LINGO2

Chr 9

leucine rich repeat and Ig domain containing 2

Also known as: LERN3, LRRN6C

NCBI Gene: 158038ENSG00000174482UniProt: Q7L985

Predicted to act upstream of or within positive regulation of synapse assembly. Predicted to be located in membrane. Predicted to be active in several cellular components, including extracellular space; glutamatergic synapse; and synaptic membrane. [provided by Alliance of Genome Resources, Apr 2025]

0
Active trials
0
Pathogenic / LP
0
ClinVar variants
2
Pubs (1 yr)
0.7
Missense Z
0.42
LOEUF
Clinical Summary— LINGO2
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.86) — some intolerance to loss-of-function variants.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.42LOEUF
pLI 0.857
Z-score 3.13
OE 0.13 (0.05–0.42)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.67Z-score
OE missense 0.90 (0.82–0.99)
311 obs / 346.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.13 (0.05–0.42)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.90 (0.82–0.99)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.23
0≤1.21.6
LoF obs/exp: 2 / 15.2Missense obs/exp: 311 / 346.3Syn Z: -2.12

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

LINGO2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Oxidation modulates LINGO2-induced inactivation of large conductance, Ca2+-activated potassium channels
Dudem S et al.·J Biol Chem
2023
Chemical Synthesis of TFF3 Reveals Novel Mechanistic Insights and a Gut-Stable Metabolite
Braga Emidio N et al.·J Med Chem
2021
Distinct domains of LINGO1 control surface expression and biophysical properties of large conductance Ca2+- and voltage-activated potassium (BK) channels
Al Kawadri Y et al.·J Biol Chem
2025
Identification of hypoxia-related gene signatures based on multi-omics analysis in lung adenocarcinoma
Luo Q et al.·J Cell Mol Med
2023
Delayed recanalization reduced neuronal apoptosis and neurological deficits by enhancing liver-derived trefoil factor 3-mediated neuroprotection via LINGO2/EGFR/Src signaling pathway after middle cerebral artery occlusion in rats.
Li D et al.·Exp Neurol
2023
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Mettl3 regulates the pathogenesis of Alzheimer's disease via fine-tuning Lingo2.
Zhao X et al.·Mol Psychiatry
2025
Soluble form of Lingo2, an autism spectrum disorder-associated molecule, functions as an excitatory synapse organizer in neurons.
Yoshida F et al.·Transl Psychiatry
2024Open Access
Xenografted human iPSC-derived neurons with the familial Alzheimer's disease APPV717I mutation reveal dysregulated transcriptome signatures linked to synaptic function and implicate LINGO2 as a disease signaling mediator.
Qu W et al.·Acta Neuropathol
2024Open Access
Variations in the LINGO2 and GLIS3 Genes and Gene-Environment Interactions Increase Gestational Diabetes Mellitus Risk in Chinese Women.
Huang X et al.·Environ Sci Technol
2024
A Trefoil factor 3-Lingo2 axis restrains proliferative expansion of type-1 T helper cells during GI nematode infection.
Ethgen LM et al.·Mucosal Immunol
2024
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients