SLC6A5 Gene – Glycine Transporter 2 (GlyT2) | Function, Mutations & Related Diseases

SLC6A5 encodes the glycine transporter 2 (GlyT2), a sodium- and chloride-dependent transmembrane protein responsible for the reuptake of glycine from the synaptic cleft into presynaptic neurons. This transporter is essential for terminating glycinergic neurotransmission and maintaining low extracellular glycine concentrations. Mutations in SLC6A5 cause hyperekplexia (startle disease), a neurological disorder characterized by exaggerated startle responses and neonatal hypertonia. The gene is predominantly expressed in the brainstem and spinal cord.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• REACT:13685 – Neurotransmitter release cycle

• REACT:13686 – Glycine degradation

• REACT:13687 – Transport of inorganic cations/anions and amino acids/oligopeptides

The SLC6A5 protein (GlyT2) is a 799-amino acid transmembrane transporter with 12 putative transmembrane domains. It belongs to the SLC6 family of sodium- and chloride-dependent neurotransmitter transporters. GlyT2 is primarily localized to presynaptic terminals of glycinergic neurons in the spinal cord and brainstem, where it clears glycine from the synapse. The protein requires Na+ and Cl- for substrate binding and transport. Mutations that disrupt its trafficking, expression, or transport activity lead to hyperekplexia.