LINGO1

Chr 15AR

leucine rich repeat and Ig domain containing 1

Also known as: LERN1, LRRN6A, MRT64, UNQ201

NCBI Gene: 84894 ENSG00000169783 UniProt: Q96FE5 OMIM: 609791

LINGO1 encodes a functional component of the Nogo receptor signaling complex that negatively regulates oligodendrocyte differentiation, axonal myelination, and neuronal precursor cell motility during cortical development. Mutations cause autosomal recessive intellectual developmental disorder 64. The gene is highly constrained (pLI 0.99, LOEUF 0.20), indicating intolerance to loss-of-function variants in the general population.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Predicted to enable epidermal growth factor receptor binding activity and signaling receptor activity. Predicted to be involved in neuron development. 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. Located in plasma membrane. Implicated in autosomal recessive intellectual developmental disorder 64 and glaucoma. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Intellectual developmental disorder, autosomal recessive 64MIM #618103

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Intellectual developmental disorder, autosomal recessive 64; no ClinGen or GenCC tier

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.20

LOEUF· LoF intol.

LOF

Mechanism· G2P

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

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?

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?

LoF OE?0.00 (0.00–0.20)

0≤0.351.4

Missense OE?0.61 (0.54–0.67)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 0 / 15.3Missense obs/exp: 242 / 399.5Syn Z: -0.72

Background carrier burden — how many people carry a rare variant somewhere in LINGO1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

629 rare PASS variants

Rare truncating (LoF)

1 in 7,600

30 rare PASS variants

Rare synonymous (reference)

1 in 77

405 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for LINGO1. 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 130	1 in 16,000
South Asian	~43k	1 in 100	1 in 7,900
Remaining (unassigned)	~30k	1 in 85	none seen
European (Finnish)	~27k	1 in 310	1 in 2,900
Admixed American	~22k	1 in 94	≈ 1 in 4,500
African / African American	~21k	1 in 120	≈ 1 in 21,000
East Asian	~20k	1 in 110	1 in 920
Ashkenazi Jewish	~13k	1 in 870	none seen
Middle Eastern	~2,884	1 in 99	≈ 1 in 2,200

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.

Exome coverage (gnomAD): 1 of 2 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 2.? see exons ↓