LINGO1

protein-coding

leucine rich repeat and Ig domain containing 1, the group of I-set domain containing

Gene summary

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]

Previous symbols:

LRRN6A

MANE transcript

NM_032808.7

Inheritance

ClinVar variants

P:3U:88B:36

Top phenotype

Intellectual developmental disorder, autosomal recessive 64

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr15:77,613,027-77,820,900

External References & Databases

Ensembl (ENSG00000169783)

Transcript & Mutation Effects

hg38 • Region Span ~207.9 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

intellectual disability, autosomal recessive 64STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0020846

Submitter: G2P

intellectual disability, autosomal recessive 64LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0020846

Submitter: Labcorp Genetics (formerly Invitae)

intellectual disability, autosomal recessive 64MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0020846

Submitter: PanelApp Australia

intellectual disability, autosomal recessive 64LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0020846

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Intellectual developmental disorder, autosomal recessive 64AR

Manifestation: Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 28837161

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to LINGO1 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 87

not providedTotal: 30

LINGO1-related disorderTotal: 15

Intellectual disability, autosomal recessive 64Total: 9

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_032808.7. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				31 clinvar	3 clinvar	34
missense	2 clinvar	1 clinvar	88 clinvar	2 clinvar		93
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	2	1	88	33	3	127

Highest pathogenic variant AF is 0.000024165007

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 28 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_032808.7	RefSeq	NP_116197.4	2	MANE Select
ENST00000355300.7	Ensembl	ENSP00000347451.6	2	MANE Select
NM_001301186.2	RefSeq	NP_001288115.1	1	Standard
NM_001301187.2	RefSeq	NP_001288116.1	1	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
lingo1b	Danio rerio	Structure: neuron Quality: increased thickness abnormal

Gene / Model

Organism

Observed Phenotype

lingo1b

Danio rerio

Structure: neuron

Quality: increased thickness

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Brain-Derived Neurotrophic Factor (BDNF) signaling pathway
Signal Transduction
BDNF
Death Receptor Signalling
Axonal growth inhibition (RHOA activation)

Biological Process

negative regulation of axonogenesis

Molecular Function

epidermal growth factor receptor binding
protein binding

Cellular Component

extracellular space
plasma membrane
integral component of membrane
extracellular matrix

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000355300
Coding exons: 2
Length: 207874
Individuals with no LoFs: 124118
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 124119
p: 0.00000403

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.80	242	400	0.606	0.0000291	3945
Missense (PolyPhen)		50	134.77	0.37101		1410
Synonymous	-0.717	210	197	1.06	0.0000158	1311
Loss of Function	3.62	0	15.3	0.00	8.32e-7	164

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0.00017	0.00017	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Functional component of the Nogo receptor signaling complex (RTN4R/NGFR) in RhoA activation responsible for some inhibition of axonal regeneration by myelin-associated factors (PubMed:14966521, PubMed:15694321). Is also an important negative regulator of oligodentrocyte differentiation and axonal myelination (PubMed:15895088). Acts in conjunction with RTN4 and RTN4R in regulating neuronal precursor cell motility during cortical development (By similarity). {ECO:0000250|UniProtKB:Q9D1T0, ECO:0000269|PubMed:14966521, ECO:0000269|PubMed:15694321, ECO:0000269|PubMed:15895088}.;

Recessive Scores

pRec: 0.170

Intolerance Scores

RVIS EVS: -1.42
RVIS percentile EVS: 4.1

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.856

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium