding affinity to human cloned muscarinic receptor M5 expressed in CHO cells	ki	0.0008	uM
methyl 3-[2-(1-azabicyclo[2.2.2]oct-2-en-3-yl)furan-3-yl]benzoate	141151: Ability of compound to displace (-)-[3H]3-Quinuclidinyl benzilate (-)-[3H]-QNB from Muscarinic acetylcholine receptors in the parotid gland from Guinea Pig.	ki	0.0008	uM
N,N-dimethylpyridin-4-amine	2114043: Displacement of [3H] N-Methylscopolamine from human recombinant M5 receptor expressed in CHO-K1 cell membranes incubated for 2 hrs	ki	0.0010	uM
(8-methyl-8-propan-2-yl-8-azoniabicyclo[3.2.1]octan-3-yl) 3-hydroxy-2-phenylpropanoate;bromide;hydrate	627083: Displacement of [3H]-NMS from human recombinant M5 receptor expressed in CHO cells after 24 hrs by filter binding assay	ki	0.0010	uM
5-[(1R)-2-[2-[4-[2-[4-[[3-[(R)-cyclohexyl-hydroxy-phenylmethyl]-1,2,4-triazol-1-yl]methyl]piperidin-1-yl]ethyl]phenyl]ethylamino]-1-hydroxyethyl]-8-hydroxy-1H-quinolin-2-one	1253956: Antagonist activity at muscarinic M5 receptor (unknown origin)	ki	0.0011	uM
(2R)-2-[(2R,5R)-2-cyclohexyl-2-phenyl-1,3-oxathiolan-5-yl]-1-methylpyrrolidine	280355: Binding affinity to human cloned muscarinic receptor M5 expressed in CHO cells	ki	0.0012	uM
Acetylcholine	511603: Agonist activity at human muscarinic M5 receptor expressed in BHK-21 cells assessed as increase of acetylcholine-induced calcium flux by FLIPR assay	ec50	0.0012	uM
(2S)-2-[(2R,5S)-2-cyclohexyl-2-phenyl-1,3-oxathiolan-5-yl]-1-methylpyrrolidine	280355: Binding affinity to human cloned muscarinic receptor M5 expressed in CHO cells	ki	0.0013	uM
[(1S,2S,4R,5R)-9-methyl-3-oxa-9-azatricyclo[3.3.1.02,4]nonan-7-yl] (2S)-3-hydroxy-2-phenylpropanoate	1185261: Displacement of [3H]-NMS from wild-type human muscarinic M5 receptor expressed in CHO-K1 cells by liquid scintillation counting	ki	0.0013	uM
3-(5-bromo-3-phenylfuran-2-yl)-1-azabicyclo[2.2.2]oct-2-ene	141149: Ability of compound to displace (-)-[3H]3-Quinuclidinyl benzilate (-)-[3H]-QNB from Muscarinic acetylcholine receptors in cerebral cortex from Guinea Pig.	ki	0.0015	uM
1-[(2S,6S)-6-cyclohexyl-6-phenyl-1,4-dioxan-2-yl]-N,N-dimethylmethanamine	1654801: Displacement of [3H]NMS from human recombinant muscarinic receptor M5 expressed in CHO-K1 cell membranes incubated for 2 hrs by scintillation counting method	ki	0.0015	uM
(R)-cyclohexyl-[5-[(2R)-1,1-dimethylpyrrolidin-1-ium-2-yl]furan-2-yl]-phenylmethanol iodide	445081: Displacement of [3H]NMS from human cloned muscarinic M5 receptor expressed in CHO cells by scintillation counting	ki	0.0015	uM
1-cyclohexyl-4-[1-[4-(4-methoxyphenyl)sulfinylphenyl]ethyl]piperidine	142156: The compound was tested for the binding affinity against Muscarinic acetylcholine receptor M5	ki	0.0017	uM
[(2S)-6,6-diphenyl-1,4-dioxan-2-yl]methyl-trimethylazanium iodide	668959: Displacement of [3H]N-methylscopolamine from human muscarinic M5 receptor expressed in CHO cells after 120 mins by scintillation counting	ki	0.0017	uM
1-azabicyclo[2.2.2]octan-3-yl N-[2-(4-fluorophenyl)ethyl]-N-phenylcarbamate	1574984: Displacement of [3H]NMS from human M5 AChR expressed in CHO cell membranes after 1 to 2 hrs by liquid scintillation spectrometry method	ki	0.0018	uM
1-[(2S)-6,6-diphenyl-1,4-dioxan-2-yl]-N,N-dimethylmethanamine	1491321: Displacement of [3H]NMS from recombinant human muscarinic M5 receptor expressed in CHOK1 cell membranes after 120 mins by scintillation counting method	ki	0.0018	uM
1-[(2S)-6,6-diphenyl-1,4-dioxan-2-yl]-N,N-dimethylmethanamine;oxalic acid	668959: Displacement of [3H]N-methylscopolamine from human muscarinic M5 receptor expressed in CHO cells after 120 mins by scintillation counting	ki	0.0018	uM
3-[3-(3-ethylphenyl)furan-2-yl]-1-azabicyclo[2.2.2]oct-2-ene	141150: Ability of compound to displace (-)-[3H]3-Quinuclidinyl benzilate (-)-[3H]-QNB from Muscarinic acetylcholine receptors in the heart from Guinea Pig.	ki	0.0019	uM
(2R)-2-[(2S,5R)-2-cyclohexyl-2-phenyl-1,3-oxathiolan-5-yl]-1-methylpyrrolidine	280355: Binding affinity to human cloned muscarinic receptor M5 expressed in CHO cells	ki	0.0020	uM
(2S)-2-[(2S,5S)-2-cyclohexyl-2-phenyl-1,3-oxathiolan-5-yl]-1-methylpyrrolidine	280355: Binding affinity to human cloned muscarinic receptor M5 expressed in CHO cells	ki	0.0020	uM
(1S,9R)-1-methyl-16-azatetracyclo[7.6.1.02,7.010,15]hexadeca-2,4,6,10,12,14-hexaene	255298: Percent inhibition against Muscarinic acetylcholine receptor M5 at 1 uM	ic50	0.0020	uM
methyl 4-[2-(1-azabicyclo[2.2.2]oct-2-en-3-yl)furan-3-yl]benzoate	141151: Ability of compound to displace (-)-[3H]3-Quinuclidinyl benzilate (-)-[3H]-QNB from Muscarinic acetylcholine receptors in the parotid gland from Guinea Pig.	ki	0.0022	uM
Tolterodine	320807: Displacement of [3H]N-methyl Scopolamine from human cloned muscarinic M5 receptor expressed in CHO cells	ki	0.0022	uM
4-[3-[2-(1-azabicyclo[2.2.2]oct-2-en-3-yl)furan-3-yl]phenyl]morpholine	141150: Ability of compound to displace (-)-[3H]3-Quinuclidinyl benzilate (-)-[3H]-QNB from Muscarinic acetylcholine receptors in the heart from Guinea Pig.	ki	0.0023	uM
1-[3-[4-[7-[[4-(1-methyl-3,6-dihydro-2H-pyridin-5-yl)-1,2,5-thiadiazol-3-yl]oxy]heptyl]piperidin-1-yl]propyl]-3,4-dihydroquinolin-2-one	1167232: Displacement of [3H]NMS from human M5 receptor expressed in CHO cells by microplate scintillation counting based radioligand binding assay	ki	0.0023	uM
Darifenacin	142153: Binding affinity (Ki) against binding of [3H]NMS using membranes from CHO cells expressing cloned human Muscarinic acetylcholine receptor M5	ki	0.0023	uM
3-(5-methyl-3-phenylfuran-2-yl)-1-azabicyclo[2.2.2]oct-2-ene	141149: Ability of compound to displace (-)-[3H]3-Quinuclidinyl benzilate (-)-[3H]-QNB from Muscarinic acetylcholine receptors in cerebral cortex from Guinea Pig.	ki	0.0024	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
N-Methylscopolamine	affects binding, decreases reaction, increases reaction, affects reaction	5
Gallamine Triethiodide	increases reaction, decreases reaction, affects binding, affects reaction	3
aristolochic acid I	increases expression	1
sodium arsenite	increases expression	1
4-diphenylacetoxy-1,1-dimethylpiperidinium	affects binding, decreases reaction	1
methoctramine	affects binding, decreases reaction	1
brucine N-oxide	affects binding, increases reaction	1
CGP 52608	affects binding, increases reaction	1
dimethyl-W84	affects reaction, affects binding	1
5-(3-(3-hydroxyphenoxy)azetidin-1-yl)-5-methyl-2,2-diphenylhexanamide	affects binding	1
theaflavin-3,3’-digallate	affects expression	1
Tiotropium Bromide	affects binding	1
Rocuronium	affects binding, decreases reaction	1
Acetylcholine	increases activity, decreases reaction	1
Atropine	decreases reaction, increases activity	1
Benzo(a)pyrene	decreases methylation	1
Carbon Tetrachloride	increases expression	1
Crotalid Venoms	affects binding, decreases reaction	1
Hydrogen Peroxide	decreases expression	1
Pancuronium	affects binding, decreases reaction	1
Pilocarpine	increases expression	1
Pirenzepine	affects binding, decreases reaction	1
Quinuclidinyl Benzilate	affects binding, decreases reaction	1
Smoke	decreases expression	1
Tropicamide	affects binding, decreases reaction	1
Valproic Acid	decreases methylation	1
Vecuronium Bromide	affects binding, decreases reaction	1
Pipecuronium	affects binding, decreases reaction	1
Okadaic Acid	increases expression	1
Simvastatin	decreases reaction, affects expression, affects response to substance	1

ChEMBL screening assays

620 unique, capped per target: 421 binding, 188 functional, 10 admet, 1 unclassified

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1006040	Binding	Binding affinity to human muscarinic M5 receptor expressed in insect Sf9 cells	Nocardimicins A, B, C, D, E, and F, siderophores with muscarinic M3 receptor inhibiting activity from Nocardia sp. TP-A0674. — J Nat Prod
CHEMBL1071910	Functional	Agonist activity at human muscarinic M5 expressed in CHO cells assessed as stimulation of calcium mobilization	Chemical lead optimization of a pan G(q) mAChR M(1), M(3), M(5) positive allosteric modulator (PAM) lead. Part I: Development of the first highly selective M(5) PAM. — Bioorg Med Chem Lett
CHEMBL1738128	Unclassified	PUBCHEM_BIOASSAY: Late-stage radioligand binding dose response assay to identify inhibitors of NADPH oxidase 1 (NOX1): PDSP screen Ki. (Class of assay: screening) [Related pubchem assays (depositor defined):AID1792, AID1796, AID1823, AID253	PubChem BioAssay data set

Cellosaurus cell lines

10 cell lines: 6 spontaneously immortalized cell line, 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_F4BJ	CHO-K1 hm5	Spontaneously immortalized cell line	Female
CVCL_H458	CHO-K1/M5	Spontaneously immortalized cell line	Female
CVCL_KW70	PathHunter CHO-K1 CHRM5 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_LA06	PathHunter U2OS CHRM5 Activated GPCR Internalization	Cancer cell line	Female
CVCL_RQ20	ValiScreen human CHRM5	Spontaneously immortalized cell line	Female
CVCL_U004	CHO-CHRM5	Spontaneously immortalized cell line	Female
CVCL_YK39	U2OS CHRM5 calcium-Nomad	Cancer cell line	Female
CVCL_YK40	U2OS CHRM5 DAG-Nomad	Cancer cell line	Female
CVCL_YK41	U2OS CHRM5 HiTSeeker	Cancer cell line	Female
CVCL_ZK79	GeneBLAzer M5-NFAT-bla CHO-K1	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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