SLC6A3 solute carrier family 6 member 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: SLC6A3provided by HGNC
Official Full Name: solute carrier family 6 member 3provided by HGNC
Primary source: HGNC:HGNC:11049
See related: Ensembl:ENSG00000142319 MIM:126455; AllianceGenome:HGNC:11049
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: DAT; DAT1; PKDYS; PKDYS1
Summary: 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.[provided by RefSeq, Nov 2009]
Expression: Low expression observed in reference dataset See more
Orthologs: mouse all
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Genomic context

Location:: 5p15.33

Exon count:: 15

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	5	NC_000005.10 (1392794..1445440, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	5	NC_060929.1 (1303172..1357405, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	5	NC_000005.9 (1392909..1445555, complement)

Chromosome 5 - NC_000005.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Structure of the human dopamine transporter in complex with cocaine.
Title: Structure of the human dopamine transporter in complex with cocaine.
Gene Interaction of Dopaminergic Synaptic Pathway Genes in Attention-Deficit Hyperactivity Disorder: a Case-Control Study in Chinese Children.
Title: Gene Interaction of Dopaminergic Synaptic Pathway Genes in Attention-Deficit Hyperactivity Disorder: a Case-Control Study in Chinese Children.
Association between longitudinal changes in striatal dopamine transporter uptake and clinical features of dementia with Lewy bodies.
Title: Association between longitudinal changes in striatal dopamine transporter uptake and clinical features of dementia with Lewy bodies.
Effects of STN-DBS surgery on cerebral glucose metabolism and distribution of DAT in Parkinson's disease.
Title: Effects of STN-DBS surgery on cerebral glucose metabolism and distribution of DAT in Parkinson's disease.
LRP5, SLC6A3, and SOX10 Expression in Conventional Ameloblastoma.
Title: LRP5, SLC6A3, and SOX10 Expression in Conventional Ameloblastoma.
Structure-Based Discovery of a Novel Allosteric Inhibitor against Human Dopamine Transporter.
Title: Structure-Based Discovery of a Novel Allosteric Inhibitor against Human Dopamine Transporter.
Striatal dopamine transporter and receptor availability correlate with relative cerebral blood flow measured with [[11]C]PE2I, [[18]F]FE-PE2I and [[11]C]raclopride PET in healthy individuals.
Title: Striatal dopamine transporter and receptor availability correlate with relative cerebral blood flow measured with [(11)C]PE2I, [(18)F]FE-PE2I and [(11)C]raclopride PET in healthy individuals.
A novel hypervariable variable number tandem repeat in the dopamine transporter gene (SLC6A3).
Title: A novel hypervariable variable number tandem repeat in the dopamine transporter gene (SLC6A3).
Driving risks of young drivers with symptoms of attention deficit hyperactivity disorder: association with the dopamine transporter gene VNTR polymorphism.
Title: Driving risks of young drivers with symptoms of attention deficit hyperactivity disorder: association with the dopamine transporter gene VNTR polymorphism.
Disordered eating in early childhood: DRD4 and DAT1 gene polymorphisms and quality of mother-child interaction.
Title: Disordered eating in early childhood: DRD4 and DAT1 gene polymorphisms and quality of mother-child interaction.

Submit: New GeneRIF Correction See all GeneRIFs (641)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Classic dopamine transporter deficiency syndrome MedGen: C5700336 OMIM: 613135 GeneReviews: SLC6A3-Related Dopamine Transported Deficiency Syndrome	Compare labs
Tobacco addiction, susceptibility to MedGen: C1861063 OMIM: 188890 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 gp120 and HIV-1 Tat decrease dopamine uptake into striatal synaptosomes by decreasing the V(max) of the dopamine transporter (DAT); 17beta-Estradiol prevents the oxidative stress and loss of DAT function associated with gp120/Tat neurotoxicity	PubMed
Nef	nef	HIV-1 Nef-mediated downregulation of HLA (MHCI) may be affected by/inhibited by SLC6A3 as demonstrated by siRNA genome-wide screen [in HeLa cells)	PubMed
Tat	tat	HIV-1 Tat inhibits SLC6A3 (hDAT) and dopamine uptake	PubMed
	tat	A three-dimensional structural model for HIV-1 Tat binding with human dopamine transporter is developed by computational modeling and molecular dynamics simulations	PubMed
	tat	Mutation of either Tyr88 (Y88F) or Lys92 (K92M) in human dopamine transporter (hDAT) attenuates HIV-1 Tat-induced inhibition of hDAT function in cells	PubMed
	tat	Co-immunoprecipitation analysis indicates that HIV-1 Tat directly binds to human dopamine transporter (hDAT). The hDAT Y470H mutant attenuates Tat-induced reduction of hDAT function	PubMed
	tat	HIV-1 Tat allosterically modulates DAT activity in HEK293 cells	PubMed
	tat	HIV-1 Tat increases plasma membrane (PM) dopamine transporter (DAT) activity and calpain protease activity at the PM	PubMed
	tat	HIV-1 gp120 and HIV-1 Tat decrease dopamine uptake into striatal synaptosomes by decreasing the V(max) of the dopamine transporter (DAT); 17beta-Estradiol prevents the oxidative stress and loss of DAT function associated with gp120/Tat neurotoxicity	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

GDB:392133 (e-PCR)
- UniSTS:157184

GDB:194281 (e-PCR)
- UniSTS:155786

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables amine binding	IEA Inferred from Electronic Annotation more info
enables dopamine binding	IEA Inferred from Electronic Annotation more info
enables dopamine:sodium symporter activity	IDA Inferred from Direct Assay more info	PubMed
enables dopamine:sodium symporter activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables heterocyclic compound binding	IEA Inferred from Electronic Annotation more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables monoamine transmembrane transporter activity	IDA Inferred from Direct Assay more info	PubMed
enables monoamine transmembrane transporter activity	ISS Inferred from Sequence or Structural Similarity more info
enables monoamine transmembrane transporter activity	TAS Traceable Author Statement more info
enables neurotransmitter transmembrane transporter activity	ISS Inferred from Sequence or Structural Similarity more info
enables protease binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein phosphatase 2A binding	IEA Inferred from Electronic Annotation more info
enables protein-containing complex binding	IEA Inferred from Electronic Annotation more info
enables signaling receptor binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in adenohypophysis development	IEA Inferred from Electronic Annotation more info
involved_in amino acid transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in cognition	IEA Inferred from Electronic Annotation more info
involved_in dopamine biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in dopamine catabolic process	IEA Inferred from Electronic Annotation more info
involved_in dopamine transport	IDA Inferred from Direct Assay more info	PubMed
involved_in dopamine uptake	IDA Inferred from Direct Assay more info	PubMed
involved_in dopamine uptake	ISS Inferred from Sequence or Structural Similarity more info
involved_in dopamine uptake involved in synaptic transmission	TAS Traceable Author Statement more info
involved_in hyaloid vascular plexus regression	ISS Inferred from Sequence or Structural Similarity more info
involved_in lactation	IEA Inferred from Electronic Annotation more info
involved_in locomotory behavior	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within monoamine transport	IDA Inferred from Direct Assay more info	PubMed
involved_in neurotransmitter transport	ISS Inferred from Sequence or Structural Similarity more info
involved_in norepinephrine uptake	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of multicellular organism growth	IEA Inferred from Electronic Annotation more info
involved_in prepulse inhibition	IEA Inferred from Electronic Annotation more info
involved_in regulation of dopamine metabolic process	IEA Inferred from Electronic Annotation more info
involved_in response to cAMP	IEA Inferred from Electronic Annotation more info
involved_in response to cocaine	IEA Inferred from Electronic Annotation more info
involved_in response to ethanol	IEA Inferred from Electronic Annotation more info
involved_in response to iron ion	IEA Inferred from Electronic Annotation more info
involved_in response to nicotine	IEA Inferred from Electronic Annotation more info
involved_in response to xenobiotic stimulus	IEA Inferred from Electronic Annotation more info
involved_in sensory perception of smell	IEA Inferred from Electronic Annotation more info
involved_in sodium ion transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
located_in axon	IDA Inferred from Direct Assay more info	PubMed
located_in axon terminus	IEA Inferred from Electronic Annotation more info
located_in cell surface	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	TAS Traceable Author Statement more info	PubMed
located_in dopaminergic synapse	IEA Inferred from Electronic Annotation more info
part_of flotillin complex	IDA Inferred from Direct Assay more info	PubMed
located_in membrane	TAS Traceable Author Statement more info	PubMed
located_in membrane raft	IDA Inferred from Direct Assay more info	PubMed
located_in neuron projection	IDA Inferred from Direct Assay more info	PubMed
located_in neuronal cell body	IDA Inferred from Direct Assay more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
located_in postsynaptic membrane	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: sodium-dependent dopamine transporter

Names: DA transporter; dopamine transporter 1; solute carrier family 6 (neurotransmitter transporter), member 3; solute carrier family 6 (neurotransmitter transporter, dopamine), member 3

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.