• 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
L1CAM (HGNC:6470) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
L1 cell adhesion molecule
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
HSAS1, SPG1, HSAS, MASA, MIC5, S10
Alias symbols
CD171, NCAM-L1, CAML1
%HI
15.59(Read more about the DECIPHER Haploinsufficiency Index)
pLI
1(Read more about gnomAD pLI score)
LOEUF
0.13(Read more about gnomAD LOEUF score)
Cytoband
Xq28
Genomic Coordinates
GRCh37/hg19: chrX:153126969-153151627 NCBI Ensembl UCSC
GRCh38/hg38: chrX:153861514-153886173 NCBI Ensembl UCSC
MANE Select Transcript
NM_001278116.2 ENST00000370060.7 (Read more about MANE Select)
Function
Neural cell adhesion molecule involved in the dynamics of cell adhesion and in the generation of transmembrane signals at tyrosine kinase receptors. During brain development, critical in multiple processes, including neuronal migration, axonal growth and fasciculation, and synaptogenesis. In the mature brain, plays a role in the dynamics of neuronal structure and function, including synaptic plasticity. {ECO:0000269|PubMed:20621658, ECO:0000305}. (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-31516
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
12/02/2020

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
  • X-linked hydrocephalus with stenosis of the aqueduct of Sylvius Monarch
HI Evidence:
  • PUBMED: 19846429
    Vos et al. (2010) reviewed the literature and described the L1CAM mutational spectrum. In this review, the authors document L1CAM variants identified in 143 different patients with L1 disease, including 36% missense mutations, 13% nonsense mutations, 24% deletions, 3% insertions, and 24% splice site changes. Genotype-phenotype correlations were proposed: variants leading to extracellular truncation of L1 protein are much more likely to produce a severe phenotype than missense mutations in the extracellular domains; mutations of the cytoplasmic domain tend to produce the mildest form of disease.
  • PUBMED: 23820807
    Adle-Biassette et al. (2013) described a large cohort of 138 cases with hydrocephalus and other neuropathological findings referred to their genetic testing laboratory for L1CAM sequencing. Fifty-seven cases had deleterious L1CAM variants. Among these fifty-seven cases, missense variants were detected in 16 patients (28.1 %), frameshift variants (small deletions, duplications, insertions) in 13 patients (22.8 %), splice variants in 14 patients (24.6 %), nonsense variants in 12 patients (21.0 %) and large rearrangements in 2 patients (3.5 %). Of note, case 14 includes triplication of whole L1CAM gene which is not clearly described.
HI Evidence Comments:
L1CAM encodes the L1 protein which is a member of the immunoglobulin superfamily of neuronal cell adhesion molecules. Loss-of-function pathogenic variants in L1CAM have been associated with L1 syndrome. L1 syndrome includes X-linked hydrocephalus (OMIM 307000), MASA syndrome (OMIM 303350), X-linked complicated spastic paraplegia type 1 (OMIM 303350), and X-linked agenesis of the corpus callosum (OMIM 304100). L1 syndrome is an X linked intellectual disability syndrome and is characterized by hydrocephalus, agenesis or hypoplasia of corpus callosum and corticospinal tracts, mental retardation, spastic paraplegia, and adducted thumbs. Loss-of-function of L1CAM is a well-known mechanism of L1 syndrome. Numerous pathogenic variants have been reported in the medical literature (PMIDs 29960101,11968085, etc.) and public/commercial variant databases. Genotype-phenotype correlation has been established based on literature review. Variants leading to extracellular truncation of L1 protein are much more likely to produce a severe phenotype than missense mutations in the extracellular domains; mutations of the cytoplasmic domain tend to produce the mildest form of disease.
NOTE:

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Published Evidence:
  • PUBMED: 23820807
    Adle-Biassette et al (2013) reported 1 single case (case 14) carrying a triplication of whole L1CAM gene among total 138 L1 sydrome patients cohort. However, no detail information about the breakpoints is included in this report.
TS Evidence Comments:
There have not been any reports of focal duplications of the entire L1CAM gene that do not disrupt gene function. Larger duplications including L1CAM and other genes have been reported (PMID: 20860806, 18854860, 16080119).
NOTE:

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.

Genomic View

Select assembly: (NC_000023.10) (NC_000023.11)