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FLASH GENE
Symbol LINGO1 contributors: mct/pgu - updated : 26-09-2017
HGNC name leucine rich repeat and Ig domain containing 1
HGNC id 21205
Corresponding disease
MRT61 mental retardation, autosomal recessive 61
Location 15q24.3      Physical location : 77.905.368 - 77.924.709
Genatlas name Leucine-rich repeat and Ig-like domain-containing Nogo receptor interacting protein 1
Synonym name
  • leucine rich repeat neuronal 6A
  • leucine-rich repeat neuronal protein 1
  • Synonym symbol(s) FLJ14594, LERN1, LRRN6A, MGC17422, UNQ201, LINGO-1
    DNA
    TYPE functioning gene
    STRUCTURE 19.34 kb     5 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    5 - 2932 70 620 - 2015 25666623
    6 - 3394 - 614 - 2015 25666623
    6 - 3411 - 614 - 2015 25666623
    6 - 3405 - 614 - 2015 25666623
    4 - 3346 - 614 - 2015 25666623
    5 - 3528 - 614 - 2015 25666623
    6 - 3590 - 614 - 2015 25666623
    4 - 3281 - 614 - 2015 25666623
    4 - 3294 - 614 - 2015 25666623
    3 - 3091 - 614 - 2015 25666623
    4 - 3264 - 614 - 2015 25666623
    4 - 3337 - 614 - 2015 25666623
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Nervousbrain   predominantly Homo sapiens
     gangliasensory gangliadorsal root   Homo sapiens
     nervecranial nervefacial nerve   Homo sapiens
    Visualeye    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Nervouscentral    Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron Homo sapiens
    Nervousoligodendrocyte Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    Text oligodendrocyte progenitor cells
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • leucine-rich repeat (LRR)
  • immunoglobulin (Ig)-like modules
  • a ligand-binding ectodomain
  • intracellular domain that may interact with the postmitotic neuronal-specific zinc-finger protein myelin transcription factor 1-like and regulate its activity by affecting its subcellular localization1
  • mono polymer tetramer
    HOMOLOGY
    Homologene
    FAMILY
    CATEGORY regulatory
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,cytoplasm
    text
  • endogenous LINGO1 expression in neurons in the cortex and cerebellum is intracellular
  • basic FUNCTION
  • playing essential roles in nervous system development and maintenance
  • playing an inhibitory role particularly important in regulation of oligodendrocyte differentiation and myelination
  • negatively regulates myelination by oligodendrocytes
  • playing a role in the pathophysiological responses of midbrain dopaminergic neurons in Parkinson disease
  • negative regulator of oligodendrocyte differentiation and myelination
  • playing an important role in modulating axonal outgrowth
  • potent axonal inhibitor of oligodendrocyte differentiation and myelination that is regulated by nerve growth factor and its cognate receptor NTRK1 in a dose-dependent manner
  • functions as a negative regulator of oligodendrocyte differentiation and myelination, neuronal survival and axonal regeneration
  • may participate in activities in developing neurons apart from the oligodendrocyte maturation or axon extension inhibition it influences in the adult
  • involved in the regulation of neuronal survival and axonal regeneration
  • potent negative regulator of oligodendrocyte differentiation and hence may play a pivotal restrictive role during remyelination in demyelinating diseases such as multiple sclerosis
  • inhibits multiple aspects of oligodendrocyte differentiation independently of the LRRs via a process that requires NGFR signalling
  • key negative regulator of myelination, that is a transmembrane signaling protein expressed in both neurons and oligodendrocytes
  • acts as both a ligand and a receptor and the mechanism by which it negatively regulates oligodendrocyte precursor cells differentiation and myelination is mediated by a homophilic intercellular interaction
  • functions as a negative feedback regulator of signaling by cognate receptor tyrosine kinases including NTRK1, NTRK2 and NTRK3
  • is a negative regulator of oligodendrocyte progenitor cells (OPCs) differentiation
  • regulates oligodendrocyte differentiation and maturation through the cytoplasmic gelsolin signaling pathway
  • crucial role of LINGO1 in normal neuronal development and central nervous system myelination by negatively regulating oligodendrocyte differentiation and neuronal survival
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • functional component of the RTN4R/TNFRSF1B/LINGO1 and RTN4R/TNFRSF19(TROY)/LINGO1 signaling complexes that mediate inhibition of axonal outgrowth
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with RTN4R, resulting in neurite and axonal collapse (associated with the RTN4R complex and is endowed with a canonical EGF receptor (EGFR)-like tyrosine phosphorylation site)
  • as in neurons, physically associated with endogenous NGFR
  • interactions of RTN4R with its co-receptors LINGO1, NGFR and the myelin inhibitor RTN4 is facilitated by gangliosides
  • on oligodendroglial cells, LINGO1 interacts with NGFR to constitutively inhibit multiple aspects of oligodendrocyte differentiation
  • binding of RTN4R and LINGO1 was similarly inhibited by OLFM1 coexpression
  • potentiates neuronal apoptosis, likely by inhibiting WNK3 kinase activity
  • LINGO1 can directly bind to ERBB2, block ERBB2 translocation into lipid rafts, and inhibit its phosphorylation for activation
  • NGFR associated predominantly with natively expressed LINGO1 containing immature N-glycans, characteristic of protein that has not completed trans-Golgi-mediated processing
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) MRT61
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in the substantia nigra of Parkinson's disease (PD) patients
    constitutional     --over  
    in the cerebellar cortex of Essential tremor (ET) in patients compared with controls, particularly in individuals with longer disease duration
    Susceptibility to essential tremor (ET)
    Variant & Polymorphism SNP
  • Significant association was found with allele G of marker rs9652490 in essential tremor
  • a marker rs9652490, showing significant genome-wide association with essential tremor (ET)
  • relationship between LINGO1 rs11856808 polymorphism and the risk for ET and for familial ET, while rs9652490 polymorphism was only related with the risk for familial ET
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    neurologyneurodegenerative 
    targeted inhibition of LINGO1 presents a novel therapeutic approach for the treatment of neurological diseases
    neurologydystonia 
    antagonism of LINGO1 may be a worthwhile approach to the treatment of some diseases of the central nervous system (essential tremor is on the top of the list of diseases to be assessed)
    neuromuscularneuropathy 
    Antagonism of LINGO-1 or its pathway is therefore a promising approach for the treatment of demyelinating diseases of the CNS
    neurologyacquired 
    treatment with LINGO-1-Fc can significantly enhance recovery after spinal cord injury
    neurologyneurodegenerative 
    target for the treatment of demyelination diseases
    neurologyneurodegenerative 
    is a potential drug target for essential tremor
    ANIMAL & CELL MODELS
    Increased axon integrity observed in LINGO1 mouse knockout models highlights the potential role of LINGO1 in the pathophysiology of essential tremor and opens up a new field in the research into essential tremor