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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

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	MRT64 mental retardation, autosomal recessive 64
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

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_032808 5 - 2932 70 620 - 2015 25666623 NM_001301186 6 - 3394 NP_001288115 - 614 - 2015 25666623 NM_001301187 6 - 3411 NP_001288116 - 614 - 2015 25666623 NM_001301189 6 - 3405 NP_001288118 - 614 - 2015 25666623 NM_001301194 4 - 3346 NP_001288123 - 614 - 2015 25666623 NM_001301192 5 - 3528 NP_001288121 - 614 - 2015 25666623 NM_001301191 6 - 3590 NP_001288120 - 614 - 2015 25666623 NM_001301195 4 - 3281 NP_001288124 - 614 - 2015 25666623 NM_001301197 4 - 3294 NP_001288126 - 614 - 2015 25666623 NM_001301198 3 - 3091 NP_001288127 - 614 - 2015 25666623 NM_001301199 4 - 3264 NP_001288128 - 614 - 2015 25666623 NM_001301200 4 - 3337 NP_001288129 - 614 - 2015 25666623

EXPRESSION

Type	restricted

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Nervous brain       predominantly Homo sapiens   ganglia sensory ganglia dorsal root     Homo sapiens   nerve cranial nerve facial nerve     Homo sapiens Visual eye

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Nervous central       Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Nervous neuron Homo sapiens Nervous oligodendrocyte 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)

MRT64

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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
	System Type Disorder Pubmed neurology neurodegenerative   targeted inhibition of LINGO1 presents a novel therapeutic approach for the treatment of neurological diseases neurology dystonia   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) neuromuscular neuropathy   Antagonism of LINGO-1 or its pathway is therefore a promising approach for the treatment of demyelinating diseases of the CNS neurology acquired   treatment with LINGO-1-Fc can significantly enhance recovery after spinal cord injury neurology neurodegenerative   target for the treatment of demyelination diseases neurology neurodegenerative   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