LINGO2

Chr 9

leucine rich repeat and Ig domain containing 2

Also known as: LERN3, LRRN6C

NCBI Gene: 158038 ENSG00000174482 UniProt: Q7L985 OMIM: 609793

LINGO2 encodes a membrane protein that positively regulates synapse assembly and is active at glutamatergic synapses and synaptic membranes. The gene is highly constrained against loss-of-function variants (pLI=0.86, LOEUF=0.42), suggesting that mutations likely cause significant developmental or neurological phenotypes. However, specific disease associations and inheritance patterns for LINGO2 have not been established in the current literature.

OMIM ResearchSummary from RefSeq

Predicted to enable signaling receptor activity. Predicted to act upstream of or within positive regulation of synapse assembly. Predicted to be located in membrane. Predicted to be active in glutamatergic synapse and synaptic membrane. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.42

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

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?

0.67Z-score

OE missense 0.90 (0.82–0.99)

311 obs / 346.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.13 (0.05–0.42)

0≤0.351.4

Missense OE?0.90 (0.82–0.99)

0≤0.61.4

Synonymous OE?1.23

0≤1.21.6

LoF obs/exp: 2 / 15.2Missense obs/exp: 311 / 346.3Syn Z: -2.12

Background carrier burden — how many people carry a rare variant somewhere in LINGO2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

788 rare PASS variants

Rare truncating (LoF)

1 in 4,300

50 rare PASS variants

Rare synonymous (reference)

1 in 120

343 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for LINGO2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 150	1 in 4,800
South Asian	~43k	1 in 100	1 in 1,400
Remaining (unassigned)	~30k	1 in 81	≈ 1 in 14,000
European (Finnish)	~27k	1 in 340	1 in 2,900
Admixed American	~22k	1 in 91	1 in 1,300
African / African American	~21k	1 in 94	none seen
East Asian	~20k	1 in 110	1 in 2,600
Ashkenazi Jewish	~13k	1 in 440	≈ 1 in 5,600
Middle Eastern	~2,884	1 in 100	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.