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7 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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LINGO3
leucine rich repeat and Ig domain containing 3
Chromosome 19 · 19p13.3
NCBI Gene: 645191Ensembl: ENSG00000220008.5HGNC: HGNC:21206UniProt: P0C6S8
5PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
signaling receptor activityplasma membraneregulation of nervous system developmentmembranemyoepithelial tumorage-related macular degenerationX-linked retinal dysplasiaFamilial exudative vitreoretinopathy
✦AI Summary

LINGO3 (leucine rich repeat and Ig domain containing 3) is a plasma membrane-localized signaling receptor that functions in tissue regeneration and neurological processes. LINGO3 is broadly expressed on enterocytes and in the intestinal crypt niche, where it plays a role in mucosal wound healing and intestinal stem cell maintenance 1. The protein promotes recovery from colitis through interaction with TFF2, regulating signaling pathways critical for cell proliferation and wound repair 1. In the central nervous system, LINGO3 is differentially expressed and forms heteromeric complexes with other LINGO family members, suggesting regulatory complexity in nervous system function 2. LINGO3 has emerged as clinically relevant in psychiatric and environmental health contexts. DNA methylation changes in LINGO3 are associated with stress-related depression 3 and with perinatal asphyxia in patients with schizophrenia and bipolar disorder, where divergent epigenetic responses may contribute to psychiatric disease risk 4. Additionally, LINGO3 methylation associates with chr19 arsenic exposure in low-to-moderate exposure populations 5, and LINGO3 expression is upregulated in inflamed dental pulp tissues of COVID-19-affected individuals 6. These findings suggest LINGO3 involvement in tissue repair, neurodevelopment, and stress-responsive processes with potential biomarker applications.

Sources cited
1
LINGO3 is expressed on enterocytes and regulates intestinal tissue regeneration and stem cell maintenance through TFF2-dependent signaling pathways
PMID: 33941035
2
LINGO3 is differentially expressed in the central nervous system and forms heteromeric complexes with other LINGO family members
PMID: 32862444
3
Stress-associated epigenetic changes in LINGO3 are correlated with depression
PMID: 31005627
4
LINGO3 shows divergent epigenetic responses to perinatal asphyxia in schizophrenia and bipolar disorder patients and is involved in oligodendrocyte survival and axonal myelination
PMID: 38191519
5
LINGO3 methylation is associated with urinary arsenic levels in chronically exposed populations
PMID: 32603190
6
LINGO3 is upregulated in dental pulp tissues of individuals with symptomatic irreversible pulpitis and COVID-19 history
PMID: 37178757
Disease Associationsⓘ20
myoepithelial tumorOpen Targets
0.11Weak
age-related macular degenerationOpen Targets
0.07Suggestive
X-linked retinal dysplasiaOpen Targets
0.06Suggestive
Familial exudative vitreoretinopathyOpen Targets
0.06Suggestive
retinitis pigmentosaOpen Targets
0.05Suggestive
severe early-childhood-onset retinal dystrophyOpen Targets
0.05Suggestive
Stargardt diseaseOpen Targets
0.05Suggestive
reticular dystrophy of the retinal pigment epitheliumOpen Targets
0.05Suggestive
Benign familial choreaOpen Targets
0.05Suggestive
Familial drusenOpen Targets
0.04Suggestive
X-linked retinoschisisOpen Targets
0.04Suggestive
Sorsby fundus dystrophyOpen Targets
0.04Suggestive
Sorsby's fundus dystrophyOpen Targets
0.04Suggestive
age related macular degeneration 11Open Targets
0.04Suggestive
age related macular degeneration 2Open Targets
0.04Suggestive
age related macular degeneration 4Open Targets
0.04Suggestive
age related macular degeneration 6Open Targets
0.04Suggestive
age related macular degeneration 7Open Targets
0.04Suggestive
late-onset retinal degenerationOpen Targets
0.04Suggestive
birdshot chorioretinopathyOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
GBX1Shared pathway100%LINGO2Shared pathway100%LINGO4Shared pathway100%LINGO1Shared pathway50%GBX2Shared pathway50%RTN4Shared pathway5%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
37%
Lung
28%
Liver
8%
Ovary
3%
Heart
0%
Gene Interaction Network
Click a node to explore
LINGO3GBX1LINGO2LINGO4LINGO1GBX2RTN4
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt P0C6S8
View on AlphaFold ↗
RankingsWhere LINGO3 stands among ~20K protein-coding genes
  • #18,359of 20,598
    Most Researched5
Genes detectedLINGO3
Sources retrieved7 papers
Response time—
📄 Sources
7▼
1
Stress, epigenetics and depression: A systematic review.
PMID: 31005627
Neurosci Biobehav Rev · 2019
1.00
2
Divergent epigenetic responses to perinatal asphyxia in severe mental disorders.
PMID: 38191519
Transl Psychiatry · 2024
0.86
3
LINGO3 regulates mucosal tissue regeneration and promotes TFF2 dependent recovery from colitis.
PMID: 33941035
Scand J Gastroenterol · 2021
0.71
4
Network-based co-expression analysis for exploring the potential diagnostic biomarkers of metastatic melanoma.
PMID: 29377892
PLoS One · 2018
0.57
5
Locus-Specific Differential DNA Methylation and Urinary Arsenic: An Epigenome-Wide Association Study in Blood among Adults with Low-to-Moderate Arsenic Exposure.
PMID: 32603190
Environ Health Perspect · 2020
0.43