L1CAM |
- 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)
Haploinsufficiency (HI) Score Details
- X-linked hydrocephalus with stenosis of the aqueduct of Sylvius Monarch
-
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.
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
-
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.
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.