SLC6A4 solute carrier family 6 member 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: SLC6A4provided by HGNC
Official Full Name: solute carrier family 6 member 4provided by HGNC
Primary source: HGNC:HGNC:11050
See related: Ensembl:ENSG00000108576 MIM:182138; AllianceGenome:HGNC:11050
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: HTT; 5HTT; OCD1; SERT; 5-HTT; SERT1; hSERT; 5-HTTLPR
Summary: 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. There have been conflicting results in the literature about the possible effect, if any, that this polymorphism may play in behavior and depression. [provided by RefSeq, May 2019]
Expression: Biased expression in lung (RPKM 18.0), small intestine (RPKM 13.9) and 3 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 17q11.2

Exon count:: 15

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	17	NC_000017.11 (30194319..30235697, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	17	NC_060941.1 (31138872..31180231, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	17	NC_000017.10 (28521337..28562715, complement)

Chromosome 17 - NC_000017.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The Association between Post-Traumatic Stress Disorder, 5HTTLPR, and the Role of Ethnicity: A Meta-Analysis.
Title: The Association between Post-Traumatic Stress Disorder, 5HTTLPR, and the Role of Ethnicity: A Meta-Analysis.
Early-life adversity severity, timing, and context type are associated with SLC6A4 methylation in emerging adults: Results from a prospective cohort study.
Title: Early-life adversity severity, timing, and context type are associated with SLC6A4 methylation in emerging adults: Results from a prospective cohort study.
Connection Failure: Differences in White Matter Microstructure Are Associated with 5-HTTLPR but Not with Risk Seeking for Losses.
Title: Connection Failure: Differences in White Matter Microstructure Are Associated with 5-HTTLPR but Not with Risk Seeking for Losses.
PPARgamma dependent PEX11beta counteracts the suppressive role of SIRT1 on neural differentiation of HESCs.
Title: PPARgamma dependent PEX11beta counteracts the suppressive role of SIRT1 on neural differentiation of HESCs.
[The association of polymorphisms of the serotonin transporter gene SLC6A4 with depression].
Title: [The association of polymorphisms of the serotonin transporter gene SLC6A4 with depression].
Tailoring Type II Diabetes Treatment: Investigating the Effect of 5-HTT Polymorphisms on HbA1c Levels after Metformin Initiation.
Title: Tailoring Type II Diabetes Treatment: Investigating the Effect of 5-HTT Polymorphisms on HbA1c Levels after Metformin Initiation.
SLC6A4 gene variants moderate associations between childhood food insecurity and adolescent mental health.
Title: SLC6A4 gene variants moderate associations between childhood food insecurity and adolescent mental health.
DNA methylation levels of the serotonin transporter gene are not associated with the outcome of highly standardized one-session exposure-based fear treatment.
Title: DNA methylation levels of the serotonin transporter gene are not associated with the outcome of highly standardized one-session exposure-based fear treatment.
Neuropeptide Y gene variants and Agreeableness: interaction effect with the birth cohort and the serotonin transporter promoter polymorphism.
Title: Neuropeptide Y gene variants and Agreeableness: interaction effect with the birth cohort and the serotonin transporter promoter polymorphism.
Molecular Photoswitches Regulating the Activity of the Human Serotonin Transporter.
Title: Molecular Photoswitches Regulating the Activity of the Human Serotonin Transporter.

Submit: New GeneRIF Correction See all GeneRIFs (1847)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Anxiety MedGen: C0003467 OMIM: 607834 GeneReviews: Not available	Compare labs
Obsessive-compulsive disorder MedGen: C0028768 OMIM: 164230 GeneReviews: Not available	Compare labs

Copy number response

Description
Copy number response Haploinsufficency No evidence available (Last evaluated 2012-05-10) ClinGen Genome Curation Page Triplosensitivity No evidence available (Last evaluated 2012-05-10) ClinGen Genome Curation Page

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Tat	tat	HIV-1 clade B Tat up-regulates IDO and down-regulates 5-HTT gene and protein expressions in immature dendritic cells	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH70982 (e-PCR)
- UniSTS:88611

PMC209526P1 (e-PCR)
- UniSTS:271998

PMC24806P1 (e-PCR)
- UniSTS:272274

SHGC-11022 (e-PCR)
- UniSTS:4290

GDB:271277 (e-PCR)
- UniSTS:156355

SLC6A4 (e-PCR)
- UniSTS:480207

RH80031 (e-PCR)
- UniSTS:91103

RH70057 (e-PCR)
- UniSTS:25063

A004R12 (e-PCR)
- UniSTS:61950

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables actin filament binding	ISS Inferred from Sequence or Structural Similarity more info
enables antiporter activity	IDA Inferred from Direct Assay more info	PubMed
enables cocaine binding	IEA Inferred from Electronic Annotation more info
enables identical protein binding	ISS Inferred from Sequence or Structural Similarity more info
enables integrin binding	IDA Inferred from Direct Assay more info	PubMed
enables monoamine transmembrane transporter activity	IDA Inferred from Direct Assay more info	PubMed
enables monoamine transmembrane transporter activity	ISS Inferred from Sequence or Structural Similarity more info
enables monoatomic cation channel activity	ISS Inferred from Sequence or Structural Similarity more info
enables neurotransmitter transmembrane transporter activity	ISS Inferred from Sequence or Structural Similarity more info
enables nitric-oxide synthase binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables serotonin binding	IBA Inferred from Biological aspect of Ancestor more info
enables serotonin binding	IDA Inferred from Direct Assay more info	PubMed
enables serotonin:sodium:chloride symporter activity	IBA Inferred from Biological aspect of Ancestor more info
enables serotonin:sodium:chloride symporter activity	IDA Inferred from Direct Assay more info	PubMed
enables serotonin:sodium:chloride symporter activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables serotonin:sodium:chloride symporter activity	TAS Traceable Author Statement more info
enables sodium ion binding	IDA Inferred from Direct Assay more info	PubMed
enables syntaxin-1 binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in amino acid transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in behavioral response to cocaine	IEA Inferred from Electronic Annotation more info
involved_in brain morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in cellular response to cGMP	IEA Inferred from Electronic Annotation more info
involved_in cellular response to retinoic acid	IEA Inferred from Electronic Annotation more info
involved_in circadian rhythm	IEA Inferred from Electronic Annotation more info
involved_in conditioned place preference	IEA Inferred from Electronic Annotation more info
involved_in enteric nervous system development	IEA Inferred from Electronic Annotation more info
involved_in membrane depolarization	ISS Inferred from Sequence or Structural Similarity more info
involved_in memory	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within monoamine transport	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of cerebellar granule cell precursor proliferation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of neuron differentiation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of organ growth	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of synaptic transmission, dopaminergic	IEA Inferred from Electronic Annotation more info
involved_in neurotransmitter transport	ISS Inferred from Sequence or Structural Similarity more info
involved_in platelet aggregation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of cell cycle	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of gene expression	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of serotonin secretion	IEA Inferred from Electronic Annotation more info
involved_in regulation of thalamus size	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to estradiol	IEA Inferred from Electronic Annotation more info
involved_in response to hypoxia	IEA Inferred from Electronic Annotation more info
involved_in response to nutrient	IEA Inferred from Electronic Annotation more info
involved_in response to toxic substance	IDA Inferred from Direct Assay more info	PubMed
involved_in response to xenobiotic stimulus	IEA Inferred from Electronic Annotation more info
involved_in serotonin uptake	IBA Inferred from Biological aspect of Ancestor more info
involved_in serotonin uptake	IDA Inferred from Direct Assay more info	PubMed
involved_in serotonin uptake	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in serotonin uptake	ISS Inferred from Sequence or Structural Similarity more info
involved_in serotonin uptake	TAS Traceable Author Statement more info
involved_in sodium ion transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in sperm ejaculation	IEA Inferred from Electronic Annotation more info
involved_in vasoconstriction	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in endomembrane system	IDA Inferred from Direct Assay more info	PubMed
located_in endosome membrane	IEA Inferred from Electronic Annotation more info
located_in focal adhesion	ISS Inferred from Sequence or Structural Similarity more info
located_in membrane raft	IDA Inferred from Direct Assay more info	PubMed
is_active_in neuron projection	IBA Inferred from Biological aspect of Ancestor more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
located_in postsynaptic membrane	IEA Inferred from Electronic Annotation more info
located_in presynaptic membrane	IEA Inferred from Electronic Annotation more info
located_in serotonergic synapse	IEA Inferred from Electronic Annotation more info
is_active_in synapse	IBA Inferred from Biological aspect of Ancestor more info
located_in synapse	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: sodium-dependent serotonin transporter

Names: 5-hydroxytryptamine (serotonin) transporter; 5HT transporter; Na+/Cl- dependent serotonin transporter; serotonin transporter 1; solute carrier family 6 (neurotransmitter transporter), member 4; solute carrier family 6 (neurotransmitter transporter, serotonin), member 4

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_011747.2 RefSeqGene

Range

5240..46618

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001045.6 → NP_001036.1 sodium-dependent serotonin transporter

See identical proteins and their annotated locations for NP_001036.1

Status: REVIEWED

Source sequence(s)

AC104984, AK313166, AY902473, BE645279, DC345903

Consensus CDS

CCDS11256.1

UniProtKB/Swiss-Prot

P31645, Q5EE02

UniProtKB/TrEMBL

B2R7Y7

Related

ENSP00000498537.1, ENST00000650711.1

Conserved Domains (2) summary

cd11513
Location:79 → 615

SLC6sbd_SERT; Na(+)- and Cl(-)-dependent serotonin transporter SERT; solute-binding domain

pfam03491
Location:24 → 64

5HT_transport_N; Serotonin (5-HT) neurotransmitter transporter, N-terminus