SLC18A3

Summary

SLC18A3 (solute carrier family 18 member A3, HGNC:10936) is a protein-coding gene on chromosome 10q11.23, encoding Vesicular acetylcholine transporter (Q16572). Electrogenic antiporter that exchanges one cholinergic neurotransmitter, acetylcholine or choline, with two intravesicular protons across the membrane of synaptic vesicles.

This gene is a member of the vesicular amine transporter family. The encoded transmembrane protein transports acetylcholine into secretory vesicles for release into the extracellular space. Acetylcholine transport utilizes a proton gradient established by a vacuolar ATPase. This gene is located within the first intron of the choline acetyltransferase gene.

Source: NCBI Gene 6572 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital myasthenic syndrome 21 (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 30 total — 1 likely-pathogenic
• Phenotypes (HPO): 101
• Druggable target: yes
• MANE Select transcript: NM_003055

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10936
Approved symbol	SLC18A3
Name	solute carrier family 18 member A3
Location	10q11.23
Locus type	gene with protein product
Status	Approved
Aliases	VACHT
Ensembl gene	ENSG00000187714
Ensembl biotype	protein_coding
OMIM	600336
Entrez	6572

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000374115

RefSeq mRNA: 1 — MANE Select: NM_003055 NM_003055

CCDS: CCDS7231

Canonical transcript exons

ENST00000374115 — 1 exons

Exon	Start	End
ENSE00001462507	49610310	49612720

Expression profiles

Bgee: expression breadth broad, 60 present calls, max score 91.46.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2922 / max 75.3896, expressed in 61 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
104892	0.0843	26
104891	0.0747	21
104893	0.0470	20
104888	0.0375	13
104890	0.0273	12
104889	0.0213	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.46	gold quality
endometrium epithelium	UBERON:0004811	68.03	gold quality
putamen	UBERON:0001874	65.62	gold quality
buccal mucosa cell	CL:0002336	65.05	gold quality
middle frontal gyrus	UBERON:0002702	64.29	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	63.02	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	63.00	gold quality
inferior olivary complex	UBERON:0002127	61.93	gold quality
gluteal muscle	UBERON:0002000	61.57	gold quality
triceps brachii	UBERON:0001509	61.50	gold quality
parotid gland	UBERON:0001831	61.17	gold quality
paraflocculus	UBERON:0005351	60.99	gold quality
frontal pole	UBERON:0002795	60.87	gold quality
caudate nucleus	UBERON:0001873	60.41	gold quality
tendon of biceps brachii	UBERON:0008188	59.81	gold quality
heart right ventricle	UBERON:0002080	59.13	gold quality
pancreatic ductal cell	CL:0002079	57.74	silver quality
decidua	UBERON:0002450	57.73	gold quality
myocardium	UBERON:0002349	57.54	gold quality
nasal cavity epithelium	UBERON:0005384	57.25	gold quality
medial globus pallidus	UBERON:0002477	56.61	gold quality
placenta	UBERON:0001987	56.06	gold quality
muscle layer of sigmoid colon	UBERON:0035805	55.82	gold quality
nucleus accumbens	UBERON:0001882	54.19	gold quality
epithelium of esophagus	UBERON:0001976	53.97	gold quality
cartilage tissue	UBERON:0002418	53.93	gold quality
globus pallidus	UBERON:0001875	53.92	gold quality
esophagus squamous epithelium	UBERON:0006920	53.90	gold quality
quadriceps femoris	UBERON:0001377	53.87	gold quality
vastus lateralis	UBERON:0001379	53.78	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.46

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HAND2, SATB2, STAT3

miRNA regulators (miRDB)

19 targeting SLC18A3, 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-4533	100.00	69.48	2758
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-4520-2-3P	99.14	69.28	1009
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-3135B	98.61	65.33	1470
HSA-MIR-6827-5P	98.46	64.88	1256
HSA-MIR-5681A	97.99	67.17	1658
HSA-MIR-6858-5P	96.05	64.59	1020
HSA-MIR-920	95.97	63.95	811

Literature-anchored findings (GeneRIF, showing 20)

• Three non-coding SNPs were detected in SLC18A3. None demonstrated any reproducible association with late-onset AD in our samples. (PMID:12759818)
• An 11.2 kb transgene (named hV11.2) that spanned about 5 kb upstream of the start of VACHT translation down to the first choline acetyltransferase coding exon gave variable expression in the medial habenular nucleus of transgenic mice (PMID:14622097)
• presence of VAChT in cutaneous nerves and in both epidermal melanocytes and keratinocytes as well as in their nuclei (PMID:16763548)
• Time-dependent dissociation of bound [3H]vesamicol is biphasic, but equilibrium saturation curves are not. The contrasting phasicity suggests that the pathway to and from the [3H]vesamicol binding site exists in open and at least partially closed states. (PMID:19685929)
• The colocalisation of CHT1 immunoreactivity with VAChT immunoreactivity in cholinergic enteric nerves in the human bowel thus suggests that CHT1 represents another marker of cholinergic nerves. (PMID:20490865)
• Mutations in the vesicular acetylcholine transporter demonstrate decreased affinity for acetylcholine and vesamicol. (PMID:20831599)
• overexpressed ChAT enhanced transcription of the CHT1 gene but not the VACHT gene (PMID:21163949)
• Multiple abnormalities with intellectual and developmental disability result from recurrent deletions and reciprocal duplications of 10q11.21q11.23 including CHAT and SLC18A3. (PMID:21948486)
• alpha-Synuclein expression in axons to the distal gut correlates closely with expression of the cholinergic marker, VAChT. (PMID:22821666)
• Data indicate that siRNA-mediated attenuation of vesicular acetylcholine transporter (VAChT, SLC18A3) reversed the apoptotic activity of vesamicol. (PMID:23222296)
• Expression of VAChT is increased in neuronal cell lines following upregulation of Lhx8. (PMID:24316404)
• PCMC expression of ADAM29, FLRT2, and SLC18A3 could be assessed as part of a routine screen to help identify individuals at risk of severe Obstructive sleep apnea in Asian populations (PMID:24732660)
• The results of this study suggest that the Gly360Arg mutant VAChT protein undergoes posttranslational degradation. (PMID:28188302)
• There is a distinctive pattern of human neocortical VChAT expression. The patterns of thalamic and cerebellar cortical cholinergic terminal distribution are likely unique to humans (PMID:30255936)
• In Parkinson’s disease patients, freezing of gait status is associated with reduced VACHT expression in striatal cholinergic neurons. (PMID:30720884)
• results underline the importance of including SLC18A3 sequencing in the differential diagnostics of fetuses with arthrogryposis, fetal akinesia deformation sequence, or lethal multiple pterygium syndrome of unknown etiology (PMID:31059209)
• Variants of SLC18A3 leading to congenital myasthenic syndrome in two children with varying presentations. (PMID:33462016)
• Striatal and cerebellar vesicular acetylcholine transporter expression is disrupted in human DYT1 dystonia. (PMID:33638639)
• Expression of VAChT and 5-HT in Ulcerative colitis dendritic cells. (PMID:33940317)
• Phenotypical and Myopathological Consequences of Compound Heterozygous Missense and Nonsense Variants in SLC18A3. (PMID:34943989)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc18a3a	ENSDARG00000006356
danio_rerio	slc18a3b	ENSDARG00000107527
mus_musculus	Slc18a3	ENSMUSG00000100241
drosophila_melanogaster	VAChT	FBGN0270928
caenorhabditis_elegans		WBGENE00006756

Paralogs (3): SLC18A1 (ENSG00000036565), SLC18B1 (ENSG00000146409), SLC18A2 (ENSG00000165646)

Protein

Protein identifiers

Vesicular acetylcholine transporter — Q16572 (reviewed: Q16572)

Alternative names: Solute carrier family 18 member 3

All UniProt accessions (1): Q16572

UniProt curated annotations — full annotation on UniProt →

Function. Electrogenic antiporter that exchanges one cholinergic neurotransmitter, acetylcholine or choline, with two intravesicular protons across the membrane of synaptic vesicles. Uses the electrochemical proton gradient established by the V-type proton-pump ATPase to store neurotransmitters inside the vesicles prior to their release via exocytosis. Determines cholinergic vesicular quantal size at presynaptic nerve terminals in developing neuro-muscular junctions with an impact on motor neuron differentiation and innervation pattern. Part of forebrain cholinergic system, regulates hippocampal synapse transmissions that underlie spatial memory formation. Can transport serotonin.

Subunit / interactions. Interacts with SEC14L1.

Subcellular location. Cytoplasmic vesicle. Secretory vesicle. Synaptic vesicle membrane.

Tissue specificity. Peripheral and central cholinergic nervous systems.

Disease relevance. Myasthenic syndrome, congenital, 21, presynaptic (CMS21) [MIM:617239] A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness. CMS21 is an autosomal recessive, pre-synaptic form characterized by ptosis, ophthalmoplegia, fatigable weakness, apneic crises, and deterioration of symptoms in cold water. Learning difficulties and left ventricular dysfunction may be present in some patients. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Potently inhibited by L-vesamicol, reserpine and tetrabenazine.

Similarity. Belongs to the major facilitator superfamily. Vesicular transporter family.

RefSeq proteins (1): NP_003046* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011701	MFS	Family
IPR020846	MFS_dom	Domain
IPR036259	MFS_trans_sf	Homologous_superfamily
IPR050930	MFS_Vesicular_Transporter	Family

Pfam: PF07690

Catalyzed reactions (Rhea), 3 shown:

• acetylcholine(out) + 2 H(+)(in) = acetylcholine(in) + 2 H(+)(out) (RHEA:72891)
• serotonin(in) + 2 H(+)(out) = serotonin(out) + 2 H(+)(in) (RHEA:73743)
• choline(in) + 2 H(+)(out) = choline(out) + 2 H(+)(in) (RHEA:73819)

UniProt features (71 total): helix 22, topological domain 13, transmembrane region 12, sequence variant 6, mutagenesis site 4, turn 4, strand 3, region of interest 2, site 2, glycosylation site 2, chain 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
8XTY	ELECTRON MICROSCOPY	2.7
9KKN	ELECTRON MICROSCOPY	2.72
9KQ5	ELECTRON MICROSCOPY	3.21
9KKO	ELECTRON MICROSCOPY	3.25
8XTW	ELECTRON MICROSCOPY	3.3
8XTX	ELECTRON MICROSCOPY	3.4
9WJH	ELECTRON MICROSCOPY	3.4
9WJI	ELECTRON MICROSCOPY	3.4
8ZMR	ELECTRON MICROSCOPY	3.5
9KQM	ELECTRON MICROSCOPY	3.5
8ZMS	ELECTRON MICROSCOPY	3.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16572-F1	75.88	0.41

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 (2): 193 (important for transporter activity); 398 (important for transporter activity)

Glycosylation sites (2): 89, 96

Mutagenesis-validated functional residues (4):

Position	Phenotype
309	loss of activity.
309	has normal transporter activity. retains the transporter activity; when associated with e-398.
309	has normal transporter activity. loss of activity; when associated with n-398.
398	loss of activity.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-264642	Acetylcholine Neurotransmitter Release Cycle
R-HSA-8856825	Cargo recognition for clathrin-mediated endocytosis
R-HSA-8856828	Clathrin-mediated endocytosis

MSigDB gene sets: 405 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, GOBP_NEUROMUSCULAR_JUNCTION_DEVELOPMENT, GOBP_NEUROTRANSMITTER_UPTAKE, MODULE_45, MODULE_64, GOBP_SYNAPTIC_TRANSMISSION_CHOLINERGIC, GOBP_NEUROTRANSMITTER_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, CAGCTG_AP4_Q5, SP1_Q2_01, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_CELL_CELL_SIGNALING, GOBP_ORGANIC_HYDROXY_COMPOUND_TRANSPORT, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_CELL_JUNCTION_ORGANIZATION

GO Biological Process (9): neurotransmitter transport (GO:0006836), chemical synaptic transmission (GO:0007268), positive regulation of acetylcholine secretion, neurotransmission (GO:0014057), serotonin uptake (GO:0051610), acetylcholine uptake (GO:0051630), positive regulation of long-term synaptic potentiation (GO:1900273), positive regulation of neuromuscular junction development (GO:1904398), transmembrane transport (GO:0055085), proton transmembrane transport (GO:1902600)

GO Molecular Function (5): acetylcholine transmembrane transporter activity (GO:0005277), acetylcholine:proton antiporter activity (GO:0005278), monoamine:proton antiporter activity (GO:0015311), protein binding (GO:0005515), transmembrane transporter activity (GO:0022857)

GO Cellular Component (10): plasma membrane (GO:0005886), AP-1 adaptor complex (GO:0030121), AP-2 adaptor complex (GO:0030122), clathrin-coated endocytic vesicle membrane (GO:0030669), synaptic vesicle membrane (GO:0030672), terminal bouton (GO:0043195), clathrin-sculpted acetylcholine transport vesicle membrane (GO:0060201), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Neurotransmitter release cycle	1
Clathrin-mediated endocytosis	1
Membrane Trafficking	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	2
proton transmembrane transporter activity	2
antiporter activity	2
clathrin adaptor complex	2
clathrin-coated vesicle membrane	2
anterograde trans-synaptic signaling	1
positive regulation of neurotransmitter secretion	1
acetylcholine secretion, neurotransmission	1
regulation of acetylcholine secretion, neurotransmission	1
positive regulation of synaptic transmission, cholinergic	1
positive regulation of amine transport	1
organic hydroxy compound transport	1
nitrogen compound transport	1
neurotransmitter reuptake	1
acetylcholine transport	1
positive regulation of synaptic transmission	1
long-term synaptic potentiation	1
regulation of long-term synaptic potentiation	1
neuromuscular junction development	1
positive regulation of cellular component organization	1
regulation of neuromuscular junction development	1
cellular process	1
monoatomic cation transmembrane transport	1
neurotransmitter transmembrane transporter activity	1
acetate ester transmembrane transporter activity	1
acetylcholine transmembrane transporter activity	1
monoamine transmembrane transporter activity	1
binding	1
transporter activity	1
transmembrane transport	1
membrane	1
cell periphery	1
clathrin coat of trans-Golgi network vesicle	1
clathrin coat of endocytic vesicle	1
clathrin coat of coated pit	1
plasma membrane protein complex	1
endocytic vesicle membrane	1
clathrin-coated endocytic vesicle	1
synaptic vesicle	1
exocytic vesicle membrane	1

Protein interactions and networks

STRING

1522 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC18A3	CHAT	P28329	980
SLC18A3	SLC5A7	Q9GZV3	854
SLC18A3	ACHE	P22303	844
SLC18A3	SLC17A7	Q9P2U7	802
SLC18A3	SLC32A1	Q9H598	793
SLC18A3	SLC17A8	Q8NDX2	775
SLC18A3	TH	P07101	771
SLC18A3	PAWR	Q96IZ0	712
SLC18A3	SLC17A6	Q9P2U8	708
SLC18A3	SIGMAR1	Q99720	678
SLC18A3	GAL	P22466	673
SLC18A3	GDF2	Q9UK05	661
SLC18A3	BCHE	P06276	659
SLC18A3	DBH	P09172	649
SLC18A3	GAD1	Q99259	643

IntAct

12 interactions, top by confidence:

A	B	Type	Score
MFF	SLC18A3	psi-mi:“MI:0915”(physical association)	0.560
SLC18A3	MFF	psi-mi:“MI:0915”(physical association)	0.560
PEDS1-UBE2V1	SLC18A3	psi-mi:“MI:0915”(physical association)	0.560
SLC18A3	CCDC167	psi-mi:“MI:0915”(physical association)	0.560
DNAJC5	SLC18A3	psi-mi:“MI:0915”(physical association)	0.400
SLC18A3	ORC4	psi-mi:“MI:0914”(association)	0.350
PEDS1-UBE2V1	SLC18A3	psi-mi:“MI:0915”(physical association)	0.000
CCDC167	SLC18A3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (34): SLC18A3 (Affinity Capture-Luminescence), SLC18A3 (Two-hybrid), SLC18A3 (Two-hybrid), CCDC167 (Two-hybrid), SEC14L1 (Two-hybrid), SEC14L1 (Affinity Capture-Western), SLC18A3 (Negative Genetic), SLC18A3 (Protein-peptide), ACOX1 (Affinity Capture-MS), APMAP (Affinity Capture-MS), CLPTM1 (Affinity Capture-MS), COA7 (Affinity Capture-MS), CTPS1 (Affinity Capture-MS), CYP2J2 (Affinity Capture-MS), CYP4X1 (Affinity Capture-MS)

ESM2 similar proteins: A0A084AFH0, A1Z7R6, A9JTG4, B2RXV4, O17444, O35304, O75387, O88444, P19754, P25107, P25961, P26770, P27922, P34711, P41593, P50133, P51828, P51829, P58872, P58873, P59845, P81721, Q03431, Q08828, Q08C75, Q16572, Q1LZF7, Q29450, Q5BIZ0, Q5RAQ1, Q5RCN7, Q62666, Q6DG19, Q6PDC8, Q7SXB7, Q8C0T7, Q8HYW2, Q8K0H7, Q8N468, Q8NBP5

Diamond homologs: A0A166Z003, A0A455ZIM5, O35304, O74852, P51564, P54219, Q08C75, Q16572, Q62666, O17444, P39886, P81721, Q01827, Q05940, Q27963, Q8BRU6, Q91498, Q91514, P34711, P59845, P9WJY4, P9WJY5, Q01818, Q8R090, P32369, P33449, P39843, P9WG90, P9WG91, Q28487, A0A254TZW7, A0A7L8UVD5, G3Y4N5, Q6GIU7, E8ZB61, O34724, O59700, P0A0J4, P0A0J5, P0A0J6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	14
Likely benign	13
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
148682	GRCh38/hg38 10q11.22-11.23(chr10:45810008-50066466)x1	Likely pathogenic

SpliceAI

18 predictions. Top by Δscore:

Variant	Effect	Δscore
10:49612526:G:A	acceptor_gain	0.6300
10:49612523:AATGG:A	acceptor_gain	0.6200
10:49612525:T:TA	acceptor_gain	0.6000
10:49610331:G:T	donor_gain	0.5800
10:49612523:AATG:A	acceptor_gain	0.5600
10:49612523:AAT:A	acceptor_gain	0.5500
10:49610326:G:T	donor_gain	0.4300
10:49612523:A:AG	acceptor_gain	0.3900
10:49612524:ATGG:A	acceptor_gain	0.3000
10:49612524:ATG:A	acceptor_gain	0.2900
10:49610331:G:GT	donor_gain	0.2800
10:49610625:G:T	donor_gain	0.2600
10:49610327:G:T	donor_gain	0.2500
10:49610326:G:GT	donor_gain	0.2300
10:49611238:A:AG	acceptor_gain	0.2100
10:49611239:G:GG	acceptor_gain	0.2100
10:49611239:GTCCT:G	acceptor_gain	0.2100
10:49612524:AT:A	acceptor_gain	0.2000

AlphaMissense

3366 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:49610876:G:C	D46H	0.999
10:49610877:A:C	D46A	0.999
10:49610877:A:T	D46V	0.999
10:49611133:G:C	K131N	0.999
10:49611133:G:T	K131N	0.999
10:49611213:G:A	G158D	0.999
10:49611287:A:C	S183R	0.999
10:49611289:C:A	S183R	0.999
10:49611289:C:G	S183R	0.999
10:49611296:G:C	G186R	0.999
10:49611297:G:A	G186D	0.999
10:49611305:T:C	S189P	0.999
10:49611404:A:C	S222R	0.999
10:49611406:C:A	S222R	0.999
10:49611406:C:G	S222R	0.999
10:49611411:G:A	G224E	0.999
10:49611126:C:A	A129D	0.998
10:49611131:A:G	K131E	0.998
10:49611212:G:C	G158R	0.998
10:49611296:G:T	G186C	0.998
10:49611302:G:C	G188R	0.998
10:49611303:G:A	G188D	0.998
10:49611309:C:A	A190D	0.998
10:49611333:C:A	A198D	0.998
10:49611410:G:A	G224R	0.998
10:49611410:G:C	G224R	0.998
10:49611413:A:C	S225R	0.998
10:49611415:C:A	S225R	0.998
10:49611415:C:G	S225R	0.998
10:49611473:T:C	F245L	0.998

dbSNP variants (sampled 300 via entrez): RS1000230060 (10:49610630 C>G), RS1000234617 (10:49610416 C>A,T), RS1000604518 (10:49611373 T>C), RS1000895425 (10:49610656 A>C,G), RS1001805564 (10:49612323 A>C,G), RS1002845136 (10:49613188 C>A), RS1003576668 (10:49608649 G>C,T), RS1003598452 (10:49609521 G>C), RS1003693295 (10:49609260 C>A,T), RS1004034223 (10:49608429 C>T), RS1004192166 (10:49612893 AG>A), RS1004745842 (10:49608934 C>G), RS1004798157 (10:49608748 A>G), RS1005598084 (10:49609217 C>A,T), RS1006364980 (10:49610023 G>T)

Disease associations

OMIM: gene MIM:600336 | disease phenotypes: MIM:254210, MIM:617239

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital myasthenic syndrome 21	Strong	Autosomal recessive
presynaptic congenital myasthenic syndrome	Supportive	Autosomal dominant
fetal akinesia deformation sequence 1	Supportive	Autosomal recessive

Mondo (4): congenital myasthenic syndrome 6 (MONDO:0009689), congenital myasthenic syndrome 21 (MONDO:0014983), (MONDO:0020345), fetal akinesia deformation sequence 1 (MONDO:0100101)

Orphanet (1): Congenital myasthenic syndrome (Orphanet:590)

HPO phenotypes

101 total (30 of 101 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000175	Cleft palate
HP:0000218	High palate
HP:0000276	Long face
HP:0000308	Microretrognathia
HP:0000316	Hypertelorism
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000407	Sensorineural hearing impairment
HP:0000467	Neck muscle weakness
HP:0000476	Cystic hygroma
HP:0000508	Ptosis
HP:0000565	Esotropia
HP:0000602	Ophthalmoplegia
HP:0000639	Nystagmus
HP:0000651	Diplopia
HP:0000666	Horizontal nystagmus
HP:0000768	Pectus carinatum
HP:0000961	Cyanosis
HP:0001059	Pterygium
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001262	Excessive daytime somnolence
HP:0001265	Hyporeflexia
HP:0001270	Motor delay
HP:0001283	Bulbar palsy

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST007995_11	Asthma (childhood onset)	4.000000e-12

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C535759	Congenital myasthenic syndrome with episodic apnea (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4767 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — SLC18 family of vesicular amine transporters

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
aminobenzovesamicol	Inhibition	10.9	pKi
vesamicol	Inhibition	8.7	pKi
[3H]vesamicol		8.4	pKd

Binding affinities (BindingDB)

14 measured of 15 human assays (15 total across all organisms); most potent 14 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
[4-(3-fluoropropylsulfanyl)phenyl]-[1-[(2R,3R)-3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl]piperidin-4-yl]methanone	KI	2.3 nM	US-10421722: Sulfur-containing compounds targeting vesicular acetylcholine transporter
[1-[(2R,3R)-3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl]piperidin-4-yl]-(4-methylsulfanylphenyl)methanone	KI	2.4 nM	US-10421722: Sulfur-containing compounds targeting vesicular acetylcholine transporter
[4-(2-fluoroethylsulfanyl)phenyl]-[1-[(2R,3R)-3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl]piperidin-4-yl]methanone	KI	2.4 nM	US-10421722: Sulfur-containing compounds targeting vesicular acetylcholine transporter
[1-[(2R,3R)-3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl]piperidin-4-yl]-(4-methylsulfonylphenyl)methanone	KI	5.4 nM	US-10421722: Sulfur-containing compounds targeting vesicular acetylcholine transporter
4-[1-[(2R,3R)-3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-4-carbonyl]-N-methylbenzenesulfonamide	KI	6.3 nM	US-10421722: Sulfur-containing compounds targeting vesicular acetylcholine transporter
[1-[(2R,3R)-3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl]piperidin-4-yl]-(4-methylsulfinylphenyl)methanone	KI	6.5 nM	US-10421722: Sulfur-containing compounds targeting vesicular acetylcholine transporter
V-100	KI	9.9 nM	US-10421722: Sulfur-containing compounds targeting vesicular acetylcholine transporter
1-(4-Bromo-phenyl)-3-(3-phenyl-8-aza-bicyclo[3.2.1]oct-8-yl)-propan-2-ol	KI	10 nM
[4-(3-fluoropropylsulfonyl)phenyl]-[1-[(2R,3R)-3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl]piperidin-4-yl]methanone	KI	12.8 nM	US-10421722: Sulfur-containing compounds targeting vesicular acetylcholine transporter
N-(2-fluoroethyl)-4-[1-[(2R,3R)-3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-4-carbonyl]benzenesulfonamide	KI	13 nM	US-10421722: Sulfur-containing compounds targeting vesicular acetylcholine transporter
1-(4-Fluoro-phenyl)-4-(3-phenyl-8-aza-bicyclo[3.2.1]oct-8-yl)-butan-1-ol	KI	380 nM
1-(4-Fluoro-phenyl)-2-(3-phenyl-8-aza-bicyclo[3.2.1]oct-8-yl)-ethanone	KI	3400 nM
2-(4-Phenyl-piperidin-1-yl)-bicyclo[2.2.1]heptan-7-ol	IC50	10000 nM
4-(2-hydroxycyclohexyl)-10-methoxy-12-oxa-4-azapentacyclo[9.6.1.01,13.05,17.07,18]octadeca-7(18),8,10,15-tetraen-14-ol	IC50	80000 nM

ChEMBL bioactivities

243 potent at pChembl≥5 of 253 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.26	Ki	0.055	nM	BENZOVESAMICOL
9.89	Ki	0.13	nM	CHEMBL50880
9.66	Ki	0.22	nM	CHEMBL129530
9.60	Ki	0.25	nM	CHEMBL473547
9.59	Ki	0.26	nM	CHEMBL330635
9.52	Ki	0.3	nM	CHEMBL97524
9.49	Ki	0.32	nM	CHEMBL1956465
9.44	Ki	0.36	nM	CHEMBL87594
9.44	Ki	0.36	nM	CHEMBL87414
9.40	Ki	0.4	nM	CHEMBL95701
9.36	Ki	0.44	nM	CHEMBL129530
9.36	Ki	0.44	nM	CHEMBL316520
9.36	Ki	0.44	nM	CHEMBL1956464
9.35	Ki	0.45	nM	CHEMBL510679
9.32	Ki	0.48	nM	CHEMBL473751
9.23	Ki	0.59	nM	CHEMBL3597321
9.17	Ki	0.67	nM	CHEMBL314170
9.11	Ki	0.78	nM	CHEMBL2409366
9.11	Ki	0.77	nM	CHEMBL462659
9.06	Ki	0.87	nM	CHEMBL3597316
9.03	Ki	0.93	nM	CHEMBL2409373
9.00	Ki	0.99	nM	CHEMBL95857
8.91	Ki	1.23	nM	CHEMBL3597317
8.85	Ki	1.4	nM	CHEMBL1645202
8.81	Ki	1.55	nM	CHEMBL3597320
8.78	Ki	1.68	nM	CHEMBL473548
8.76	Ki	1.74	nM	CHEMBL3597315
8.70	Ki	2	nM	VESAMICOL
8.64	Ki	2.3	nM	CHEMBL5849810
8.62	Ki	2.4	nM	CHEMBL5767700
8.62	Ki	2.4	nM	CHEMBL6052535
8.57	Ki	2.7	nM	CHEMBL473129
8.57	Ki	2.7	nM	CHEMBL3597324
8.52	Ki	3.03	nM	CHEMBL2409374
8.52	Kd	3	nM	CHEMBL461783
8.39	Ki	4.1	nM	CHEMBL473129
8.37	Ki	4.3	nM	CHEMBL1186644
8.37	Ki	4.3	nM	CHEMBL473546
8.36	Ki	4.4	nM	VESAMICOL
8.33	Ki	4.64	nM	CHEMBL3597318
8.30	Ki	5	nM	CHEMBL1089205
8.28	Ki	5.2	nM	CHEMBL330386
8.27	Ki	5.4	nM	CHEMBL5842461
8.20	Ki	6.3	nM	CHEMBL5856700
8.19	Ki	6.5	nM	CHEMBL6020525
8.12	Ki	7.6	nM	CHEMBL315146
8.11	Ki	7.7	nM	CHEMBL330635
8.08	Ki	8.36	nM	CHEMBL2409385
8.07	Ki	8.5	nM	CHEMBL338411
8.07	Ki	8.5	nM	CHEMBL125795

PubChem BioAssay actives

234 with measured affinity, of 269 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
(3R,4R)-1-[(3-iodophenyl)methyl]-3-(4-phenylpiperidin-1-yl)piperidin-4-ol	216232: Binding to vesicular acetylcholine transporter of torpedo synaptic vesicles	ki	0.0001	uM
(2R,3R)-3-(4-phenylpiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-ol	216232: Binding to vesicular acetylcholine transporter of torpedo synaptic vesicles	ki	0.0001	uM
(3R,4R)-1-[(4-fluorophenyl)methyl]-3-(4-phenylpiperidin-1-yl)piperidin-4-ol	346599: Displacement of [3H]vesamicol from human vesicular acetylcholine transporter expressed in rat PC12 cells by liquid scintillation spectrometry	ki	0.0002	uM
(4aR,6R,7R,8aR)-1-[(3-iodophenyl)methyl]-7-(4-phenylpiperidin-1-yl)-3,4,4a,5,6,7,8,8a-octahydro-2H-quinolin-6-ol	216233: Displacement of [3H]vesamicol from Vesicular Acetylcholine Transporter (VAChT)	ki	0.0003	uM
(4-bromophenyl)-[1-[(2R,3R)-3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl]piperidin-4-yl]methanone;hydrochloride	346599: Displacement of [3H]vesamicol from human vesicular acetylcholine transporter expressed in rat PC12 cells by liquid scintillation spectrometry	ki	0.0003	uM
N-ethyl-2-(18F)fluoro-N-[(6R,7R)-6-hydroxy-7-(4-phenylpiperidin-1-yl)-5,6,7,8-tetrahydronaphthalen-1-yl]acetamide	649866: Binding affinity to VAchT	ki	0.0003	uM
[(4aR,6R,7R,8aR)-6-hydroxy-7-(4-phenylpiperidin-1-yl)-3,4,4a,5,6,7,8,8a-octahydro-2H-quinolin-1-yl]-phenylmethanone	216233: Displacement of [3H]vesamicol from Vesicular Acetylcholine Transporter (VAChT)	ki	0.0003	uM
(3R,4R)-1-[(4-fluorophenyl)methyl]-3-spiro[1,2-dihydroindene-3,4’-piperidine]-1’-ylpiperidin-4-ol	216232: Binding to vesicular acetylcholine transporter of torpedo synaptic vesicles	ki	0.0004	uM
(4aR,6R,7R,8aR)-7-(4-phenylpiperidin-1-yl)-1,2,3,4,4a,5,6,7,8,8a-decahydroquinolin-6-ol	216233: Displacement of [3H]vesamicol from Vesicular Acetylcholine Transporter (VAChT)	ki	0.0004	uM
(4aR,6R,7R,8aR)-1-[(E)-3-iodoprop-2-enyl]-7-(4-phenylpiperidin-1-yl)-3,4,4a,5,6,7,8,8a-octahydro-2H-quinolin-6-ol	216233: Displacement of [3H]vesamicol from Vesicular Acetylcholine Transporter (VAChT)	ki	0.0004	uM
(2R,3R)-3-spiro[1,2-dihydroindene-3,4’-piperidine]-1’-yl-1,2,3,4-tetrahydronaphthalen-2-ol	216232: Binding to vesicular acetylcholine transporter of torpedo synaptic vesicles	ki	0.0004	uM
(3R,4R)-1-[(4-fluorophenyl)methyl]-3-(4-phenylpiperidin-1-yl)piperidin-4-ol	649866: Binding affinity to VAchT	ki	0.0004	uM
(2R,3R)-5-[(E)-3-iodoprop-2-enoxy]-3-(4-phenylpiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-ol	346599: Displacement of [3H]vesamicol from human vesicular acetylcholine transporter expressed in rat PC12 cells by liquid scintillation spectrometry	ki	0.0004	uM
[1-[(2R,3R)-3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl]piperidin-4-yl]-(4-nitrophenyl)methanone	346599: Displacement of [3H]vesamicol from human vesicular acetylcholine transporter expressed in rat PC12 cells by liquid scintillation spectrometry	ki	0.0005	uM
[1-[8-(2-fluoroethoxy)-3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl]piperidin-4-yl]-(4-fluorophenyl)methanone	1237778: Displacement of [3H]-vesamicol from human VAChT after 24 hrs by by liquid scintillation spectrometry analysis	ki	0.0006	uM
(3R,4R)-1-[(3-iodophenyl)methyl]-3-spiro[1,2-dihydroindene-3,4’-piperidine]-1’-ylpiperidin-4-ol	216232: Binding to vesicular acetylcholine transporter of torpedo synaptic vesicles	ki	0.0007	uM
(2R,3R)-5-(3-fluoropropoxy)-3-(4-phenylpiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-ol	346599: Displacement of [3H]vesamicol from human vesicular acetylcholine transporter expressed in rat PC12 cells by liquid scintillation spectrometry	ki	0.0008	uM
[1-[(2S,3S)-3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl]piperidin-4-yl]-[4-((111C)methylamino)phenyl]methanone	761721: Displacement of (-)-[3H]vesamicol from human VAChT expressed in rat PC12 cell membrane after 20 hrs	ki	0.0008	uM
[4-[2-(2-fluoroethoxy)ethoxy]phenyl]-[1-[(2R,3R)-3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl]piperidin-4-yl]methanone	1237778: Displacement of [3H]-vesamicol from human VAChT after 24 hrs by by liquid scintillation spectrometry analysis	ki	0.0009	uM
[4-(dimethylamino)phenyl]-[1-[(2R,3R)-3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl]piperidin-4-yl]methanone	761721: Displacement of (-)-[3H]vesamicol from human VAChT expressed in rat PC12 cell membrane after 20 hrs	ki	0.0009	uM
(4aR,6R,7R,8aR)-1-[(4-fluorophenyl)methyl]-7-(4-phenylpiperidin-1-yl)-3,4,4a,5,6,7,8,8a-octahydro-2H-quinolin-6-ol	216233: Displacement of [3H]vesamicol from Vesicular Acetylcholine Transporter (VAChT)	ki	0.0010	uM
[4-[2-[2-(2-fluoroethoxy)ethoxy]ethoxy]phenyl]-[1-[(2R,3R)-3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl]piperidin-4-yl]methanone	1237778: Displacement of [3H]-vesamicol from human VAChT after 24 hrs by by liquid scintillation spectrometry analysis	ki	0.0012	uM
1’-benzyl-1-(2-fluoroethyl)spiro[1H-2-benzofuran-3,4’-piperidine]	642502: Binding affinity to VAChT	ki	0.0014	uM
[1-[(2R,3R)-8-(2-fluoroethoxy)-3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl]piperidin-4-yl]-(4-fluorophenyl)methanone	1237778: Displacement of [3H]-vesamicol from human VAChT after 24 hrs by by liquid scintillation spectrometry analysis	ki	0.0015	uM
[4-(2-fluoroethoxy)phenyl]-[1-[(2R,3R)-3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl]piperidin-4-yl]methanone	1237778: Displacement of [3H]-vesamicol from human VAChT after 24 hrs by by liquid scintillation spectrometry analysis	ki	0.0017	uM
(4-aminophenyl)-[1-[(2R,3R)-3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl]piperidin-4-yl]methanone	346599: Displacement of [3H]vesamicol from human vesicular acetylcholine transporter expressed in rat PC12 cells by liquid scintillation spectrometry	ki	0.0017	uM
trans-(1R,2R)-2-(4-phenylpiperidin-1-yl)cyclohexan-1-ol	216232: Binding to vesicular acetylcholine transporter of torpedo synaptic vesicles	ki	0.0020	uM
(4-fluorophenyl)-[(6R,7R)-6-hydroxy-7-(4-phenylpiperidin-1-yl)-5,6,7,8-tetrahydronaphthalen-1-yl]methanone	1237778: Displacement of [3H]-vesamicol from human VAChT after 24 hrs by by liquid scintillation spectrometry analysis	ki	0.0027	uM
(4-fluorophenyl)-[1-[(2R,3R)-3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl]piperidin-4-yl]methanone	346599: Displacement of [3H]vesamicol from human vesicular acetylcholine transporter expressed in rat PC12 cells by liquid scintillation spectrometry	ki	0.0027	uM
(2R,3R)-3-[4-(aminomethyl)-4-phenylpiperidin-1-yl]-5-iodo-1,2,3,4-tetrahydronaphthalen-2-ol	346599: Displacement of [3H]vesamicol from human vesicular acetylcholine transporter expressed in rat PC12 cells by liquid scintillation spectrometry	kd	0.0030	uM
[1-[(2R,3R)-3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl]piperidin-4-yl]-[4-(methylamino)phenyl]methanone	761721: Displacement of (-)-[3H]vesamicol from human VAChT expressed in rat PC12 cell membrane after 20 hrs	ki	0.0030	uM
[1-[(2R,3R)-3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl]piperidin-4-yl]-phenylmethanone	761721: Displacement of (-)-[3H]vesamicol from human VAChT expressed in rat PC12 cell membrane after 20 hrs	ki	0.0043	uM
[1-[(2R,3R)-3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl]piperidin-4-yl]-phenylmethanone;hydrochloride	346599: Displacement of [3H]vesamicol from human vesicular acetylcholine transporter expressed in rat PC12 cells by liquid scintillation spectrometry	ki	0.0043	uM
[1-[(2R,3R)-3,8-dihydroxy-1,2,3,4-tetrahydronaphthalen-2-yl]piperidin-4-yl]-(4-fluorophenyl)methanone	1237778: Displacement of [3H]-vesamicol from human VAChT after 24 hrs by by liquid scintillation spectrometry analysis	ki	0.0046	uM
[1-[(2R,3R)-3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl]piperidin-4-yl]-thiophen-2-ylmethanone	761721: Displacement of (-)-[3H]vesamicol from human VAChT expressed in rat PC12 cell membrane after 20 hrs	ki	0.0050	uM
(4aR,6R,7R,8aR)-1-[(3-iodophenyl)methyl]-6-(4-phenylpiperidin-1-yl)-3,4,4a,5,6,7,8,8a-octahydro-2H-quinolin-7-ol	216233: Displacement of [3H]vesamicol from Vesicular Acetylcholine Transporter (VAChT)	ki	0.0052	uM
trans-(1R,2R)-2-spiro[1,2-dihydroindene-3,4’-piperidine]-1’-ylcyclohexan-1-ol	216232: Binding to vesicular acetylcholine transporter of torpedo synaptic vesicles	ki	0.0076	uM
[1-[(2R,3R)-3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl]piperidin-4-yl]-(6-methoxy-3-pyridinyl)methanone	761721: Displacement of (-)-[3H]vesamicol from human VAChT expressed in rat PC12 cell membrane after 20 hrs	ki	0.0084	uM
(2S,3S)-3-(3-phenyl-8-azabicyclo[3.2.1]octan-8-yl)-1,2,3,4-tetrahydronaphthalen-2-ol	216232: Binding to vesicular acetylcholine transporter of torpedo synaptic vesicles	ki	0.0085	uM
trans-(1S,2S)-2-(3-phenyl-8-azabicyclo[3.2.1]octan-8-yl)cyclohexan-1-ol	216232: Binding to vesicular acetylcholine transporter of torpedo synaptic vesicles	ki	0.0085	uM
(4aR,6R,7R,8aR)-1-[(4-fluorophenyl)methyl]-6-(4-phenylpiperidin-1-yl)-3,4,4a,5,6,7,8,8a-octahydro-2H-quinolin-7-ol	216233: Displacement of [3H]vesamicol from Vesicular Acetylcholine Transporter (VAChT)	ki	0.0100	uM
3-(4-phenylpiperidin-1-yl)-1,2,3,4,4a,5,6,7,8,8a-decahydronaphthalen-2-ol	30531: Inhibition of active transport of [3H]acetylcholine using purified Torpedo californica synaptic vesicles	ic50	0.0100	uM
(5-fluoro-3-pyridinyl)-[1-[(2R,3R)-3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl]piperidin-4-yl]methanone	761721: Displacement of (-)-[3H]vesamicol from human VAChT expressed in rat PC12 cell membrane after 20 hrs	ki	0.0101	uM
[1-[(3R,4R)-4-hydroxy-1-(3-methylthiophene-2-carbonyl)piperidin-3-yl]piperidin-4-yl]-(4-methoxyphenyl)methanone;oxalic acid	671079: Displacement of [3H]vesamicol from human VAChT expressed in rat PC12 cells after 24 hrs by liquid scintillation counting	ki	0.0102	uM
1-(4-bromophenyl)-3-(3-phenyl-8-azabicyclo[3.2.1]octan-8-yl)propan-2-ol	216232: Binding to vesicular acetylcholine transporter of torpedo synaptic vesicles	ki	0.0103	uM
(1R,2R,4S)-4-[(4-fluorophenyl)methoxy]-2-(4-phenylpiperidin-1-yl)cyclohexan-1-ol	346599: Displacement of [3H]vesamicol from human vesicular acetylcholine transporter expressed in rat PC12 cells by liquid scintillation spectrometry	ki	0.0107	uM
1-[(2-bromophenyl)methyl]-4-(4-phenylpiperazin-1-yl)piperidin-3-ol	264704: Displacement of [3H]vesamicol from human VAChT transfected in PC12 cell line	ic50	0.0110	uM
(4-fluorophenyl)-[1-[(3R,4R)-4-hydroxy-1-(3-methylthiophene-2-carbonyl)piperidin-3-yl]piperidin-4-yl]methanone;oxalic acid	671079: Displacement of [3H]vesamicol from human VAChT expressed in rat PC12 cells after 24 hrs by liquid scintillation counting	ki	0.0114	uM
2-[4-[4-(2-hydroxy-4,4-dimethylmorpholin-4-ium-2-yl)phenyl]phenyl]-4,4-dimethylmorpholin-4-ium-2-ol dibromide	255282: Percent inhibition against Acetylcholine transporter at 1 uM	ic50	0.0120	uM
(2-fluoro-3-pyridinyl)-[1-[(2R,3R)-3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl]piperidin-4-yl]methanone	761721: Displacement of (-)-[3H]vesamicol from human VAChT expressed in rat PC12 cell membrane after 20 hrs	ki	0.0127	uM

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
potassium perchlorate	decreases expression	1
sodium arsenite	decreases expression	1
CGP 52608	affects binding, increases reaction	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Tamoxifen	affects cotreatment, decreases expression	1
Testosterone	decreases expression	1
Triclosan	increases expression	1
Valproic Acid	affects expression	1
Raloxifene Hydrochloride	decreases expression, affects cotreatment	1
Particulate Matter	increases abundance, increases expression	1

ChEMBL screening assays

17 unique, capped per target: 17 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1827957	Binding	Displacement of (-)-[3H]vesamicol from human VAChT expressed in rat PC12 A123.7 cells after 20 hrs	Synthesis and in vitro biological evaluation of carbonyl group-containing analogues for σ1 receptors. — J Med Chem

Clinical trials (associated diseases)

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