SLC6A4
Homo sapiens
Gene Name: solute carrier family 6 (neurotransmitter transporter, serotonin), member 4
Aliases: HTT, 5HTT, OCD1, SERT, 5-HTT, hSERT
Chromosome No: 17
Chromosome Band: 17q11.2
Genetic Category: Genetic Association--Rare Single Gene variant, Genetic Association-Rare single gene variant-Genetic association/rare single gene variant-Functional
Aliases: HTT, 5HTT, OCD1, SERT, 5-HTT, hSERT
Chromosome No: 17
Chromosome Band: 17q11.2
Genetic Category: Genetic Association--Rare Single Gene variant, Genetic Association-Rare single gene variant-Genetic association/rare single gene variant-Functional
Summary Statistics:
ASD Reports: 31
Recent Reports: 4
Annotated variants: 51
Associated CNVs: 3
Evidence score: 2
ASD Reports: 31
Recent Reports: 4
Annotated variants: 51
Associated CNVs: 3
Evidence score: 2
| Associated Disorders: |
|
Relevance to Autism
Several studies have found genetic association between the SLC6A4 gene and autism in AGRE, CPEA, French-Caucasian, Portuguese and several mixed US population cohorts. However, several other studies found no genetic association between the SLC6A4 gene and autism in AGRE, SARC, US and Chinese Han population cohorts. Separately, genetic association has been found between the SLC6A4 gene and pervasive developmental disorder (PDD) in a Dutch population cohort. In addition, rare mutations in the SLC6A4 gene have been identified in individuals with ASD (Neale et al., 2012).
Molecular Function
The encoded protein has serotonin transporter activity, serotonin:sodium symport er activity.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Evidence of linkage between the serotonin transporter and autistic disorder.
ASD
Positive Association
Serotonin transporter intron 2 polymorphism associated with rigid-compulsive behaviors in Dutch individuals with pervasive developmental disorder.
PDD
Positive Association
Variants of the serotonin transporter gene (SLC6A4) significantly contribute to hyperserotonemia in autism.
ASD
Positive Association
Serotonin transporter promoter variants in autism: functional effects and relationship to platelet hyperserotonemia.
ASD
Positive Association
Association study in siblings and case-controls of serotonin- and oxytocin-related genes with high functioning autism.
ASD
Positive Association
Transmission disequilibrium mapping at the serotonin transporter gene (SLC6A4) region in autistic disorder.
ASD
Positive Association
Common and rare alleles of the serotonin transporter gene, SLC6A4, associated with Tourette's disorder.
TS
Positive Association
Autism and the serotonin transporter: the long and short of it.
ASD
Positive Association
Allelic heterogeneity at the serotonin transporter locus (SLC6A4) confers susceptibility to autism and rigid-compulsive behaviors.
ASD
Negative Association
Lack of evidence for association between the serotonin transporter gene (SLC6A4) polymorphisms and autism in the Chinese trios.
ASD
Negative Association
Linkage and association analysis at the serotonin transporter (SLC6A4) locus in a rigid-compulsive subset of autism.
ASD
Negative Association
Association Between 5-HTTLPR Polymorphism and the Risk of Autism: A Meta-Analysis Based on Case-Control Studies.
ASD
Negative Association
Association of the FGA and SLC6A4 genes with autistic spectrum disorder in a Korean population.
ASD
Negative Association
Lack of evidence for association of the serotonin transporter gene SLC6A4 with autism.
ASD
Support
Performance comparison of bench-top next generation sequencers using microdroplet PCR-based enrichment for targeted sequencing in patients with aut...
ASD
ID, epilepsy
Support
Patterns and rates of exonic de novo mutations in autism spectrum disorders.
ASD
Support
Sex-biased effects on hippocampal circuit development by perinatal SERT expression in CA3 pyramidal neurons
Support
Autism gene variant causes hyperserotonemia, serotonin receptor hypersensitivity, social impairment and repetitive behavior.
Support
The serotonin reuptake transporter modulates mitochondrial copy number and mitochondrial respiratory complex gene expression in the frontal cortex and cerebellum in a sexually dimorphic manner
Support
Autism associated with low 5-hydroxyindolacetic acid in CSF and the heterozygous SLC6A4 gene Gly56Ala plus 5-HTTLPR L/L promoter variants.
ASD
Support
The influence of 5-HTTLPR transporter genotype on amygdala-subgenual anterior cingulate cortex connectivity in autism spectrum disorder.
Support
Maternal serotonin transporter genotype affects risk for ASD with exposure to prenatal stress.
Support
Synaptic, transcriptional and chromatin genes disrupted in autism.
ASD
Highly Cited
Serotonin transporter genetic variation and the response of the human amygdala.
Recent Recommendation
Haploinsufficiency for Pten and Serotonin transporter cooperatively influences brain size and social behavior.
Recent Recommendation
Social approach in genetically engineered mouse lines relevant to autism.
Recent Recommendation
The molecular genetic architecture of human personality: beyond self-report questionnaires.
Recent Recommendation
De Novo Synonymous Mutations in Regulatory Elements Contribute to the Genetic Etiology of Autism and Schizophrenia.
Rare
Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
GEN235R022b
indel, 2KB_upstream_variant
Promoter
Familial
Both parents
Unknown
GEN235R025
missense_variant
c.1273A>G
p.Ile425Val
Familial
Paternal
Multi-generational
GEN235R027
frameshift_variant
c.1745dup
p.Thr583AsnfsTer23
Familial
Maternal
Simplex
Common
Variant ID
Polymorphism
SNP ID
Allele Change
Residue Change
Population Origin
Population Stage
Author, Year
GEN235C002
indel, 2KB_upstream_variant
N/A
N/A
US-Mixed; 81 new ASD trios
Replication
GEN235C003
intron_variant
rs2020934
c.-221+1171T>C;c.-95+1171T>C
US-Mixed; 81 new ASD trios
Discovery
GEN235C004
intron_variant
rs2066713
c.-220-1732C>T;c.-94-1732C>T
US-Mixed; 81 new ASD trios
Discovery
GEN235C005
intron_variant
rs2020936
c.-220-881C>T;c.-94-881C>T
US-Mixed; 81 new ASD trios
Discovery
GEN235C006
intron_variant
rs2020937
c.-220-824T>A;c.-94-824T>A
US-Mixed; 81 new ASD trios
Discovery
GEN235C007
5_prime_UTR_variant
rs6354
c.-185C>A;c.-59C>A
US-Mixed; 81 new ASD trios
Discovery
GEN235C008
microsatellite, intron_variant
rs57098334
c.343+38_343+46GGGTGGGCT[9][10][12][1];c.469+38_469+46GGGTGGGCT[9][10][12][1]
US-Mixed; 81 new ASD trios
Discovery
GEN235C009
intron_variant
rs2020942
c.344-965G>A;c.470-965G>A
US-Mixed; 81 new ASD trios
Discovery
GEN235C010
microsatellite, intron_variant
N/A
Intron 7
US-Mixed; 81 new ASD trios
Discovery
GEN235C011
indel, 2KB_upstream_variant
N/A
N/A
French-Caucasian
Replication
GEN235C013
microsatellite, intron_variant
rs57098334
c.343+38_343+46GGGTGGGCT[9][10][12][1];c.469+38_469+46GGGTGGGCT[9][10][12][1]
Portuguese
Replication
GEN235C014
microsatellite, intron_variant
rs57098334
c.343+38_343+46GGGTGGGCT[9][10][12][1];c.469+38_469+46GGGTGGGCT[9][10][12][1]
Dutch
Replication
GEN235C015
intron_variant
rs140700
c.838-155G>A;c.964-155G>A
US, AGRE
Discovery
GEN235C019
intron_variant
rs140700
c.838-155G>A;c.964-155G>A
US, AGRE
Replication
GEN235C020
intron_variant
rs2020935
c.-221+1176A>T;c.-95+1176A>T
SARC, AGRE
Discovery
GEN235C021
intron_variant
rs140701
c.1205-90G>A;c.1331-90G>A
A/G
195 ASD cases & 305 controls from Korea
Discovery
GEN235C022
indel, 2KB_upstream_variant
N/A
N/A
76 children with high-functioning autism (HFA, IQ>80), 78 siblings, and 99 controls (all of Caucasian descent) collected in Dept. of Child and Adolescent Psychiatry at Univ. of Zurich
Replication
GEN235C023
2KB_upstream_variant
rs25531
c.-1936A>G;c.-1810A>G
151 Tourette probands of European ancestry with DSM-IV-TR diangoses, 858 controls from three independent sources (all controls of European ancestry)
Discovery
