LGI1
Chr 10ARADleucine rich glioma inactivated 1
Also known as: ADLTE, ADPAEF, ADPEAF, DEE121, EPITEMPIN, EPT, ETL1, IB1099
The protein regulates voltage-gated potassium channels and serves as a ligand for ADAM22 to modulate synaptic transmission mediated by AMPA-type glutamate receptors. Mutations cause autosomal dominant familial temporal lobe epilepsy and autosomal recessive developmental and epileptic encephalopathy. This gene is highly constrained against loss-of-function variants, reflecting its critical role in neuronal function.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Moderately missense-constrained (top ~2.5%)
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
197 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 9 | 6 | 13 | 0 | 28 |
Likely Pathogenic | 10 | 3 | 1 | 0 | 14 |
VUS | 0 | 68 | 9 | 1 | 78 |
Likely Benign | 0 | 3 | 12 | 23 | 38 |
Benign | 0 | 0 | 7 | 0 | 7 |
Conflicting | — | 29 | |||
| Total | 19 | 80 | 42 | 24 | 194 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
LGI1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Analysis of the Role of AIRE in Autoimmune Neurological Diseases Associated With Autoantibodies
RECRUITINGSafety and Efficacy of CT103A Cells for Relapsed/Refractory Antibody-associated Inflammatory Diseases of the Nervous System
RECRUITINGAntibody-mediated LGI1 Encephalitis: Symptoms, Biomarkers, and Mechanisms of the Chronic Phase of the Disease
RECRUITINGExternal Resources
Links to major genomics databases and tools