Human Gene SLC6A2 (ENST00000568943.6) from GENCODE V44
  Description: Homo sapiens solute carrier family 6 member 2 (SLC6A2), transcript variant 2, mRNA. (from RefSeq NM_001172501)
RefSeq Summary (NM_001172501): 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].
Gencode Transcript: ENST00000568943.6
Gencode Gene: ENSG00000103546.19
Transcript (Including UTRs)
   Position: hg38 chr16:55,655,988-55,706,192 Size: 50,205 Total Exon Count: 15 Strand: +
Coding Region
   Position: hg38 chr16:55,656,695-55,702,346 Size: 45,652 Coding Exon Count: 14 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr16:55,655,988-55,706,192)mRNA (may differ from genome)Protein (617 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
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HGNCHPRDMalacardsMGIneXtProtOMIM
PubMedReactomeUniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: SC6A2_HUMAN
DESCRIPTION: RecName: Full=Sodium-dependent noradrenaline transporter; AltName: Full=Norepinephrine transporter; Short=NET; AltName: Full=Solute carrier family 6 member 2;
FUNCTION: Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals.
SUBUNIT: Interacts with PRKCABP.
SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
DISEASE: Defects in SLC6A2 are a cause of orthostatic intolerance (OI) [MIM:604715]. OI is a syndrome characterized by lightheadedness, fatigue, altered mentation and syncope. It is associated with postural tachycardia. Plasma norepinephrine concentration is abnormally high.
MISCELLANEOUS: This protein is the target of psychomotor stimulants such as amphetamines or cocaine.
SIMILARITY: Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A2 subfamily.
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/SLC6A5";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: SLC6A2
Diseases sorted by gene-association score: orthostatic intolerance* (1711), syncope (37), oppositional defiant disorder (16), ocular hyperemia (15), generalized anxiety disorder (12), cocaine abuse (9), attention deficit-hyperactivity disorder (9), panic disorder (9), amphetamine abuse (9), anxiety disorder (8), corneal endothelial dystrophy, autosomal recessive (7), agoraphobia (6), hyperekplexia (5), mental depression (5), specific developmental disorder (4), pheochromocytoma (3), mood disorder (2), narcolepsy (2), central nervous system disease (1), schizophrenia (1), disease of mental health (1), hypertension, essential (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 3.07 RPKM in Testis
Total median expression: 6.94 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -104.00233-0.446 Picture PostScript Text
3' UTR -1267.803846-0.330 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR000175 - Na/ntran_symport
IPR002435 - Na/ntran_symport_noradrenaline

Pfam Domains:
PF00209 - Sodium:neurotransmitter symporter family

ModBase Predicted Comparative 3D Structure on P23975
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005328 neurotransmitter:sodium symporter activity
GO:0005333 norepinephrine transmembrane transporter activity
GO:0005334 norepinephrine:sodium symporter activity
GO:0005515 protein binding
GO:0008504 monoamine transmembrane transporter activity
GO:0015293 symporter activity
GO:0043014 alpha-tubulin binding
GO:0046872 metal ion binding
GO:0048487 beta-tubulin binding
GO:0005330 dopamine:sodium symporter activity

Biological Process:
GO:0006836 neurotransmitter transport
GO:0007268 chemical synaptic transmission
GO:0015844 monoamine transport
GO:0015874 norepinephrine transport
GO:0035725 sodium ion transmembrane transport
GO:0042493 response to drug
GO:0048265 response to pain
GO:0055085 transmembrane transport
GO:0051583 dopamine uptake involved in synaptic transmission

Cellular Component:
GO:0005886 plasma membrane
GO:0005887 integral component of plasma membrane
GO:0009986 cell surface
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0043005 neuron projection
GO:0045121 membrane raft


-  Descriptions from all associated GenBank mRNAs
  AB022847 - Homo sapiens mRNA for norepinephrine transporter isoform 2, partial cds.
AK312793 - Homo sapiens cDNA, FLJ93211, Homo sapiens solute carrier family 6 (neurotransmitter transporter,noradrenalin), member 2 (SLC6A2), mRNA.
M65105 - Human noradrenaline transporter mRNA, complete cds.
BC060831 - Homo sapiens solute carrier family 6 (neurotransmitter transporter, noradrenalin), member 2, mRNA (cDNA clone IMAGE:30338878).
JD348253 - Sequence 329277 from Patent EP1572962.
JD522923 - Sequence 503947 from Patent EP1572962.
BC156903 - Synthetic construct Homo sapiens clone IMAGE:100062757, MGC:190603 solute carrier family 6 (neurotransmitter transporter, noradrenalin), member 2 (SLC6A2) mRNA, encodes complete protein.
BC039309 - Homo sapiens solute carrier family 6 (neurotransmitter transporter, noradrenalin), member 2, mRNA (cDNA clone IMAGE:5270717), with apparent retained intron.
AK301811 - Homo sapiens cDNA FLJ58297 complete cds, highly similar to Sodium-dependent noradrenaline transporter.
BC000563 - Homo sapiens solute carrier family 6 (neurotransmitter transporter, noradrenalin), member 2, mRNA (cDNA clone IMAGE:3162672), partial cds.
AK310410 - Homo sapiens cDNA, FLJ17452.
AB022846 - Homo sapiens mRNA for norepinephrine transporter isoform 1, partial cds.
JD292258 - Sequence 273282 from Patent EP1572962.
JD060585 - Sequence 41609 from Patent EP1572962.
JD124190 - Sequence 105214 from Patent EP1572962.
JD386332 - Sequence 367356 from Patent EP1572962.
JD290650 - Sequence 271674 from Patent EP1572962.
JD551958 - Sequence 532982 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein P23975 (Reactome details) participates in the following event(s):

R-HSA-443997 SLC6A2 cotransports NAd, Na+ from extracellular region to cytosol
R-HSA-442660 Na+/Cl- dependent neurotransmitter transporters
R-HSA-425366 Transport of bile salts and organic acids, metal ions and amine compounds
R-HSA-425428 Amine compound SLC transporters
R-HSA-425407 SLC-mediated transmembrane transport
R-HSA-382551 Transport of small molecules

-  Other Names for This Gene
  Alternate Gene Symbols: B2R707, ENST00000568943.1, ENST00000568943.2, ENST00000568943.3, ENST00000568943.4, ENST00000568943.5, NAT1, NET1, NM_001172501, P23975, Q96KH8, SC6A2_HUMAN, SLC6A5, uc002eif.1, uc002eif.2, uc002eif.3, uc002eif.4, uc002eif.5
UCSC ID: ENST00000568943.6
RefSeq Accession: NM_001172501
Protein: P23975 (aka SC6A2_HUMAN or S6A2_HUMAN)

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.