SLC6A2 solute carrier family 6 member 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: SLC6A2provided by HGNC
Official Full Name: solute carrier family 6 member 2provided by HGNC
Primary source: HGNC:HGNC:11048
See related: Ensembl:ENSG00000103546 MIM:163970; AllianceGenome:HGNC:11048
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: NET; NAT1; NET1; SLC6A5
Summary: This gene encodes a member of the sodium:neurotransmitter symporter family. This member is a multi-pass membrane protein, which is responsible for reuptake of norepinephrine into presynaptic nerve terminals and is a regulator of norepinephrine homeostasis. Mutations in this gene cause orthostatic intolerance, a syndrome characterized by lightheadedness, fatigue, altered mentation and syncope. Alternatively spliced transcript variants encoding different isoforms have been identified in this gene.[provided by RefSeq, Feb 2010]
Annotation information: Note: NET is an alias on both SLC6A2 (Gene ID: 6530, "norepinephrine transporter") and ELK3 (Gene ID: 2004). [01 Jun 2018]
Expression: Biased expression in adrenal (RPKM 4.7), placenta (RPKM 2.3) and 3 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 16q12.2

Exon count:: 18

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	16	NC_000016.10 (55655988..55706192)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	16	NC_060940.1 (61454123..61504416)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	16	NC_000016.9 (55689900..55740104)

Chromosome 16 - NC_000016.10 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
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?

Relationship between SLC6A2 gene polymorphisms and brain volume in Han Chinese adults who lost their sole child.
Title: Relationship between SLC6A2 gene polymorphisms and brain volume in Han Chinese adults who lost their sole child.
Genotype-by-diagnosis interaction influences self-control in human cocaine addiction.
Title: Genotype-by-diagnosis interaction influences self-control in human cocaine addiction.
The norepinephrine transporter gene modulates intrinsic brain activity, visual memory, and visual attention in children with attention-deficit/hyperactivity disorder.
Title: The norepinephrine transporter gene modulates intrinsic brain activity, visual memory, and visual attention in children with attention-deficit/hyperactivity disorder.
Association between genetic variants of the norepinephrine transporter gene (SLC6A2) and bipolar I disorder.
Title: Association between genetic variants of the norepinephrine transporter gene (SLC6A2) and bipolar I disorder.
Delayed retinal vein recovery responses indicate both non-adaptation to stress as well as increased risk for stroke: the SABPA study.
Title: Delayed retinal vein recovery responses indicate both non-adaptation to stress as well as increased risk for stroke: the SABPA study.
Label-free high-throughput screening assay for the identification of norepinephrine transporter (NET/SLC6A2) inhibitors.
Title: Label-free high-throughput screening assay for the identification of norepinephrine transporter (NET/SLC6A2) inhibitors.
Rare Variant in the SLC6A2 Encoding a Norepinephrine Transporter Is Associated with Elite Athletic Performance in the Polish Population.
Title: Rare Variant in the SLC6A2 Encoding a Norepinephrine Transporter Is Associated with Elite Athletic Performance in the Polish Population.
The Role of the Second Extracellular Loop of Norepinephrine Transporter, Neurotrophin-3 and Tropomyosin Receptor Kinase C in T Cells: A Peripheral Biomarker in the Etiology of Schizophrenia.
Title: The Role of the Second Extracellular Loop of Norepinephrine Transporter, Neurotrophin-3 and Tropomyosin Receptor Kinase C in T Cells: A Peripheral Biomarker in the Etiology of Schizophrenia.
The T-182C Polymorphism Enhances Promoter Activity of the Norepinephrine Transporter Gene, but may not be Associated with Antidepressant Response.
Title: The T-182C Polymorphism Enhances Promoter Activity of the Norepinephrine Transporter Gene, but may not be Associated with Antidepressant Response.
Association of norepinephrine transporter methylation with in vivo NET expression and hyperactivity-impulsivity symptoms in ADHD measured with PET.
Title: Association of norepinephrine transporter methylation with in vivo NET expression and hyperactivity-impulsivity symptoms in ADHD measured with PET.

Submit: New GeneRIF Correction See all GeneRIFs (157)

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
Neurocirculatory asthenia MedGen: C1535893 OMIM: 604715 GeneReviews: Not available	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-61051 (e-PCR)
- UniSTS:31090

SHGC-155920 (e-PCR)
- UniSTS:185238

SHGC-149089 (e-PCR)
- UniSTS:176793

D16S3351 (e-PCR)
- UniSTS:6392

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables actin binding	IPI Inferred from Physical Interaction more info	PubMed
enables alpha-tubulin binding	IEA Inferred from Electronic Annotation more info
enables beta-tubulin binding	IEA Inferred from Electronic Annotation more info
enables dopamine:sodium symporter activity	IBA Inferred from Biological aspect of Ancestor more info
enables dopamine:sodium symporter activity	IDA Inferred from Direct Assay more info	PubMed
enables metal ion binding	IEA Inferred from Electronic Annotation more info
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 neurotransmitter transmembrane transporter activity	ISS Inferred from Sequence or Structural Similarity more info
enables neurotransmitter:sodium symporter activity	IEA Inferred from Electronic Annotation more info
enables norepinephrine:sodium symporter activity	IBA Inferred from Biological aspect of Ancestor more info
enables norepinephrine:sodium symporter activity	IDA Inferred from Direct Assay more info	PubMed
enables norepinephrine:sodium symporter activity	TAS Traceable Author Statement more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in amino acid transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in chemical synaptic transmission	TAS Traceable Author Statement more info	PubMed
involved_in dopamine uptake involved in synaptic transmission	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within monoamine transport	IDA Inferred from Direct Assay more info	PubMed
involved_in neuron cellular homeostasis	TAS Traceable Author Statement more info	PubMed
involved_in neurotransmitter transport	ISS Inferred from Sequence or Structural Similarity more info
involved_in norepinephrine transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in norepinephrine uptake	ISS Inferred from Sequence or Structural Similarity more info
involved_in response to pain	IEA Inferred from Electronic Annotation more info
involved_in response to xenobiotic stimulus	IEA Inferred from Electronic Annotation more info
involved_in sodium ion transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
is_active_in axon	IBA Inferred from Biological aspect of Ancestor more info
located_in cell surface	IEA Inferred from Electronic Annotation more info
located_in membrane	TAS Traceable Author Statement more info	PubMed
is_active_in neuronal cell body membrane	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
is_active_in presynaptic membrane	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: sodium-dependent noradrenaline transporter

Names: neurotransmitter transporter; norepinephrine transporter; solute carrier family 6 (neurotransmitter transporter), member 2; solute carrier family 6 (neurotransmitter transporter, noradrenalin), member 2; solute carrier family 6 member 5

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_016969.1 RefSeqGene

Range

5359..55563

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001043.3 → NP_001034.1 sodium-dependent noradrenaline transporter isoform 2

See identical proteins and their annotated locations for NP_001034.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) has an alternate 3' exon including the coding region, as compared to variant 1. The resulting isoform (2) is shorter and has a different C-terminus, as compared to isoform 1.

Source sequence(s)

AC136621, AK301811, AU132072, BC060831

Consensus CDS

CCDS10754.1

UniProtKB/Swiss-Prot

B2R707, B4DX48, P23975, Q96KH8

UniProtKB/TrEMBL

H3BML6

Related

ENSP00000369237.2, ENST00000379906.6

Conserved Domains (1) summary

cd11512
Location:56 → 615

SLC6sbd_NET; Na(+)- and Cl(-)-dependent norepinephrine transporter NET; solute-binding domain
NM_001172501.3 → NP_001165972.1 sodium-dependent noradrenaline transporter isoform 2

See identical proteins and their annotated locations for NP_001165972.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) has an alternate 3' exon including the coding region, as compared to variant 1. The resulting isoform (2) is shorter and has a different C-terminus, as compared to isoform 1.

Source sequence(s)

AC136621, AK312793, DA853047

Consensus CDS

CCDS10754.1

UniProtKB/Swiss-Prot

B2R707, B4DX48, P23975, Q96KH8

UniProtKB/TrEMBL

H3BML6

Related

ENSP00000457473.1, ENST00000568943.6

Conserved Domains (1) summary

cd11512
Location:56 → 615

SLC6sbd_NET; Na(+)- and Cl(-)-dependent norepinephrine transporter NET; solute-binding domain
NM_001172502.1 → NP_001165973.1 sodium-dependent noradrenaline transporter isoform 3

See identical proteins and their annotated locations for NP_001165973.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) has alternate 5' and 3' sequences including the 5' and 3' coding regions, as compared to variant 1. The resulting isoform (3) is shorter and has different N- and C-termini, as compared to isoform 1.

Source sequence(s)

AC136621, AK301811, BC039309

Consensus CDS

CCDS58463.1

UniProtKB/Swiss-Prot

P23975

Related

ENSP00000457375.1, ENST00000567238.1

Conserved Domains (1) summary

cl00456
Location:27 → 510

SLC5-6-like_sbd; Solute carrier families 5 and 6-like; solute binding domain
NM_001172504.1 → NP_001165975.1 sodium-dependent noradrenaline transporter isoform 1

See identical proteins and their annotated locations for NP_001165975.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform (1).

Source sequence(s)

AC136621

Consensus CDS

CCDS54011.1

UniProtKB/TrEMBL

H3BML6

Related

ENSP00000219833.8, ENST00000219833.13

Conserved Domains (1) summary

cd11512
Location:56 → 612

SLC6sbd_NET; Na(+)- and Cl(-)-dependent norepinephrine transporter NET; solute-binding domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000016.10 Reference GRCh38.p14 Primary Assembly

Range

55655988..55706192

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011523295.3 → XP_011521597.1 sodium-dependent noradrenaline transporter isoform X1

See identical proteins and their annotated locations for XP_011521597.1

UniProtKB/TrEMBL

H3BML6

Conserved Domains (1) summary

cd11512
Location:56 → 612

SLC6sbd_NET; Na(+)- and Cl(-)-dependent norepinephrine transporter NET; solute-binding domain
XM_006721263.2 → XP_006721326.1 sodium-dependent noradrenaline transporter isoform X1

See identical proteins and their annotated locations for XP_006721326.1

UniProtKB/TrEMBL

H3BML6

Conserved Domains (1) summary

cd11512
Location:56 → 612

SLC6sbd_NET; Na(+)- and Cl(-)-dependent norepinephrine transporter NET; solute-binding domain
XM_047434511.1 → XP_047290467.1 sodium-dependent noradrenaline transporter isoform X3

UniProtKB/TrEMBL

H3BRE9, I3L368

Related

ENSP00000460214.2, ENST00000574918.2
XM_047434510.1 → XP_047290466.1 sodium-dependent noradrenaline transporter isoform X2
XM_047434512.1 → XP_047290468.1 sodium-dependent noradrenaline transporter isoform X4
XM_047434513.1 → XP_047290469.1 sodium-dependent noradrenaline transporter isoform X5

Related

ENSP00000508367.1, ENST00000682050.1
XM_011523300.3 → XP_011521602.1 sodium-dependent noradrenaline transporter isoform X6

See identical proteins and their annotated locations for XP_011521602.1

UniProtKB/TrEMBL

Q9BW84

Conserved Domains (1) summary

cl00456
Location:1 → 374

SLC5-6-like_sbd; Solute carrier families 5 and 6-like; solute binding domain
XM_011523299.3 → XP_011521601.1 sodium-dependent noradrenaline transporter isoform X6

See identical proteins and their annotated locations for XP_011521601.1

UniProtKB/TrEMBL

Q9BW84

Conserved Domains (1) summary

cl00456
Location:1 → 374

SLC5-6-like_sbd; Solute carrier families 5 and 6-like; solute binding domain

Alternate T2T-CHM13v2.0

Genomic

NC_060940.1 Alternate T2T-CHM13v2.0

Range

61454123..61504416

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054313748.1 → XP_054169723.1 sodium-dependent noradrenaline transporter isoform X1
XM_054313752.1 → XP_054169727.1 sodium-dependent noradrenaline transporter isoform X5
XM_054313751.1 → XP_054169726.1 sodium-dependent noradrenaline transporter isoform X4
XM_054313747.1 → XP_054169722.1 sodium-dependent noradrenaline transporter isoform X1
XM_054313749.1 → XP_054169724.1 sodium-dependent noradrenaline transporter isoform X2
XM_054313750.1 → XP_054169725.1 sodium-dependent noradrenaline transporter isoform X3

UniProtKB/TrEMBL

H3BRE9, I3L368
XM_054313754.1 → XP_054169729.1 sodium-dependent noradrenaline transporter isoform X6
XM_054313753.1 → XP_054169728.1 sodium-dependent noradrenaline transporter isoform X6