LGI1

Chr 10ARAD

leucine rich glioma inactivated 1

Also known as: ADLTE, ADPAEF, ADPEAF, DEE121, EPITEMPIN, EPT, ETL1, IB1099

NCBI Gene: 9211ENSG00000108231UniProt: O95970OMIM: 604619

This gene encodes a member of the secreted leucine-rich repeat (LRR) superfamily and shares homology with members of the SLIT protein family. The encoded protein may regulate the activity of voltage-gated potassium channels and may be involved in neuronal growth regulation and cell survival. This gene is rearranged as a result of translocations in glioblastoma cell lines, and it is frequently down-regulated or rearranged in malignant gliomas. Mutations in this gene result in autosomal dominant lateral temporal epilepsy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

GeneReviewsOMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Developmental and epileptic encephalopathy 121MIM #621475
AR
Epilepsy, familial temporal lobe, 1MIM #600512
AD

Clinical highlights

Gene-disease validity (ClinGen)
autosomal dominant epilepsy with auditory features · ADDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.
3
Active trials
207
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.19
LOEUF· LoF intol.
Multiple*
Mechanism· predicted
📖
GeneReview available — LGI1
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?
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?
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?
LoF OE?0.04 (0.01–0.19)
0≤0.351.4
Missense OE?0.54 (0.47–0.62)
0≤0.61.4
Synonymous OE?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.

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients