LINGO1

Chr 15AR

leucine rich repeat and Ig domain containing 1

Also known as: LERN1, LRRN6A, MRT64, UNQ201

NCBI Gene: 84894ENSG00000169783UniProt: Q96FE5

Predicted to enable epidermal growth factor receptor binding activity. Predicted to act upstream of or within negative regulation of oligodendrocyte differentiation; negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; and neuron development. Predicted to be located in plasma membrane. Predicted to be active in several cellular components, including extracellular space; glutamatergic synapse; and presynapse. Implicated in autosomal recessive intellectual developmental disorder 64 and glaucoma. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

Intellectual developmental disorder, autosomal recessive 64MIM #618103
AR
154
ClinVar variants
22
Pathogenic / LP
0.99
pLI score· haploinsufficient
0
Active trials
Clinical Summary— LINGO1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
22 Pathogenic / Likely Pathogenic· 89 VUS of 154 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.20LOEUF
pLI 0.994
Z-score 3.62
OE 0.00 (0.00–0.20)
Highly constrained

Highly LoF-intolerant (top ~10% 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.
2.80Z-score
OE missense 0.61 (0.54–0.67)
242 obs / 399.5 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.00 (0.00–0.20)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.61 (0.54–0.67)
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.1.06
0≤1.21.6
LoF obs/exp: 0 / 15.3Missense obs/exp: 242 / 399.5Syn Z: -0.72

ClinVar Variant Classifications

154 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19
Likely Pathogenic3
VUS89
Likely Benign34
Benign8
Conflicting1
19
Pathogenic
3
Likely Pathogenic
89
VUS
34
Likely Benign
8
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
2
17
0
19
Likely Pathogenic
0
0
3
0
3
VUS
0
86
3
0
89
Likely Benign
0
2
4
28
34
Benign
0
0
1
7
8
Conflicting
—1
Total0902835154

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

LINGO1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

LINGO1 related intellectual disability with microcephaly, speech and motor delay

strong
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Intellectual developmental disorder, autosomal recessive 64

MIM #618103

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
LINGO1 and risk for essential tremor: results of a meta-analysis of rs9652490 and rs11856808.
Jiménez-Jiménez FJ et al.·J Neurol Sci
2012Meta-analysis
Shift work tolerance.
Degenfellner J et al.·Occup Med (Lond)
2021
Genetics of essential tremor.
Tio M et al.·Parkinsonism Relat Disord
2016Review
Tremor.
Raethjen J et al.·Curr Opin Neurol
2009Review
Analysis and meta-analysis of five polymorphisms of the LINGO1 and LINGO2 genes in Parkinson's disease and multiple system atrophy in a Chinese population.
Chen Y et al.·J Neurol
2015Meta-analysis
Genetics of essential tremor.
Jasinska-Myga B et al.·Parkinsonism Relat Disord
2012Review
Nogo-A Antibodies for Progressive Multiple Sclerosis.
Ineichen BV et al.·CNS Drugs
2017Review
Analysis of Lingo1 variant in sporadic and familial essential tremor among Asians.
Wu YW et al.·Acta Neurol Scand
2011
LINGO1 variants in essential tremor and Parkinson's disease.
Deng H et al.·Acta Neurol Scand
2012Review
LINGO1 and LINGO2 variants are associated with essential tremor and Parkinson disease.
Vilariño-Güell C et al.·Neurogenetics
2010
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Transcriptional activation of LINGO1 facilitates proliferation and immune escape in colorectal cancer.
Ma P et al.·Sci Rep
2026
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🔓 Open Access
Analyses of Nogo-Family Genes in Mouse and Human Microglia Omics Datasets Identify LINGO1 as a Candidate Drug Target in Alzheimer's Disease.
Glotfelty EJ et al.·Curr Neuropharmacol
2025🔓 Open AccessFunctional
Lingo1 in the hippocampus contributes to cognitive dysfunction after anesthesia and surgery in aged mice.
Liu C et al.·Int J Biol Sci
2025🔓 Open Access
Inhibition of LINGO1 as a therapeutic target to promote axonal regeneration and repair for neurological disorders.
Atta A et al.·3 Biotech
2023
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools