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Category   Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21
GIFtS

SLC6A4 Gene

protein-coding   GIFtS: 67
GCID: GC17M028521

Solute Carrier Family 6 (Neurotransmitter Transporter),...

(Previous names: solute carrier family 6 (neurotransmitter transporter, serotonin),...)
(Previous symbol: HTT)
Alzheimer's & Parkinson's Diseases Congress
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(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
About This Section

Aliases
Solute Carrier Family 6 (Neurotransmitter Transporter), Member 41 2     5-HTT2
HTT1 2 3 5     5-HTTLPR2
5-Hydroxytryptamine (Serotonin) Transporter1 2     5-Hydroxytryptamine Transporter2
Solute Carrier Family 6 (Neurotransmitter Transporter, Serotonin), Member
41 2
     SERT12
Serotonin Transporter 11 2     hSERT2
5HTT2 3     Na+/Cl- Dependent Serotonin Transporter2
5HT Transporter2 3     Sodium-Dependent Serotonin Transporter2
SERT2 3     Solute Carrier Family 6 Member 43
OCD12 5     

External Ids:    HGNC: 110501   Entrez Gene: 65322   Ensembl: ENSG000001085767   OMIM: 1821385   UniProtKB: P316453   

Export aliases for SLC6A4 gene to outside databases

Previous GC identifers: GC17M028278 GC17M030431 GC17M028670 GC17M025549 GC17M024733


(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

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 obsessive-compulsive disorder, and borderline personality disorder, and among its related super-pathways are Venlafaxine Pathway, Pharmacokinetics and Synaptic vesicle cycle. GO annotations related to this gene include Rab GTPase binding and protein homodimerization activity. An important paralog of this gene is SLC6A6.

UniProtKB/Swiss-Prot: SC6A4_HUMAN, P31645
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

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 (Serotonin transporter) Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 73), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section
RefSeq DNA sequence:
NC_000017.10  NT_010799.15  NC_018928.2  
Regulatory elements:
   SABiosciences Regulatory transcription factor binding sites in the SLC6A4 gene promoter:
         C/EBPbeta   Nkx2-5   POU3F2   C/EBPalpha   AREB6   MEF-2A   RORalpha1   aMEF-2   NF-kappaB1   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidSLC6A4 promoter sequence
   Search SABiosciences Chromatin IP Primers for SLC6A4

Epigenetics:
QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat SLC6A4


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 17q11.2   Ensembl cytogenetic band:  17q11.2   HGNC cytogenetic band: 17q11.2

SLC6A4 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
SLC6A4 gene location

GeneLoc information about chromosome 17         GeneLoc Exon Structure

GeneLoc location for GC17M028521:  view genomic region     (about GC identifiers)

Start:
28,521,337 bp from pter      End:
28,563,020 bp from pter
Size:
41,684 bases      Orientation:
minus strand

(According to UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MAXQB RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Ontologies according to Gene Ontology Consortium 01 Oct 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
About This Section

UniProtKB/Swiss-Prot: SC6A4_HUMAN, P31645 (See protein sequence)
Recommended Name: Sodium-dependent serotonin transporter  
Size: 630 amino acids; 70325 Da
Subunit: 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
Subcellular location: 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
Miscellaneous: This protein is the target of psychomotor stimulants such as amphetamines or cocaine
Secondary accessions: Q5EE02
Alternative splicing: 2 isoforms:  P31645-1   P31645-2   

Explore the universe of human proteins at neXtProt for SLC6A4: NX_P31645

Explore proteomics data for SLC6A4 at MOPED 

Post-translational modifications:

  • UniProtKB: Glycosylated; modification with sialylated N-glycans is a requirement for transporters to associate with each
    other and to function as homooligomeric forms (By similarity)
  • UniProtKB: 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
  • View modification sites using PhosphoSitePlus
  • View neXtProt modification sites for NX_P31645

  • SLC6A4 Protein expression data from MOPED1, PaxDb2 and MAXQB3 :    About this image 

    SLC6A4 Protein Expression
    REFSEQ proteins: NP_001036.1  
    ENSEMBL proteins: 
     ENSP00000385822   ENSP00000463172   ENSP00000378298   ENSP00000261707  

    Human Recombinant Protein Products for SLC6A4: 
    Browse Purified and Recombinant Proteins at EMD Millipore
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    Browse recombinant and purified proteins available from Enzo Life Sciences
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    OriGene Protein Over-expression Lysate for SLC6A4
    OriGene Custom MassSpec 
    OriGene Custom Protein Services for SLC6A4
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    Novus Biologicals SLC6A4 Proteins
    Novus Biologicals SLC6A4 Lysates
    Browse Sino Biological Recombinant Proteins
    Browse Sino Biological Cell Lysates 
    Browse ProSpec Recombinant Proteins
    Browse Proteins at Cloud-Clone Corp. 

    Gene Ontology (GO): 5/8 cellular component terms (GO ID links to tree view) (see all 8):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005829cytosol IDA19270731
    GO:0005886plasma membrane IDA16870614
    GO:0005887integral to plasma membrane IC19270731
    GO:0010008endosome membrane IEA--
    GO:0012505endomembrane system IDA17506858

    SLC6A4 for ontologies           About GeneDecksing



    SLC6A4 Antibody Products: 
    EMD Millipore Mono- and Polyclonal Antibodies for the study of SLC6A4
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    Abcam antibodies for SLC6A4
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    LSBio Antibodies in human, mouse, rat for SLC6A4 

    Assay Products for SLC6A4: 
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    GenScript Custom Assay Services for SLC6A4
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    Browse ELISAs at Cloud-Clone Corp. 
    Browse CLIAs at Cloud-Clone Corp.


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
    About This Section
    HGNC Gene Families: 
    SLC: Solute carriers

    IUPHAR Guide to PHARMACOLOGY protein family classification: SERT 
    Monoamine transporter subfamily

    2 InterPro protein domains:
     IPR000175 Na/ntran_symport
     IPR013086 Na/ntran_symport_serotonin_N

    Graphical View of Domain Structure for InterPro Entry P31645

    ProtoNet protein and cluster: P31645

    1 Blocks protein domain: IPB013086 Serotonin (5-HT) neurotransmitter transporter signature

    UniProtKB/Swiss-Prot: SC6A4_HUMAN, P31645
    Similarity: Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A4 subfamily


    SLC6A4 for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    bound targets from SABiosciences, miRNA Gene Targets from miRTarBase, shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Sirion Biotech, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, Vector BioLabs, and Sirion Biotech, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Oct 2013 via Entrez Gene.)
    About This Section

    Molecular Function:

         UniProtKB/Swiss-Prot Summary: SC6A4_HUMAN, P31645
    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
    Induction: Down-regulated when plasma serotonin is elevated

         Genatlas biochemistry entry for SLC6A4:
    solute carrier family 6,member A4,neurotransmitter transporter,serotonin

         Gene Ontology (GO): 5/12 molecular function terms (GO ID links to tree view) (see all 12):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005328neurotransmitter:sodium symporter activity ----
    GO:0005335serotonin:sodium symporter activity IMP19270731
    GO:0005515protein binding IPI11343649
    GO:0008504monoamine transmembrane transporter activity IDA16024787
    GO:0015222serotonin transmembrane transporter activity IMP19270731
         
    SLC6A4 for ontologies           About GeneDecksing


    Phenotypes:
         2 GenomeRNAi human phenotypes for SLC6A4:
     Decreased G3BP1 protein expres  Decreased nuclei size in G2M 

         11 MGI mutant phenotypes (inferred from 7 alleles(MGI details for Slc6a4):
     behavior/neurological  cardiovascular system  craniofacial  endocrine/exocrine gland  growth/size 
     homeostasis/metabolism  integument  mortality/aging  muscle  nervous system 
     normal 

    SLC6A4 for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-outs for SLC6A4: Slc6a4tm1Kpl Slc6a4tm1Grch

       inGenious Targeting Laboratory - Custom generated mouse model solutions for SLC6A4 
       inGenious Targeting Laboratory - Custom generated inducible mouse model solutions for SLC6A4

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for SLC6A4 
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for SLC6A4 

    miRNA
    Products:
        
    QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat SLC6A4
    8/37 QIAGEN miScript miRNA Assays for microRNAs that regulate SLC6A4 (see all 37):
    hsa-miR-3146 hsa-miR-15a hsa-miR-513a-5p hsa-miR-500a hsa-miR-424 hsa-miR-376a* hsa-miR-325 hsa-miR-510
    SwitchGear 3'UTR luciferase reporter plasmidSLC6A4 3' UTR sequence
    Inhib. RNA
    Products:
        
    Browse for Gene Knock-down Tools from EMD Millipore
    OriGene RNAi products in human, mouse, rat for SLC6A4
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    Gene Editing
    Products:
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    Sirion Biotech Customized adenovirus for overexpression of SLC6A4

    Clone
    Products:
         
    Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore
    OriGene clones in human, mouse for SLC6A4 (see all 7)
    OriGene ORF clones in mouse, rat for SLC6A4
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector: SLC6A4 (NM_001045)
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    Cell Line
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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for SLC6A4


    (Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Oct 2013 via Entrez Gene).
    About This Section

    SuperPaths for SLC6A4 About   (see all 7)                                                                                              See pathways by source

    SuperPathContained pathways About
    1Citalopram Pathway, Pharmacokinetics
    Citalopram Pathway, Pharmacokinetics0.67
    Fluoxetine Pathway, Pharmacokinetics0.57
    Venlafaxine Pathway, Pharmacokinetics0.67
    2Synaptic vesicle cycle
    Synaptic Vesicle Pathway0.50
    3Potassium Channels
    Potassium transporters: outward current0.42
    4Monoamine GPCRs
    Selective Serotonin Reuptake Inhibitor Pathway, Pharmacodynamics0.33
    5Circadian entrainment
    Serotonergic synapse0.33

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    1 EMD Millipore Pathway for SLC6A4
        Potassium transporters- outward current


    3 BioSystems Pathways for SLC6A4
        SIDS Susceptibility Pathways
    Monoamine Transport
    Synaptic Vesicle Pathway

    4 PharmGKB Pathways for SLC6A4
        Citalopram Pathway, Pharmacokinetics
    Fluoxetine Pathway, Pharmacokinetics
    Selective Serotonin Reuptake Inhibitor Pathway, Pharmacodynamics
    Venlafaxine Pathway, Pharmacokinetics

    1         Kegg Pathway  (Kegg details for SLC6A4):
        Serotonergic synapse


    SLC6A4 for pathways           About GeneDecksing

    Interactions:

        SABiosciences Gene Network CentralTM Interacting Genes and Proteins Network for SLC6A4

    STRING Interaction Network Preview (showing 5 interactants - click image to see 6)

    5/6 Interacting proteins for SLC6A4 (P316452, 3 ENSP000002617074) via UniProtKB, MINT, STRING, and/or I2D (see all 6)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    PICK1Q9NRD52, 3, ENSP000003494654MINT-73296 I2D: score=1 STRING: ENSP00000349465
    CALRP277973, ENSP000003208664I2D: score=2 STRING: ENSP00000320866
    CANXP278243, ENSP000002474614I2D: score=1 STRING: ENSP00000247461
    STX1AQ166233, ENSP000002228124I2D: score=2 STRING: ENSP00000222812
    YBX1P678093, ENSP000003616264I2D: score=1 STRING: ENSP00000361626
    About this table

    Gene Ontology (GO): 5/29 biological process terms (GO ID links to tree view) (see all 29):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001666response to hypoxia IEA--
    GO:0006836neurotransmitter transport ----
    GO:0006837serotonin transport IDA19270731
    GO:0007420brain development ----
    GO:0007584response to nutrient IEA--

    SLC6A4 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
    About This Section

    SLC6A4 for compounds           About GeneDecksing

    Browse Small Molecules at EMD Millipore
    Enzo Life Sciences drugs & compounds for SLC6A4

    Compounds for SLC6A4 available from Tocris Bioscience    About this table
    CompoundAction CAS #
    Venlafaxine hydrochlorideDual serotonin/noradrenalin re-uptake inhibitor[99300-78-4]
    Paroxetine maleateHighly potent and selective 5-HT uptake inhibitor[64006-44-6]
    Sertraline hydrochloride5-HT re-uptake inhibitor[79559-97-0]
    Citalopram hydrobromideHighly potent and selective 5-HT uptake inhibitor[59729-33-8]
    Fluoxetine hydrochloride5-HT re-uptake inhibitor[56296-78-7]

    8 HMDB Compounds for SLC6A4    About this table
    CompoundSynonyms CAS #PubMed Ids
    CitalopramBonitrile (see all 4)59729-33-8--
    DextromethorphanBayer Select Flu Relief (see all 58)6700-34-1--
    Escitalopram(+)-Citalopram (see all 7)128196-01-0--
    ImipramineAntideprin (see all 27)50-49-7--
    Serotonin3-(2-Aminoethyl)-1H-indol-5-ol (see all 14)50-67-9--
    Sertraline(+)-Sertraline (see all 3)79617-96-2--
    SodiumSodium (see all 2)7440-23-5--
    VenlafaxineEfectin (see all 6)93413-69-5--

    10/48 DrugBank Compounds for SLC6A4 (see all 48)    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    DuloxetineDuloxetine HCl (see all 2)136434-34-9targetinhibitor15892657 15695064 15316838 12481192 16032412 16650830 17335951 9669506 18408530 2784100 20432324 14744476 19480470 16199241
    Citalopram-- 59729-33-8targetinhibitor11300876 19500602 11180498 19616061 9537821 10546982 15955412 7548008 10188639 10063489
    transportersubstrate inhibitor11300876 19500602 11180498 19616061 9537821 10546982 15955412 7548008 10188639 10063489 17916059
    SibutramineSibutramina [Spanish] (see all 2)106650-56-0targetinhibitor10929704 17544870 19475780 16678551 12417543 11152984 15382615 15685250 18671470 15944869 17284621
    FluvoxamineFluvoxamina [INN-Spanish] (see all 4)54739-18-3targetinhibitor16316311 12695316 12721776 12208313 15170064 11817517 11304754 20687077 11166521 18568110
    SertralineSertralina [Spanish] (see all 3)79617-96-2targetinhibitor12647451 8664165 10575045 16963794 11243491 9537821 18751896 15606893 12151556 12955294
    Venlafaxine-- 93413-69-5targetinhibitor9305421 15695064 19238127 16140280 19728573 10884561 15910402 9537821 17224717
    Escitalopram-- 128196-01-0targetinhibitor12665392 17916059 11543737 12876551 12232544 19616061 12719960 12387707
    3,4-MethylenedioxymethamphetamineEcstasy (see all 2)42542-10-9targetnegative modulator14700733 12398910 12742084 11756522 11994534 10607865
    transporter--14700733 12398910 12742084 11756522 11994534 10607865 16220332
    4-Methoxyamphetamine-- 23239-32-9targetinhibitor14700733 12398910 12742084 11041537 11756522 11994534 10607865
    Clomipramine3-Chloroimipramine (see all 6)303-49-1targetinhibitor9305421 12695316 17471183 12647451 10613618 14993096 9537821

    5 IUPHAR Ligands for SLC6A4 (SERT)    About this table 
    LigandTypeActionAffinityPubmed IDs
    [3H]paroxetine
    NoneNone9.7--
    paroxetine
    InhibitorInhibition9.69537821
    sertraline
    InhibitorInhibition9.1--
    fluoxetine
    InhibitorInhibition8.59537821
    [3H]citalopram
    NoneNone8.3--

    10/120 Novoseek inferred chemical compound relationships for SLC6A4 gene (see all 120)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    (r)-citalopram 88.5 41 19616061 (6), 15037515 (5), 16918708 (2), 15695064 (2) (see all 18)
    dasb 88.2 24 14610240 (4), 15312176 (2), 12439295 (1), 17437611 (1) (see all 11)
    (123i)-2beta-carbomethoxy-3beta-(4-iodophenyl)tropane 87.2 12 10664833 (2), 10715354 (1), 8110440 (1), 14992979 (1) (see all 10)
    citalopram 85.1 122 16955282 (7), 17235610 (6), 18216289 (4), 18618621 (3) (see all 66)
    maoa 83.6 88 20332182 (5), 18261931 (4), 18937309 (4), 15523490 (3) (see all 42)
    paroxetine 83.4 156 17033844 (5), 18830236 (5), 14566196 (4), 12457263 (4) (see all 65)
    5-hydroxytryptamine 79.6 234 16943551 (5), 12605580 (4), 11325413 (3), 19572987 (3) (see all 93)
    dopamine 79.5 461 2308472 (6), 10612583 (3), 10494878 (3), 8110440 (3) (see all 99)
    fluoxetine 79.5 110 16490163 (6), 17289086 (4), 14604448 (3), 14571357 (2) (see all 62)
    escitalopram 78.8 114 16955282 (8), 19892699 (6), 15037515 (6), 19616061 (6) (see all 33)

    3 PharmGKB related drug/compound annotations for SLC6A4 gene    About this table
    Drug/compound PharmGKB Annotation
    clomipramineCA  
    escitalopramCA  
    fluoxetineCA  

    Search CenterWatch for drugs/clinical trials and news about SLC6A4 / SC6A4

    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    RNAi Products from EMD Millipore,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
    Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Sirion Biotech, Primers from OriGene, SABiosciences, and/or QIAGEN )
    About This Section

    REFSEQ mRNAs for SLC6A4 gene: 
    NM_001045.5  

    Unigene Cluster for SLC6A4:

    Solute carrier family 6 (neurotransmitter transporter, serotonin), member 4
    Hs.29792  [show with all ESTs]
    Unigene Representative Sequence: NM_001045
    5 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000401766(uc010csg.3) ENST00000579221 ENST00000578609 ENST00000394821
    ENST00000261707(uc002hey.4)

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    Additional mRNA sequence: 

    AK308014.1 AK309538.1 AK313166.1 AY902473.1 BC069484.1 L05568.1 X70697.1 

    3 DOTS entries:

    DT.207569  DT.308332  DT.100682832 

    15 AceView cDNA sequences:

    BC069484 NM_001045 L05568 AU138385 BX360891 BQ017027 X70697 BU619456 
    BQ017574 BX399758 AA700070 BX339773 AA700086 BM990651 BX329107 

    GeneLoc Exon Structure

    5 Alternative Splicing Database (ASD) splice patterns (SP) for SLC6A4    About this scheme

    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:                                                                                                                              


    ECgene alternative splicing isoforms for SLC6A4

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

    SLC6A4 expression in normal human tissues (normalized intensities)      SLC6A4 embryonic expression: see
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: --
    SLC6A4 Expression
    About this image


    SLC6A4 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database 
     5/5 selected tissues (see all 5) fully expand
     
     Brain (Nervous System)    fully expand to see all 24 entries
             Thalamus
             Septum   
     
     Neural Tube (Nervous System)    fully expand to see all 2 entries
             Metencephalon
             brain/midbrain/lateral wall   
     
     Liver (Hepatobiliary System)
             Liver Lobule
     
     Lung (Respiratory System)
     
     Placenta (Extraembryonic Tissues)

    See SLC6A4 Protein Expression from SPIRE MOPED and PaxDB
    Genevestigator expression for SLC6A4

    SOURCE GeneReport for Unigene cluster: Hs.29792

    UniProtKB/Swiss-Prot: SC6A4_HUMAN, P31645
    Tissue specificity: Expressed in platelets (at protein level)

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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
    About This Section

    This gene was present in the common ancestor of animals.

    Orthologs for SLC6A4 gene from 6/13 species (see all 13)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Slc6a41 , 5 solute carrier family 6 (neurotransmitter transporter, more1, 5 87.83(n)1
    92.54(a)1
      11 (46.18 cM)5
    155671  NM_010484.21  NP_034614.21 
     769986035 
    chicken
    (Gallus gallus)
    Aves SLC6A41 solute carrier family 6 (neurotransmitter transporter, more 76.63(n)
    81.4(a)
      404747  NM_213572.1  NP_998737.1 
    lizard
    (Anolis carolinensis)
    Reptilia SLC6A46
    Transporter
    74(a)
    1 ↔ 1
    GL343462.1(525671-547551)
    zebrafish
    (Danio rerio)
    Actinopterygii slc6a4a1 solute carrier family 6 (neurotransmitter transporter, more 69.29(n)
    72.58(a)
      664719  NM_001039972.1  NP_001035061.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta SerT3 serotonin transporter 56(a)
    (best of 7)
      60C8   --
    worm
    (Caenorhabditis elegans)
    Secernentea mod-53   -- 49(a)
    (best of 6)
      I(3035239-3047795)   --


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

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
    About This Section
    Paralogs for SLC6A4 gene
    SLC6A62  SLC6A112  SLC6A122  SLC6A82  SLC6A52  SLC6A142  SLC6A32  SLC6A12  
    SLC6A132  SLC6A72  SLC6A22  SLC6A92  
    18/21 SIMAP similar genes for SLC6A4 using alignment to 15 protein entries:     SC6A4_HUMAN (see all proteins) (see all similar genes):
    5HTT    SLC6A3    DAT1    SLC6A2    SLC6A9    SLC6A12
    SLC6A16    SLC6A7    SLC6A8    SLC6A1    SLC6A14    SLC6A15
    SLC6A13    SLC6A5    SLC6A11    SLC6A6    SLC6A18    SLC6A20

    SLC6A4 for paralogs           About GeneDecksing



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
    About This Section

    UniProtKB/Swiss-Prot: SC6A4_HUMAN, P31645
    Polymorphism: 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
    Polymorphism: The polymorphism Val-425 seems to be linked to a susceptibility to obsessive-compulsive disorder
    (OCD) [MIM:164230]
    Polymorphism: Genetic variations in SLC6A4 determine the genetic susceptibility to alcoholism [MIM:103780]


    10/1302 SNPs in SLC6A4 are shown (see all 1302)    About this table     
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 17 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs1478670561,2
    Cuntested128609735(+) GTGGTC/TGCTGG 2 A syn10--------
    rs289148321,2,4
    C,Fother128599327(-) TTGCCA/C/GTCATC 2 I V mis15NA EU 6119
    VAR_0267514
    ----see VAR_0267512 I V mis40--------
    rs2004541771,2
    --24744078(+) TTTCT-/TTTC  
            
    TTTTT
    1 -- int10--------
    rs72170651,2
    C,A--24744082(+) cttttC/Tttttt 1 -- int1 trp32Minor allele frequency- T:0.25WA CSA 4
    rs255321,2
    C,F--24774511(-) CCCGGC/TATCCC 1 -- us2k17Minor allele frequency- T:0.07NA NS 328
    rs2020795181,2
    C--24775237(+) GTCTC-/TGTT  
            
    TGTGA
    1 -- us2k10--------
    rs113676561,2
    C--28522837(+) AACAA-/TTTTTT 1 -- ut311Minor allele frequency- T:0.00CSA 2
    rs58198821,2
    C--28533260(+) AAGACA/-AAAAA 1 -- int1 trp31Minor allele frequency- -:0.00NA 2
    rs556880531,2
    C,F--28541045(-) GCTCAA/CACCTG 1 -- int16Minor allele frequency- C:0.06NS WA 308

    HapMap Linkage Disequilibrium report for SLC6A4 (28521337 - 28563020 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 1 variation for SLC6A4:    About this table     
    Variant IDTypeSubtypePubMed ID
    esv2715808CNV Deletion23290073


    Human Gene Mutation Database (HGMD): SLC6A4
    SABiosciences Cancer Mutation PCR Assays
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    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
    About This Section
    OMIM gene information: 182138   
    OMIM disorders: 607834  164230  
    20/142 diseases for SLC6A4 (see all 142):    About MalaCards
    obsessive-compulsive disorder    borderline personality disorder    alcoholic psychosis    obsessive-compulsive disorder 1
    premature ejaculation    slc6a4-related behavior disorders    personality disorder    melancholia
    irritable bowel syndrome    seasonal affective disorder    cocaine dependence    antisocial personality disorder
    postpartum depression    asperger syndrome    retrograde amnesia    major depressive disorder
    anxiety disorder    sudden infant death syndrome    heroin dependence    social phobia

    20/21 diseases from the University of Copenhagen DISEASES database for SLC6A4 (see all 21):
    Anxiety disorder     Alcohol dependence     Irritable bowel syndrome     Autistic disorder
    Schizophrenia     Attention deficit hyperactivity disorder     Borderline personality disorder     Antisocial personality disorder
    Conduct disorder     Substance abuse     Toxic encephalopathy     Bipolar disorder
    Constipation     Sudden infant death syndrome     Migraine     Premature ejaculation
    Nicotine dependence     obsessive-compulsive personality disorder     Eating disorder     Hypertension

    SLC6A4 for disorders           About GeneDecksing


    Congresses - knowledge worth sharing:  
    The International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD) 9 - 13 March 2014
    Alzheimer's & Parkinson's Diseases Congress (ADPD) 18 - 22 March 2015

    10/92 Novoseek inferred disease relationships for SLC6A4 gene (see all 92)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    major depression 79.4 193 10862800 (5), 10920459 (5), 18268503 (4), 16640648 (4) (see all 99)
    mood disorders 76 125 11983185 (4), 19233297 (4), 9154246 (4), 9514579 (3) (see all 69)
    obsessive-compulsive disorder 69 65 18354388 (3), 16139170 (2), 18186076 (2), 16112691 (2) (see all 32)
    bipolar disorder 68.6 85 9514585 (4), 10490710 (4), 11772685 (3), 8723051 (3) (see all 44)
    psychiatric disorder 65.8 68 12218657 (3), 19854262 (2), 20150867 (2), 7865169 (1) (see all 42)
    neuroticism 65.7 40 10405095 (4), 17336939 (4), 11443919 (3), 14992987 (2) (see all 23)
    alcoholism 64.2 61 10064377 (3), 16288736 (2), 14574222 (2), 15635638 (2) (see all 41)
    anxiety disorders 58.7 20 11256582 (1), 12660809 (1), 18314311 (1), 10368856 (1) (see all 14)
    attention-deficit hyperactivity disorder 56.9 11 14574222 (1), 17948872 (1), 19894072 (1), 12782968 (1) (see all 9)
    autistic 54.1 38 10686565 (4), 15094787 (3), 12192626 (3), 11920155 (3) (see all 14)

    Genetic Association Database (GAD): SLC6A4
    Human Genome Epidemiology (HuGE) Navigator: SLC6A4 (1155 documents)

    Export disorders for SLC6A4 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
    About This Section

    PubMed articles for SLC6A4 gene, integrated from 9 sources (see all 2748):
    (articles sorted by number of sources associating them with SLC6A4)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Age-dependent antidepressant pharmacogenomics: polymorphisms of the serotonin transporter and G protein beta3 subunit as predictors of response to fluoxetine and nortriptyline. (PubMed id 14604448)1, 4, 7, 9 Joyce P.R....Kennedy M.A. (2003)
    2. Meta-analysis of the association of a functional serotonin transporter promoter polymorphism with alcohol dependence. (PubMed id 15635638)1, 2, 4, 9 Feinn R.... Kranzler H.R. (2005)
    3. Alteration of gastric functions and candidate genes associated with weight reduction in response to sibutramine. (PubMed id 17544870)1, 4, 7, 9 Vazquez Roque M.I....Zinsmeister A.R. (2007)
    4. The serotonin transporter polymorphism, 5HTTLPR, is associated with a faster response time to sertraline in an elderly population with major depressive disorder. (PubMed id 12955294)1, 4, 7, 9 Durham L.K....Seymour A.B. (2004)
    5. Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. (PubMed id 12869766)1, 2, 4, 9 Caspi A....Poulton R. (2003)
    6. Influence of the serotonin transporter gene-linked polymorphic region on the antidepressant response to fluvoxamine in Japanese depressed patients. (PubMed id 11817517)1, 4, 7, 9 Yoshida K....Otani K. (2002)
    7. Allelic variation in the serotonin transporter promoter affects onset of paroxetine treatment response in late-life depression. (PubMed id 11027924)1, 4, 7, 9 Pollock B.G....Kupfer D.J. (2000)
    8. Antidepressant- and cocaine-sensitive human serotonin transporter: molecular cloning, expression, and chromosomal localization. (PubMed id 7681602)1, 2, 3, 9 Ramamoorthy S.... Blakely R.D. (1993)
    9. Serotonin transporter polymorphisms and measures of impulsivity, aggression, and sensation seeking among African-American cocaine-dependent individuals. (PubMed id 12057823)1, 4, 7 Patkar A.A....Weinstein S.P. (2002)
    10. Subcellular redistribution of the serotonin transporter by secretory carrier membrane protein 2. (PubMed id 16870614)1, 2, 9 Muller H.K....Haase J. (2006)

    (in PubMed, OMIM, and NCBI Bookshelf)
    About This Section
     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
    About This Section
    Entrez Gene: 6532 HGNC: 11050 AceView: SLC6A4 Ensembl:ENSG00000108576 euGenes: HUgn6532
    ECgene: SLC6A4 Kegg: 6532 H-InvDB: SLC6A4

    (According to HUGE)
    About This Section
      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
    Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
    About This Section
    NameDescription
    PharmGKB entry for SLC6A4 Pharmacogenomics, SNPs, Pathways
    GeneReviewshttp://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/SLC6A4
    SHMPDhttp://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=SLC6A4
    Wikipedia http://en.wikipedia.org/wiki/Serotonin_transporter
    Protein Spotlighthttp://web.expasy.org/spotlight/back_issues/sptlt123.shtml
    NIEHS-SNPshttp://egp.gs.washington.edu/data/slc6a4/

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
    About This Section
    Patent Information for SLC6A4 gene:
    Search GeneIP for patents involving SLC6A4

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



    (Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, SABiosciences, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, Gene Editing from DNA2.0 and Sirion Biotech, Clones from EMD Millipore, OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Sirion Biotech, Cell lines from GenScript, and LifeMap BioReagents, PCR Arrays from SABiosciences, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, and/or Enzo Life Sciences, In Situ Hybridization Assays from
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    About This Section

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     SwitchGear 3'UTR luciferase reporter plasmids for SLC6A4
     SwitchGear Promoter luciferase reporter plasmids for SLC6A4
     ThermoFisher Antibodies for SLC6A4
     Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat SLC6A4
     inGenious Targeting Laboratory - Custom generated mouse model solutions for SLC6A4
     inGenious Targeting Laboratory - Custom generated inducible mouse model solutions for SLC6A4
    Customized:
     lentivirus for stable overexpression of SLC6A4
     lentivirus expression plasmids for stable overexpression of SLC6A4
     adenovirus for overexpression of SLC6A4
     LSBio Antibodies in human, mouse, rat for SLC6A4
    Customized transgenic rodents for:
     Humanization
     Biomarker expression
     Off-target effect monitoring
     Translational medicine
     Tissue-specific gene expresssion
     Time-controlled gene expresssion
           
    GeneCards Homepage - Last full update: 23 Oct 2013 - Incrementals: 3 Nov 2013 , 7 Nov 2013 , 23 Jan 2014

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