Affinage

SLC6A4

Sodium-dependent serotonin transporter · UniProt P31645

Length
630 aa
Mass
70.3 kDa
Annotated
2026-06-10
100 papers in source corpus 10 papers cited in narrative 10 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SLC6A4 encodes the serotonin transporter (SERT/5-HTT), a sodium-dependent membrane transporter that clears serotonin (5-HT) from the extracellular space and assembles into oligomeric (dimeric/tetrameric) complexes at the membrane (PMID:8925924, PMID:35066124). Its transcription is under combined hormonal and epigenetic control: glucocorticoids upregulate expression through a GC-rich element ~1.4 kb upstream of the start site within the 5-HTTLPR region in a genotype-dependent, RU 38486–reversible manner (PMID:12911615), small-molecule inducers (berberine, evodiamine) drive promoter activity in an allele-specific fashion across 5-HTTLPR variants (PMID:21647174), and DNA methylation of the distal promoter inversely tracks with mRNA levels in human tissue (PMID:28650965). In vivo, loss of 5-HTT shapes neural circuit function and plasticity: knockout mice show impaired fear extinction recall with altered amygdala–prefrontal theta synchronization (PMID:21818344), increased hippocampal adult neurogenesis and immediate-early gene expression with heightened corticosterone stress responses (PMID:24167611), and blunted 5-HT2C receptor–mediated behavioral and neurochemical responses downstream of chronic loss of 5-HT reuptake (PMID:25522398). Beyond the nervous system, SLC6A4 participates in a c-Myc/TRIB3-driven positive feedback loop in non-small cell lung cancer in which 5-HT induces its own transporter, enhancing 5-HT uptake to promote tumorigenicity and metastasis (PMID:35066124). Notably, some neuroplastic effects of fluoxetine occur independently of 5-HTT, as fluoxetine still activates BDNF/TrkB signaling in 5-HTT-knockout neurons (PMID:31004120).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1996 Medium

    Established that SERT is not an isolated monomer but assembles into higher-order oligomers at the membrane, defining its quaternary structure.

    Evidence Chemical cross-linking (DMS) and sulfhydryl oxidation of recombinant rat SERT1 in HEK293 cells resolved by SDS-PAGE

    PMID:8925924

    Open questions at the time
    • No mutagenesis or structural data defining the oligomerization interface
    • Functional consequence of oligomerization for transport not addressed
    • Demonstrated for rat ortholog in heterologous cells only
  2. 2003 High

    Resolved how stress hormones control transporter abundance, showing glucocorticoid induction of SLC6A4 operates through a defined upstream GC-rich element in a genotype-dependent way.

    Evidence Reporter assays, 5-HT uptake, radioligand binding, promoter deletional mutagenesis and RU 38486 antagonism in human lymphoblastoid cells

    PMID:12911615

    Open questions at the time
    • Whether the same element governs glucocorticoid regulation in neurons not tested
    • Direct receptor binding to the element not demonstrated
  3. 2010 Medium

    Tested whether the 5-HTTLPR genotype alters transporter density in the living human brain, and found no significant effect, redirecting interpretation toward neurodevelopmental rather than adult-density mechanisms.

    Evidence PET with [11C]DASB binding potential across seven brain regions in 63 genotyped healthy volunteers

    PMID:20406689

    Open questions at the time
    • Negative finding in adults does not exclude developmental or regional micro-scale effects
    • Does not address functional (uptake kinetics) differences independent of density
  4. 2011 Medium

    Connected 5-HTT loss to a specific behavioral circuit, showing it is required for fear extinction recall and normal amygdala-prefrontal oscillatory coupling.

    Evidence Pavlovian fear conditioning with paired in vivo electrophysiology in 5-HTT knockout, heterozygous, and wild-type mice

    PMID:21818344

    Open questions at the time
    • Developmental vs acute contribution of 5-HTT loss not separated
    • Cell-type and circuit-specific mediators of theta change unresolved
  5. 2011 Medium

    Showed that the transcriptional response of SLC6A4 to pharmacological inducers is shaped by 5-HTTLPR allelic identity, extending allele-specific regulation beyond glucocorticoids.

    Evidence RT-PCR, Western blot, and luciferase reporter assays across S, XS, LG, LA, XL17, XL18 variants in RN46A serotonergic cells

    PMID:21647174

    Open questions at the time
    • No in vivo validation
    • Mechanism linking compounds to promoter not defined
    • Not independently replicated
  6. 2014 Medium

    Demonstrated that chronic loss of reuptake reshapes hippocampal plasticity and stress reactivity, establishing a role for SLC6A4 in neurogenesis and corticosterone responses.

    Evidence Quantitative immunohistochemistry (Ki67, NeuroD, cFos, Arc), plasma corticosterone, and maze behavioral testing in 5-HTT knockout mice

    PMID:24167611

    Open questions at the time
    • Whether plasticity changes are cause or consequence of altered behavior unclear
    • Single-lab study
  7. 2014 Medium

    Identified a downstream consequence of chronic reuptake loss on receptor signaling, showing blunted 5-HT2C receptor responsiveness without changes in receptor expression or editing.

    Evidence Behavioral, neurochemical (5-HT turnover), RT-qPCR, mRNA editing, and c-fos IHC analyses in 5-HTT knockout mice

    PMID:25522398

    Open questions at the time
    • Mechanism of functional 5-HT2C desensitization not defined
    • Elevated basal c-fos not mechanistically explained
  8. 2017 Medium

    Established epigenetic control of SLC6A4 expression in a peripheral tissue, showing distal-promoter methylation inversely tracks mRNA and is modulated by maternal metabolic state.

    Evidence Bisulfite sequencing, RT-qPCR, and genotyping in human placenta from 50 mother-infant pairs

    PMID:28650965

    Open questions at the time
    • Causality of methylation on expression not demonstrated
    • Modest sample size
    • Tissue-specificity vs neuronal regulation unaddressed
  9. 2019 Medium

    Dissociated fluoxetine's neuroplastic action from its target, showing BDNF/TrkB activation persists without 5-HTT.

    Evidence Western blotting and RT-qPCR in primary cortical neurons from 5-Htt knockout and wild-type mice, with in vivo proliferation assessment

    PMID:31004120

    Open questions at the time
    • Alternative direct fluoxetine target not identified
    • Relevance to therapeutic antidepressant action not established
  10. 2022 Medium

    Extended SLC6A4 function beyond neurons, defining a c-Myc/TRIB3 positive feedback loop in which 5-HT induces its own transporter to drive tumor progression.

    Evidence Western blot, immunofluorescence, colony-formation, migration/invasion assays, patient IHC, and xenograft with uptake inhibitor in NSCLC cells

    PMID:35066124

    Open questions at the time
    • Direct c-Myc binding to the SLC6A4 promoter not shown
    • Generalizability to other tumor types untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How transporter oligomerization, allele- and methylation-dependent transcriptional control, and circuit-level neuroplasticity phenotypes mechanistically interconnect remains unresolved.
  • No structural model linking oligomerization to transport function in the captured corpus
  • Causal chain from transcriptional/epigenetic regulation to in vivo behavioral phenotypes not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 2
Localization
GO:0005886 plasma membrane 1

Evidence

Reading pass · 10 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 The rat serotonin transporter SERT1 (SLC6A4 ortholog) forms oligomeric complexes at the membrane. Treatment of recombinantly expressed SERT1 in HEK293 cells with sulfhydryl oxidizing agents and the cross-linker dimethyl suberimidate (DMS) generated adducts of 130–180 kDa and 220–270 kDa, indicating an oligomeric (likely dimeric/tetrameric) quaternary structure. Chemical cross-linking (DMS), sulfhydryl oxidation, SDS-PAGE of recombinantly expressed SERT1 in HEK293 cells FEBS letters Medium 8925924
2003 Glucocorticoid (dexamethasone) administration increases SLC6A4 (5-HTT) expression in a genotype-dependent manner in human B-lymphoblastoid cells. Reporter gene assays, 5-HT uptake, and inhibitor binding measures showed a dose-response to dexamethasone that was antagonized by RU 38486, and depended on a repetitive GC-rich sequence ~1.4 kb upstream of the transcription start site (within the 5-HTTLPR region), as deletion of this sequence abolished the steroid effect. Reporter gene (luciferase) assays, 5-HT uptake assay, radioligand binding, deletional mutagenesis of promoter constructs, pharmacological antagonism (RU 38486) in human lymphoblastoid cells Journal of neurochemistry High 12911615
2011 Berberine and evodiamine increase SLC6A4 (5-HTT) mRNA and protein expression, and increase 5-HTT promoter activity in a serotonergic neuronal cell line (RN46A). The magnitude of the promoter activity increase was allele-specific across S, XS, LG, LA, XL17, and XL18 variants of the 5-HTTLPR, demonstrating that the 5-HTTLPR polymorphism modulates the transcriptional response to these compounds. RT-PCR (mRNA), Western blot (protein), luciferase reporter assays across multiple allelic variants in RN46A cells The pharmacogenomics journal Medium 21647174
2019 Fluoxetine activates BDNF/TrkB signaling and promotes neuroplasticity through a 5-HTT-independent mechanism. In primary cortical neurons from 5-Htt knockout mice, fluoxetine (10 µM) still activated BDNF/TrkB pathways and increased plasticity gene expression, demonstrating that 5-HTT blockade is not required for these neuroplastic effects of fluoxetine. Western blotting, RT-qPCR in primary cortical neurons from 5-Htt wild-type and knockout mice; in vivo treatment (15 mg/kg/day i.p.) with assessment of hippocampal cell proliferation Scientific reports Medium 31004120
2011 Loss of 5-HTT (SLC6A4) in mice impairs extinction recall of conditioned fear and is accompanied by increased theta synchronization between the lateral amygdala and infralimbic prefrontal cortex during extinction learning, establishing a role for 5-HTT in amygdala-prefrontal circuit function underlying fear extinction. Pavlovian fear conditioning, in vivo electrophysiology (simultaneous recording in lateral amygdala and mPFC), behavioral testing in 5-HTT knockout (-/-), heterozygous (+/-), and wild-type (+/+) mice PloS one Medium 21818344
2014 5-HTT deficiency in mice increases hippocampal adult neurogenesis (elevated Ki67+ and NeuroD+ cell counts) and immediate early gene expression (cFos, Arc), and heightens corticosterone responses to spatial learning tasks, establishing that SLC6A4 regulates hippocampal neuroplasticity and stress reactivity in vivo. Quantitative immunohistochemistry (Ki67, NeuroD, cFos, Arc), plasma corticosterone measurement, Morris water maze and Barnes maze behavioral testing in 5-HTT knockout and wild-type mice PloS one Medium 24167611
2014 5-HT2C receptor responsiveness is blunted in 5-HTT-deficient mice: 5-HTT(-/-) mice show reduced 5-HT2CR-mediated anxiety behavior and attenuated 5-HT2CR-mediated inhibition of stress-induced 5-HT turnover, without changes in 5-HT2CR protein, mRNA levels, or pre-mRNA editing. However, basal c-fos mRNA in 5-HT2CR-expressing cortical cells was elevated in knockouts, indicating altered basal cellular activity downstream of chronic 5-HT reuptake inactivation. Behavioral tests (social interaction, novelty-suppressed feeding, hypolocomotion), neurochemical assays (5-HT turnover), RT-qPCR, mRNA editing analysis, c-fos immunohistochemistry in 5-HTT(-/-) mice The international journal of neuropsychopharmacology Medium 25522398
2022 In non-small cell lung cancer (NSCLC) cells, 5-HT promotes SLC6A4 expression via a c-Myc/TRIB3-dependent signaling loop: 5-HT activates TRIB3, which stimulates c-Myc transcriptional activity, and c-Myc upregulates SLC6A4 expression, thereby enhancing 5-HT uptake into tumor cells and creating a positive feedback loop that promotes tumorigenicity and metastasis. Western blotting, immunofluorescence, colony-formation assay, Transwell migration/invasion assay, immunohistochemistry in NSCLC patient tissues and A549 cells; in vivo xenograft model with 5-HT uptake inhibitor Biochimica et biophysica acta. General subjects Medium 35066124
2017 DNA methylation of the SLC6A4 distal promoter region inversely correlates with SLC6A4 mRNA expression in human placenta, and gestational diabetes mellitus decreases average methylation at this region, suggesting epigenetic regulation of placental SLC6A4 expression by maternal metabolic state. No significant association was found between SLC6A4 genotype (5-HTTLPR, STin2, rs25531) and placental mRNA levels, indicating a predominant epigenetic over genetic regulation of expression in this tissue. Bisulfite sequencing (quantitative CpG methylation at 7 sites), RT-qPCR (mRNA expression), PCR-based genotyping in human placental tissue from 50 mother-infant pairs PloS one Medium 28650965
2010 PET imaging with [11C]DASB in 63 healthy volunteers showed that 5-HTTLPR polymorphic variation (biallelic S/L or triallelic LA/LG/S classification) does not significantly affect 5-HTT binding potential in any of seven brain regions in vivo, suggesting that reported effects of 5-HTTLPR on emotion and depression risk are more likely mediated through neurodevelopmental effects rather than adult transporter density differences. Positron emission tomography (PET) with [11C]DASB radioligand, binding potential quantification in seven brain regions, genotyping for 5-HTTLPR and rs25531 NeuroImage Medium 20406689

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science (New York, N.Y.) 4900 12869766
2008 Oxytocin receptor (OXTR) and serotonin transporter (5-HTT) genes associated with observed parenting. Social cognitive and affective neuroscience 339 19015103
2023 Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6, CYP2C19, CYP2B6, SLC6A4, and HTR2A Genotypes and Serotonin Reuptake Inhibitor Antidepressants. Clinical pharmacology and therapeutics 322 37032427
1997 Serotonin transporter (5-HTT) gene variants associated with autism? Human molecular genetics 199 9361027
2009 Early adversity and 5-HTT/BDNF genes: new evidence of gene-environment interactions on depressive symptoms in a general population. Psychological medicine 196 19215635
2008 Evidence of biologic epistasis between BDNF and SLC6A4 and implications for depression. Molecular psychiatry 184 18347599
2008 How the serotonin story is being rewritten by new gene-based discoveries principally related to SLC6A4, the serotonin transporter gene, which functions to influence all cellular serotonin systems. Neuropharmacology 168 18824000
1998 Evidence for linkage disequilibrium between serotonin transporter protein gene (SLC6A4) and obsessive compulsive disorder. Molecular psychiatry 151 9672904
2006 Meta-analysis supports association between serotonin transporter (5-HTT) and suicidal behavior. Molecular psychiatry 129 16969368
2007 Mechanical, thermal and formalin-induced nociception is differentially altered in 5-HT1A-/-, 5-HT1B-/-, 5-HT2A-/-, 5-HT3A-/- and 5-HTT-/- knock-out male mice. Pain 124 17250964
2009 Serotonin transporter gene (SLC6A4) promoter polymorphisms and the susceptibility to posttraumatic stress disorder in the general population. The American journal of psychiatry 111 19487392
2009 SLC6A4 variation and citalopram response. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 110 18618621
2005 AVPR1a and SLC6A4 gene polymorphisms are associated with creative dance performance. PLoS genetics 105 16205790
1998 Serotonin transporter (5-HTT) gene polymorphisms are not associated with susceptibility to mood disorders. American journal of medical genetics 105 9514579
2007 Evidence for epistasis between SLC6A4 and ITGB3 in autism etiology and in the determination of platelet serotonin levels. Human genetics 100 17203304
2016 SLC6A4 methylation as an epigenetic marker of life adversity exposures in humans: A systematic review of literature. Neuroscience and biobehavioral reviews 95 27565518
2011 Social defeat: impact on fear extinction and amygdala-prefrontal cortical theta synchrony in 5-HTT deficient mice. PloS one 95 21818344
2003 Glucocorticoid-regulated human serotonin transporter (5-HTT) expression is modulated by the 5-HTT gene-promotor-linked polymorphic region. Journal of neurochemistry 94 12911615
2004 Association studies of MAO-A, COMT, and 5-HTT genes polymorphisms in patients with anxiety disorders of the phobic spectrum. Psychiatry research 90 15450911
2009 Sex-specific association between the 5-HTT gene-linked polymorphic region and basal cortisol secretion. Psychoneuroendocrinology 88 19249159
2008 Amygdala function and 5-HTT gene variants in adolescent anxiety and major depressive disorder. Biological psychiatry 85 18950748
2008 Polymorphisms in the SLC6A4 and HTR2A genes influence treatment outcome following antidepressant therapy. The pharmacogenomics journal 79 18253134
2011 Human serotonin transporter gene (SLC6A4) variants: their contributions to understanding pharmacogenomic and other functional G×G and G×E differences in health and disease. Current opinion in pharmacology 78 21439906
2010 Serotonin transporter polymorphisms (SLC6A4 insertion/deletion and rs25531) do not affect the availability of 5-HTT to [11C] DASB binding in the living human brain. NeuroImage 76 20406689
2009 Modulation of behavioural profile and stress response by 5-HTT genotype and social experience in adulthood. Behavioural brain research 74 19782704
2014 The potential of SLC6A4 gene methylation analysis for the diagnosis and treatment of major depression. Journal of psychiatric research 72 24657235
2015 DNA methylation of the serotonin transporter gene (SLC6A4) is associated with brain function involved in processing emotional stimuli. Journal of psychiatry & neuroscience : JPN 68 25825812
2010 Emotional eating in adolescents: a gene (SLC6A4/5-HTT) - depressive feelings interaction analysis. Journal of psychiatric research 66 20416884
2013 A longitudinal study of SLC6A4 DNA promoter methylation and poststroke depression. Journal of psychiatric research 64 23702251
2008 Panic disorder is associated with the serotonin transporter gene (SLC6A4) but not the promoter region (5-HTTLPR). Molecular psychiatry 63 18663369
2018 Genotype-dependent associations between serotonin transporter gene (SLC6A4) DNA methylation and late-life depression. BMC psychiatry 62 30180828
2009 5-HTT genotype effect on prefrontal-amygdala coupling differs between major depression and controls. Psychopharmacology 57 19387615
1998 Serotonin transporter (5-HTT) gene and bipolar affective disorder. American journal of medical genetics 57 9514585
2008 The effect of 5-HTT gene promoter polymorphism on impulsivity depends on family relations in girls. Progress in neuro-psychopharmacology & biological psychiatry 56 18495314
2013 5-HTT and 5-HT(1A) receptor occupancy of the novel substance vortioxetine (Lu AA21004). A PET study in control subjects. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology 55 23428337
2010 The serotonin transporter gene (5-HTT) variant and psychiatric disorders: review of current literature. Neuro endocrinology letters 54 20150867
2007 A genetic association study of 5-HTT LPR and GNbeta3 C825T polymorphisms with irritable bowel syndrome. Neurogastroenterology and motility 54 17564628
1996 The membrane-bound rat serotonin transporter, SERT1, is an oligomeric protein. FEBS letters 54 8925924
2020 Increased methylation of NR3C1 and SLC6A4 is associated with blunted cortisol reactivity to stress in major depression. Neurobiology of stress 50 33344725
2012 Serotonin transporter gene (SLC6A4) polymorphism in patients with irritable bowel syndrome and healthy controls. Journal of gastrointestinal and liver diseases : JGLD 48 22457857
2016 Influence of 5-HTT variation, childhood trauma and self-efficacy on anxiety traits: a gene-environment-coping interaction study. Journal of neural transmission (Vienna, Austria : 1996) 47 27145764
2019 5-HTT independent effects of fluoxetine on neuroplasticity. Scientific reports 45 31004120
2013 5-HTT deficiency affects neuroplasticity and increases stress sensitivity resulting in altered spatial learning performance in the Morris water maze but not in the Barnes maze. PloS one 45 24167611
2006 LEPR, ADBR3, IRS-1 and 5-HTT genes polymorphisms do not associate with obesity. Endocrine journal 45 17124363
2009 Interaction of child maltreatment and 5-HTT polymorphisms: suicidal ideation among children from low-SES backgrounds. Journal of pediatric psychology 44 19779024
2006 Stressful life events, 5-HTT genotype and risk of depression. The British journal of psychiatry : the journal of mental science 44 16507957
2018 BDNF mediates the protective effects of scopolamine in reserpine-induced depression-like behaviors via up-regulation of 5-HTT and TPH1. Psychiatry research 41 30529315
2012 Genetic polymorphisms of 5-HTT and DAT but not COMT differentially affect verbal and visuospatial working memory functioning. European archives of psychiatry and clinical neuroscience 40 22454241
2015 Associations between serotonin transporter gene (SLC6A4) methylation and clinical characteristics and cortical thickness in children with ADHD. Psychological medicine 38 26017091
2014 Prenatal stress-induced programming of genome-wide promoter DNA methylation in 5-HTT-deficient mice. Translational psychiatry 38 25335169
2010 Association and gene-gene interaction of SLC6A4 and ITGB3 in autism. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 38 19588468
2013 Common and rare alleles of the serotonin transporter gene, SLC6A4, associated with Tourette's disorder. Movement disorders : official journal of the Movement Disorder Society 37 23630162
2013 Multi-cultural association of the serotonin transporter gene (SLC6A4) with substance use disorder. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 36 23518607
2011 Presynaptic 5-HT1A is related to 5-HTT receptor density in the human brain. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 36 21750580
2006 ITGB3 shows genetic and expression interaction with SLC6A4. Human genetics 35 16721604
2014 Endotoxaemia resulting from decreased serotonin tranporter (5-HTT) function: a reciprocal risk factor for depression and insulin resistance? Behavioural brain research 34 24815315
2009 5-HT(1A) receptor and 5-HTT binding during the menstrual cycle in healthy women examined with [(11)C] WAY100635 and [(11)C] MADAM PET. Psychiatry research 34 19118985
2007 A PET study on regional coexpression of 5-HT1A receptors and 5-HTT in the human brain. Psychopharmacology 34 17874074
2015 Methylation of NR3C1 and SLC6A4 and internalizing problems. The TRAILS study. Journal of affective disorders 33 25889020
2017 Interplay between maternal Slc6a4 mutation and prenatal stress: a possible mechanism for autistic behavior development. Scientific reports 32 28821725
2007 Association study of serotonin 2A receptor (5-HT2A) and serotonin transporter (5-HTT) gene polymorphisms with schizophrenia. Progress in neuro-psychopharmacology & biological psychiatry 32 17291660
2007 Serotonin transporter gene (5-Htt): association analysis with temporal lobe epilepsy. Neuroscience letters 31 17548158
2010 Panic disorder and serotonergic genes (SLC6A4, HTR1A and HTR2A): Association and interaction with childhood trauma and parenting. Neuroscience letters 30 20817074
2017 Epigenetic adaptation of the placental serotonin transporter gene (SLC6A4) to gestational diabetes mellitus. PloS one 29 28650965
2011 Association of 5-HTT gene polymorphisms with migraine: a systematic review and meta-analysis. Journal of the neurological sciences 29 21450309
2014 SLC6A4 markers modulate platelet 5-HT level and specific behaviors of autism: a study from an Indian population. Progress in neuro-psychopharmacology & biological psychiatry 28 25261775
2007 The long and the short of it: associations between 5-HTT genotypes and coping with stress. Psychosomatic medicine 28 17766691
2001 Serotonin transporter (5-HTT) gene polymorphisms and susceptibility to cocaine dependence among African-American individuals. Addiction biology 28 11900612
2016 SLC6A4 promoter region methylation and socio-emotional stress response in very preterm and full-term infants. Epigenomics 27 27381173
2022 Maternal and infant NR3C1 and SLC6A4 epigenetic signatures of the COVID-19 pandemic lockdown: when timing matters. Translational psychiatry 25 36114180
2015 Association of serotonin transporter (SLC6A4) and receptor (5HTR1A, 5HTR2A) polymorphisms with response to treatment with escitalopram in patients with major depressive disorder: A preliminary study. The Indian journal of medical research 25 26261165
2011 Berberine and evodiamine influence serotonin transporter (5-HTT) expression via the 5-HTT-linked polymorphic region. The pharmacogenomics journal 25 21647174
2012 The role of 5-HTT LPR and GNβ3 825C>T polymorphisms and gene-environment interactions in irritable bowel syndrome (IBS). Digestive diseases and sciences 24 22855291
2015 Association of DRD3, COMT, and SLC6A4 Gene Polymorphisms with Type 2 Diabetes in Southern Chinese: A Hospital-Based Case-Control Study. Diabetes technology & therapeutics 23 25927430
2019 Differential SLC6A4 methylation: a predictive epigenetic marker of adiposity from birth to adulthood. International journal of obesity (2005) 22 30622309
2014 SLC6A4 polymorphism, population genetics, and psychiatric traits. Human genetics 22 24385047
2010 Relevance of perceived childhood neglect, 5-HTT gene variants and hypothalamus-pituitary-adrenal axis dysregulation to substance abuse susceptibility. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 22 19824018
2013 Association of serotonin transporter gene (SLC6A4) polymorphisms with schizophrenia susceptibility and symptoms in a Chinese-Han population. Progress in neuro-psychopharmacology & biological psychiatry 21 23583772
2013 A serotonin transporter gene (SLC6A4) polymorphism is associated with reduced risk of irritable bowel syndrome in American and Asian population: a meta-analysis. PloS one 21 24069428
2010 Gene-gene interaction between serotonin transporter (SLC6A4) and CLOCK modulates the risk of metabolic syndrome in rotating shiftworkers. Chronobiology international 21 20653450
2018 5-HTT, BMPR2, EDN1, ENG, KCNA5 gene polymorphisms and susceptibility to pulmonary arterial hypertension: A meta-analysis. Gene 20 30218748
2018 Epigenetic variation at the SLC6A4 gene promoter in mother-child pairs with major depressive disorder. Journal of affective disorders 20 30447571
2017 Association analysis of SLC6A4 and HTR2A genes with obsessive-compulsive disorder: Influence of the STin2 polymorphism. Comprehensive psychiatry 20 29331882
2016 Correlation of 5-HTT, BDNF and NPSR1 gene polymorphisms with anxiety and depression in asthmatic patients. International journal of molecular medicine 20 27176146
2014 Association study of serotonin transporter SLC6A4 gene with Chinese Han irritable bowel syndrome. PloS one 20 24392134
2013 Serotonergic genes (5-HTT and HTR1A) and separation life events: gene-by-environment interaction for panic disorder. Neuropsychobiology 20 23635830
2011 Stressful life events and the serotonin transporter gene (5-HTT) in recurrent clinical depression. Journal of affective disorders 20 21982504
2007 Monoamine metabolites level in CSF is related to the 5-HTT gene polymorphism in treatment-resistant depression. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20 17299512
2021 Role of NR3C1 and SLC6A4 methylation in the HPA axis regulation in burnout. Journal of affective disorders 19 34509065
2020 Amygdala 5-HTT Gene Network Moderates the Effects of Postnatal Adversity on Attention Problems: Anatomo-Functional Correlation and Epigenetic Changes. Frontiers in neuroscience 19 32256307
2018 Negative social acts and pain: evidence of a workplace bullying and 5-HTT genotype interaction. Scandinavian journal of work, environment & health 19 29313869
2015 Effect of Simvastatin on 5-HT and 5-HTT in a Rat Model of Pulmonary Artery Hypertension. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 19 26544069
2014 The association of 5-HT2A, 5-HTT, and LEPR polymorphisms with obstructive sleep apnea syndrome: a systematic review and meta-analysis. PloS one 19 24755731
2023 Serotonin Transporter (5-Hydroxytryptamine Transporter, SERT, SLC6A4) and Sodium-dependent Reuptake Inhibitors as Modulators of Pain Behaviors and Analgesic Responses. The journal of pain 18 37852405
2018 Association between the SLC6A4 gene and schizophrenia: an updated meta-analysis. Neuropsychiatric disease and treatment 18 30643413
2022 5-Hydroxytryptamine activates a 5-HT/c-Myc/SLC6A4 signaling loop in non-small cell lung cancer. Biochimica et biophysica acta. General subjects 17 35066124
2014 5-HT2C receptor desensitization moderates anxiety in 5-HTT deficient mice: from behavioral to cellular evidence. The international journal of neuropsychopharmacology 17 25522398
2013 Gender-specific association of the SLC6A4 and DRD2 gene variants in bipolar disorder. The international journal of neuropsychopharmacology 17 24229495
2012 AVPR1A and SLC6A4 polymorphisms in choral singers and non-musicians: a gene association study. PloS one 17 22384070
2010 Interaction of SLC6A4 and DRD2 polymorphisms is associated with a history of delirium tremens. Addiction biology 17 20002020

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