Slc6A2 — Norepinephrine Transporter is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
SLC6A2
| Symbol | SLC6A2 |
| Full Name | Norepinephrine Transporter (NET) |
| Chromosome | 16q12.2 |
| NCBI Gene ID | 6530 |
| OMIM | 163910 |
| Ensembl ID | ENSG00000170270 |
| UniProt ID | P23975 |
| Encoded Protein | Norepinephrine Transporter |
| Associated Diseases | Parkinson's Disease, Noradrenergic System in Neurodegeneration |
This section provides a summary of the gene/protein's function, expression, and relevance to neurodegenerative diseases.
The norepinephrine transporter (NET), encoded by the SLC6A2 gene, is a member of the Na+/Cl- dependent neurotransmitter transporter family. NET is responsible for the reuptake of norepinephrine (noradrenaline) from the synaptic cleft back into presynaptic neurons, terminating noradrenergic signaling and regulating the availability of norepinephrine for subsequent neurotransmission.
NET functions as a symporter that couples the uptake of norepinephrine to the inward flow of Na+ and Cl- ions down their electrochemical gradients. The transporter has high affinity for norepinephrine (Km ~ 0.1-0.5 μM) and is also capable of transporting dopamine, albeit with lower affinity. This broad substrate specificity has implications for neuropsychiatric disorders and drug responses.
NET is a target for various pharmacological agents including:
| Disease | Inheritance | Key Mutations |
|---|---|---|
| Parkinson's Disease | Complex | Reduced NET expression in locus coeruleus |
| Orthostatic Intolerance | Autosomal Dominant | Val316Ile, Ala457Pro |
| ADHD | Complex | Promoter variants affecting expression |
| Major Depression | Complex | Altered NET binding and function |
NET is expressed primarily in noradrenergic neurons of the:
High expression regions include:
NET expression is a key marker for identifying noradrenergic neurons in the brain and is used in neuroimaging as a target for PET ligands (e.g., [11C]MRB) to assess noradrenergic integrity in neurodegenerative diseases.
The study of Slc6A2 — Norepinephrine Transporter has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.