SLC6A3

Summary

SLC6A3 (solute carrier family 6 member 3, HGNC:11049) is a protein-coding gene on chromosome 5p15.33, encoding Sodium-dependent dopamine transporter (Q01959). Mediates sodium- and chloride-dependent transport of dopamine.

This gene encodes a dopamine transporter which is a member of the sodium- and chloride-dependent neurotransmitter transporter family. The 3’ UTR of this gene contains a 40 bp tandem repeat, referred to as a variable number tandem repeat or VNTR, which can be present in 3 to 11 copies. Variation in the number of repeats is associated with idiopathic epilepsy, attention-deficit hyperactivity disorder, dependence on alcohol and cocaine, susceptibility to Parkinson disease and protection against nicotine dependence.

Source: NCBI Gene 6531 — RefSeq curated summary.

At a glance

• Gene–disease (curated): SLC6A3-related dopamine transporter deficiency syndrome (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 565 total — 12 pathogenic, 9 likely-pathogenic
• Phenotypes (HPO): 35
• Druggable target: yes — 466 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_001044

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11049
Approved symbol	SLC6A3
Name	solute carrier family 6 member 3
Location	5p15.33
Locus type	gene with protein product
Status	Approved
Aliases	DAT
Ensembl gene	ENSG00000142319
Ensembl biotype	protein_coding
OMIM	126455
Entrez	6531

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000270349, ENST00000511750, ENST00000512002, ENST00000713696, ENST00000713697, ENST00000713698, ENST00000936841, ENST00000941790

RefSeq mRNA: 1 — MANE Select: NM_001044 NM_001044

CCDS: CCDS3863

Canonical transcript exons

ENST00000270349 — 15 exons

Exon	Start	End
ENSE00000953490	1420569	1420703
ENSE00000953491	1416098	1416201
ENSE00000953494	1409721	1409849
ENSE00000953495	1409026	1409125
ENSE00000953496	1406188	1406288
ENSE00001135543	1392794	1394758
ENSE00001135553	1400915	1400986
ENSE00001166348	1402922	1403089
ENSE00001362536	1421876	1422014
ENSE00001362539	1432464	1432698
ENSE00001362541	1441359	1441490
ENSE00001362544	1445348	1445440
ENSE00001379479	1411243	1411355
ENSE00001386442	1414691	1414815
ENSE00001433746	1442912	1443242

Expression profiles

Bgee: expression breadth broad, 84 present calls, max score 81.75.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0935 / max 33.1235, expressed in 28 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
60781	0.0935	28

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
substantia nigra	UBERON:0002038	81.75	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.91	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	70.22	gold quality
left lobe of thyroid gland	UBERON:0001120	56.85	gold quality
thyroid gland	UBERON:0002046	56.78	gold quality
right ovary	UBERON:0002118	54.26	gold quality
omental fat pad	UBERON:0010414	54.21	gold quality
endocervix	UBERON:0000458	52.86	gold quality
ovary	UBERON:0000992	52.68	gold quality
left ovary	UBERON:0002119	52.55	gold quality
right lobe of thyroid gland	UBERON:0001119	52.45	gold quality
body of uterus	UBERON:0009853	51.79	gold quality
cortex of kidney	UBERON:0001225	51.08	gold quality
hypothalamus	UBERON:0001898	50.96	gold quality
uterine cervix	UBERON:0000002	50.37	gold quality
lower esophagus mucosa	UBERON:0035834	50.19	gold quality
ectocervix	UBERON:0012249	49.92	gold quality
upper lobe of left lung	UBERON:0008952	49.29	gold quality
metanephros cortex	UBERON:0010533	49.28	gold quality
left uterine tube	UBERON:0001303	48.58	gold quality
vagina	UBERON:0000996	48.38	gold quality
myometrium	UBERON:0001296	47.22	gold quality
left coronary artery	UBERON:0001626	47.15	gold quality
kidney	UBERON:0002113	46.71	gold quality
lung	UBERON:0002048	46.51	gold quality
adipose tissue	UBERON:0001013	46.38	gold quality
urinary bladder	UBERON:0001255	46.09	gold quality
fallopian tube	UBERON:0003889	45.61	gold quality
hindlimb stylopod muscle	UBERON:0004252	45.54	gold quality
colonic epithelium	UBERON:0000397	44.87	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-25	yes	538.23
E-ANND-3	no	1.83

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HEY1, LMX1A, NR1I2, NR4A2, OTP, PITX3, SP1, SP3, STAT6, ZBTB14

miRNA regulators (miRDB)

82 targeting SLC6A3, 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-513A-5P	100.00	69.77	2465
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-3151-5P	99.86	63.83	1069

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• A VNTR polymorphism in this gene is not associated with schizophrenia or with therapeutic response to typical neuroleptics in schizophrenic patients (PMID:11104840)
• DAT variation in humans links robustly with variation in both baseline and/or psychostimulant-induced locomotion. (PMID:11803442)
• Variability in the length or the sequence of the 3’-UTR of the DAT gene may influence levels of DAT protein in the brain. (PMID:11803445)
• results suggest that both the DRD2 promoter region and the DAT gene do not play a significant role in conferring vulnerability to alcoholism (Dopamine Transporter DAT) (PMID:11807408)
• Cocaine-induced increases in cell surface expression of dopamine transporter and associated changes in dopamine clearance represent a novel mechanism that may play a role in its addictive properties. (PMID:11820798)
• variable number of tandem repeat polymorphism affects the expression of the dopamine transporter DAT1 (PMID:11911442)
• Conventional protein kinase C isoforms regulate human dopamine transporter activity in Xenopus oocytes. (PMID:11959130)
• findings indicate CFT(2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane)binding requires DAT sequences in the regions encompassing the 3rd and 6-8th transmembrane domain;these regions might contribute to form the 3-dimensional pocket for CFT binding. (PMID:11989984)
• Lack of association between VNTR polymorphism of DAT gene and schizophrenia. (PMID:12149916)
• There is an association between homozygosity for the 10-repeat allele at dopamine transporter gene locus and poor response to MPH. (PMID:12172219)
• VNTR polymorphisms in male opiate addicts (PMID:12173460)
• The dopamine transporter (DAT) gene (SLC6A3) encodes a protein that regulates synaptic levels of dopamine in the brain and is a candidate gene for addictive behaviors (PMID:12215242)
• association of the dopamine transporter (DAT) SLC6A3 3’ variable number tandem repeat (VNTR) polymorphism with post traumatic stress disorder (PMID:12232785)
• The 3’UTR of the DAT1 gene affects vulnerability to severe alcohol withdrawal. (PMID:12401557)
• the dopamine transporter (DAT) polymorphism (1215A/G) does not play a major role in the susceptibility to Parkinson’s disease (PMID:12422069)
• assembly of DAT monomers plays a critical role in the expression and function of the dopamine transporter (PMID:12429746)
• The VNTR region was highly variable among the primates, intra-species variation also found in the chimpanizees and cynomolgus macaques. (PMID:12453630)
• Measured DAT1 mRNA levels in brain and lymphocytes. Observed that increased levels of DAT1 expression were associated with the number of 10-repeat alleles of the 3’UTR VNTR polymorphism. (PMID:12457396)
• Neonatal 6-hydroxydopamine lesion induced Slc6a3 express in young adult rats is in good agreement with in ADHD patients (PMID:12459514)
• the major phosphorylation sites in DAT are within the distal N terminus, which contains several serines (PMID:12464618)
• results suggest that variants of the dopamine transporter gene may be related to obesity in African-American smokers (PMID:12490667)
• An association analysis for dopamine transporter polymorphism and p300 component in normal young women is negative. (PMID:12605102)
• Review. DAT1 gene has a VNTR polymorphism in the 3’-untranslated region of the mRNA, which changes its gene expression. DAT1 polymorphisms are good candidates for etiological involvement in various psychiatric conditions. (PMID:12630565)
• No significant difference was demonstrated for genotype or allele frequency, when comparing methamphetamine dependent and control cases for dopamine transporter polymorphisms. (PMID:12658362)
• confirmed the DAT1 association with attention deficit disorder with hyperactivity (PMID:12660802)
• The homozygote 10-copy genotype of the VNTR polymorphism within the DAT may confer protection against Parkinson disease for male, but not for female patients (PMID:12686408)
• DAT1 VNTR polymorphism is associated with attention-deficit hyperactivity disease in a Taiwanese sample. (PMID:12740596)
• function of the TM7/8 region with the occurrence of distinct Na+-, substrate-, and perhaps inhibitor-induced conformational changes critical for the proper function of the transporter. (PMID:12773538)
• The 10-repeat DAT1 risk allele is associated with medication response, may help to predict positive clinical outcome in attention deficit hyperactivity disorder (PMID:12898575)
• dopamine transporter forms a tetramer in the plasma membrane (PMID:14519759)
• the dopamine transporter has intracellular residues critical for regulation of transporter conformation and cocaine binding (PMID:14597628)
• dopamine transporter residue aspartate 345 is critical for conformational changes in substrate translocation and cocaine binding (PMID:14660644)
• There may be an interactive effect between the SLC6A3 and early smoking onset on modulating the susceptibility of nicotine dependence (PMID:14685824)
• No differences are found between hallucinators with Parkinson’s disease (PD)and non-hallucinators with PD in either the genotypic or allelic distributions. (PMID:14732464)
• Significantly stronger stress-induced cigarette craving is found in individuals carrying the SLC6A3 nine-repeat allelic variant compared to those without the allelic variant. (PMID:14732864)
• These findings are in broad agreement with other studies of the expression of alpha-synuclein mRNA in human brain and suggest that Lewy body formation is unlikely to be the result of overexpression of alpha-synuclein. (PMID:14978671)
• Non-glycosylated DAT at the cell surface displays appreciably reduced catalytic activity and altered inhibitor sensitivity compared with wild type. (PMID:15024013)
• N-terminal phosphorylation of the dopamine transporter is required for amphetamine-induced efflux (PMID:15024426)
• No significant associations were found between DAT polymorphism in genotype & allele frequency & clinical outcome of MAP abusers. The biological relevance of the VNTR polymorphism in the 3’-untranslated region in MAP abusers was not demonstrated. (PMID:15091313)
• dopamine transporter (DAT) function requires alpha-synuclein (review) (PMID:15135042)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc6a3	ENSDARG00000004219
mus_musculus	Slc6a3	ENSMUSG00000021609
rattus_norvegicus	Slc6a3	ENSRNOG00000017302

Paralogs (19): SLC6A13 (ENSG00000010379), SLC6A7 (ENSG00000011083), SLC6A16 (ENSG00000063127), SLC6A15 (ENSG00000072041), SLC6A2 (ENSG00000103546), SLC6A4 (ENSG00000108576), SLC6A12 (ENSG00000111181), SLC6A8 (ENSG00000130821), SLC6A6 (ENSG00000131389), SLC6A11 (ENSG00000132164), SLC6A1 (ENSG00000157103), SLC6A20 (ENSG00000163817), SLC6A18 (ENSG00000164363), SLC6A5 (ENSG00000165970), SLC6A19 (ENSG00000174358), SLC6A9 (ENSG00000196517), SLC6A17 (ENSG00000197106), SLC6A14 (ENSG00000268104), (ENSG00000273554)

Protein

Protein identifiers

Sodium-dependent dopamine transporter — Q01959 (reviewed: Q01959)

Alternative names: Solute carrier family 6 member 3

All UniProt accessions (4): Q01959, A0AAQ5BGN6, A0AAQ5BGQ7, A0AAQ5BGS7

UniProt curated annotations — full annotation on UniProt →

Function. Mediates sodium- and chloride-dependent transport of dopamine. Also mediates sodium- and chloride-dependent transport of norepinephrine (also known as noradrenaline). Regulator of light-dependent retinal hyaloid vessel regression, downstream of OPN5 signaling.

Subunit / interactions. Monomer. Homooligomer; disulfide-linked (Ref.16). Interacts with PRKCABP and TGFB1I1. Interacts (via N-terminus) with SYNGR3 (via N-terminus). Interacts with SLC18A2. Interacts with TOR1A (ATP-bound); TOR1A regulates SLC6A3 subcellular location. Interacts with alpha-synuclein/SNCA. Interacts with SEPTIN4.

Subcellular location. Cell membrane. Cell projection. Neuron projection. Axon.

Tissue specificity. Highly expressed in substantia nigra. Expressed in axonal varicosities in dopaminergic nerve terminals (at protein level). Expressed in the striatum (at protein level).

Disease relevance. Parkinsonism-dystonia 1, infantile-onset (PKDYS1) [MIM:613135] An autosomal recessive neurodegenerative disorder characterized by infantile onset of parkinsonism and dystonia. Other neurologic features include global developmental delay, bradykinesia and pyramidal tract signs. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by cocaine, which occupies the same binding site as dopamine. Inhibited by zinc ions. Enhanced by the antibiotic valinomycin. Inhibited by benztropine. Inhibited by GBR 12909 dihydrochloride and amphetamine. Inhibited by mazindol, GBR 12783 dihydrochloride, nomifensine, diclofensine, amfonelic acid, Lu 19005, Win-35428, bupropion and ritalin.

Miscellaneous. This protein is the target of psychomotor stimulants such as amphetamines or cocaine.

Similarity. Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A3 subfamily.

RefSeq proteins (1): NP_001035* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000175	Na/ntran_symport	Family
IPR002436	Na/ntran_symport_dopamine	Family
IPR037272	SNS_sf	Homologous_superfamily

Pfam: PF00209

Catalyzed reactions (Rhea), 3 shown:

• dopamine(out) + chloride(out) + Na(+)(out) = dopamine(in) + chloride(in) + Na(+)(in) (RHEA:70919)
• (R)-noradrenaline(out) + chloride(out) + Na(+)(out) = (R)-noradrenaline(in) + chloride(in) + Na(+)(in) (RHEA:70923)
• dopamine(out) + chloride(out) + 2 Na(+)(out) = dopamine(in) + chloride(in) + 2 Na(+)(in) (RHEA:70931)

UniProt features (117 total): helix 37, binding site 20, mutagenesis site 16, transmembrane region 12, topological domain 7, sequence variant 6, strand 5, turn 4, glycosylation site 3, disulfide bond 2, sequence conflict 2, chain 1, region of interest 1, site 1

Structure

Experimental structures (PDB)

17 structures.

PDB	Method	Resolution (Å)
9EO4	ELECTRON MICROSCOPY	2.66
9JKI	ELECTRON MICROSCOPY	2.69
9JKJ	ELECTRON MICROSCOPY	2.69
8Y2D	ELECTRON MICROSCOPY	2.8
9J6S	ELECTRON MICROSCOPY	2.8
8Y2G	ELECTRON MICROSCOPY	2.83
9J6U	ELECTRON MICROSCOPY	2.9
8Y2F	ELECTRON MICROSCOPY	2.97
9JKK	ELECTRON MICROSCOPY	3
8Y2E	ELECTRON MICROSCOPY	3.03
8Y2C	ELECTRON MICROSCOPY	3.16
8VBY	ELECTRON MICROSCOPY	3.19
9J6R	ELECTRON MICROSCOPY	3.2
9JKH	ELECTRON MICROSCOPY	3.2
9J6T	ELECTRON MICROSCOPY	3.4
9JKM	ELECTRON MICROSCOPY	3.44
9J6V	ELECTRON MICROSCOPY	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q01959-F1	87.58	0.76

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 (1): 105 (contributes to high-affinity binding to cocaine)

Ligand- & substrate-binding residues (20): 75; 77; 78; 79; 79; 79; 82; 149; 153; 317; 320; 321 …

Disulfide bonds (2): 180–189, 306

Glycosylation sites (3): 181, 188, 205

Mutagenesis-validated functional residues (16):

Position	Phenotype
79	abolishes dopamine uptake.
152	reduces dopamine uptake.
211	enhances the inhibition on dopamine uptake by zinc ions.
317	reduces dopamine uptake. reduces glycosylation and cell surface expression.
320	reduces dopamine uptake. reduces glycosylation and cell surface expression.
321	reduces dopamine uptake. reduces glycosylation and cell surface expression.
326	reduces the inhibition on dopamine uptake by amphetamine. reduces dopamine uptake. reduces glycosylation and cell surfac
353	reduces dopamine uptake. reduces glycosylation and cell surface expression.
357	reduces dopamine uptake. reduces glycosylation and cell surface expression.
364	no effect on dopamine uptake. reduces dopamine uptake; when associated with l-390.
390	reduces dopamine uptake. reduces dopamine uptake; when associated with i-364.
394	reduces dopamine uptake.
414	reduces dopamine uptake.
421	reduces dopamine uptake. reduces glycosylation and cell surface expression.
422	reduces the inhibition on dopamine uptake by amphetamine. reduces dopamine uptake. reduces glycosylation and cell surfac
426	reduces dopamine uptake. reduces glycosylation and cell surface expression.

Function

Pathways and Gene Ontology

Reactome pathways

13 pathways

ID	Pathway
R-HSA-379401	Dopamine clearance from the synaptic cleft
R-HSA-442660	SLC-mediated transport of neurotransmitters
R-HSA-5619081	Defective neurotransmitter clearance by SLC6A3 causes Parkinsonism-dystonia infantile (PKDYS)
R-HSA-5660724	Defective transport of neurotransmitters by SLC6A3 causes Parkinsonism-dystonia infantile (PKDYS)
R-HSA-112311	Neurotransmitter clearance
R-HSA-112315	Transmission across Chemical Synapses
R-HSA-112316	Neuronal System
R-HSA-1643685	Disease
R-HSA-382551	Transport of small molecules
R-HSA-425366
R-HSA-425407	SLC-mediated transmembrane transport
R-HSA-5619102	SLC transporter disorders
R-HSA-5619115	Disorders of transmembrane transporters

MSigDB gene sets: 295 (showing top): GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_ETHANOL, BENPORATH_ES_WITH_H3K27ME3, GOBP_COGNITION, GOBP_PHENOL_CONTAINING_COMPOUND_BIOSYNTHETIC_PROCESS, GOBP_BEHAVIOR, GOBP_RESPONSE_TO_COCAINE, MODULE_162, GOBP_NEUROTRANSMITTER_UPTAKE, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, MODULE_64, GOBP_GROWTH, GOCC_CELL_SURFACE

GO Biological Process (27): neurotransmitter transport (GO:0006836), amino acid transport (GO:0006865), lactation (GO:0007595), sensory perception of smell (GO:0007608), locomotory behavior (GO:0007626), response to xenobiotic stimulus (GO:0009410), response to iron ion (GO:0010039), obsolete monoamine transport (GO:0015844), obsolete dopamine transport (GO:0015872), adenohypophysis development (GO:0021984), response to nicotine (GO:0035094), sodium ion transmembrane transport (GO:0035725), positive regulation of multicellular organism growth (GO:0040018), regulation of dopamine metabolic process (GO:0042053), response to cocaine (GO:0042220), dopamine biosynthetic process (GO:0042416), dopamine catabolic process (GO:0042420), response to ethanol (GO:0045471), cognition (GO:0050890), dopamine uptake involved in synaptic transmission (GO:0051583), response to cAMP (GO:0051591), prepulse inhibition (GO:0060134), dopamine uptake (GO:0090494), hyaloid vascular plexus regression (GO:1990384), neurotransmitter uptake (GO:0001504), norepinephrine uptake (GO:0051620), transmembrane transport (GO:0055085)

GO Molecular Function (15): protease binding (GO:0002020), signaling receptor binding (GO:0005102), neurotransmitter transmembrane transporter activity (GO:0005326), dopamine:sodium symporter activity (GO:0005330), norepinephrine:sodium symporter activity (GO:0005334), monoamine transmembrane transporter activity (GO:0008504), dopamine binding (GO:0035240), amine binding (GO:0043176), protein-containing complex binding (GO:0044877), metal ion binding (GO:0046872), protein phosphatase 2A binding (GO:0051721), heterocyclic compound binding (GO:1901363), protein binding (GO:0005515), symporter activity (GO:0015293), transmembrane transporter activity (GO:0022857)

GO Cellular Component (14): cytoplasm (GO:0005737), plasma membrane (GO:0005886), cell surface (GO:0009986), membrane (GO:0016020), flotillin complex (GO:0016600), axon (GO:0030424), presynaptic membrane (GO:0042734), neuron projection (GO:0043005), neuronal cell body (GO:0043025), axon terminus (GO:0043679), membrane raft (GO:0045121), postsynaptic membrane (GO:0045211), dopaminergic synapse (GO:0098691), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
SLC transporter disorders	2
Neurotransmitter clearance	1
SLC-mediated transmembrane transport	1
Transmission across Chemical Synapses	1
Neuronal System	1
Transport of small molecules	1
Disorders of transmembrane transporters	1
Disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
dopamine metabolic process	3
binding	3
transport	2
response to chemical	2
dopamine uptake	2
monoamine transmembrane transporter activity	2
sodium:chloride symporter activity	2
cation binding	2
synaptic membrane	2
presynapse	2
body fluid secretion	1
mammary gland development	1
milk ejection reflex	1
sensory perception of chemical stimulus	1
behavior	1
response to metal ion	1
pituitary gland development	1
anatomical structure development	1
sodium ion transport	1
monoatomic cation transmembrane transport	1
multicellular organism growth	1
regulation of multicellular organism growth	1
positive regulation of developmental growth	1
positive regulation of multicellular organismal process	1
regulation of catecholamine metabolic process	1
response to alkaloid	1
response to oxygen-containing compound	1
catecholamine biosynthetic process	1
catecholamine catabolic process	1
response to alcohol	1
nervous system process	1
synaptic transmission, dopaminergic	1
neurotransmitter reuptake	1
enzyme binding	1
protein binding	1
neurotransmitter transport	1
transmembrane transporter activity	1
norepinephrine uptake	1
active transmembrane transporter activity	1

Protein interactions and networks

STRING

2022 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC6A3	DRD2	P14416	995
SLC6A3	SNCA	P37840	980
SLC6A3	DRD4	P21917	960
SLC6A3	SLC18A2	Q05940	950
SLC6A3	TH	P07101	944
SLC6A3	SYNGR3	O43761	924
SLC6A3	COMT	P21964	917
SLC6A3	DRD1	P21728	906
SLC6A3	MAOA	P21397	890
SLC6A3	MAOB	P27338	883
SLC6A3	DDC	P20711	860
SLC6A3	STX1A	Q16623	858
SLC6A3	DRD5	P21918	841
SLC6A3	ATP13A2	Q9NQ11	816
SLC6A3	ADRA2A	P08913	815

IntAct

146 interactions, top by confidence:

A	B	Type	Score
SLC6A3	SCRIB	psi-mi:“MI:0407”(direct interaction)	0.590
SLC6A3	PALS2	psi-mi:“MI:0407”(direct interaction)	0.590
SLC6A3	LIN7C	psi-mi:“MI:0407”(direct interaction)	0.590
SLC6A3	Pick1	psi-mi:“MI:0407”(direct interaction)	0.560
PICK1	SLC6A3	psi-mi:“MI:0403”(colocalization)	0.540
SLC6A3	PICK1	psi-mi:“MI:0915”(physical association)	0.540
SLC6A3	SNCA	psi-mi:“MI:2364”(proximity)	0.540
SNCA	SLC6A3	psi-mi:“MI:0915”(physical association)	0.540
SLC6A3	Rit2	psi-mi:“MI:0915”(physical association)	0.520
GPR37	SLC6A3	psi-mi:“MI:0915”(physical association)	0.520
WLS	SLC6A3	psi-mi:“MI:0915”(physical association)	0.520
DRD2	SLC6A3	psi-mi:“MI:0915”(physical association)	0.520
SLC6A3	DRD2	psi-mi:“MI:0915”(physical association)	0.520
SLC6A3	RIT2	psi-mi:“MI:0915”(physical association)	0.500
SLC6A3	RIT2	psi-mi:“MI:0403”(colocalization)	0.500
SLC6A3	RIT2	psi-mi:“MI:2364”(proximity)	0.500
WLS	SLC6A3	psi-mi:“MI:0915”(physical association)	0.490
SLC6A3	LNX2	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (77): SLC6A3 (Two-hybrid), STX1A (Affinity Capture-Western), SLC6A3 (Affinity Capture-Western), SNCA (Affinity Capture-Western), SLC6A3 (Synthetic Lethality), SLC6A3 (Affinity Capture-MS), SYNGR3 (Affinity Capture-Western), SYNGR3 (Reconstituted Complex), SLC6A3 (Reconstituted Complex), SLC6A3 (Affinity Capture-Western), SLC18A2 (Affinity Capture-Western), TGFB1I1 (Two-hybrid), TGFB1I1 (Reconstituted Complex), Tgfb1i1 (Affinity Capture-Western), PICK1 (Two-hybrid)

ESM2 similar proteins: A1A4N1, A2VE54, A5PJX7, B0S5Y3, B5X4H8, O00400, O01840, O18875, O54699, P23977, P28570, P28573, P31661, P47040, P48029, P48055, P91679, Q01959, Q08B29, Q14542, Q1KKV8, Q28E13, Q2PG55, Q4HX89, Q4X0S3, Q5SPF7, Q61327, Q61672, Q69JW3, Q6BZ39, Q6BZW3, Q6DDL7, Q6DG19, Q6GMG6, Q710D3, Q758C3, Q80WK7, Q84XI3, Q86WB7, Q8VBW1

Diamond homologs: A5PJX7, A7Y2W8, A7Y2X0, B3MRS1, B3NV41, B4GVM9, B4JMC1, B4L7U0, B4MEG2, B4NDL8, B4PZQ4, B4R4T6, G5EBN9, O18875, O35316, O35899, O45813, O55192, O76689, O88575, O88576, P23975, P23977, P23978, P27799, P27922, P28570, P28571, P28572, P28573, P30531, P31641, P31643, P31645, P31646, P31647, P31648, P31649, P31650, P31651

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
QOCYWLABLBUJOR-UHFFFAOYSA-N	“down-regulates activity”	SLC6A3	“chemical inhibition”
levomilnacipran	“down-regulates activity”	SLC6A3	“chemical inhibition”
trimipramine	“down-regulates activity”	SLC6A3	“chemical inhibition”
Phenelzine	“down-regulates activity”	SLC6A3	“chemical inhibition”
clomipramine	“down-regulates activity”	SLC6A3	“chemical inhibition”
SLC6A3	“up-regulates quantity”	dopamine	relocalization
atomoxetine	“down-regulates activity”	SLC6A3	“chemical inhibition”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 88 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
Dopamine Neurotransmitter Release Cycle	6	48.8×	1e-07
Ras activation upon Ca2+ influx through NMDA receptor	5	46.8×	2e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	44.6×	2e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	44.6×	2e-06
Assembly and cell surface presentation of NMDA receptors	10	41.6×	3e-12
Long-term potentiation	5	39.0×	4e-06
Neurotransmitter release cycle	5	36.0×	6e-06
Neurexins and neuroligins	11	35.5×	2e-12

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	10	70.0×	6e-14
protein localization to synapse	6	55.4×	2e-07
receptor clustering	7	52.6×	1e-08
regulation of postsynaptic membrane neurotransmitter receptor levels	6	35.8×	2e-06
protein-containing complex assembly	9	12.3×	4e-06
cell-cell adhesion	10	12.2×	1e-06
establishment of localization in cell	5	9.7×	4e-03
chemical synaptic transmission	10	9.3×	7e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	12
Likely pathogenic	9
Uncertain significance	167
Likely benign	271
Benign	75

Top pathogenic / likely-pathogenic (21)

Variant ID	HGVS	Classification
1072228	NC_000005.9:g.(?1253823)(1448148_?)del	Pathogenic
16763	NM_001044.5(SLC6A3):c.1103T>A (p.Leu368Gln)	Pathogenic
16764	NM_001044.5(SLC6A3):c.1184C>T (p.Pro395Leu)	Pathogenic
2499597	NM_001044.5(SLC6A3):c.1569_1592delinsA (p.Cys523_Phe531delinsTer)	Pathogenic
2655276	NM_001044.5(SLC6A3):c.1389C>A (p.Cys463Ter)	Pathogenic
29685	NM_001044.5(SLC6A3):c.1269+1G>A	Pathogenic
3246392	NC_000005.9:g.(?1432559)(1443312_?)del	Pathogenic
3641931	NM_001044.5(SLC6A3):c.341del (p.Phe114fs)	Pathogenic
4537266	NC_000005.9:g.(?1392908)(1445556_?)del	Pathogenic
4807211	NM_001044.5(SLC6A3):c.1762C>T (p.Arg588Ter)	Pathogenic
939537	NM_001044.5(SLC6A3):c.892del (p.Tyr297_Leu298insTer)	Pathogenic
97017	NM_001044.5(SLC6A3):c.671T>C (p.Leu224Pro)	Pathogenic
1525470	NM_001044.5(SLC6A3):c.1767+2T>C	Likely pathogenic
2054045	NM_001044.5(SLC6A3):c.1156G>A (p.Gly386Arg)	Likely pathogenic
3349872	NM_001044.5(SLC6A3):c.1767+2_1767+3del	Likely pathogenic
3662870	NM_001044.5(SLC6A3):c.1032-1G>C	Likely pathogenic
421417	NM_001044.5(SLC6A3):c.253C>T (p.Arg85Trp)	Likely pathogenic
4813769	NM_001044.5(SLC6A3):c.1708dup (p.Ala570fs)	Likely pathogenic
817293	NM_001044.5(SLC6A3):c.1639dup (p.His547fs)	Likely pathogenic
931466	NM_001044.5(SLC6A3):c.1398+5G>A	Likely pathogenic
97016	NM_001044.5(SLC6A3):c.1031+1G>A	Likely pathogenic

SpliceAI

3367 predictions. Top by Δscore:

Variant	Effect	Δscore
5:1394759:C:CC	acceptor_gain	1.0000
5:1400982:AGTTT:A	acceptor_gain	1.0000
5:1400983:GTTT:G	acceptor_gain	1.0000
5:1400984:TTT:T	acceptor_gain	1.0000
5:1400985:TT:T	acceptor_gain	1.0000
5:1400985:TTCTG:T	acceptor_loss	1.0000
5:1400986:TCTG:T	acceptor_loss	1.0000
5:1400987:C:CC	acceptor_gain	1.0000
5:1400987:CTG:C	acceptor_loss	1.0000
5:1400988:T:C	acceptor_loss	1.0000
5:1403086:CGAA:C	acceptor_gain	1.0000
5:1403090:C:CC	acceptor_gain	1.0000
5:1406183:CTTAC:C	donor_loss	1.0000
5:1406184:TTACC:T	donor_loss	1.0000
5:1406185:TACCA:T	donor_loss	1.0000
5:1406186:A:AC	donor_gain	1.0000
5:1406186:A:C	donor_loss	1.0000
5:1406187:C:CC	donor_gain	1.0000
5:1406285:ACAC:A	acceptor_gain	1.0000
5:1406286:CAC:C	acceptor_gain	1.0000
5:1406286:CACC:C	acceptor_gain	1.0000
5:1406287:AC:A	acceptor_gain	1.0000
5:1406288:CC:C	acceptor_gain	1.0000
5:1406289:C:CC	acceptor_gain	1.0000
5:1406289:C:T	acceptor_gain	1.0000
5:1409021:CTCA:C	donor_loss	1.0000
5:1409022:TCA:T	donor_loss	1.0000
5:1409023:CA:C	donor_loss	1.0000
5:1409122:CACC:C	acceptor_gain	1.0000
5:1409124:CC:C	acceptor_gain	1.0000

AlphaMissense

4046 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:1406203:G:C	S528R	0.999
5:1406203:G:T	S528R	0.999
5:1406205:T:G	S528R	0.999
5:1406217:A:G	W524R	0.999
5:1406217:A:T	W524R	0.999
5:1411246:G:C	S422R	0.999
5:1411246:G:T	S422R	0.999
5:1411248:T:G	S422R	0.999
5:1411257:C:G	G419R	0.999
5:1414741:C:T	G369E	0.999
5:1414752:G:C	F365L	0.999
5:1414752:G:T	F365L	0.999
5:1414754:A:G	F365L	0.999
5:1414776:G:C	S357R	0.999
5:1414776:G:T	S357R	0.999
5:1414778:T:G	S357R	0.999
5:1416149:C:T	G327E	0.999
5:1416150:C:A	G327W	0.999
5:1416150:C:G	G327R	0.999
5:1416150:C:T	G327R	0.999
5:1416155:C:T	G325E	0.999
5:1416198:A:G	W311R	0.999
5:1416198:A:T	W311R	0.999
5:1420687:G:T	A270D	0.999
5:1441415:C:T	G121D	0.999
5:1441424:A:G	L118P	0.999
5:1441483:G:C	F98L	0.999
5:1441483:G:T	F98L	0.999
5:1441485:A:G	F98L	0.999
5:1442940:G:C	F86L	0.999

dbSNP variants (sampled 300 via entrez): RS1000025503 (5:1400738 G>A), RS1000056633 (5:1401069 C>T), RS1000090805 (5:1437501 G>A), RS1000142656 (5:1420842 C>T), RS1000155081 (5:1436389 A>T), RS1000157714 (5:1440298 T>A,C), RS1000221728 (5:1405749 G>A), RS1000256012 (5:1415739 C>T), RS1000318757 (5:1424236 A>G), RS1000342737 (5:1410959 T>C), RS1000362262 (5:1394004 C>A), RS1000363117 (5:1426956 A>G), RS1000420051 (5:1437167 C>T), RS1000835292 (5:1441280 G>A,T), RS1000856396 (5:1431237 G>A)

Disease associations

OMIM: gene MIM:126455 | disease phenotypes: MIM:613135, MIM:188890, MIM:181500

GenCC curated gene-disease

Disease	Classification	Inheritance
classic dopamine transporter deficiency syndrome	Definitive	Autosomal recessive
parkinsonism-dystonia, infantile	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
SLC6A3-related dopamine transporter deficiency syndrome	Definitive	AR

Mondo (5): parkinsonism-dystonia, infantile (MONDO:0013150), classic dopamine transporter deficiency syndrome (MONDO:0054835), tobacco addiction, susceptibility to (MONDO:0100460), schizophrenia (MONDO:0005090), hereditary ataxia (MONDO:0100309)

Orphanet (3): Infantile dystonia-parkinsonism (Orphanet:238455), Hereditary ataxia (Orphanet:183518), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140)

HPO phenotypes

35 total (30 of 35 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000338	Hypomimic face
HP:0000737	Irritability
HP:0001263	Global developmental delay
HP:0001276	Hypertonia
HP:0001300	Parkinsonism
HP:0001332	Dystonia
HP:0001337	Tremor
HP:0001344	Absent speech
HP:0002019	Constipation
HP:0002020	Gastroesophageal reflux
HP:0002062	Abnormal pyramidal tract morphology
HP:0002063	Rigidity
HP:0002067	Bradykinesia
HP:0002072	Chorea
HP:0002194	Delayed gross motor development
HP:0002310	Orofacial dyskinesia
HP:0002375	Hypokinesia
HP:0002396	Cogwheel rigidity
HP:0002451	Limb dystonia
HP:0002487	Hyperkinetic movements
HP:0002509	Limb hypertonia
HP:0003593	Infantile onset
HP:0003623	Neonatal onset
HP:0003676	Progressive
HP:0004354	Abnormal circulating carboxylic acid concentration
HP:0007256	Abnormal pyramidal sign
HP:0008936	Axial hypotonia
HP:0010553	Oculogyric crisis
HP:0011968	Feeding difficulties

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002553_8	Pancreatic cancer	1.000000e-13
GCST012484_19	Cerebral amyloid angiopathy x APOEe4 status interaction in Alzheimer’s disease	5.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007659	APOE carrier status

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C531684	Hereditary spinal ataxia (supp.)
C567730	Parkinsonism-Dystonia, Infantile (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2095201 (SELECTIVITY GROUP), CHEMBL2096990 (SELECTIVITY GROUP), CHEMBL2363064 (PROTEIN FAMILY), CHEMBL238 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

466 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 772,527 (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
CHEMBL1000	CETIRIZINE	4	26,030
CHEMBL1008	BEPRIDIL	4	11,776
CHEMBL1014	CANDESARTAN CILEXETIL	4	11,194
CHEMBL1023	BEXAROTENE	4	40,951
CHEMBL104	CLOTRIMAZOLE	4	56,325
CHEMBL1046	AMINOCAPROIC ACID	4	95,343
CHEMBL1064	SIMVASTATIN	4	123,163
CHEMBL1070	NABUMETONE	4	55,063
CHEMBL1078261	PROPIVERINE	4	4,890
CHEMBL1085	ACETOPHENAZINE	4	5,134
CHEMBL1088	MESORIDAZINE	4	12,814
CHEMBL109	VALPROIC ACID	4	65,937
CHEMBL1094636	NIRAPARIB	4	6,433
CHEMBL1095777	INDACATEROL	4	2,735
CHEMBL11	IMIPRAMINE	4	48,893
CHEMBL1107	HALOFANTRINE	4	9,722
CHEMBL111	RIMONABANT	4	15,726
CHEMBL1112	ARIPIPRAZOLE	4	24,205
CHEMBL1113	AMOXAPINE	4	20,128
CHEMBL1117	IDARUBICIN	4	136,065
CHEMBL1118	DESVENLAFAXINE	4
CHEMBL1138	EZETIMIBE	4
CHEMBL114	SAQUINAVIR	4
CHEMBL1171837	PONATINIB	4
CHEMBL1172	DESLORATADINE	4
CHEMBL1173655	AFATINIB	4
CHEMBL1175	DULOXETINE	4
CHEMBL1177	PEMOLINE	4
CHEMBL118	CELECOXIB	4
CHEMBL1187833	UMECLIDINIUM	4

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

PharmGKB clinical annotations

7 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs28363170	Other	3	ethanol
rs28363170	Efficacy	3	disulfiram	Cocaine dependence
rs28363170	Toxicity	3	ethanol	Alcohol abuse
rs2975226	Efficacy	3	clozapine	Schizophrenia
rs3836790	Efficacy	3	levodopa	Parkinson Disease
rs6350	Toxicity	3	ethanol

PharmGKB variants

23 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs6347	SLC6A3		0.00	0
rs27072	SLC6A3		0.00	0
rs460000	SLC6A3		0.00	0
rs2292023	LPCAT1, SLC6A3		0.00	0
rs2550948	SLC6A3		0.00	0
rs2550956	SLC6A3		0.00	0
rs2975226	SLC6A3	3	3.00	1	clozapine
rs3836790	SLC6A3	3	4.25	1	levodopa
rs3863145	SLC6A3		0.00	0
rs28363170	SLC6A3	3	2.50	4	ethanol;disulfiram
rs6350	SLC6A3	3	3.00	1	ethanol
rs2652511	SLC6A3		0.00	0
rs2981359	SLC6A3		0.00	0
rs403636	SLC6A3		0.00	0
rs460700	SLC6A3		0.00	0
rs464049	SLC6A3		0.00	0
rs37020	SLC6A3		0.00	0
rs37022	SLC6A3		0.00	0
rs27048	SLC6A3		0.00	0
rs11133767	SLC6A3		0.00	0
rs40184	SLC6A3		0.00	0
rs10064525	SLC6A3		0.00	0
rs1042098	SLC6A3		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — Monoamine transporter subfamily

Most potent curated ligand interactions (23 total), top 23:

Ligand	Action	Affinity	Parameter
vanoxerine	Inhibition	9.0	pKi
[3H]GBR12935	Inhibition	8.5	pKd
[3H]WIN35428	Inhibition	8.0	pKd
mazindol	Inhibition	8.0	pKi
WIN35428	Inhibition	7.9	pKi
GBR12935	Inhibition	7.6	pKi
dexmethylphenidate	Inhibition	7.6	pKi
cocaine	Inhibition	7.1	pIC50
methylphenidate	Inhibition	7.1	pIC50
dexamfetamine	Inhibition	6.96	pKi
benzatropine	Inhibition	6.93	pKi
bupropion	Inhibition	6.35	pIC50
toludesvenlafaxine	Inhibition	6.31	pIC50
sibutramine	Inhibition	6.3	pKi
desvenlafaxine	Inhibition	6.07	pKi
atomoxetine	Inhibition	5.97	pKd
clomipramine	Inhibition	5.66	pKd
levomilnacipran	Inhibition	5.49	pIC50
trimipramine	Inhibition	5.42	pKi
modafinil	Inhibition	5.42	pKi
compound 58 [PMID: 25037917]	Inhibition	5.21	pIC50
phenelzine	Inhibition	5.08	pKi
solriamfetol	Inhibition	4.85	pKi

Binding affinities (BindingDB)

750 measured of 810 human assays (833 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(1R,2R,3S,5S)-2-(2,2-dibromovinyl)-8-methyl-3-p-tolyl-8-aza-bicyclo[3.2.1]octane hydrochloride	IC50	0.23 nM
(S,S)-reboxetine	KI	0.3 nM
3-(3,4-Dichloro-phenyl)-7-hydroxy-8-methyl-8-aza-bicyclo[3.2.1]octane-2-carboxylic acid methyl ester	IC50	0.3 nM
(1R,2R,3S,5S)-3-(4-chlorophenyl)-2-(2,2-dibromovinyl)-8-methyl-8-aza-bicyclo[3.2.1]octane hydrochloride	IC50	0.32 nM
N-((E)-4-Fluorobut-2-en-1-yl)-2beta-carbomethoxy-3beta-(4’-bromophenyl)nortropane	KI	0.4 nM
8-Methyl-3-naphthalen-2-yl-8-aza-bicyclo[3.2.1]octane-2-carboxylic acid methyl ester	IC50	0.49 nM
N-((E)-4-Fluorobut-2-en-1-yl)-2beta-carbomethoxy-3beta-(4’-iodophenyl)nortropane	KI	0.5 nM
3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-N-methylpropan-1-amine	KI	0.6 nM
1-(3,4-dichlorophenyl)-5-[6-(trifluoromethyl)pyridazin-3-yl]oxy-9-azatricyclo[7.2.2.02,7]trideca-2(7),3,5-triene	IC50	0.7 nM	US-9045468: 2,5-methano- and 2,5-ethano-tetrahydrobenzazepine derivatives and use thereof to block reuptake of norepinephrine, dopamine, and serotonin
3beta-(4-Methylphenyl)-2beta-(phenylethynyl)tropane hydrochloride	IC50	0.8 nM
3beta-(4-Chlorophenyl)-2beta-(phenylethynyl)tropane hydrochloride	IC50	0.8 nM
(1R,2S,3S,5R)-methyl 3-(4-chloro-3-methylphenyl)-8-methyl-8-aza-bicyclo[3.2.1]octane-2-carboxylate hydrochloride	IC50	0.82 nM
CHEMBL1947088	KI	0.87 nM
2-beta-(4-fluorophenyl)-3-beta-(4-methylphenyl)tropane	IC50	0.9 nM
3beta-(4-Chlorophenyl)-2beta-(4-nitrophenylethynyl)tropane hydrochloride	IC50	0.9 nM
4-[[(3R)-4-[1-(3,4-dichlorophenyl)cyclobutyl]-3-methylbutyl]amino]butanamide	KI	0.91 nM	US-9296681: Cycloalkylmethylamines
4-(aminomethyl)-1-[2,5-difluoro-3-(3-fluorophenoxy)phenyl]piperidin-4-ol (E15)	IC50	0.912 nM	US-9920053: N-(hetero)aryl-substituted heteroyclic derivatives useful for the treatment of diseases or conditions related to the central nervous system
(2R,3S)-3-(4-Chloro-phenyl)-2-((E)-2-chloro-vinyl)-8-methyl-8-aza-bicyclo[3.2.1]octane	IC50	0.99 nM
(1R)-1-[1-(3,4-dichlorophenyl)cyclobutyl]-N-(4-ethoxybutyl)-3-methylbutan-1-amine	KI	1.16 nM	US-10035761: Compositions, synthesis, and methods of using phenylcycloalkylmethylamine derivatives
14C-5-hydroxy tryptamine creatinine disulfate	KI	1.2 nM
9-[4-(3-fluorophenoxy)-6-(trifluoromethyl)pyrimidin-2-yl]-1,4,9-triazaspiro[5.5]undecane	IC50	1.32 nM	US-9908897: Spirocyclic derivatives
(2S,3S)-3-(3,4-Dichloro-phenyl)-8-aza-bicyclo[3.2.1]octane-2-carboxylic acid methyl ester	IC50	1.4 nM
3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-N,N,2-trimethylpropan-1-amine	KI	1.4 nM
3beta-(4-chlorophenyl)-2a-(2,2-dibromovinyl)tropane	IC50	1.4 nM
4-[[4-[1-(3,4-dichlorophenyl)cyclobutyl]-3-methylbutyl]amino]butanamide	KI	1.5 nM	US-9096515: Methods of using cycloalkylmethylamine derivatives
4-[[1-[1-(3,4-dichlorophenyl)cyclobutyl]-3-methylbutyl]amino]butanamide	KI	1.5 nM	US-9296681: Cycloalkylmethylamines
4-(aminomethyl)-1-[3-fluoro-5-(3-fluorophenoxy)phenyl]piperidin-4-ol (E14)	IC50	1.51 nM	US-9920053: N-(hetero)aryl-substituted heteroyclic derivatives useful for the treatment of diseases or conditions related to the central nervous system
MOLI000038	KI	1.53 nM
(3S,8R)-3-(4-Iodo-phenyl)-8-methyl-8-aza-bicyclo[3.2.1]octane-2-carboxylic acid methyl ester	IC50	1.6 nM
4-(3,4-dichlorophenyl)-1,1-dimethyl-7-pyrazin-2-yl-3,4-dihydro-2H-isoquinoline	IC50	1.8 nM	US-9034899: Aryl, heteroaryl, and heterocycle substituted tetrahydroisoquinolines and use thereof
3-[(cyclopropylamino)methyl]-1-[4-(3-fluorophenoxy)-6-(trifluoromethyl)pyrimidin-2-yl]pyrrolidin-3-ol (E30)	IC50	1.91 nM	US-9920053: N-(hetero)aryl-substituted heteroyclic derivatives useful for the treatment of diseases or conditions related to the central nervous system
4-(3,4-dichlorophenyl)-1,1-dimethyl-7-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-3,4-dihydro-2H-isoquinoline	IC50	2.1 nM	US-9034899: Aryl, heteroaryl, and heterocycle substituted tetrahydroisoquinolines and use thereof
3beta-(4-Chlorophenyl)-2beta-(4-aminophenylethynyl)tropane hydrochloride	IC50	2.2 nM
1-[1-(3,4-dichlorophenyl)cyclobutyl]-N-(2-ethoxyethyl)-3-methylbutan-1-amine	KI	2.38 nM	US-10035761: Compositions, synthesis, and methods of using phenylcycloalkylmethylamine derivatives
(1R)-1-[1-(3,4-dichlorophenyl)cyclobutyl]-N-(4-methoxybutyl)-3-methylbutan-1-amine	KI	2.39 nM	US-10035761: Compositions, synthesis, and methods of using phenylcycloalkylmethylamine derivatives
6-[4-(3,4-dichlorophenyl)-1,1-dimethyl-3,4-dihydro-2H-isoquinolin-7-yl]pyridazin-3-amine	IC50	2.4 nM	US-9034899: Aryl, heteroaryl, and heterocycle substituted tetrahydroisoquinolines and use thereof
2-(3-fluorophenoxy)-6-(1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)pyridine-4-carbonitrile	IC50	2.45 nM	US-9908897: Spirocyclic derivatives
(1R,2S,3S,5R)-4-amino-3-iodophenethyl 3-(4-methoxyphenyl)-8-methyl-8-aza-bicyclo[3.2.1]octane-2-carboxylate hydrochloride	IC50	2.5 nM
(6R)-2-[4-(3-fluorophenoxy)-6-(trifluoromethyl)pyrimidin-2-yl]-2,8-diazaspiro[4.5]decan-6-ol	IC50	2.57 nM	US-9908897: Spirocyclic derivatives
(2S,3S)-3-(4-Chloro-phenyl)-2-ethyl-8-methyl-8-aza-bicyclo[3.2.1]octane	IC50	2.6 nM
CHEMBL2048520	KI	2.64 nM
methyl 3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate	KI	2.7 nM
3-(4-Chloro-phenyl)-8-methyl-2-vinyl-8-aza-bicyclo[3.2.1]octane	IC50	2.8 nM
(2S,3R)-methyl 3-(4-iodophenyl)-8-methyl-8-aza-bicyclo[3.2.1]octane-2-carboxylate	IC50	2.9 nM
(S)-mianserin	KI	3 nM
3-(3,4-Dichloro-phenyl)-7-hydroxy-8-methyl-8-aza-bicyclo[3.2.1]octane-2-carboxylic acid methyl ester	IC50	3.04 nM
3-[4-((Z)-2-Bromo-vinyl)-phenyl]-8-methyl-8-aza-bicyclo[3.2.1]octane-2-carboxylic acid methyl ester	KI	3.1 nM
3-(4-Chloro-phenyl)-8-methyl-8-aza-bicyclo[3.2.1]octane-2-carboxylic acid methyl ester	IC50	3.2 nM
(1R,2S,3S,5R)-4-amino-3-bromophenethyl 3-(4-methoxyphenyl)-8-methyl-8-aza-bicyclo[3.2.1]octane-2-carboxylate hydrochloride	IC50	3.3 nM
3beta-(4-methylphenyl)-2a-(2,2-dibromovinyl)tropane hydrochloride	IC50	3.6 nM

ChEMBL bioactivities

4898 potent at pChembl≥5 of 5303 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.92	Ki	0.12	nM	CHEMBL353333
9.84	IC50	0.146	nM	Rhenium complex
9.80	Ki	0.1585	nM	CHEMBL1818444
9.70	Ki	0.2	nM	CHEMBL42553
9.70	Ki	0.1995	nM	CHEMBL1818445
9.66	Ki	0.22	nM	CHEMBL28394
9.64	IC50	0.227	nM	CHEMBL422290
9.64	IC50	0.23	nM	CHEMBL495464
9.52	IC50	0.3	nM	CHEMBL91184
9.49	IC50	0.32	nM	CHEMBL494626
9.44	Ki	0.36	nM	VANOXERINE
9.44	IC50	0.36	nM	CHEMBL28394
9.43	IC50	0.37	nM	CHEMBL1643896
9.42	IC50	0.38	nM	CHEMBL87031
9.40	Ki	0.4	nM	CHEMBL380406
9.40	Ki	0.4	nM	CHEMBL1214007
9.40	IC50	0.4	nM	CHEMBL87031
9.40	Ki	0.3981	nM	CHEMBL1947100
9.35	Ki	0.45	nM	CHEMBL137718
9.32	Ki	0.48	nM	CHEMBL348552
9.32	Ki	0.48	nM	CHEMBL311347
9.31	Ki	0.49	nM	DESIPRAMINE
9.31	IC50	0.49	nM	CHEMBL87567
9.30	Ki	0.5	nM	CHEMBL381256
9.30	Ki	0.5	nM	CHEMBL1214059
9.30	Ki	0.5012	nM	CHEMBL1944824
9.24	IC50	0.57	nM	CHEMBL318138
9.24	IC50	0.57	nM	CHEMBL87567
9.22	Ki	0.6	nM	CHEMBL1214006
9.22	IC50	0.6	nM	CHEMBL50858
9.22	Ki	0.6026	nM	CHEMBL1947099
9.20	Ki	0.631	nM	CHEMBL1224321
9.18	IC50	0.66	nM	CHEMBL169471
9.17	Ki	0.67	nM	CHEMBL2112916
9.17	Ki	0.6761	nM	CHEMBL1944827
9.16	Ki	0.69	nM	CHEMBL14613
9.15	IC50	0.7	nM	CHEMBL3673167
9.15	IC50	0.71	nM	VANOXERINE
9.15	Ki	0.71	nM	CHEMBL416409
9.14	IC50	0.73	nM	CHEMBL28394
9.14	Ki	0.73	nM	CHEMBL538405
9.12	Ki	0.75	nM	CHEMBL27646
9.12	IC50	0.75	nM	CHEMBL1812741
9.12	IC50	0.76	nM	CHEMBL606929
9.11	IC50	0.776	nM	CHEMBL5967874
9.10	Ki	0.8	nM	CHEMBL383682
9.10	IC50	0.8	nM	CHEMBL494814
9.10	IC50	0.8	nM	CHEMBL494807
9.10	Ki	0.7943	nM	CHEMBL1224321
9.10	Ki	0.7943	nM	INDATRALINE

PubChem BioAssay actives

2597 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
methyl (2S,3S)-3-(4-iodophenyl)-8-azabicyclo[3.2.1]octane-2-carboxylate	64525: In vitro competitive binding versus [N-methyl-3H]WIN-35428 in murine kidney cells transfected with cDNA for human dopamine transporter (DAT)	ki	0.0001	uM
[(2S,3S)-3-(4-fluorophenyl)-8-methyl-8-azabicyclo[3.2.1]octan-2-yl]methyl 3-(2-methylsulfanylethylsulfanyl)propanoate	64368: The compound was tested in vitro for high binding affinity for the Dopamine transporter (DAT) using competitive binding assay.	ic50	0.0002	uM
(1R,2R,3S,5S)-2-(2,2-dibromoethenyl)-8-methyl-3-(4-methylphenyl)-8-azabicyclo[3.2.1]octane;hydrochloride	408564: Displacement of [3H]WIN-35428 from dopamine transporter	ic50	0.0002	uM
methyl (5S,7R)-3-(3,4-dichlorophenyl)-7-hydroxy-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate	64212: Inhibition of [3H]WIN-35428 binding to Dopamine transporter in rhesus (Macaca mulatta) or cynomolgus monkey (Macaca fascicularis) caudate-putamen	ic50	0.0003	uM
(1R,2R,3S,5S)-3-(4-chlorophenyl)-2-(2,2-dibromoethenyl)-8-methyl-8-azabicyclo[3.2.1]octane;hydrochloride	408564: Displacement of [3H]WIN-35428 from dopamine transporter	ic50	0.0003	uM
(2S)-1-[4-[2-[bis(4-fluorophenyl)methoxy]ethyl]piperidin-1-yl]-3-phenylpropan-2-ol;oxalic acid	261082: Displacement of [125I]RTI-55 from DAT	ki	0.0004	uM
4-[2-[bis(4-fluorophenyl)methoxy]ethyl]-1-[(E)-3-phenylprop-2-enyl]piperidine	65799: Binding affinity towards dopamine transporter (DAT) by using [125I]RTI-55 radioligand	ki	0.0004	uM
1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine	64510: Competitive binding versus [N-methyl-3H]WIN-35428 in murine kidney cells transfected with human dopamine transporter	ki	0.0004	uM
4-[2-[bis(4-fluorophenyl)methoxy]ethyl]-1-[[(1R,2R)-2-phenylcyclopropyl]methyl]piperidine;oxalic acid	261082: Displacement of [125I]RTI-55 from DAT	ki	0.0005	uM
methyl 8-methyl-3-naphthalen-2-yl-8-azabicyclo[3.2.1]octane-2-carboxylate	64210: Inhibition of [3H]WIN-35428 binding to the dopamine transporter in cynomolgus (macaca fascicularis) monkey caudate putamen.	ic50	0.0005	uM
Desipramine	64525: In vitro competitive binding versus [N-methyl-3H]WIN-35428 in murine kidney cells transfected with cDNA for human dopamine transporter (DAT)	ki	0.0005	uM
methyl (3S)-3-(4-iodophenyl)-6-methyl-6-azabicyclo[3.2.2]nonane-4-carboxylate	64514: In vitro affinity determined using [3H]WIN-35428 in murine kidney cells transfected with human dopamine transporter (DAT)	ki	0.0005	uM
methyl (2S,3S,5R)-3-(4-iodophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate	64509: Binding affinity to dopamine transporter in membranes of cells selectively expressing the human genes for DAT	ki	0.0005	uM
methyl (2S)-8-methyl-3-naphthalen-2-yl-8-azabicyclo[3.2.1]octane-2-carboxylate	64210: Inhibition of [3H]WIN-35428 binding to the dopamine transporter in cynomolgus (macaca fascicularis) monkey caudate putamen.	ic50	0.0006	uM
methyl (3S,5R)-3-(4-chloro-3-methylphenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate	64365: Inhibition of dopamine (DA) reuptake using cloned human dopamine transporter was determined	ic50	0.0006	uM
[3-(3,3-dimethylbutyl)pyrrolidin-3-yl]-(7-fluoro-1H-indol-5-yl)methanone	502244: Inhibition of [3H]dopamine reuptake at dopamine transporter	ki	0.0006	uM
[(2S)-1-fluoropropan-2-yl] 3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate	64523: Inhibition constant against [N-methyl-3H]WIN-35428 in murine kidney cells transfected with human dopamine transporter.	ki	0.0007	uM
4-[2-[bis(4-fluorophenyl)methoxy]ethyl]-1-(naphthalen-2-ylmethyl)piperidine	65799: Binding affinity towards dopamine transporter (DAT) by using [125I]RTI-55 radioligand	ki	0.0007	uM
[(2S)-1-fluoropropan-2-yl] (1R,2S,3S,5S)-3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate	644411: Displacement of [3H]WIN35428 from human cloned DAT receptor expressed in human HEK293 cells	ki	0.0007	uM
2-[[4-[2-[bis(4-fluorophenyl)methoxy]ethyl]piperidin-1-yl]methyl]-1H-indole	65799: Binding affinity towards dopamine transporter (DAT) by using [125I]RTI-55 radioligand	ki	0.0007	uM
methyl 3-(3,4-dichlorophenyl)-8-azabicyclo[3.2.1]octane-2-carboxylate	64205: Inhibition of [3H]3-beta-(4-fluorophenyl)tropane-2beta-carboxylic acid methyl ester binding to dopamine transporter of cynomolgus monkey striatum	ic50	0.0007	uM
(2S)-1-[4-[2-[bis(4-fluorophenyl)methoxy]ethyl]piperazin-1-yl]-3-phenylpropan-2-ol	384550: Displacement of [125I]RTI55 from DAT	ki	0.0008	uM
3-ethyl-5-[(1R,2S,3S,5S)-8-methyl-3-(4-methylphenyl)-8-azabicyclo[3.2.1]octan-2-yl]-1,2-oxazole	610457: Inhibition of human DAT expressed in HEK293 cells assessed as inhibition of [3H]DA reuptake after 10 mins by scintillation counting	ic50	0.0008	uM
(1R)-3-[4-[2-[bis(4-fluorophenyl)methoxy]ethyl]piperidin-1-yl]-1-phenylpropan-1-ol;oxalic acid	261082: Displacement of [125I]RTI-55 from DAT	ki	0.0008	uM
1-[4-[2-[bis(4-fluorophenyl)methylsulfinyl]ethyl]piperazin-1-yl]-3-phenylpropan-2-ol	2097429: Inhibition of [3H]dopamine uptake from wild type human DAT expressed in COS-7 cells preincubated for 30 mins followed by [3H]dopamine addition and measured after 5 mins by beta scintillation counting analysis	ki	0.0008	uM
3-(3,4-dichlorophenyl)-N-methyl-2,3-dihydro-1H-inden-1-amine	613078: Displacement of [3H]WIN-35428 from human recombinant DAT by scintillation proximity assay	ki	0.0008	uM
ethyl (7R)-3-(3,4-dichlorophenyl)-7-hydroxy-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate	64212: Inhibition of [3H]WIN-35428 binding to Dopamine transporter in rhesus (Macaca mulatta) or cynomolgus monkey (Macaca fascicularis) caudate-putamen	ic50	0.0008	uM
(1R,2R,3S,5S)-8-methyl-3-(4-methylphenyl)-2-(2-phenylethynyl)-8-azabicyclo[3.2.1]octane;hydrochloride	408564: Displacement of [3H]WIN-35428 from dopamine transporter	ic50	0.0008	uM
(1R,2R,3S,5S)-3-(4-chlorophenyl)-8-methyl-2-(2-phenylethynyl)-8-azabicyclo[3.2.1]octane;hydrochloride	408564: Displacement of [3H]WIN-35428 from dopamine transporter	ic50	0.0008	uM
methyl (1R,2S,3S,5R)-3-(4-chloro-3-methylphenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate;hydrochloride	412885: Displacement of [3H]WIN-35428 from DAT	ic50	0.0008	uM
methyl (2R,5S,7R)-3-(3,4-dichlorophenyl)-7-hydroxy-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate	64212: Inhibition of [3H]WIN-35428 binding to Dopamine transporter in rhesus (Macaca mulatta) or cynomolgus monkey (Macaca fascicularis) caudate-putamen	ic50	0.0008	uM
4-[2-[bis(4-fluorophenyl)methoxy]ethyl]-1-[(2R)-2-methyl-3-phenylpropyl]piperidine;oxalic acid	261082: Displacement of [125I]RTI-55 from DAT	ki	0.0009	uM
(1S)-3-[4-[2-[bis(4-fluorophenyl)methoxy]ethyl]piperidin-1-yl]-1-phenylpropan-1-ol;oxalic acid	261082: Displacement of [125I]RTI-55 from DAT	ki	0.0009	uM
propan-2-yl (3S)-3-(4-chlorophenyl)-6-methyl-6-azabicyclo[3.2.2]nonane-4-carboxylate	64523: Inhibition constant against [N-methyl-3H]WIN-35428 in murine kidney cells transfected with human dopamine transporter.	ki	0.0009	uM
(2R,3S)-2-(4-fluorophenyl)-8-methyl-3-(4-methylphenyl)-8-azabicyclo[3.2.1]octane	283002: Displacement of [3H]WIN-35428 from DAT	ic50	0.0009	uM
(1R,2R,3S,5S)-3-(4-chlorophenyl)-8-methyl-2-[2-(4-nitrophenyl)ethynyl]-8-azabicyclo[3.2.1]octane;hydrochloride	408564: Displacement of [3H]WIN-35428 from dopamine transporter	ic50	0.0009	uM
4-[2-[bis(4-fluorophenyl)methoxy]ethyl]-1-[(E)-3-(furan-2-yl)prop-2-enyl]piperidine	65799: Binding affinity towards dopamine transporter (DAT) by using [125I]RTI-55 radioligand	ki	0.0010	uM
1-(1-benzofuran-2-ylmethyl)-4-[2-[bis(4-fluorophenyl)methoxy]ethyl]piperidine	65799: Binding affinity towards dopamine transporter (DAT) by using [125I]RTI-55 radioligand	ki	0.0010	uM
2-[1-(3,4-dichlorophenyl)butyl]piperidine	275441: Displacement of [125I]RTI-55 from human DAT expressing HEK293 cells	ki	0.0010	uM
2-[1-(3,4-dichlorophenyl)-3-methylbutyl]piperidine	275441: Displacement of [125I]RTI-55 from human DAT expressing HEK293 cells	ki	0.0010	uM
1-[1-(3,4-dichlorophenyl)cyclohexyl]-3-methylbutan-1-amine	578421: Inhibition of [3H]dopamine reuptake at human recombinant DAT expressed in COS-7 cells by scintillation counting	ic50	0.0010	uM
(5R,8S)-5-(3,4-dichlorophenyl)-8-(methylamino)-5,6,7,8-tetrahydronaphthalene-2-sulfonamide	262047: Inhibition of dopamine re-uptake at human dopamine transporter expressed in HEK293 cells	ic50	0.0010	uM
4-[4,5-difluoro-2-(4-fluorophenoxy)phenyl]piperidine	438206: Displacement of [125I]RTI-55 from human DAT expressed in HEK293 cells	ki	0.0010	uM
6-[4-[[(2S,3S)-3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carbonyl]oxymethyl]triazol-1-yl]hexyl (2R,3S)-3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate	450451: Displacement of [125I]methyl 3-(4-iodophenyl)-8-methyl-8-aza-bicyclo[3.2.1]octane-2-carboxylate from human recombinant DAT expressed in african green monkey COS1 cells by liquid scintillation counting	ki	0.0010	uM
6-(1,3-benzodioxol-5-yl)-3,4-dihydro-2H-pyrimido[1,2-b]isoindol-6-ol;hydrochloride	64349: Inhibition of [3H]WIN-35428 radioligand binding to the Dopamine Transporter in guinea pig striatal membrane	ic50	0.0011	uM
4-[2-[bis(4-fluorophenyl)methoxy]ethyl]-1-(3,4-dihydronaphthalen-2-ylmethyl)piperidine;oxalic acid	261082: Displacement of [125I]RTI-55 from DAT	ki	0.0011	uM
methyl 3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate	64511: Compound was tested for inhibition of [125I]RTI-55 binding to dopamine transporter in HEK cells	ki	0.0011	uM
4-[2-[bis(4-fluorophenyl)methoxy]ethyl]-1-(3-phenylpropyl)piperidine	65799: Binding affinity towards dopamine transporter (DAT) by using [125I]RTI-55 radioligand	ki	0.0011	uM
methyl (3S,5R)-3-(4-iodophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate	64206: Displacement of [3H]WIN-35428 from monkey dopamine transporter	ic50	0.0011	uM
methyl (3S,5R)-3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate	281805: Displacement of [3H]WIN-35428 from DAT	ic50	0.0011	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cocaine	increases uptake, increases activity, increases localization, increases import, increases transport (+9 more)	16
Dopamine	increases transport, decreases reaction, increases uptake, affects cotreatment, increases expression (+9 more)	16
Methamphetamine	increases activity, increases reaction, decreases activity, decreases expression, increases response to substance (+2 more)	10
Amphetamine	affects localization, affects cotreatment, increases expression, decreases localization, increases export (+7 more)	8
1-Methyl-4-phenylpyridinium	decreases activity, increases uptake, increases response to substance, decreases response to substance, increases reaction (+5 more)	8
Methylphenidate	increases uptake, affects response to substance, affects cotreatment, increases expression, increases reaction (+5 more)	7
Manganese	affects response to substance, affects cotreatment, increases response to substance, affects localization	4
N-Methyl-3,4-methylenedioxyamphetamine	increases uptake, decreases reaction, increases import	4
(1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester	affects binding, decreases reaction, increases reaction	3
vanoxerine	decreases activity, decreases response to substance, affects binding, decreases reaction, increases uptake	3
Rotenone	decreases expression, increases response to substance	3
Bupropion	increases reaction, affects cotreatment, increases expression, decreases reaction, increases import (+4 more)	3
para-methyl-4-methylaminorex	decreases reaction, increases reaction, increases uptake, affects binding, decreases activity	2
bisphenol A	affects cotreatment, decreases methylation, increases expression	2
phenethylamine	decreases reaction, increases transport, increases activity, increases reaction	2
4-fluoroamphetamine	decreases reaction, increases import, increases uptake	2
2-(3-methoxyphenyl)-2-(ethylamino)cyclohexanone	decreases reaction, increases import, increases uptake, affects response to substance, affects uptake	2
Aluminum Hydroxide	decreases expression, increases reaction, increases expression, decreases reaction, affects cotreatment	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Fluoxetine	increases import, increases uptake, decreases reaction	2
Mazindol	decreases reaction, increases uptake, decreases activity, decreases response to substance	2
Melitten	increases localization, affects binding, increases uptake, affects cotreatment, decreases reaction	2
Nomifensine	decreases reaction, increases uptake, decreases activity, decreases response to substance	2
Norepinephrine	increases activity, increases reaction, increases uptake	2
Paraquat	decreases expression, decreases reaction, affects response to substance	2
Serotonin	increases activity, increases reaction, increases uptake	2
Tetradecanoylphorbol Acetate	increases localization, increases expression, affects cotreatment	2
Tretinoin	decreases expression, increases reaction, decreases reaction, increases expression, affects cotreatment	2
4-methylaminorex	decreases reaction, increases uptake, decreases activity	1
1-phenyl-2-(1-pyrrolidinyl)-1-pentanone	increases import, decreases reaction	1

ChEMBL screening assays

1043 unique, capped per target: 993 binding, 24 functional, 24 admet, 2 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL805625	Binding	Selectivity ratio between serotonin and dopamine transporters	Design, synthesis, and biological evaluation of novel non-piperazine analogues of 1-[2-(diphenylmethoxy)ethyl]- and 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazines as dopamine transporter inhibitors. — J Med Chem
CHEMBL1069372	Functional	Agonist activity at DAT	Design, synthesis, and pharmacological evaluation of phenoxy pyridyl derivatives as dual norepinephrine reuptake inhibitors and 5-HT1A partial agonists. — Bioorg Med Chem Lett
CHEMBL4032124	ADMET	Substrate activity at human DAT expressed in HEK293 cells assessed as induction of DAT-mediated [3H]MPP+ release at 10 uM measured every 2 mins by liquid scintillation counting	Heterocyclic Analogues of Modafinil as Novel, Atypical Dopamine Transporter Inhibitors. — J Med Chem

Cellosaurus cell lines

2 cell lines: 1 spontaneously immortalized cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_F1X4	ValiScreen human SLC6A3	Spontaneously immortalized cell line	Female
CVCL_HQ16	GM25291	Transformed cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
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