Gene Report

Approved Symbol	SLC6A4
Previous Symbol	HTT, OCD1
Symbol Alias	5-HTT, SERT1
Approved Name	solute carrier family 6 (neurotransmitter transporter), member 4
Previous Name	solute carrier family 6 (neurotransmitter transporter, serotonin), member 4, "5-hydroxytryptamine (serotonin) transporter", "obsessive-compulsive disorder 1"
Name Alias	serotonin transporter 1
Location	17q11.2
Position	chr17:30194319-30236002, -1
External Links	HGNC: 11050 Entrez Gene: 6532 Ensembl: ENSG00000108576 UCSC: uc002hey.5
No. of Studies	44 (Positive: 18; Negative: 26; trend: 0)
Overlap with SZ?	YES
Overlap with MDD?	YES

Reference	Tested Markers	Statistical Values/Author Comments	Result Category	Comment on Study
Mynett-Johnson, L.,2000	Haplotype: (5-HTTLPR) - ( SLC6A4_3'UTR_G/T)(), (5-HTTLPR) - ( SLC6A4_VNTR)(), (5-HTTLPR) - ( SLC6A4_VNTR) - ( SLC6A4_3'UTR_G/T)(), (SLC6A4_VNTR) - (SLC6A4_3'UTR_G/T)() Other variant: SLC6A4_3'UTR_G/T, SLC6A4_intron2_VNTR, 5HTTLPR	Data from two and three polymorphic marker haplotypes revealed a number of marker combinations that showed evidence supportive of association.	Positive	Comment on Study
Mundo, E.,2000	Other variant: 5HTTLPR	It appears unlikely that the SLC6A4 plays a fundamental role in the pathogenesis of BP disorder.	Negative	Comment on Study
Mellerup, E.,2001	Other variant: 5HTTLPR, SLC6A4_intron2_VNTR	No association related to the polymorphism was found in the promoter region of the serotonin transporter gene.	Negative	Comment on Study
Piccardi, M. P.,2002	Other variant: 5HTTLPR	In our trios sample, the transmission disequilibrium test revealed no preferential transmission of alleles of the 5-HTTLPR from heterozygous parents to probands.	Negative	Comment on Study
Bocchetta, A.,1999	Other variant: SERT_VNTR	Using TDT, no significant differences were found with regard to DRD4, DRD2, DAT, and SERT polymorphism.	Negative	Comment on Study
Saleem, Q.,2000	Other variant: SLC6A4_intron2_VNTR	There were no significant differences either in allele frequency or genotype frequency between the two groups.	Negative	Comment on Study
Ospina-Duque, J.,2000	Other variant: 5HTTLPR	We did not detect an association between bipolar disorder and the 5-HTT promoter polymorphism in this sample.	Negative	Comment on Study
Oliveira, J. R.,2000	Other variant: 5HTTLPR	Our data suggest that this functional transporter polymorphism does not seem to play a major role in the genetics of bipolar disorder and major depression in Brazilian patients.	Negative	Comment on Study
Lin, C. I.,2010	Haplotype: (DRD3_Ser9Gly) - (5-HTTLPR)() Other variant: 5HTTLPR	Our study showed no difference between 5-HTTLPR genotypes and BP-I, BP-II and normal controls.	Negative	Comment on Study
Serretti, A.,2002	Other variant: 5HTTLPR	Our study did not support the involvement of 5-HTTLPR, TPH, MAO-A, or DRD4 polymorphisms in bipolar disorder.	Negative	Comment on Study
Soronen, P.,2011	SNP: rs3794808 Other variant: SLC6A4_intron2_VNTR, 5HTTLPR	No significant association of this gene was observed in BD.	Negative	Comment on Study
Mansour, H. A.,2005	SNP: rs140701, rs2020930, rs2020933, rs2020934, rs2020935, rs2020937, rs2020939, rs2020942, rs2066713, rs25532, rs6354 Other variant: 5HTTLPR	No significant associations were detected at the individual polymorphism or haplotype level using the case-control or family-based analyses. Our analyses do not support association between SLC6A4 and BDI families.	Negative	Comment on Study
Dimitrova, A.,2002	Other variant: SLC6A4_intron2_VNTR	The VNTR polymorphism in the 5-HTT gene does not appear to be a major risk factor for increasing susceptibility to major psychiatric disorders.	Negative	Comment on Study
Serretti, A.,2002	Other variant: 5HTTLPR	No significant association of 5HTTLPR was observed in BD.	Negative	Comment on Study
Rotondo, A.,2002	Other variant: 5HTTLPR	The findings support the hypothesis that comorbid panic disorder identifies a genetic subtype of bipolar disorder and suggest a role for COMT and 5-HTT in vulnerability to these disorders.	Positive	Comment on Study
Hauser, J.,2003	Other variant: 5HTTLPR	In summary, we found an association between the less active form of polymorphism in the serotonin transporter gene and bipolar or unipolar affective illness.	Positive	Comment on Study
Alaerts, M.,2009	SNP: rs1050565, rs11080123, rs12150214, rs12601963, rs140700, rs140701, rs2020930, rs2020933, rs2020936, rs2020942, rs2066713, rs2129785, rs2628179, rs3794730, rs3794808, rs3813034, rs3816828, rs4251417, rs4392119, rs4436830, rs4567782, rs4583306, rs7215330, rs8073965 Haplotype: 5-HTTVNTR - 5-HTTLPR(), rs3813034-5 - HTTLPR(), rs3813034-5 - HTTVNTR(), rs3813034-5 - HTTVNTR - 5HTTLPR() Other variant: 5HTTLPR, SLC6A4_intron2_VNTR	Taken together our findings from the association study, mutation analysis and CNV analysis, we can conclude that the serotonin transporter is unlikely to be a risk factor for BPI disorder in the Northern Swedish population.	Negative	Comment on Study
Mick, E.,2009	Other variant: 5HTTLPR	Our study suggests that markers examined thus far in SLC6A4 are not associated with pediatric bipolar disorder.	Negative	Comment on Study
Mohammadi, S., 2015	Other variant: 5HTTLPR	Our findings demonstrate 5-HTTLPR polymorphism might be a risk factor for BID and adult-onset BID in Kurds population.	Positive	Comment on Study
Meira-Lima, I.,2005	Other variant: 5HTTLPR	Our results suggest that the low-activity s variant does not influence susceptibility to BPD in our population.	Negative	Comment on Study
Shah, M. P.,2009	Other variant: 5HTTLPR	The findings suggest that the 5-HTTLPR s allele may contribute to a trait-related, genetically derived, neurobiological subgroup within BD characterized by prominent vACC dysfunction. Future treatment may be optimized for this BD subgroup by targeting the serotonergic system and the vACC.	Positive	Comment on Study
Cho, H. J.,2005	Other variant: 5HTTLPR, SLC6A4_intron2_VNTR	The observed ORs could be regarded simply as a very small but detectable effect of the 5-HTT, which has an additive effect when combined with other susceptibility loci. Alternative hypotheses on this finding were also discussed: a stronger effect of the haplotypes involving the two polymorphisms or other SNP markers; a more direct effect of these polymorphisms on specific phenotypes of BPD; and the presence of gene-environment interaction as a mediator of the genetic effects of 5-HTT.	Positive	Comment on Study
Lasky-Su, J. A.,2005	Other variant: 5HTTLPR, SLC6A4_intron2_VNTR	In conclusion, these meta-analytic findings suggest that the 44-bp deletion of 5-HTT increases the risk of BP.	Positive	Comment on Study
Oruc, L., 1997 (b)	Other variant: 5-HTT_PstI RFLP	These results suggest that variations in these genes may be responsible for a minor increase in susceptibility for bipolar disorder in women.	Negative	Comment on Study
Rees, M., 1997	Haplotype: SLC6A4 _intron 2_VNTR_5HTTLPR(12 allele-deleted allele) Other variant: 5HTTLPR, 5-HTT_intron 2_VNTR	Our findings add to the evidence that variation at or near hSERT influences susceptibility to bipolar disorder in the British Caucasian population.	Positive	Comment on Study
Jiang HY, 2013	Other variant: 5HTTLPR	The short allele (S allele) of 5-HTTLPR showed a significant association with bipolar disorder in our meta-analysis, suggesting it is likely a risk polymorphism for the illness.	Positive	Comment on Study
Mohamed Saini, S., 2013	Other variant: 5HTTLPR	The present study showed no significant association between the homozygous short variant of the 5-HTTLPR and bipolar disorder in the pooled subject and after stratification into the three main ethnic groups in Malaysia.	Negative	Comment on Study
Wang, T. Y., 2013	Other variant: 5HTTLPR	We provide preliminary evidence for a gender-specific effect of the SLC6A4 and DRD2 gene variants for the risk of BP-I and of BP-II. We also found gender-specific interaction between 5-HTTLPR and DRD2 Taq-IA polymorphisms in patients with bipolar disorder.	Positive	Comment on Study
Van Den Bogaert, A., 2006 (b)	Other variant: 5HTTLPR	Together, our data suggest that these functional variants are not involved in the etiology of bipolar disorder in the northern Swedish population nor did gene-gene interaction analysis support a central role of these variants in bipolar disorder..	Negative	Comment on Study
Sun, H. S., 2004	SNP: rs1042173, rs1532042, rs25528, rs6352, rs6354, rs956304 Haplotype: SLC6A4_5HTTLPR - rs956304 - rs25528 - rs6354 - SLC6A4_5HTTVNTR - rs6352 - rs1042173 - rs1532042(1-1-1-1-1-1-1-1), SLC6A4_5HTTLPR - rs956304 - rs25528 - rs6354 - SLC6A4_5HTTVNTR - rs6352 - rs1042173 - rs1532042(2-1-1-1-1-1-1-1), SLC6A4_5HTTLPR - rs956304 - rs25528 - rs6354 - SLC6A4_5HTTVNTR - rs6352 - rs1042173 - rs1532042(1-1-2-2-1-1-2-2), SLC6A4_5HTTLPR - rs956304 - rs25528 - rs6354 - SLC6A4_5HTTVNTR - rs6352 - rs1042173 - rs1532042(2-1-2-2-1-1-2-2), SLC6A4_5HTTLPR - rs956304 - rs25528 - rs6354 - SLC6A4_5HTTVNTR - rs6352 - rs1042173 - rs1532042(1-1-1-1-2-1-2-2), SLC6A4_5HTTLPR - rs956304 - rs25528 - rs6354 - SLC6A4_5HTTVNTR - rs6352 - rs1042173 - rs1532042(2-1-1-1-2-1-2-2), SLC6A4_5HTTLPR - rs956304 - rs25528 - rs6354 - SLC6A4_5HTTVNTR - rs6352 - rs1042173 - rs1532042(2-1-2-2-1-1-1-1), SLC6A4_5HTTLPR - rs956304 - rs25528 - rs6354 - SLC6A4_5HTTVNTR - rs6352 - rs1042173 - rs1532042(2-2-1-1-1-2-1-1) Other variant: 5HTTLPR, SLC6A4_intron2_VNTR	This study suggested that a particular SLC6A4 haplotype harboring functional sequence variant could play a significant role in BPD etiology in Taiwan. However, due to its modest sample size, the conclusion is not final and should be confirmed in the future studies.	Positive	Comment on Study
Mendes de Oliveira, J. R., 1998	Other variant: 5HTTLPR	Although it will be important to extend the present analysis in a larger sample, our preliminary results suggest that the 5-HTTLPR does not seem to play a major role in the genetics of bipolar and schizophrenic disorders at least in this group of Brazilian psychiatric patients.	Negative	Comment on Study
Hoehe, M. R., 1998	Other variant: 5-HTT_intron 2_VNTR, 5HTTLPR	our data suggest that the 5-HTT gene is not commonly involved in the susceptibility to mood disorders.	Negative	Comment on Study
Furlong, R. A., 1998 (a)	Other variant: 5-HTT_intron 2_VNTR, 5HTTLPR	These results suggest that the promoter allele 2 of 5-HTT, which has previously been shown to result in lower levels of serotonin transporter transcription, may be associated with affective disorder risk.	Positive	Comment on Study
Esterling, L. E., 1998	Other variant: 5HTTLPR	By using the TDT, no significant evidence for association between the 5-HTTLPR alleles and bipolar disorder was detected under either the stringent ASM I classification or the broader ASM II criteria, which includes recurrent unipolar illness.	Negative	Comment on Study
Bellivier, F., 1998 (b)	Other variant: 5HTTLPR, 5-HTT_intron 2_VNTR	The interaction between the two markers suggests that the two polymorphisms probably have independent effects to determine the susceptibility to affective disorder. Further studies are required to identify the precise phenotype associated with 5HTT polymorphisms in depressed patients.	Positive	Comment on Study
Gutierrez, B., 1998	Other variant: 5HTTLPR, 5-HTT_intron 2_VNTR	Our results suggest that the genetic variability of the 5-HTT gene is not a major risk factor for manic depression.	Negative	Comment on Study
Kirov, G.,1999(c)	Other variant: SLC6A4_intron2_VNTR, 5HTTLPR	The 12 repeat of the VNTR in intron 2 of the serotonin transporter gene might be a susceptibility factor in bipolar affective disorder.	Positive	Comment on Study
Liu, W,1999	Other variant: SERT_VNTR	Thus, we conclude that the SERT VNTR polymorphism may be a risk factor for both schizophrenia and unipolar depression, but not for bipolar disorder, in the Han Chinese.	Negative	Comment on Study
Vincent, J. B.,1999(a)	Other variant: SERT_VNTR, SERT_insertion/deletion	Statistically significant positive associations were found in original Study.	Positive	Comment on Study
Battersby, S.,1996	Other variant: SLC6A4_intron2_VNTR	There was a significant difference between patients with bipolar disorder and controls in the proportion of individuals carrying the STin2.9 allele.The findings support the hypothesis that allelic variation in the serotonin transporter gene may contribute to susceptibility for both major depression and bipolar disorder.	Positive	Comment on Study
Collier, D. A.,1996	Other variant: SERT_VNTR	An increased frequency of allele 12 of the VNTR was observed in subjects with bipolar affective disorder .We hypothesize that either the VNTR affects regulation of expression of hSERT at the transcriptional level or it is in linkage disequilibrium with another functional polymorphism in the gene, and this results in an increased risk for the development of bipolar affective disorder.	Positive	Comment on Study
Kunugi, H.,1997(a)	Other variant: 5HTTLPR, SLC6A4_intron2_VNTR	Our results suggest that the VNTR itself or another unknown functional polymorphism which would be in linkage disequilibrium to the VNTR has an effect on susceptibility to bipolar disorder.	Positive	Comment on Study
Ikeda, M., 2006	SNP: rs1050565, rs2020934, rs3813034, rs6352 Haplotype: rs1050565 - rs2020934(), rs1050565 - rs2020934 - SLC6A4_5HTTVNTR(), rs1050565 - rs2020934 - SLC6A4_5HTTVNTR - rs3813034(), rs2020934 - SLC6A4_5HTTVNTR(), rs2020934 - SLC6A4_5HTTVNTR - rs3813034(), SLC6A4_5HTTVNTR - rs3813034() Other variant: 5HTTLPR, SLC6A4_intron2_VNTR	These results indicate that SLC6A4 might not play a major role in SCZ and BP in Japanese patients.	Negative	Comment on Study
Masoliver, E., 2006	Other variant: 5HTTLPR, SLC6A4_intron2_VNTR	No significant differences in the genotype distribution of analyzed polymorphisms within this gene were observed in this study.	Negative	Comment on Study

Region: chr17:30194319..30236002 View in gBrowse