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10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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LINGO1
leucine rich repeat and Ig domain containing 1
Chromosome 15 Β· 15q24.3
NCBI Gene: 84894Ensembl: ENSG00000169783.13HGNC: HGNC:21205UniProt: Q96FE5
69PubMed Papers
21Diseases
1Drugs
2Pathogenic Variants
CLINICAL
Clinical TrialsOMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingplasma membraneepidermal growth factor receptor bindingneuron developmentintellectual disability, autosomal recessive 64type 1 diabetes mellitusmajor depressive disordermathematical ability
✦AI Summary

LINGO1 (leucine rich repeat and Ig domain containing 1) is a membrane protein that functions as a key negative regulator of central nervous system development and regeneration. The protein serves as a functional component of the Nogo receptor signaling complex, contributing to RhoA activation and inhibition of axonal regeneration by myelin-associated factors 12. LINGO1 acts as an important negative regulator of oligodendrocyte differentiation and axonal myelination, playing a crucial role in the initial myelination process in the CNS 34. The gene shows significant disease associations, particularly with movement disorders. Meta-analysis studies demonstrate that LINGO1 polymorphisms (rs11856808 and rs9652490) are associated with increased risk for essential tremor, especially familial forms 5. Additionally, LINGO1 variants show protective effects against Parkinson's disease in Italian populations 6. Recent omics analyses reveal that LINGO1 is highly enriched in human Alzheimer's disease microglia, suggesting potential involvement in neurodegeneration 7. In cancer contexts, LINGO1 appears to function as a positive prognostic marker in primary glioblastoma 8. These findings establish LINGO1 as a critical regulator of neuronal development, myelination, and neurological disease susceptibility.

Sources cited
1
LINGO1 functions as a component of the Nogo receptor signaling complex in RhoA activation
PMID: 14966521
2
LINGO1 contributes to inhibition of axonal regeneration by myelin-associated factors
PMID: 15694321
3
LINGO1 is an important negative regulator of oligodendrocyte differentiation and axonal myelination
PMID: 15895088
4
LINGO1 plays a role in the initial myelination process in the CNS
PMID: 36974372
5
LINGO1 polymorphisms rs11856808 and rs9652490 are associated with essential tremor risk, particularly familial forms
PMID: 22425540
6
LINGO1 variants show protective effects against Parkinson's disease in Italian populations
PMID: 21752692
7
LINGO1 is highly enriched in human Alzheimer's disease microglia
PMID: 40754867
8
LINGO1 functions as a positive prognostic marker in primary glioblastoma
PMID: 30064229
Disease Associationsβ“˜21
intellectual disability, autosomal recessive 64Open Targets
0.67Moderate
type 1 diabetes mellitusOpen Targets
0.38Weak
major depressive disorderOpen Targets
0.37Weak
mathematical abilityOpen Targets
0.34Weak
neurotic disorderOpen Targets
0.34Weak
Abnormality of the skeletal systemOpen Targets
0.34Weak
smoking initiationOpen Targets
0.33Weak
essential tremorOpen Targets
0.33Weak
post-traumatic stress disorderOpen Targets
0.33Weak
coffee consumptionOpen Targets
0.32Weak
type 2 diabetes mellitusOpen Targets
0.30Weak
obesityOpen Targets
0.28Weak
schizophreniaOpen Targets
0.28Weak
intelligenceOpen Targets
0.28Weak
health study participationOpen Targets
0.27Weak
mood disorderOpen Targets
0.27Weak
attention deficit hyperactivity disorderOpen Targets
0.19Weak
substance abuseOpen Targets
0.19Weak
Failure to thriveOpen Targets
0.19Weak
placental retentionOpen Targets
0.18Weak
Intellectual developmental disorder, autosomal recessive 64UniProt
Pathogenic Variants2
NM_032808.7(LINGO1):c.869G>A (p.Arg290His)Pathogenic
Intellectual disability, autosomal recessive 64
β˜†β˜†β˜†β˜†2018β†’ Residue 290
NM_032808.7(LINGO1):c.863A>G (p.Tyr288Cys)Pathogenic
Intellectual disability, autosomal recessive 64
β˜†β˜†β˜†β˜†2018β†’ Residue 288
View on ClinVar β†—
Drug Targets1
OPICINUMABPhase II
Leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein 1 inhibitor
multiple sclerosis
Related Genes
MAGProtein interaction100%NGFRProtein interaction100%OMGProtein interaction100%TNFRSF19Protein interaction100%RTN4Protein interaction100%RTN4RProtein interaction100%
Tissue Expression6 tissues
Brain
100%
Heart
47%
Ovary
9%
Liver
5%
Lung
2%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
LINGO1MAGNGFROMGTNFRSF19RTN4RTN4R
PROTEIN STRUCTURE
Preparing viewer…
PDB2ID5 Β· 2.70 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.55Moderately Constrained
pLIβ“˜
0.91Intolerant
Observed/Expected LoF0.33 [0.21–0.55]
RankingsWhere LINGO1 stands among ~20K protein-coding genes
  • #6,810of 20,598
    Most Researched69
  • #4,382of 5,498
    Most Pathogenic Variants2
  • #3,529of 17,882
    Most Constrained (LOEUF)0.55 Β· top quartile
Genes detectedLINGO1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
LINGO1 and risk for essential tremor: results of a meta-analysis of rs9652490 and rs11856808.
PMID: 22425540
J Neurol Sci Β· 2012
1.00
2
Tremor.
PMID: 19553813
Curr Opin Neurol Β· 2009
0.90
3
Shift work tolerance.
PMID: 34729606
Occup Med (Lond) Β· 2021
0.80
4
LINGO1, C7orf31 and VEGFA are prognostic genes of primary glioblastoma: analysis of gene expression microarray.
PMID: 30064229
Neoplasma Β· 2018
0.70
5
The Initial Myelination in the Central Nervous System.
PMID: 36974372
ASN Neuro Β· 2023
0.60