Seroatlas · Human Serome Atlas

SLC6A2

Sodium-dependent noradrenaline transporter

Also known as: NAT1, NET, NET1, SC6A2_HUMAN, SLC6A5

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession
P23975
Gene
SLC6A2
Ensembl
ENSG00000103546
Chromosome
16
Canonical length
617 aa
Protein class
Disease related genes, FDA approved drug targets, Human disease related genes, Metabolic proteins, Plasma proteins, Predicted membrane proteins, Transporters
Subcellular location
Mitochondria,Cytosol
Quaternary structure
Homodimer

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

617 residues, UniProt reviewed canonical sequence.

>P23975|SLC6A2
     1  MLLARMNPQV QPENNGADTG PEQPLRARKT AELLVVKERN GVQCLLAPRD GDAQPRETWG
    61  KKIDFLLSVV GFAVDLANVW RFPYLCYKNG GGAFLIPYTL FLIIAGMPLF YMELALGQYN
   121  REGAATVWKI CPFFKGVGYA VILIALYVGF YYNVIIAWSL YYLFSSFTLN LPWTDCGHTW
   181  NSPNCTDPKL LNGSVLGNHT KYSKYKFTPA AEFYERGVLH LHESSGIHDI GLPQWQLLLC
   241  LMVVVIVLYF SLWKGVKTSG KVVWITATLP YFVLFVLLVH GVTLPGASNG INAYLHIDFY
   301  RLKEATVWID AATQIFFSLG AGFGVLIAFA SYNKFDNNCY RDALLTSSIN CITSFVSGFA
   361  IFSILGYMAH EHKVNIEDVA TEGAGLVFIL YPEAISTLSG STFWAVVFFV MLLALGLDSS
   421  MGGMEAVITG LADDFQVLKR HRKLFTFGVT FSTFLLALFC ITKGGIYVLT LLDTFAAGTS
   481  ILFAVLMEAI GVSWFYGVDR FSNDIQQMMG FRPGLYWRLC WKFVSPAFLL FVVVVSIINF
   541  KPLTYDDYIF PPWANWVGWG IALSSMVLVP IYVIYKFLST QGSLWERLAY GITPENEHHL
   601  VAQRDIRQFQ LQHWLAI

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SLC6A2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability
Cell surface
Secreted
No
Transmembrane segments
12
Mean surface accessibility (rSASA)
0.24
Highest tissue expression
9.9 nTPM

Expression across tissuesHPA

Tissue

  • adrenal gland: 9.9 nTPM
  • placenta: 6.4 nTPM
  • skin: 4.4 nTPM
  • testis: 4.2 nTPM
  • endometrium: 2.2 nTPM
  • cervix: 1.1 nTPM

Single-cell type

  • epididymal efferent duct absorptive cells: 51 nCPM
  • adrenal medulla cells: 32 nCPM
  • extravillous trophoblasts: 20 nCPM
  • late primary spermatocytes: 16 nCPM
  • syncytiotrophoblasts: 9.8 nCPM
  • late spermatids: 9 nCPM

Immune cell

  • basophil: 0 nTPM
  • classical monocyte: 0 nTPM
  • eosinophil: 0 nTPM
  • gdT-cell: 0 nTPM
  • intermediate monocyte: 0 nTPM
  • MAIT T-cell: 0 nTPM

Brain region

  • pons: 193 nTPM
  • medulla oblongata: 5.5 nTPM
  • white matter: 0.6 nTPM
  • midbrain: 0.3 nTPM
  • amygdala: 0.2 nTPM
  • cerebral cortex: 0.2 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about SLC6A2.

Disease | AllUniProt

Conditions SLC6A2 is implicated in, by any mechanism.

Disease | GeneticClinVar

1 pathogenic / likely-pathogenic of 105 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

  • Neurocirculatory asthenia

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)
0.48
gnomAD pLI
0.08
gnomAD missense Z
2.02
DepMap mean gene effect
-0.05
DepMap dependency class
selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of SLC6A2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

  • PRKCABP

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads SLC6A2 as an antibody target. Whether an autoantibody or antibody against SLC6A2 could matter depends on whether native SLC6A2 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

SLC6A2 is annotated at the cell surface, where native SLC6A2 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.

Annotation status

The present source text does not explicitly label SLC6A2 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/SLC6A2. Study-independent annotations aggregated from UniProt, Human Protein Atlas, PubMed, IEDB, Pfam, InterPro, Gene Ontology, AlphaFold, gnomAD, DepMap, ClinVar, TCGA. Catalog release seroatlas-reviewed-human-uniprot-20260313.

Seroatlas is the reference for exploring autoantibody and antibody serology at the human-protein level: the autoreactome and human serome, multiplex serology (HuProt, HuScan, VirScan, PhIP-Seq).

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