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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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LGI2
leucine rich repeat LGI family member 2
Chromosome 4 · 4p15.2
NCBI Gene: 55203Ensembl: ENSG00000153012.13HGNC: HGNC:18710UniProt: Q8N0V4
17PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
inhibitory synapse assemblyextracellular regionneurodegenerative diseasemajor salivary gland cancertemporomandibular joint disorderasthma
✦AI Summary

LGI2 (leucine rich repeat LGI family member 2) is a secreted protein that plays a critical role in neural development and synaptic function. The protein belongs to the LGI family of beta-propeller domain proteins with EPTP/EAR epilepsy-associated repeats and is secreted to the extracellular medium in glycosylated form, similar to its family member LGI1 1. LGI2 is required for the development of soma-targeting inhibitory GABAergic synapses made by parvalbumin-positive basket cells, functioning in inhibitory synapse assembly within the extracellular region. The protein shares structural and functional similarities with LGI1, including similar secretion mechanisms and molecular pathogenesis pathways 1. Mutations in LGI2 are associated with epilepsy disorders, particularly in canine models where an LGI2 mutation has been identified in Lagotto Romagnolo dogs with focal, juvenile remitting epilepsy 2. LGI2 has been proposed as a prime candidate gene for partial epilepsy with pericentral spikes (PEPS) in humans, based on its chr4 location at 4p15 and protein sequence analysis 3. The LGI gene family evolved early in vertebrate lineage and experiences high levels of purifying selection, indicating essential roles in neural development and function 4.

Sources cited
1
LGI2 is secreted to extracellular medium in glycosylated form and shares molecular pathogenesis mechanisms with LGI1
PMID: 20863412
2
LGI2 mutation identified in Lagotto Romagnolo dogs with focal, juvenile remitting epilepsy
PMID: 22037590
3
LGI2 proposed as prime candidate gene for partial epilepsy with pericentral spikes based on chromosomal location and sequence analysis
PMID: 20183877
4
LGI gene family evolved early in vertebrates and experiences high purifying selection indicating essential neural function
PMID: 16014869
⚠Limited data available — This gene has 4 indexed publications. Summary and analysis may be incomplete.
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.33Weak
major salivary gland cancerOpen Targets
0.33Weak
temporomandibular joint disorderOpen Targets
0.31Weak
asthmaOpen Targets
0.28Weak
body weight gainOpen Targets
0.16Weak
epilepsyOpen Targets
0.05Suggestive
acute tonsillitisOpen Targets
0.03Suggestive
ovarian dysfunctionOpen Targets
0.03Suggestive
tooth diseaseOpen Targets
0.03Suggestive
obesityOpen Targets
0.02Suggestive
lymphatic system diseaseOpen Targets
0.02Suggestive
esophageal squamous cell carcinomaOpen Targets
0.01Suggestive
COVID-19Open Targets
0.01Suggestive
autosomal dominant epilepsy with auditory featuresOpen Targets
0.01Suggestive
ulcerative colitisOpen Targets
0.01Suggestive
attention deficit hyperactivity disorderOpen Targets
0.01Suggestive
partial epilepsyOpen Targets
0.01Suggestive
Tetralogy of FallotOpen Targets
0.01Suggestive
supranuclear palsy, progressive, 1Open Targets
0.00Suggestive
temporal lobe epilepsyOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
ADAM23Protein interaction92%ADAM22Protein interaction92%CBLN4Shared pathway33%HAPLN4Shared pathway20%CLSTN2Shared pathway20%GABREShared pathway17%
Tissue Expression6 tissues
Heart
100%
Brain
29%
Ovary
19%
Lung
11%
Liver
4%
Bone Marrow
2%
Gene Interaction Network
Click a node to explore
LGI2ADAM23ADAM22CBLN4HAPLN4CLSTN2GABRE
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q8N0V4
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.81LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.57 [0.41–0.81]
RankingsWhere LGI2 stands among ~20K protein-coding genes
  • #15,040of 20,598
    Most Researched17
  • #6,759of 17,882
    Most Constrained (LOEUF)0.81
Genes detectedLGI2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Canine epilepsy genetics.
PMID: 22037590
Mamm Genome · 2012
1.00
2
Similarity of molecular phenotype between known epilepsy gene LGI1 and disease candidate gene LGI2.
PMID: 20863412
BMC Biochem · 2010
0.90
3
LGI Proteins and Epilepsy in Human and Animals.
PMID: 26032921
J Vet Intern Med · 2015
0.80
4
Using gene-history and expression analyses to assess the involvement of LGI genes in human disorders.
PMID: 16014869
Mol Biol Evol · 2005
0.70
5
The Arsenic Resistance-Associated Listeria Genomic Island LGI2 Exhibits Sequence and Integration Site Diversity and a Propensity for Three Listeria monocytogenes Clones with Enhanced Virulence.
PMID: 28842547
Appl Environ Microbiol · 2017
0.60