LINGO1

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

Basic information

Region (hg38): 15:77613027-77820900

Previous symbols: [ "LRRN6A" ]

Links

ENSG00000169783

∙ NCBI:84894 ∙ OMIM:609791 ∙ HGNC:21205 ∙ Uniprot:Q96FE5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

intellectual disability, autosomal recessive 64 (Limited), mode of inheritance: AR
intellectual disability, autosomal recessive 64 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, autosomal recessive 64	AR	General	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	Neurologic	28837161

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LINGO1 gene.

not_specified (74 variants)
not_provided (23 variants)
LINGO1-related_disorder (15 variants)
Intellectual_disability,_autosomal_recessive_64 (9 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LINGO1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000032808.7. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				26 clinvar	3 clinvar	29
missense	2 clinvar	1 clinvar	77 clinvar	2 clinvar		82
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	2	1	77	28	3

Highest pathogenic variant AF is 0.000024165

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LINGO1	protein_coding	protein_coding	ENST00000355300	2	207874

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.994	0.00587	124118	0	1	124119	0.00000403

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.80	242	400	0.606	0.0000291	3945
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.000166	0.000166

dbNSFP

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}.;
Pathway: Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;Signal Transduction;BDNF;Death Receptor Signalling;Axonal growth inhibition (RHOA activation);p75NTR regulates axonogenesis;p75 NTR receptor-mediated signalling;p75(NTR)-mediated signaling (Consensus)

Recessive Scores

pRec: 0.170

Intolerance Scores

loftool
rvis_EVS: -1.42
rvis_percentile_EVS: 4.1

Haploinsufficiency Scores

pHI: 0.790
hipred: Y
hipred_score: 0.814
ghis: 0.634

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.856

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Lingo1
Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan);

Zebrafish Information Network

Gene name: lingo1b
Affected structure: neuron
Phenotype tag: abnormal
Phenotype quality: increased thickness

Gene ontology

Biological process: negative regulation of axonogenesis
Cellular component: extracellular space;plasma membrane;integral component of membrane;extracellular matrix
Molecular function: epidermal growth factor receptor binding;protein binding