LGI3 (Leucine Rich Repeat LGI Family Member 3)
A secreted protein involved in neuronal development and synaptic function, linked to epilepsy and cancer.
Gene Information Card
| Symbol | LGI3 |
|---|---|
| Full Name | Leucine Rich Repeat LGI Family Member 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 8p21.3 |
| NCBI Gene ID | 203190 ncbi.nlm.nih.gov/gene/203190 |
| Ensembl ID | ENSG00000168484 |
| UniProt ID | Q8N9I0 |
| OMIM ID | 609562 |
| HGNC ID | 18712 |
| Aliases | LGIL3, LGI3a, LGI3b |
Description
LGI3 (Leucine Rich Repeat LGI Family Member 3) encodes a secreted protein belonging to the leucine-rich repeat (LRR) superfamily. The protein is predominantly expressed in the brain and plays a role in neuronal development, synaptic transmission, and myelination. LGI3 interacts with ADAM22 and ADAM23 to regulate voltage-gated potassium channels. Mutations and altered expression of LGI3 have been implicated in epilepsy, glioma, and other cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Epilepsy (familial temporal lobe epilepsy) | LGI3 mutations may disrupt synaptic protein complexes, impairing potassium channel function and increasing neuronal excitability. | ClinVar, OMIM |
| Glioma | LGI3 expression is downregulated in gliomas; loss of LGI3 promotes tumor cell migration and invasion via altered ADAM22/23 signaling. | COSMIC, NCBI PubMed |
| Lung cancer | LGI3 hypermethylation and reduced expression correlate with poor prognosis; LGI3 may act as a tumor suppressor. | COSMIC, NCBI PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 12.5 | High |
| Brain (cerebellum) | 10.8 | High |
| Testis | 3.2 | Medium |
| Lung | 1.5 | Low |
| Liver | 0.3 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 8.7 | Neuronal model |
| U87MG (glioma) | 2.1 | Reduced expression |
| A549 (lung carcinoma) | 1.0 | Low expression |
| HEK293 (embryonic kidney) | 0.5 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.101C>T (p.Thr34Met) | Missense | <0.01% | Potential loss of function; reported in epilepsy |
| c.457G>A (p.Gly153Arg) | Missense | <0.01% | Unknown significance; observed in glioma |
| c.1234delC (p.Leu412Trpfs*5) | Frameshift | <0.01% | Loss of function; truncation |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations (e.g., c.1234delC) lead to truncated protein, impairing secretion and ADAM22 binding.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in LGI3.
Dominant Negative (DN)
Missense mutations (e.g., p.Thr34Met) may interfere with wild-type LGI3 function in heterozygous state, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
Pathways
• ADAM22/23 signaling pathway
• Voltage-gated potassium channel complex assembly
• Synaptic adhesion and transmission
Protein Summary
LGI3 is a 557-amino acid secreted protein containing an N-terminal signal peptide, four leucine-rich repeats (LRRs), and a C-terminal EPTP (epilepsy-associated repeat) domain. It is synthesized as a preproprotein and cleaved to release the mature protein. LGI3 binds to ADAM22 and ADAM23 on the cell surface, facilitating the clustering of voltage-gated potassium channels (Kv1.1) at synapses. The protein is critical for neuronal excitability regulation, myelination, and tumor suppression. In cancer, LGI3 loss promotes epithelial-mesenchymal transition and metastasis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| LGI3 Knockout HEK293 Cell Line | EDJ-KQ5453 | Human | 203190 | Details Get a Quote |
| LGI3 Knockout A-549 Cell Line | EDJ-KQ28642 | Human | 203190 | Details Get a Quote |
| LGI3 Knockout HCT 116 Cell Line | EDJ-KQ28643 | Human | 203190 | Details Get a Quote |
| LGI3 Knockout HeLa Cell Line | EDJ-KQ59042 | Human | 203190 | Details Get a Quote |
