LGI1 Gene: Function, Mutations, and Role in Epilepsy | NCBI, UniProt, ClinVar

The LGI1 gene encodes a protein that belongs to the leucine-rich repeat (LRR) superfamily. It is predominantly expressed in the brain, particularly in neurons, and plays a critical role in synaptic transmission by interacting with ADAM22 and ADAM23 receptors. LGI1 regulates AMPA receptor-mediated synaptic currents and is essential for normal neuronal excitability. Mutations in LGI1 are a major cause of autosomal dominant lateral temporal epilepsy (ADLTE), also known as autosomal dominant partial epilepsy with auditory features (ADPEAF). The protein is secreted and functions as a ligand that bridges presynaptic and postsynaptic compartments.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• LGI1-ADAM22 interaction in synaptic transmission (Reactome: R-HSA-8849932)

• AMPA receptor trafficking (Reactome: R-HSA-399719)

The LGI1 protein (UniProt O95970) is a 557-amino acid secreted protein containing an N-terminal signal peptide, four leucine-rich repeats (LRRs), and a C-terminal epitempin domain. It is synthesized in neurons and released into the synaptic cleft, where it binds to ADAM22 and ADAM23 receptors on the postsynaptic membrane. This interaction stabilizes AMPA receptors at the synapse, facilitating glutamatergic transmission. LGI1 is critical for preventing neuronal hyperexcitability; loss of function leads to temporal lobe epilepsy. The protein is also implicated in glioma suppression, though its role in cancer is less defined.