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Intellectual disability

Gene: LINGO1

Amber List (moderate evidence)

LINGO1 (leucine rich repeat and Ig domain containing 1)
EnsemblGeneIds (GRCh38): ENSG00000169783
EnsemblGeneIds (GRCh37): ENSG00000169783
OMIM: 609791, Gene2Phenotype
LINGO1 is in 2 panels

2 reviews

Ivone Leong (Genomics England Curator)

Comment on list classification: New gene added by external expert and reviewed by curation team. There is insufficient evidence to promote LINO1 to green so it has been given an amber gene rating based on external expert review. Have so added the 'watchilist' tag.
Created: 15 Feb 2019, 4:30 p.m.

Konstantinos Varvagiannis (Other)

I don't know

Biallelic pathogenic variants in LINGO1 cause Mental retardation, autosomal recessive 64 (MIM 618103).

Ansar et al. (PMID: 28837161) report on 5 individuals from 2 consanguineous Pakistani families.

Affected individuals from both families presented with similar phenotype consisting of global developmental delay (5/5), intellectual disability (5/5), microcephaly (4/5) as well as abnormal behavior (5/5).

Subjects from both families were homozygous for missense variants (private to each family) affecting proximal residues (290 and 288) of the protein (NM_032808.6:c.869G>A or p.Arg290His and c.863A>G or p.Tyr288Cys).

All variants were absent in an ethnically matched control cohort (201 individuals) as well as the relevant subpopulation in gnomAD.

Functional studies were not performed.

LINGO1 is a transmembrane protein predominantly expressed in the CNS. Previous studies suggest that this protein has an important role in myelination, neuronal survival and CNS repair.

LINGO1 is rather intolerant to both missense and LoF variants (Z-score of 4 and pLI of 0.95). According to the authors these variants may be hypomorphic, which might in turn suggest that monoallelic heterozygous LoF mutations could cause ID (although this remains an assumption).

This gene is not associated with any phenotype in G2P but is included in panels for ID offered by diagnostic laboratories (incl. Radboudumc).

As a result, LINGO1 can be considered for inclusion in this panel probably as amber (2 families, no functional studies).
Sources: Literature, Radboud University Medical Center, Nijmegen
Created: 14 Dec 2018, 1:55 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Mental retardation, autosomal recessive 64 (MIM 618103)


Variants in this GENE are reported as part of current diagnostic practice


Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
  • Expert Review Amber
  • Mental retardation, autosomal recessive 64 (MIM 618103)
Clinvar variants
Variants in LINGO1
Panels with this gene

History Filter Activity

15 Feb 2019, Gel status: 2

Entity classified by Genomics England curator

Ivone Leong (Genomics England Curator)

Gene: lingo1 has been classified as Amber List (Moderate Evidence).

15 Feb 2019, Gel status: 0

Added Tag

Ivone Leong (Genomics England Curator)

Tag watchlist tag was added to gene: LINGO1.

14 Dec 2018, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes, Set penetrance

Konstantinos Varvagiannis (Other)

gene: LINGO1 was added gene: LINGO1 was added to Intellectual disability. Sources: Literature,Radboud University Medical Center, Nijmegen Mode of inheritance for gene: LINGO1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LINGO1 were set to 28837161 Phenotypes for gene: LINGO1 were set to Mental retardation, autosomal recessive 64 (MIM 618103) Penetrance for gene: LINGO1 were set to Complete Review for gene: LINGO1 was set to AMBER gene: LINGO1 was marked as current diagnostic