LGI2: Leucine-Rich Repeat LGI Family Member 2
A gene encoding a secreted protein involved in neuronal development and epilepsy susceptibility
Gene Information Card
| Symbol | LGI2 |
|---|---|
| Full Name | Leucine-rich repeat LGI family member 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 4p15.2 |
| NCBI Gene ID | 55203 ncbi.nlm.nih.gov/gene/55203 |
| Ensembl ID | ENSG00000138684 |
| UniProt ID | Q8N0U8 |
| OMIM ID | 608301 |
| HGNC ID | 18712 |
| Aliases | KIAA1916, LGI2a, LGI2b |
Description
LGI2 (Leucine-rich repeat LGI family member 2) is a protein-coding gene located on chromosome 4p15.2. It encodes a secreted protein containing leucine-rich repeats (LRRs) and an EPTP (epitempin) domain, which is involved in neuronal development and synaptic function. Mutations in LGI2 have been associated with autosomal dominant lateral temporal epilepsy (ADLTE) and other seizure disorders. The protein is thought to modulate voltage-gated potassium channels and AMPA receptor trafficking.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Autosomal dominant lateral temporal epilepsy (ADLTE) | Loss-of-function mutations in LGI2 disrupt protein secretion and interaction with ADAM22/ADAM23, impairing synaptic transmission and leading to seizure susceptibility. | ClinVar, OMIM |
| Epilepsy, familial temporal lobe, 7 (ETL7) | Missense and nonsense variants in LGI2 cause reduced protein stability or secretion, resulting in neuronal hyperexcitability. | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 4.2 | Low |
| Testis | 1.8 | Not detected |
| Lung | 0.5 | Not detected |
| Liver | 0.3 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 3.1 | Neuronal lineage |
| HEK293 (embryonic kidney) | 0.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.232C>T (p.Arg78*) | Nonsense | Rare | Loss of function; premature truncation |
| c.1019G>A (p.Cys340Tyr) | Missense | Rare | Impaired secretion and protein stability |
| c.1360C>T (p.Arg454Trp) | Missense | Rare | Reduced binding to ADAM22 |
Mutation functional classification
Loss of Function (LOF)
Nonsense and missense mutations that impair protein secretion, stability, or interaction with ADAM22/ADAM23 lead to loss of function, contributing to epilepsy.
Gain of Function (GOF)
No gain-of-function mutations reported for LGI2.
Dominant Negative (DN)
Some missense variants may exert dominant-negative effects by interfering with wild-type LGI2 secretion or complex formation.
View complete mutation data：
Gene Ontology (GO)
| • extracellular region (GO:0005576) | • protein binding (GO:0005515) |
| • chemical synaptic transmission (GO:0007268) | • synapse (GO:0045202) |
| • cell differentiation (GO:0030154) |
Pathways
• ADAM22/ADAM23 signaling pathway
• Voltage-gated potassium channel complex assembly
Protein Summary
The LGI2 protein is a secreted member of the leucine-rich repeat LGI family. It contains an N-terminal signal peptide, four leucine-rich repeats, and a C-terminal EPTP domain. LGI2 is predominantly expressed in the brain, where it modulates synaptic function by binding to ADAM22 and ADAM23 receptors, influencing potassium channel clustering and AMPA receptor trafficking. Mutations in LGI2 disrupt these interactions, leading to neuronal hyperexcitability and epilepsy.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| LGI2 Knockout HEK293 Cell Line | EDJ-KQ14061 | Human | 55203 | Details Get a Quote |
| LGI2 Knockout HeLa Cell Line | EDJ-KQ56555 | Human | 55203 | Details Get a Quote |
| LGI2 Knockout A-549 Cell Line | EDJ-KQ65050 | Human | 55203 | Details Get a Quote |
| LGI2 Knockout HCT 116 Cell Line | EDJ-KQ73495 | Human | 55203 | Details Get a Quote |
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