LGI1

Chr 10

leucine rich glioma inactivated 1

ENSG00000108231UniProt: O95970

Regulates voltage-gated potassium channels assembled from KCNA1, KCNA4 and KCNAB1. It slows down channel inactivation by precluding channel closure mediated by the KCNAB1 subunit. Ligand for ADAM22 that positively regulates synaptic transmission mediated by AMPA-type glutamate receptors (By similarity). Plays a role in suppressing the production of MMP1/3 through the phosphatidylinositol 3-kinase/ERK pathway. May play a role in the control of neuroblastoma cell survival

Primary Disease Associations & Inheritance

UniProtEpilepsy, familial temporal lobe, 1
0
ClinVar variants
0
Pathogenic / LP
1.00
pLI score· haploinsufficient
3
Active trials
Clinical Summary— LGI1
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Gene-Disease Validity (ClinGen)
autosomal dominant epilepsy with auditory features · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (2)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.19LOEUF
pLI 0.999
Z-score 4.43
OE 0.04 (0.01–0.19)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.78Z-score
OE missense 0.54 (0.47–0.62)
158 obs / 291.6 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.04 (0.01–0.19)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.54 (0.47–0.62)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.92
0≤1.21.6
LoF obs/exp: 1 / 24.8Missense obs/exp: 158 / 291.6Syn Z: 0.70

ClinVar Variant Classifications

0 submitted variants in ClinVar

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.

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Neuromuscular hyperexcitability syndromes.
De Wel B et al.·Curr Opin Neurol
2021Review
Anti-LGI1 encephalitis: Clinical syndrome and long-term follow-up.
van Sonderen A et al.·Neurology
2016Natural history
Magnetic Resonance Imaging Characteristics of LGI1-Antibody and CASPR2-Antibody Encephalitis.
Kelly MJ et al.·JAMA Neurol
2024
LGI1 antibody encephalitis: acute treatment comparisons and outcome.
Rodriguez A et al.·J Neurol Neurosurg Psychiatry
2022
Autoimmune encephalitis.
Goodfellow JA et al.·J R Coll Physicians Edinb
2019Review
Autoimmune Epilepsy.
Gaspard N·Continuum (Minneap Minn)
2016Review
Autoimmune epilepsies.
Irani SR et al.·Curr Opin Neurol
2011Review
Mechanisms of autoimmune encephalitis.
Papi C et al.·Curr Opin Neurol
2024Review
LGI1: a gene involved in epileptogenesis and glioma progression?
Gu W et al.·Neurogenetics
2005Review
Biallelic LGI1 and ADAM23 variants cause hippocampal epileptic encephalopathy via the LGI1-ADAM22/23 pathway.
Hirano Y et al.·Brain
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Non-invasive Assessment of Glymphatic System Function in Patients with Anti-LGI1 Encephalitis.
Liu Z et al.·Mult Scler Relat Disord
2026Cohort
[A case of anti-leucine-rich glioma inactivated protein 1 (LGI1) antibody-positive autoimmune encephalitis with electrographic seizures without epileptic seizure symptoms].
Nakano M et al.·Rinsho Shinkeigaku
2026
Long-term cognitive outcomes and persistent executive dysfunction in LGI1 autoimmune encephalitis.
Shir D et al.·J Neurol Sci
2026
Seizure burden and treatment efficacy evaluation in anti-LGI1 autoimmune encephalitis patients using wearable device: a pilot feasibility study.
Cui J et al.·BMJ Neurol Open
2026🔓 Open AccessCohort
Anti-LGI1 encephalitis: clinical presentation, imaging features, and prognostic analysis.
Chen X et al.·Front Neurol
2025🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Limbic Encephalitis With LGI1 Antibodies

Antibody-mediated LGI1 Encephalitis: Symptoms, Biomarkers, and Mechanisms of the Chronic Phase of the Disease

RECRUITING
NCT06515106Phase NAFundacion Clinic per a la Recerca BiomédicaStarted 2023-12-18
Remote cognitive rehabilitation program
Autoimmune DiseasesAutoimmune Diseases of the Nervous SystemNeuromyelitis Optica Spectrum Disorder

Safety and Efficacy of CT103A Cells for Relapsed/Refractory Antibody-associated Inflammatory Diseases of the Nervous System

RECRUITING
NCT04561557Phase EARLY_PHASE1Tongji HospitalStarted 2020-09-22
CT103A cellsCyclophosphamide and fludarabine
AIRE Deficiency

Analysis of the Role of AIRE in Autoimmune Neurological Diseases Associated With Autoantibodies

RECRUITING
NCT06941584Fondazione Policlinico Universitario Agostino Gemelli IRCCSStarted 2024-11-06
Test for AQP4, AChR, LGI1, and CASPR2 autoantibodies using cell-based assayAIRE single gene sequencingMolecular typing of HLA class I and II alleles

External Resources

Links to major genomics databases and tools