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Aliases for SLC6A4 Gene

Aliases for SLC6A4 Gene

  • Solute Carrier Family 6 (Neurotransmitter Transporter), Member 4 2 3
  • HTT 3 4 6
  • Solute Carrier Family 6 (Neurotransmitter Transporter, Serotonin), Member 4 2 3
  • 5-Hydroxytryptamine (Serotonin) Transporter 2 3
  • Serotonin Transporter 1 2 3
  • 5HT Transporter 3 4
  • OCD1 3 6
  • 5HTT 3 4
  • SERT 3 4
  • Na+/Cl- Dependent Serotonin Transporter 3
  • Sodium-Dependent Serotonin Transporter 3
  • Solute Carrier Family 6 Member 4 4
  • Obsessive-Compulsive Disorder 1 2
  • 5-HTTLPR 3
  • 5-HTT 3
  • SERT1 3
  • HSERT 3

External Ids for SLC6A4 Gene

Previous Symbols for SLC6A4 Gene

  • HTT
  • OCD1

Summaries for SLC6A4 Gene

Entrez Gene Summary for SLC6A4 Gene

  • This gene encodes an integral membrane protein that transports the neurotransmitter serotonin from synaptic spaces into presynaptic neurons. The encoded protein terminates the action of serotonin and recycles it in a sodium-dependent manner. This protein is a target of psychomotor stimulants, such as amphetamines and cocaine, and is a member of the sodium:neurotransmitter symporter family. A repeat length polymorphism in the promoter of this gene has been shown to affect the rate of serotonin uptake and may play a role in sudden infant death syndrome, aggressive behavior in Alzheimer disease patients, and depression-susceptibility in people experiencing emotional trauma. [provided by RefSeq, Jul 2008]

GeneCards Summary for SLC6A4 Gene

SLC6A4 (Solute Carrier Family 6 (Neurotransmitter Transporter), Member 4) is a Protein Coding gene. Diseases associated with SLC6A4 include alcoholic psychosis and obsessive-compulsive disorder. Among its related pathways are SIDS Susceptibility Pathways and Circadian entrainment. GO annotations related to this gene include protein homodimerization activity and Rab GTPase binding. An important paralog of this gene is SLC6A13.

UniProtKB/Swiss-Prot for SLC6A4 Gene

  • Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into the pre-synaptic terminal for re-utilization. Plays a key role in mediating regulation of the availability of serotonin to other receptors of serotonergic systems. Terminates the action of serotonin and recycles it in a sodium-dependent manner.

Tocris Summary for SLC6A4 Gene

  • 5-HT transporters (serotonin transporters, SERT) are sodium- and chloride-dependent members of the solute carrier family 6 (SLC6) found widely distributed throughout the brain. They are responsible for re-uptake of 5-HT and undergo a conformational change to move one or more molecules per cycle. Structural motifs include 12-TM domains, extracellular loops, cytoplasmic C- and N-termini, putative phosphorylation sites acting as potential targets for PKA and PKC and regions essential for 5-HT selective affinity. There is evidence to suggest that SERTs are linked to neuroticism, sexual behavior, alcoholism, clinical depression, hypertension and obsessive-compulsive disorder.

Gene Wiki entry for SLC6A4 Gene

No data available for PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for SLC6A4 Gene

Genomics for SLC6A4 Gene

Genomic Location for SLC6A4 Gene

Start:
30,194,319 bp from pter
End:
30,236,002 bp from pter
Size:
41,684 bases
Orientation:
Minus strand

Genomic View for SLC6A4 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for SLC6A4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SLC6A4 Gene

Regulatory Elements for SLC6A4 Gene

Proteins for SLC6A4 Gene

  • Protein details for SLC6A4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P31645-SC6A4_HUMAN
    Recommended name:
    Sodium-dependent serotonin transporter
    Protein Accession:
    P31645
    Secondary Accessions:
    • Q5EE02

    Protein attributes for SLC6A4 Gene

    Size:
    630 amino acids
    Molecular mass:
    70325 Da
    Quaternary structure:
    • Monomer or homooligomer (By similarity). Interacts with TGFB1I1. Interacts (via sialylated form) with MYH9. Interacts with SEC23A, SEC24C and INADL. Interacts with NOS1; the interaction may diminish the cell surface localization of SERT in the brain and, correspondingly, reduce serotonin reuptake. Interacts with filamentous actin and STX1A (By similarity). Interacts (via C-terminus) with VIM. Interacts (via C-terminus) with SCAMP2; the interaction is direct and retains transporter molecules intracellularly. Interacts with RAB4 (GTP-bound form); the interaction retains transporter molecules intracellularly.
    Miscellaneous:
    • This protein is the target of psychomotor stimulants such as amphetamines or cocaine

    Alternative splice isoforms for SLC6A4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for SLC6A4 Gene

Proteomics data for SLC6A4 Gene at MOPED

Post-translational modifications for SLC6A4 Gene

  • Glycosylated; modification with sialylated N-glycans is a requirement for transporters to associate with each other and to function as homooligomeric forms.
  • Phosphorylation at Thr-276 increases 5-HT uptake and is required for cGMP-mediated SERT regulation. Phosphorylation upon PKC stimulation modifies the SERT distribution and density in the membrane, and diminishes the uptake capacity.
  • Modification sites at PhosphoSitePlus
  • Glycosylation at Asn208 and Asn217

Other Protein References for SLC6A4 Gene

No data available for DME Specific Peptides for SLC6A4 Gene

Domains for SLC6A4 Gene

Gene Families for SLC6A4 Gene

HGNC:
  • SLC :Solute carriers
IUPHAR :

UniProtKB/Swiss-Prot:

SC6A4_HUMAN
Family:
  • Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A4 subfamily.:
    • P31645
genes like me logo Genes that share domains with SLC6A4: view

Function for SLC6A4 Gene

Molecular function for SLC6A4 Gene

GENATLAS Biochemistry: solute carrier family 6,member A4,neurotransmitter transporter,serotonin
UniProtKB/Swiss-Prot Function: Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into the pre-synaptic terminal for re-utilization. Plays a key role in mediating regulation of the availability of serotonin to other receptors of serotonergic systems. Terminates the action of serotonin and recycles it in a sodium-dependent manner.
UniProtKB/Swiss-Prot Induction: Down-regulated when plasma serotonin is elevated.

Gene Ontology (GO) - Molecular Function for SLC6A4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005328 neurotransmitter:sodium symporter activity --
GO:0005335 serotonin:sodium symporter activity IMP 19270731
GO:0005515 protein binding IPI 11343649
GO:0008504 monoamine transmembrane transporter activity IDA 16024787
GO:0015222 serotonin transmembrane transporter activity IMP 19270731
genes like me logo Genes that share ontologies with SLC6A4: view
genes like me logo Genes that share phenotypes with SLC6A4: view

Animal Models for SLC6A4 Gene

MGI Knock Outs for SLC6A4:

miRNA for SLC6A4 Gene

miRTarBase miRNAs that target SLC6A4

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targeting and HOMER Transcription for SLC6A4 Gene

Localization for SLC6A4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SLC6A4 Gene

Cell membrane; Multi-pass membrane protein. Endomembrane system; Multi-pass membrane protein. Endosome membrane; Multi-pass membrane protein. Note=Translocates from intracellular locations to the plasma membrane. Density of transporter molecules on the plasma membrane is itself regulated by serotonin.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for SLC6A4 Gene COMPARTMENTS Subcellular localization image for SLC6A4 gene
Compartment Confidence
cytosol 5
endosome 5
plasma membrane 5
extracellular 3
nucleus 2
cytoskeleton 1

Gene Ontology (GO) - Cellular Components for SLC6A4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005768 endosome --
GO:0005829 cytosol IDA 19270731
GO:0005886 plasma membrane IDA 16870614
GO:0005887 integral component of plasma membrane IC 19270731
GO:0010008 endosome membrane IEA --
genes like me logo Genes that share ontologies with SLC6A4: view

Pathways for SLC6A4 Gene

genes like me logo Genes that share pathways with SLC6A4: view

Gene Ontology (GO) - Biological Process for SLC6A4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001666 response to hypoxia IEA --
GO:0006836 neurotransmitter transport --
GO:0006837 serotonin transport IDA 19270731
GO:0007420 brain development --
GO:0007584 response to nutrient IEA --
genes like me logo Genes that share ontologies with SLC6A4: view

Compounds for SLC6A4 Gene

(5) Tocris Compounds for SLC6A4 Gene

Compound Action Cas Number
Citalopram hydrobromide Highly potent and selective 5-HT uptake inhibitor [59729-33-8]
Fluoxetine hydrochloride 5-HT re-uptake inhibitor [56296-78-7]
Paroxetine maleate Highly potent and selective 5-HT uptake inhibitor [64006-44-6]
Sertraline hydrochloride 5-HT re-uptake inhibitor [79559-97-0]
Venlafaxine hydrochloride Dual serotonin/noradrenalin re-uptake inhibitor [99300-78-4]

(8) HMDB Compounds for SLC6A4 Gene

Compound Synonyms Cas Number PubMed IDs
Citalopram
  • Bonitrile
59729-33-8
Dextromethorphan
  • Bayer Select Flu Relief
6700-34-1
Escitalopram
  • (+)-Citalopram
128196-01-0
Imipramine
  • Antideprin
50-49-7
Serotonin
  • 3-(2-Aminoethyl)-1H-indol-5-ol
50-67-9

(50) Drugbank Compounds for SLC6A4 Gene

Compound Synonyms Cas Number Type Actions PubMed IDs
3,4-Methylenedioxymethamphetamine
  • Ecstasy
42542-10-9 target negative modulator
3,4-Methylenedioxymethamphetamine
  • Ecstasy
42542-10-9 transporter
4-Methoxyamphetamine
23239-32-9 target inhibitor
Amineptine
57574-09-1 target
Amitriptyline
  • Amitriprolidine
50-48-6 target inhibitor

(5) IUPHAR Ligand for SLC6A4 Gene

Ligand Type Action Affinity Pubmed IDs
[3H]paroxetine None None 9.7
paroxetine Inhibitor Inhibition 9.6
sertraline Inhibitor Inhibition 9.1
fluoxetine Inhibitor Inhibition 8.5
[3H]citalopram None None 8.3

(120) Novoseek inferred chemical compound relationships for SLC6A4 Gene

Compound -log(P) Hits PubMed IDs
(r)-citalopram 88.5 31
dasb 88.2 15
(123i)-2beta-carbomethoxy-3beta-(4-iodophenyl)tropane 87.2 11
citalopram 85.1 96
maoa 83.6 66

(9) PharmGKB related drug/compound annotations for SLC6A4 Gene

genes like me logo Genes that share compounds with SLC6A4: view

Transcripts for SLC6A4 Gene

mRNA/cDNA for SLC6A4 Gene

(1) REFSEQ mRNAs :
(7) Additional mRNA sequences :
(15) Selected AceView cDNA sequences:
(5) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for SLC6A4 Gene

Solute carrier family 6 (neurotransmitter transporter, serotonin), member 4:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for SLC6A4 Gene

ExUns: 1a · 1b ^ 2 ^ 3a · 3b · 3c ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10a · 10b ^ 11 ^ 12 ^ 13 ^ 14a · 14b ^ 15a · 15b
SP1: -
SP2: - -
SP3:
SP4: -
SP5:

Relevant External Links for SLC6A4 Gene

GeneLoc Exon Structure for
SLC6A4
ECgene alternative splicing isoforms for
SLC6A4

Expression for SLC6A4 Gene

mRNA expression in normal human tissues for SLC6A4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for SLC6A4 Gene

This gene is overexpressed in Lung (32.4) and Small Intestine - Terminal Ileum (5.7).

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, and MOPED for SLC6A4 Gene

SOURCE GeneReport for Unigene cluster for SLC6A4 Gene Hs.29792

mRNA Expression by UniProt/SwissProt for SLC6A4 Gene

P31645-SC6A4_HUMAN
Tissue specificity: Expressed in platelets (at protein level).
genes like me logo Genes that share expressions with SLC6A4: view

Orthologs for SLC6A4 Gene

This gene was present in the common ancestor of animals.

Orthologs for SLC6A4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia SLC6A4 36
  • 99.26 (n)
  • 99.37 (a)
SLC6A4 37
  • 93 (a)
OneToOne
cow
(Bos Taurus)
Mammalia SLC6A4 36
  • 89.74 (n)
  • 93.02 (a)
SLC6A4 37
  • 92 (a)
OneToOne
dog
(Canis familiaris)
Mammalia SLC6A4 36
  • 90.32 (n)
  • 93.49 (a)
SLC6A4 37
  • 94 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Slc6a4 36
  • 87.83 (n)
  • 92.54 (a)
Slc6a4 16
Slc6a4 37
  • 93 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia SLC6A4 37
  • 87 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia SLC6A4 37
  • 76 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Slc6a4 36
  • 88.15 (n)
  • 91.75 (a)
chicken
(Gallus gallus)
Aves SLC6A4 36
  • 76.89 (n)
  • 81.88 (a)
SLC6A4 37
  • 76 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia SLC6A4 37
  • 74 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC100493853 36
  • 71.08 (n)
  • 76.81 (a)
zebrafish
(Danio rerio)
Actinopterygii slc6a4a 36
  • 68.29 (n)
  • 70.83 (a)
slc6a4a 37
  • 67 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta SerT 37
  • 52 (a)
OneToOne
CG7075 38
  • 35 (a)
CG4476 38
  • 34 (a)
SerT 38
  • 56 (a)
DAT 38
  • 50 (a)
CG10804 38
  • 36 (a)
CG1698 38
  • 35 (a)
CG8850 38
  • 37 (a)
worm
(Caenorhabditis elegans)
Secernentea mod-5 37
  • 42 (a)
OneToOne
snf-8 38
  • 25 (a)
snf-3 38
  • 36 (a)
snf-9 38
  • 30 (a)
mod-5 38
  • 49 (a)
snf-12 38
  • 32 (a)
snf-6 38
  • 31 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 37
  • 55 (a)
OneToOne
Species with no ortholog for SLC6A4:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for SLC6A4 Gene

ENSEMBL:
Gene Tree for SLC6A4 (if available)
TreeFam:
Gene Tree for SLC6A4 (if available)

Paralogs for SLC6A4 Gene

Paralogs for SLC6A4 Gene

genes like me logo Genes that share paralogs with SLC6A4: view

Variants for SLC6A4 Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for SLC6A4 Gene

P31645-SC6A4_HUMAN
A polymorphism in the promoter region (5-HTT gene-linked polymorphic region, 5-HTTLPR) is located approximately 1 kb upstream of the transcription initiation site and is composed of 16 repeat elements. The polymorphism consists of a 44-bp insertion or deletion involving repeat elements 6 to 8. The short allele is associated with lower transcriptional efficiency of the promoter compared with the long allele. Over half of the Caucasian population has a short allele. Individuals with one or two copies of the short allele exhibit more depressive symptoms, diagnosable depression and suicidality in relation to stressful life events than individuals homozygous for the long allele

Sequence variations from dbSNP and Humsavar for SLC6A4 Gene

SNP ID Clin Chr 17 pos Sequence Context AA Info Type MAF
rs6352 - 30,203,175(-) TTTAA(A/C)GAGGT reference, missense
rs6353 -- 30,211,312(-) AGCAC(A/G)GTGAG synonymous-codon, reference
rs6354 -- 30,222,880(-) CCTCT(A/C)TTGCA utr-variant-5-prime
rs25528 -- 30,222,960(-) GGCGA(A/C)ACCAA intron-variant
rs25530 -- 30,237,332(-) TGCAC(C/T)CCCCA upstream-variant-2KB

Structural Variations from Database of Genomic Variants (DGV) for SLC6A4 Gene

Variant ID Type Subtype PubMed ID
esv2715808 CNV Deletion 23290073

Relevant External Links for SLC6A4 Gene

HapMap Linkage Disequilibrium report
SLC6A4
Human Gene Mutation Database (HGMD)
SLC6A4

Disorders for SLC6A4 Gene

(2) OMIM Diseases for SLC6A4 Gene (182138)

(92) Novoseek inferred disease relationships for SLC6A4 Gene

Disease -log(P) Hits PubMed IDs
major depression 79.4 139
mood disorders 76 87
obsessive-compulsive disorder 69 41
bipolar disorder 68.6 65
psychiatric disorder 65.8 46

Relevant External Links for SLC6A4

Genetic Association Database (GAD)
SLC6A4
Human Genome Epidemiology (HuGE) Navigator
SLC6A4
genes like me logo Genes that share disorders with SLC6A4: view

No data available for UniProtKB/Swiss-Prot for SLC6A4 Gene

Publications for SLC6A4 Gene

  1. Antidepressant- and cocaine-sensitive human serotonin transporter: molecular cloning, expression, and chromosomal localization. (PMID: 7681602) Ramamoorthy S. … Blakely R.D. (Proc. Natl. Acad. Sci. U.S.A. 1993) 2 3 4 23
  2. Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. (PMID: 12869766) Caspi A. … Poulton R. (Science 2003) 3 4 23 49
  3. Meta-analysis of the association of a functional serotonin transporter promoter polymorphism with alcohol dependence. (PMID: 15635638) Feinn R. … Kranzler H.R. (Am. J. Med. Genet. B Neuropsychiatr. Genet. 2005) 3 4 23 49
  4. The serotonin transporter polymorphism, 5HTTLPR, is associated with a faster response time to sertraline in an elderly population with major depressive disorder. (PMID: 12955294) Durham L.K. … Seymour A.B. (Psychopharmacology (Berl.) 2004) 3 23 25 49
  5. Age-dependent antidepressant pharmacogenomics: polymorphisms of the serotonin transporter and G protein beta3 subunit as predictors of response to fluoxetine and nortriptyline. (PMID: 14604448) Joyce P.R. … Kennedy M.A. (Int. J. Neuropsychopharmacol. 2003) 3 23 25 49

Products for SLC6A4 Gene

Sources for SLC6A4 Gene

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