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FLASH GENE
Symbol LGI1 contributors: mct - updated : 02-07-2016
HGNC name leucine-rich, glioma inactivated 1
HGNC id 6572
Corresponding disease
EPT lateral temporal lobe epilepsy, partial
Location 10q23.33      Physical location : 95.517.565 - 95.557.915
Synonym name
  • epitempin
  • autosomal dominant partial epilepsy with auditory features (ADPEAF)
  • Synonym symbol(s) IB1099, KIAA1916, ETL1, EPITEMPIN, ADLTE, ADPAEF, ADPEAF, EPT
    DNA
    TYPE functioning gene
    STRUCTURE 40.35 kb     8 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    motif repetitive sequence   other
    text structure two SNP and a highly polymorphic intragenic microsatellite repeat
    MAPPING cloned N linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    8 - 2366 64 557 much higher in the lateral temporal cortex than in the hippocampus 2006 16787412
    - - 1612 - 291 - 2006 16787412
    - - 2249 60 509 - 2006 16787412
    more expressed in the temporal neocortex than in the hippocampus
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticthymus    
    Nervousbrainlimbic systemhippocampus  
     brainforebraincerebral cortex   Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Lymphoid    
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES Hydrophilic
    STRUCTURE
    motifs/domains
  • N-terminal half of the protein consists of 3.5 leucine-rich repeat (LRR) sequences flanked on both sides by typical cysteine-rich repeat sequence clusters and one putative transmembrane segment, and the LRR region of the LGI1 gene is likely to play a major role in pathogenesis of EPT
  • EAR repeats (epilepsy associated repeats at the C terminus), with seven copies of a novel repeat of about 45 residues, named epitempin
  • HOMOLOGY
    interspecies homolog to C.elegans F58g11.1B
    Homologene
    FAMILY
  • LGI family
  • CATEGORY adhesion , regulatory
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane,junction
    text localizes to glutamatergic synapses
    basic FUNCTION
  • may be involved in the formation and progression of glioblastoma multiformis
  • may have a physiologic function connected to the capacity for speech and language
  • coordinates the functional maturation of both pre- and postsynaptic properties during postnatal brain development, and also mediates a structural remodeling of the apical dendrite branches and spines
  • regulated the functional maturation and structural pruning of glutamatergic synapses during postnatal development
  • acts to remodel the hippocampal dentate glutamatergic circuitry
  • regulates postnatal pruning of retinal axons in visual relay thalamus 8)
  • LGI1, LGI2, TSPEAR, ADGRV1 all have indispensable roles only in the peripheral and central auditory system, it is tempting to speculate that they are involved in similar molecular pathways
  • by finely regulating the synaptic AMPA receptors, the LGI1-ADAM22 interaction maintains likely physiological brain excitability throughout life
  • prevents the inactivation of voltage-gated potassium channels, mediates postnatal maturation of glutamatergic synapses, and regulates excitatory neurotransmission
  • is involved in the development of the cerebellum and cortex
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • forms a protein complex with the ADAM22/23 cell adhesion/receptor protein which when mutated results in seizures
  • LGI1 and ADAM22 form an essential synaptic organizing complex that coordinates the maturation of excitatory synapses by regulating the functional incorporation of DLG4
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with ADAM22 (acts as a ligand that selectively binds to the postsynaptic receptor ADAM22, thereby regulating the glutamate-AMPA neurotransmission)
  • binds a disintegrin and metalloproteinase domains 22 and 23 (ADAM22 and ADAM23), to promote glutamatergic synapse maturation and pruning
  • binds ADAM11, ADAM22, ADAM23 (LGI-ADAM system seems to be regulated not only by the affinity but also by the cell-type-specific expression of each protein)
  • bind ADAM22 through its EPTP domains
  • link between RELN and LGI1, which play key regulatory roles in both the developing and adult brain
  • critical roles of a ligand-receptor complex, LGI1-ADAM22, in synaptic transmission and brain function
  • ADAM22 and ADAM23 modulate the trafficking of LGI1, and promote its ER export and expression at the overall neuronal cell surface
  • cell & other bind on the surface of neuronal cells and affect sodium channel functioning
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) EPT
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   translocation    
    translocation t(10;19)(q24;q13)in glioblastoma cell lines
    tumoral     --low  
    in low grade brain tumors
    tumoral        
    loss of LGI1 is an important event in the progression of gliomas that leads to a more invasive phenotype
    Susceptibility to familial forms of temporal lobe epilepsy
    Variant & Polymorphism other polymorphisms increasing the risk of temporal lobe epilepsy
    Candidate gene
    Marker
    Therapy target can reduce cellular invasion and, as a secreted agent, may be developed as a means of treating metastatic cancer
    ANIMAL & CELL MODELS