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Protein / target

Sodium-dependent dopamine transporter

Encoded bySLC6A3Q01959Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
28
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Neurotransmitter transmembrane transporter

Primary biology

Neuronal / synaptic signalling

Strongest disease association

Classic dopamine transporter deficiency syndrome

Via encoding gene SLC6A3 · Genetic evidence · score 0.85

Therapeutic position

Established drug target

Small molecules

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Mediates sodium- and chloride-dependent transport of dopamine.

View complete UniProt function annotation

Mediates sodium- and chloride-dependent transport of dopamine (PubMed:10375632, PubMed:11093780, PubMed:1406597, PubMed:15505207, PubMed:19478460, PubMed:39112701, PubMed:39112703, PubMed:39112705, PubMed:8302271). Also mediates sodium- and chloride-dependent transport of norepinephrine (also known as noradrenaline) (By similarity). Regulator of light-dependent retinal hyaloid vessel regression, downstream of OPN5 signaling (By similarity)

Subcellular location

Cell membraneCell projection, neuron projectionCell projection, axon
Domains and Gene Ontology detail (38)

Gene Ontology

  • Caxon
  • Caxon terminus
  • Ccell surface
  • Ccytoplasm
  • Cdopaminergic synapse
  • Cflotillin complex
  • Cmembrane
  • Cmembrane raft
  • Cneuron projection
  • Cneuronal cell body
  • Cplasma membrane
  • Cpostsynaptic membrane

620 aa · 68 kDa

Biological roles

Reactome v97

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Synaptic signallingGOIon channel gatingGO
View supporting evidence

Synaptic signalling

  • ·dopaminergic synapse
  • ·postsynaptic membrane
  • ·presynaptic membrane
  • ·dopamine uptake involved in synaptic transmission

Ion channel gating

  • ·sodium ion transmembrane transport
View underlying pathways (4)

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Interaction neighbourhood

STRING v12.0

Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.

DRD2SNCASTX1ASLC18A2DRD4THCAMK2ASYNGR3FLOT1PRKCBSLC6A3

10 strongest partners — larger node and heavier line mean higher confidence

Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.

Approved medicines with mapped indications

2 medicines · 2 areas

Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.

Attention Deficit Disorder with Hyperactivity2 medicines
Sleep Apnea, Obstructive1 medicine

28 medicines meet Open Targets' target-level approved-medicine definition; the 2 shown here are those on this page with a canonical approved disease indication in the graph. Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

2

How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.

Amphetamine
Narrow target profileApprovedReleasing agent

Dopamine transporter releasing agent

Indicated for Attention Deficit Disorder with Hyperactivity

Direct interaction with this protein · 1 of 2 recorded protein targets — narrow recorded profile

modafinil
Narrow target profileApprovedInhibitor

Dopamine transporter inhibitor

Indicated for Attention Deficit Disorder with Hyperactivity, Sleep Apnea, Obstructive

Direct interaction with this protein · Only this protein recorded as a target

ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene SLC6A3

Gene-level evidence surfaced through the gene SLC6A3that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Classic dopamine transporter deficiency syndrome
0.85Well supported

Genetic evidence dominant · Open Targets 0.76

Infantile dystonia-parkinsonism
0.83Well supported

Genetic evidence dominant · Open Targets 0.79

Parkinsonism-dystonia, infantile
0.81Well supported

Genetic evidence dominant · Open Targets 0.75

Attention Deficit Disorder with Hyperactivity
0.79Well supported

Clinical evidence dominant · Open Targets 0.64

Major depressive disorder
0.77Well supported

Clinical evidence dominant · Open Targets 0.63

View evidence synthesis (5)
Classic dopamine transporter deficiency syndromeWell supported
0.85
agreement 0.730.97
Genetic100%Genetic literaturedup

Open Targets aggregate 0.76 · 1 independent evidence family · 1 not counted as duplicate

Infantile dystonia-parkinsonismWell supported
0.83
agreement 0.690.97
Genetic98%Literature2%Genetic literaturedup

Open Targets aggregate 0.79 · 2 independent evidence families · 1 not counted as duplicate

Parkinsonism-dystonia, infantileWell supported
0.81
agreement 0.680.95
Genetic98%Literature2%Genetic literaturedup

Open Targets aggregate 0.75 · 2 independent evidence families · 1 not counted as duplicate

Attention Deficit Disorder with HyperactivityWell supported
0.79
agreement 0.630.94
Clinical84%Literature16%

Open Targets aggregate 0.64 · 2 independent evidence families

Major depressive disorderWell supported
0.77
agreement 0.620.93
Clinical88%Literature12%

Open Targets aggregate 0.63 · 2 independent evidence families

This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations
Infantile dystonia-parkinsonism0.79
Classic dopamine transporter deficiency syndrome0.76
Parkinsonism-dystonia, infantile0.75
Attention Deficit Disorder with Hyperactivity0.64
Major depressive disorder0.63
Alzheimer's Disease0.62
Obesity disorder0.60
Sleep disorder0.57

Drug development

41 compounds recorded · 28 approved · 10 in clinical development · 3 earlier-stage

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 2 drugs that target this protein in Forefront's canonical graph (2 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (10)
LISDEXAMFETAMINE DIMESYLATEApproval
NOMIFENSINEApproval
BUPROPIONApproval
LIAFENSINEPhase 2
PHENMETRAZINEApproval
METHAMPHETAMINEApproval
METHYLPHENIDATEApproval
TESOFENSINEPhase 2
PHENDIMETRAZINE TARTRATEApproval
DASOTRALINEApproval

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small moleculesStrong

Approved Drug and Structure with Ligand support this modality.

AntibodiesEmerging

Feasibility evidence (uniprot loc high conf and go cc high conf) — no clinical-stage drug of this modality recorded.

Protein degradersEmerging

Feasibility evidence (database ubiquitination and small molecule binder) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (9)
SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMPR · Database UbiquitinationPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

acneLynch et al. (2017)addictive psychostimulationBowes et al. (2012)dyskinesiaBowes et al. (2012)alcoholismClinPGxparkinsonismLynch et al. (2017)receptor bindingToxCastdystoniaLynch et al. (2017)acneBowes et al. (2012)increased locomotor activityLynch et al. (2017)stereotypyLynch et al. (2017)parkinsonismBowes et al. (2012)depressionLynch et al. (2017)

Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.

Clinical trials

30

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

View all trials (26)

RECRUITING · via modafinil · NCT07231497

NOT_YET_RECRUITING · via modafinil · NCT06354985

RECRUITING · via modafinil · NCT05333250

ACTIVE_NOT_RECRUITING · via modafinil · NCT00262470

ACTIVE_NOT_RECRUITING · via modafinil · NCT01988883

COMPLETED · via Amphetamine · NCT02020408

COMPLETED · via modafinil · NCT00751023

TERMINATED · via modafinil · NCT00626210

COMPLETED · via modafinil · NCT00614926

COMPLETED · via modafinil · NCT00423943

COMPLETED · via modafinil · NCT00118378

TERMINATED · via modafinil · NCT00102284

ClinicalTrials.gov via the drug-target graph.

What's happening now

10

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 2 drugs that target this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.

  1. New publication2025-04-28
    Astroglial CB<sub>1</sub> Reveal Sex-Specific Synaptic Effects of Amphetamine.

    Glia · 2025 · 3 citations · Europe PMC · via Amphetamine

  2. New publication2025-01-13
    Astrocytes Mediate Psychostimulant-Induced Alterations of Spike-Timing Dependent Synaptic Plasticity.

    Glia · 2025 · 2 citations · Europe PMC · via Amphetamine

  3. Safety communication2020-11-16

    Drug Safety Update: Modafinil (Provigil): increased risk of congenital malformations if used during pregnancy

    mhra · safety · mhra · via modafinil

  4. Safety communication2014-12-11

    Drug Safety Update: Modafinil (Provigil): now restricted to narcolepsy

    mhra · safety · mhra · via modafinil

  5. Safety communication2014-12-11

    Drug Safety Update: Modafinil: restricted use recommended

    mhra · safety · mhra · via modafinil

  6. New publication2014-01-03
    A two-phased screening paradigm for evaluating candidate medications for cocaine cessation or relapse prevention: modafinil, levodopa-carbidopa, naltrexone.

    Drug and alcohol dependence · 2014 · 51 citations · Europe PMC · via modafinil

  7. New publication2011-10-01
    Animal models of schizophrenia.

    British journal of pharmacology · 2011 · 537 citations · Europe PMC · via Amphetamine

  8. New publication2011-08-12
    Modafinil for the treatment of methamphetamine dependence.

    Drug and alcohol dependence · 2012 · 85 citations · Europe PMC · via modafinil

  9. New publication2010-05-04
    Modafinil treatment for fatigue in HIV/AIDS: a randomized placebo-controlled study.

    The Journal of clinical psychiatry · 2010 · 23 citations · Europe PMC · via modafinil

  10. New publication2010-01-25
    Randomized, double-blind, placebo-controlled trial of modafinil for the treatment of methamphetamine dependence.

    Drug and alcohol dependence · 2010 · 83 citations · Europe PMC · via modafinil

Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.