Gene Report

Basic Information

Approved Symbol	SLC6A4
Approved Name	solute carrier family 6 (neurotransmitter transporter, serotonin), member 4
Previous Symbol	HTT
Symbol Alias	5-HTT, SERT1
Location	17q11.2
Position	chr17:28523376-28562954 (-)
External Links	Entrez Gene: 6532 Ensembl: ENSG00000108576 UCSC: uc002hey.4 HGNC ID: 11050
No. of Studies (Positive/Negative)	51(43/8)
Type	Literature-origin; Protein mapped

Positive relationships between SLC6A4 and MDD (count: 23)

Name in Literature	Reference	Research Type	Statistical Result	Relation Description
SLC6A4	Garriock, 2006	patients and normal controls	P-value=0.004	A statistically significant difference in genotype frequency...... A statistically significant difference in genotype frequency for the SLC6A4 intron 2 VNTR was detected between the subjects with a history of depression and controls (p = 0.004). More...
serotonin transporter gene	Sarosi, 2008	patients and normal controls		We found a significantly higher frequency of the STin2.10/St...... We found a significantly higher frequency of the STin2.10/Stin2.10 homozygous genotype in the depressed group compared to controls. In the depressed group subjects with at least one copy of the 10-repeat allele showed decreased interference threshold in Stroop III compared to patients without the 10-repeat allele. More...
Huntingtin (HTT)	erlis, 2010	patients and normal controls		In clinical populations of individuals diagnosed with major ...... In clinical populations of individuals diagnosed with major depression, approximately 3 in 1,000 carried expanded HTT CAG alleles More...
5-HTTLPR	Eker, 2011	patients and normal controls		The 5-HTTLPR polymorphism has an effect on hippocampal volum...... The 5-HTTLPR polymorphism has an effect on hippocampal volumes of depressed patients, which is apparent only in S/S genotype. More...
serotonin transporter gene	Alexopoulos, 2009	patients only		Depressed elderly S-allele carriers also had lower FA (fract...... Depressed elderly S-allele carriers also had lower FA (fractional anisotropy) than L homozygotes in frontolimbic brain areas, More...
serotonin transporter gene	Battersby, 1996	patients and normal controls		There was a significant difference between patients with aff...... There was a significant difference between patients with affective disorder and controls in the proportion of individuals carrying the STin2.9 allele More...
5-HTT	Nellissery, 2003	patients and normal controls		The frequency of the short allele in the patient group was i...... The frequency of the short allele in the patient group was in the range of those previously reported for samples with unipolar depression but was significantly more common than among controls (short allele frequency of cases, 45.8%; controls, 39.8%; chi(2)(1) = 4.02; p = 0.045). More...
5-HTTLPR	Hoefgen, 2005	patients and normal controls	P-value=0.006; odds ratio = 1.26	The short allele of 5-HTTLPR was significantly more frequent...... The short allele of 5-HTTLPR was significantly more frequent in patients than in control subjects (45.5% vs. 39.9%; p = .006; odds ratio = 1.26). More...
5-HTT	Kendler KS, 2005	nomal people		Individuals with 2 short (S) alleles at the 5-HTT locus wer...... Individuals with 2 short (S) alleles at the 5-HTT locus were more sensitive to the depressogenic effects of all SLEs than were those with 1 or 2 long (L) alleles. When level of SLE-associated threat was examined, the interaction between genotype and SLE resulted from an increased sensitivity of SS individuals to the depressogenic effects of common low-threat events. These events had little impact on risk for those possessing the SL and LL genotypes. The 5-HTT genotype did not modify the effects of SLEs on risk for generalized anxiety syndrome. More...
5-HTTLPR	Lenze, 2005	patients and normal controls		Survival analysis showed that genotype significantly predict...... Survival analysis showed that genotype significantly predicted time-to-major depressive episode. Subjects with an s allele (genotype s/l or s/s) had significantly higher Ham-D scores over 14 weeks of follow-up than those with the l/l genotype. More...
Serotonin transporter	Lima, 2005	patients and normal controls		There was a significant reduction in mRNA in depressed patie...... There was a significant reduction in mRNA in depressed patients expressing the long allele. More...
5HTT	Munafo, 2006	patients and normal controls	P-value=0.04	5HTT-LPR genotype was significantly associated with both neu...... 5HTT-LPR genotype was significantly associated with both neuroticism (p=0.02) and lifetime major depression (p=0.04), and neuroticism with lifetime major depression (p<0.001) More...
serotonin transporter gene (SERTPR)	Mandelli L, 2007	Patients and nomal controls	chi2=6.70, d.f.=2, p=0.035	COMT was associated with depression following exposure to s...... COMT was associated with depression following exposure to stressors (chi2=13.05, d.f.=2, p=0.0015) and SERTPR also showed a positive association (chi2=6.70, d.f.=2, p=0.035), mainly among women and among major depressives. The interaction between COMT and SERTPR was also significant (p=0.0005). More...
SERT	Bozina, 2006	patients and normal controls	P-value=0.04	The proportion of SERT-in2 short (s) alleles was significant...... The proportion of SERT-in2 short (s) alleles was significantly higher among MDD patients in comparison to healthy subjects (p = 0.04). More...
5-HTTLPR	Neumeister, 2006	patients and normal controls		A direct effect of 5-HTTLPR on the regulation of regional ce...... A direct effect of 5-HTTLPR on the regulation of regional cerebral metabolic rates for glucose was identified in patients with rMDD for the amygdala, hippocampus, and subgenual anterior cingulate cortex. More...
5-HTTLPR	Dorado, 2007	patients and normal controls	P-value<0.05	The frequency of subjects carrying the 5-HTTLPR-S allele was...... The frequency of subjects carrying the 5-HTTLPR-S allele was higher (P < 0.05) among MDD than in HV. More...
SLC6A4	Domotor, 2007	patients and normal controls	chi2 = 6,01, df = 2, P-value < 0.05	We found a significantly higher frequency of the STin2 10/10...... We found a significantly higher frequency of the STin2 10/10 homozygous genotype in the MDD patients' group compared to controls (chi2 = 6,01, df = 2, p < 0.05) More...
5HTTLPR	Philibert, 2008	patients and normal controls	P-value < 0.0001	We confirmed prior findings that the short (s) 5HTTLPR allel...... We confirmed prior findings that the short (s) 5HTTLPR allele is associated with lower amounts of mRNA transcription, but there was no significant effect of the Long G allele on mRNA transcription. We also found that CpG methylation was higher (P < 0.0008) and mRNA production (P < 0.0001) was lower in females as compared to males. More...
5-HTTLPR	Contreras J, 2009	Patients and nomal controls	P < 0.02; odds ratio= 2.18; 95% CI= 1.10-4.20	We found that persons carrying at least one short allele had...... We found that persons carrying at least one short allele had a statistically significant increased lifetime risk for depressive syndromes (P < 0.02, odds ratio 2.18, 95% CI 1.10-4.20). More...
SLC6A4	Wray NR, 2009	Patients and nomal controls	p = 0.0062	We found evidence for association (p = .0062, after accounti...... We found evidence for association (p = .0062, after accounting for multiple testing) for SLC6A4 SNPs rs6354 and rs2020936 (positioned in a different linkage disequilibrium [LD] block about 15.5 kb from 5HTTLPR) with anxiety and/or depression and neuroticism, with the strongest association for recurrent depression with onset in young adulthood (odds ratio = 1.55, 95% confidence interval = 1.16-2.06). More...
SLC6A4	Noskova, 2009	patients and normal controls		The results of the study suggest that genotype 10/10 of the ...... The results of the study suggest that genotype 10/10 of the SLC6A4 gene as well as genotype G/G and allele G of the HTR2A gene can predispose for increased risk of unipolar depression development in ethnic Russians. More...
SLC6A4	Belzeaux, 2010	patients and normal controls		We also observed that variations in other mRNA expression we...... We also observed that variations in other mRNA expression were associated with treatment efficacy or clinical improvement (CREB1, HDAC5, HSPA2, HTR1B, HTR2A, and SLC6A4/5HTT). More...
serotonin transporter gene	Sarosi, 2011	patients and normal controls		We found a significantly higher frequency of the STin2 10/10...... We found a significantly higher frequency of the STin2 10/10 genotype in the MDD patient group compared to controls. More...

Positive relationships between SLC6A4 and other components at different levels (count: 42)

Genetic/epigenetic locus					Protein and other molecule			Cell and molecular pathway			Neural system			Cognition and behavior		Symptoms and signs			Environment

Name in Literature	Related Components
Level	Approved Name (Name in Literature)	Type	Reference	Research Type	Statistical Result	Relation Description	All
serotonin transporter gene (SERTPR)		COMT(COMT)	gene	Mandelli L, 2007	Patients and nomal controls	p=0.0005	COMT was associated with depression following exposure to s...... COMT was associated with depression following exposure to stressors (chi2=13.05, d.f.=2, p=0.0015) and SERTPR also showed a positive association (chi2=6.70, d.f.=2, p=0.035), mainly among women and among major depressives. The interaction between COMT and SERTPR was also significant (p=0.0005). More...
5-HTT		Hydroxyindoleacetic Acid(5-hydroxyindoleacetic acid)	molecule	Kishida, 2007	patients and normal controls	P-value=0.03	In patients with mood disorders, we found significant differ...... In patients with mood disorders, we found significant difference in mean 5-HIAA concentration between 5-HTTLPR genotypes (p=0.03) More...
5-HTT		Serotonin(5-HT)	molecule	Barton, 2008	patients and normal controls	P-value=0.04	Analysis of the influence of the 5-HTT genotype in MDD indi...... Analysis of the influence of the 5-HTT genotype in MDD indicated that carriage of the s allele compared with the l allele was associated with greater than a 2-fold increase in brain serotonin turnover (mean [SD] internal jugular venoarterial 5-hydroxyindoleacetic acid plasma concentration difference, 6.5 [4.7] vs 2.7 [2.9] nmol/L, respectively; P = .04). More...
5-HTT		Hydrocortisone(cortisol)	molecule	Chen, 2009	patients and normal controls		We found 5-HTTLPR to be significantly associated with diurna...... We found 5-HTTLPR to be significantly associated with diurnal cortisol levels More...
5-HTTLPR		Serotonin(serotonin)	molecule	Eker, 2011	patients and normal controls		It seems that decreased neurogenesis by effects of reduced s...... It seems that decreased neurogenesis by effects of reduced serotoninergic transmission may be responsible for smaller hippocampal volumes observed in S/S homozygous depressed patients. More...
5-HTT		P200(P2)	neurobiological system	Chen, 2002	patients and normal controls	P-value=0.04	Analysis of the results revealed a significantly shorter P2 ...... Analysis of the results revealed a significantly shorter P2 latency for patients bearing the s/s genotype in comparison with l allele carriers, especially for the female patients (p = 0.004). The 5-HTTLPR polymorphism accounted for 3.4% of the variance in P2 latency. More...
serotonin transporter gene		White matter(white matter)	brain morphology and function	Alexopoulos, 2009	patients only		Depressed elderly S-allele carriers also had lower FA (fract...... Depressed elderly S-allele carriers also had lower FA (fractional anisotropy) than L homozygotes in frontolimbic brain areas, More...
5-HTT		Hippocampus(hippocampus)	brain morphology and function	Frodl, 2004	patients and normal controls	P-value<0.01	Patients with the L/L homozygous genotype had significantly ...... Patients with the L/L homozygous genotype had significantly smaller hippocampal gray matter (left hemisphere: P=.003; right hemisphere: P=.01) and white matter volumes (left hemisphere: P=.001; right hemisphere: P=.002) than controls with this genotype. More...
5-HTTLPR		Amygdala(amygdala)	brain morphology and function	Hariri, 2005	normal people		We now confirm the finding of 5-HTTLPR short allele-driven a...... We now confirm the finding of 5-HTTLPR short allele-driven amygdala hyperreactivity in a large independent cohort of healthy subjects with no history of psychiatric illness or treatment. More...
5-HTT		Caudate nucleus(caudate nucleus)	brain morphology and function	Hickie, 2007	patients and normal controls		In those with depression, the short allele of 5-HTT was asso...... In those with depression, the short allele of 5-HTT was associated with smaller caudate nucleus volumes. More...
5-HTTLPR		Amygdala(amygdala)	brain morphology and function	Neumeister, 2006	patients and normal controls		A direct effect of 5-HTTLPR on the regulation of regional ce...... A direct effect of 5-HTTLPR on the regulation of regional cerebral metabolic rates for glucose was identified in patients with rMDD for the amygdala, hippocampus, and subgenual anterior cingulate cortex. More...
5-HTTLPR		Hippocampus(hippocampus)	brain morphology and function	Neumeister, 2006	patients and normal controls		A direct effect of 5-HTTLPR on the regulation of regional ce...... A direct effect of 5-HTTLPR on the regulation of regional cerebral metabolic rates for glucose was identified in patients with rMDD for the amygdala, hippocampus, and subgenual anterior cingulate cortex. More...
5-HTTLPR		subgenual anterior cingulate(subgenual anterior cingulate cortex)	brain morphology and function	Neumeister, 2006	patients and normal controls		A direct effect of 5-HTTLPR on the regulation of regional ce...... A direct effect of 5-HTTLPR on the regulation of regional cerebral metabolic rates for glucose was identified in patients with rMDD for the amygdala, hippocampus, and subgenual anterior cingulate cortex. More...
SERT		Pulvinar nuclei(pulvinar)	brain morphology and function	Young, 2007	patients and normal controls		Analysis of covariance with diagnosis, SERT genotype, age, h...... Analysis of covariance with diagnosis, SERT genotype, age, hemisphere, postmortem interval, and time-in-formalin covariates identified a 20% increase in pulvinar neuron number and volume in SERT-ss subjects. More...
5-HTTLPR		Amygdala(amygdala)	brain morphology and function	Dannlowski, 2007	patients and normal controls		Risk allele carriers for either gene showed significantly in...... Risk allele carriers for either gene showed significantly increased bilateral amygdala activation in response to emotional stimuli, implicating an additive effect of both genotypes. More...
5-HTTLPR		Hippocampus(hippocampus)	brain morphology and function	Frodl, 2008	patients and normal controls		We found that healthy controls have a strong association bet...... We found that healthy controls have a strong association between the 5-HTTLPR and GM volumes of the dorsolateral prefrontal cortex, left anterior gyrus cinguli, left amygdala as well as right hippocampus, whereas there is no such association in patients with major depression. More...
serotonin transporter gene (5-HTTLPR)		Hippocampus(hippocampal gray)	brain morphology and function	Frodl, 2008	patients and normal controls		Patients with the La/La genotype had significantly smaller h...... Patients with the La/La genotype had significantly smaller hippocampal gray and white matter than La/La controls. More...
serotonin transporter gene (5-HTTLPR)		White matter(white matter)	brain morphology and function	Frodl, 2008	patients and normal controls		Patients with the La/La genotype had significantly smaller h...... Patients with the La/La genotype had significantly smaller hippocampal gray and white matter than La/La controls. More...
5-HTT		Pulvinar nuclei(pulvinar)	brain morphology and function	Young, 2008	patients and normal controls		The majority of the volume enlargement associated with the S...... The majority of the volume enlargement associated with the SERT-ss genotype occurred in the pulvinar More...
serotonin transporter gene		Amygdala(amygdala)	brain morphology and function	Lau, 2009	patients and normal controls		First, consistent with healthy adult data, healthy adolescen...... First, consistent with healthy adult data, healthy adolescents with at least one copy of the S or L(G) allele showed stronger amygdala responses to fearful faces than healthy adolescents without these alleles. Second, patients with two copies of the L(A) allele exhibited greater amygdala responses to fearful faces relative to patients with S or L(G) alleles. More...
5-HTTLPR		Amygdala(amygdala)	brain morphology and function	Ben-Shachar, 2008	patients and normal controls		Risk allele carriers (S or L(G)) demonstrated increased amyg...... Risk allele carriers (S or L(G)) demonstrated increased amygdala reactivity to masked emotional faces More...
5-HTTLPR		Amygdala(amygdala)	brain morphology and function	Frodl, 2008	patients and normal controls		We found that healthy controls have a strong association bet...... We found that healthy controls have a strong association between the 5-HTTLPR and GM volumes of the dorsolateral prefrontal cortex, left anterior gyrus cinguli, left amygdala as well as right hippocampus, whereas there is no such association in patients with major depression. More...
5-HTTLPR		Dorsolateral prefrontal cortex(dorsolateral prefrontal cortex)	brain morphology and function	Frodl, 2008	patients and normal controls		We found that healthy controls have a strong association bet...... We found that healthy controls have a strong association between the 5-HTTLPR and GM volumes of the dorsolateral prefrontal cortex, left anterior gyrus cinguli, left amygdala as well as right hippocampus, whereas there is no such association in patients with major depression. More...
5-HTTLPR		Hippocampus(hippocampus)	brain morphology and function	Frodl, 2008	patients and normal controls		Patients with the La/La genotype had significantly smaller h...... Patients with the La/La genotype had significantly smaller hippocampal gray and white matter than La/La controls. Moreover, within the patient group the La/La homozygous genotype had significantly smaller hippocampal white matter volumes than the La/(Lg + S) or (Lg + S)/(Lg + S) genotype. More...
5-HTTLPR		left anterior cingulate(left anterior gyrus cinguli)	brain morphology and function	Frodl, 2008	patients and normal controls		We found that healthy controls have a strong association bet...... We found that healthy controls have a strong association between the 5-HTTLPR and GM volumes of the dorsolateral prefrontal cortex, left anterior gyrus cinguli, left amygdala as well as right hippocampus, whereas there is no such association in patients with major depression. More...
serotonin transporter gene (5-HTTLPR)		Dorsolateral prefrontal cortex(dorsolateral prefrontal cortex)	brain morphology and function	Frodl, 2008	patients and normal controls		We found that healthy controls have a strong association bet...... We found that healthy controls have a strong association between the 5-HTTLPR and GM (gray matter) volumes of the dorsolateral prefrontal cortex, whereas there is no such association in patients with major depression. Healthy subjects carrying the S- or L(G)-allele have smaller GM volumes than those with the L(A)-allele More...
serotonin transporter gene (5-HTTLPR)		Left amygdala(left amygdala)	brain morphology and function	Frodl, 2008	patients and normal controls		We found that healthy controls have a strong association bet...... We found that healthy controls have a strong association between the 5-HTTLPR and GM (gray matter) volumes of the left amygdala , whereas there is no such association in patients with major depression. Healthy subjects carrying the S- or L(G)-allele have smaller GM volumes than those with the L(A)-allele More...
serotonin transporter gene (5-HTTLPR)		left anterior cingulate(left anterior gyrus cinguli)	brain morphology and function	Frodl, 2008	patients and normal controls		We found that healthy controls have a strong association bet...... We found that healthy controls have a strong association between the 5-HTTLPR and GM (gray matter) volumes of the left anterior gyrus cinguli, whereas there is no such association in patients with major depression. Healthy subjects carrying the S- or L(G)-allele have smaller GM volumes than those with the L(A)-allele More...
serotonin transporter gene (5-HTTLPR)		right hippocampus(right hippocampus)	brain morphology and function	Frodl, 2008	patients and normal controls		We found that healthy controls have a strong association bet...... We found that healthy controls have a strong association between the 5-HTTLPR and GM (gray matter) volumes of the right hippocampus, whereas there is no such association in patients with major depression. Healthy subjects carrying the S- or L(G)-allele have smaller GM volumes than those with the L(A)-allele More...
5-HTT		Amygdala(amygdala)	brain morphology and function	Friedel, 2009	patients and normal controls		In healthy controls prefrontal (BA10) activation and BA10-am...... In healthy controls prefrontal (BA10) activation and BA10-amygdala coupling increased with the number of 5-HTT low-expression risk alleles, this effect was abolished, and even reversed, in patients with MDD. More...
5-HTT		Prefrontal cortex(prefrontal cortex)	brain morphology and function	Friedel, 2009	patients and normal controls		In healthy controls prefrontal (BA10) activation and BA10-am...... In healthy controls prefrontal (BA10) activation and BA10-amygdala coupling increased with the number of 5-HTT low-expression risk alleles, this effect was abolished, and even reversed, in patients with MDD. More...
5-HTTLPR		Anterior cingulate cortex(anterior cingulate cortex (ACC))	brain morphology and function	Holmes, 2010	patients only		A variable number of tandem repeats (short (S) vs long (L)) ...... A variable number of tandem repeats (short (S) vs long (L)) in the promoter region of the serotonin transporter gene (5-HTTLPR), relative to L' participants, S' participants showed (1) impaired post-error and post-conflict behavioral adjustments; (2) larger error-related rostral ACC activation; and (3) lower conflict-related dorsal ACC activation. More...
serotonin transporter gene		Hippocampus(hippocampal volumes)	brain morphology and function	Frodl, 2010	patients and normal controls		Patients carrying the risk S-allele developed smaller hippoc...... Patients carrying the risk S-allele developed smaller hippocampal volumes when they had a history of emotional neglect compared with patients who only had one risk factor (environmental or genetic). I More...
SLC6A4		Hippocampus(hippocampus)	brain morphology and function	Frodl, 2010	patients and normal controls		Patients carrying the risk S-allele developed smaller hippoc...... Patients carrying the risk S-allele developed smaller hippocampal volumes when they had a history of emotional neglect compared with patients who only had one risk factor (environmental or genetic) More...
5-HTTLPR		Hippocampus(hippocampal volumes)	brain morphology and function	Eker, 2011	patients and normal controls		The 5-HTTLPR polymorphism has an effect on hippocampal volum...... The 5-HTTLPR polymorphism has an effect on hippocampal volumes of depressed patients, which is apparent only in S/S genotype. More...
serotonin transporter gene		Memory(recall)	cognition and behavior	Sarosi, 2008	patients and normal controls		Average performance of the depressed group without the 12-re...... Average performance of the depressed group without the 12-repeat allele was significantly weaker in the Rey Auditory Verbal Learning Test working memory and recall tasks compared to patients having at least one copy of the 12-repeat allele. More...
serotonin transporter gene		Working memory(working memory)	cognition and behavior	Sarosi, 2008	patients and normal controls		Average performance of the depressed group without the 12-re...... Average performance of the depressed group without the 12-repeat allele was significantly weaker in the Rey Auditory Verbal Learning Test working memory and recall tasks compared to patients having at least one copy of the 12-repeat allele. More...
serotonin transporter gene		Cognitive performance(cognitive dysfunction)	cognition and behavior	Sarosi, 2011	patients and normal controls		Our results suggest that the presence of STin2.10 and absenc...... Our results suggest that the presence of STin2.10 and absence of STin2.12 may be considered a possible genetic endophenotype for cognitive dysfunction detected in major depressive disorder. More...
5-HTT		Suicide(suicide attempt)	symptoms	Lopez de Lara, 2006	patients and normal controls	chi(2)(1) = 10.833; P-value = 0.002	We found a significant association of suicide completion wit...... We found a significant association of suicide completion with having at least one copy of the STin2 10 allele [chi(2)(1) = 10.833, p = .002]. No differences were found for the 5-HTTLPR variable number of tandem repeats. More...
5-HTT		Stress(stressful life events)	environment	Kendler KS, 2005	nomal people		Individuals with 2 short (S) alleles at the 5-HTT locus wer...... Individuals with 2 short (S) alleles at the 5-HTT locus were more sensitive to the depressogenic effects of all SLEs than were those with 1 or 2 long (L) alleles. When level of SLE-associated threat was examined, the interaction between genotype and SLE resulted from an increased sensitivity of SS individuals to the depressogenic effects of common low-threat events. These events had little impact on risk for those possessing the SL and LL genotypes. The 5-HTT genotype did not modify the effects of SLEs on risk for generalized anxiety syndrome. More...
5-HTTLPR		Life events(negative life events)	environment	Zhang, 2009	patients and normal controls		The 5-HTTLPR polymorphism was associated with negative life ...... The 5-HTTLPR polymorphism was associated with negative life events on MDD More...
5-HTT		Stress(early life stress)	environment	Quinn CR, 2012	patients only		Key findings indicated that BDNF and 5-HTT polymorphisms in ...... Key findings indicated that BDNF and 5-HTT polymorphisms in combination with ELS contributed to the development of non-melancholic depression. An interaction between BDNF and ELS increased the risk of non-melancholia by 3.327, whereas the interaction between 5-HTT and ELS increased risk by 2.406. More...

Positive relationship network of SLC6A4 in MK4MDD

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Note:
1. The different color of the nodes denotes the level of the nodes.

Genetic/Epigenetic Locus	Protein and Other Molecule	Cell and Molecular Pathway	Neural System	Cognition and Behavior	Symptoms and Signs	Environment	MDD

2. Besides the component related relationships from literature, gene mapped protein and protein mapped gene are also shown in the network. If the mapped gene or protein is not from literature, square node would be used instead of Circle node. Accordingly, the relationship is marked with dot line.
2. User can drag the nodes to rearrange the layout of the network. Click the node will enter the report page of the node. Right-click will show also the menus to link to the report page of the node and remove the node and related edges. Hover the node will show the level of the node and hover the edge will show the evidence/description of the edge.
3. The network is generated using Cytoscape Web

Negative relationships between SLC6A4 and MDD (count: 7)

Name in Literature	Reference	Research Type	Relation Description
5-HTTLPR	Minov C, 2001	Patients and nomal controls	No statistical significant differences between patients and ...... No statistical significant differences between patients and controls were found for any of the three investigated polymorphisms, neither in the distribution of the genotypes nor in allele frequencies. However, concerning the 5-HTTLPR polymorphism, the frequency of S/S (short allele) homozygotes was higher (23.1%) than in the control group (14.0%), but this failed to reach significance. More...
5-HTTLPR	Rujescu D, 2001	Patients and nomal controls	There was no significant difference in allele or genotype f...... There was no significant difference in allele or genotype frequency between patients and control subjects. There were also no differences when the patients were divided into several subgroups (suicide attempters with a violent method, and suicide attempters with a lifetime history of mood disorders, unipolar depression, personality disorders). More...
5-HTT	Yen FC, 2003	Patients and nomal controls	we investigated the prevalence of this polymorphism in an i...... we investigated the prevalence of this polymorphism in an independent Chinese population (83 bipolar disorder patients, 77 major depressive disorder patients and 169 controls), demonstrating no significant association between the 5-HTTVNTR polymorphism and mood disorders or age at onset. More...
SLC6A4	Willis-Owen SA, 2005	nomal people	No statistically significant effects of genotype could be id...... No statistically significant effects of genotype could be identified on either N or MD phenotypes (in all cases, p > or = .26), independently of the genetic mode of action applied. More...
5-HTTLPR	Middeldorp CM, 2007	nomal people	No additive effect of the s allele was found for DSM-IV depr...... No additive effect of the s allele was found for DSM-IV depression More...
5-HTT	Zaboli G, 2008	Patients and nomal controls	Haplotype-based analyses showed significant associations bet...... Haplotype-based analyses showed significant associations between 5-HTT and SCZ but not MDD. More...
5-HTT	Fisher HL, 2012	Patients and nomal controls	There was no main effect of 5-HTTLPR on depression and no e...... There was no main effect of 5-HTTLPR on depression and no evidence of interaction between total SLEs and any of the 5-HTTLPR genetic models More...

Negative relationships between SLC6A4 and other components at different levels (count: 3)

Genetic/epigenetic locus					Protein and other molecule			Cell and molecular pathway			Neural system			Cognition and behavior		Symptoms and signs			Environment

Name in Literature	Level	Approved Name (Name in Literature)	Type	Reference	Research Type	Relation Description
Name in Literature	Related Components
5HTTLPR		Hippocampus(hippocampal volume)	brain morphology and function	Cole, 2011	patients and normal controls	Hippocampal volume normalized by intracranial volume (ICV) s...... Hippocampal volume normalized by intracranial volume (ICV) showed no significant difference between 5HTTLPR S allele carriers and L/L homozygotes or between BDNF Met allele carriers and Val/Val homozygotes in the group of healthy individuals. More...
5-HTTLPR		Suicide(suicide attempt)	symptoms	Rujescu D, 2001	Patients and nomal controls	There was no significant difference in allele or genotype f...... There was no significant difference in allele or genotype frequency between patients and control subjects. There were also no differences when the patients were divided into several subgroups (suicide attempters with a violent method, and suicide attempters with a lifetime history of mood disorders, unipolar depression, personality disorders). More...
5-HTT		Stress(recent stressful life events)	environment	Fisher HL, 2012	Patients and nomal controls	There was no main effect of 5-HTTLPR on depression and no e...... There was no main effect of 5-HTTLPR on depression and no evidence of interaction between total SLEs and any of the 5-HTTLPR genetic models More...

SLC6A4 related SNPs in MK4MDD (count: 0)

SLC6A4 related proteins in MK4MDD (count: 1)

Approved Name	UniportKB	No. of Studies (Positive/Negative)	Source
Sodium-dependent serotonin transporter	P31645	17(17/0)	Literature-origin

SLC6A4 related GO terms (count: 43)

ID	Name	Type	Evidence
Gene mapped GO terms
GO:0051610	serotonin uptake	biological process	IDA[19270731]
GO:0015222	serotonin transmembrane transporter activity	molecular function	IDA[8987735]; IMP[19270731]
GO:0017022	myosin binding	molecular function	IEA
GO:0051259	protein oligomerization	biological process	ISS
GO:0042310	vasoconstriction	biological process	IEA
GO:0008504	monoamine transmembrane transporter activity	molecular function	IDA[16024787]
GO:0051015	actin filament binding	molecular function	ISS
GO:0007584	response to nutrient	biological process	IEA
GO:0042493	response to drug	biological process	IEA
GO:0017137	Rab GTPase binding	molecular function	IPI[18227069]
GO:0010008	endosome membrane	cellular component	IEA
GO:0042803	protein homodimerization activity	molecular function	IEA
GO:0005887	integral to plasma membrane	cellular component	IC[19270731]
GO:0046621	negative regulation of organ growth	biological process	ISS
GO:0009636	response to toxin	biological process	IDA[17575980]
GO:0005515	protein binding	molecular function	IPI[11343649]
GO:0032355	response to estradiol stimulus	biological process	IEA
GO:0032227	negative regulation of synaptic transmission, dopaminergic	biological process	IEA
GO:0071321	cellular response to cGMP	biological process	IEA
GO:0045665	negative regulation of neuron differentiation	biological process	IEA
GO:0048854	brain morphogenesis	biological process	ISS
GO:0001666	response to hypoxia	biological process	IEA
GO:0021941	negative regulation of cerebellar granule cell precursor proliferation	biological process	IEA
GO:0043005	neuron projection	cellular component	IEA
GO:0015844	monoamine transport	biological process	IDA[16024787]
GO:0012505	endomembrane system	cellular component	IDA[18227069]
GO:0071300	cellular response to retinoic acid	biological process	IEA
GO:0050998	nitric-oxide synthase binding	molecular function	IEA
GO:0006837	serotonin transport	biological process	IDA[19270731]
GO:0042713	sperm ejaculation	biological process	IEA
GO:0051260	protein homooligomerization	biological process	IEA
GO:0005335	serotonin:sodium symporter activity	molecular function	IDA[8987735]; IMP[19270731]
GO:0010628	positive regulation of gene expression	biological process	IEA
GO:0045787	positive regulation of cell cycle	biological process	IEA
GO:0019811	cocaine binding	molecular function	IEA
GO:0045121	membrane raft	cellular component	IDA[16870614]
GO:0007613	memory	biological process	IEA
GO:0005886	plasma membrane	cellular component	IDA[16870614]
GO:0035176	social behavior	biological process	ISS
GO:0005829	cytosol	cellular component	IDA[19270731]
GO:0017075	syntaxin-1 binding	molecular function	IEA
GO:0007623	circadian rhythm	biological process	IEA
GO:0021794	thalamus development	biological process	IMP[18378990]

SLC6A4 related KEGG pathways (count: 0)

SLC6A4 related BioCarta pathways (count: 0)

SLC6A4 related Reactome pathways (count: 0)

SLC6A4 related interactors from protein-protein interaction data in HPRD (count: 3)

Gene	Interactor	Interactor in MK4MDD?	Experiment Type	PMID
SLC6A4	YBX1	Yes	in vitro;in vivo;yeast 2-hybrid	15229244
SLC6A4	STX1A	Yes	in vivo	12175857
SLC6A4	CALR	No	in vivo	10364189

Gene Report

Gene mapped GO terms