SLC1A1 Gene - EAAT3 Glutamate Transporter | Function, Mutations & Disease

SLC1A1 (Solute Carrier Family 1 Member 1) encodes the excitatory amino acid transporter 3 (EAAT3), a sodium- and potassium-coupled high-affinity glutamate transporter. EAAT3 is primarily expressed in neurons, kidney, and intestine, where it mediates the uptake of L-glutamate and L-aspartate. It plays a critical role in terminating glutamatergic neurotransmission, maintaining glutamate homeostasis, and providing glutamate for glutathione synthesis. Mutations in SLC1A1 cause dicarboxylic aminoaciduria (OMIM 222730) and have been implicated in obsessive-compulsive disorder, schizophrenia, and epilepsy.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Glutamatergic synapse (KEGG hsa04724)

• Neuroactive ligand-receptor interaction (KEGG hsa04080)

• Transport of glucose and other sugars

• bile salts and organic acids

• metal ions and amine compounds (Reactome R-HSA-425366)

EAAT3 (Excitatory Amino Acid Transporter 3) is a 523-amino acid membrane protein with 8-10 transmembrane domains. It couples the transport of one glutamate molecule with the co-transport of three Na+ and one H+ and the counter-transport of one K+. EAAT3 is the major neuronal glutamate transporter in the brain and also mediates the uptake of cysteine for glutathione synthesis, linking it to antioxidant defense. The protein is localized to the plasma membrane and intracellular vesicles, with regulated trafficking in response to neuronal activity.