L1CAM
L1 cell adhesion molecule, the group of CD molecules|Ig-like cell adhesion molecule family|Fibronectin type III domain containing|I-set domain containing
Basic information
Region (hg38): X:153861514-153886173
Previous symbols: [ "HSAS1", "SPG1", "HSAS", "MASA", "MIC5", "S10" ]
Links
Phenotypes
GenCC
Source:
- X-linked complicated corpus callosum dysgenesis (Strong), mode of inheritance: XL
- MASA syndrome (Strong), mode of inheritance: XL
- X-linked hydrocephalus with stenosis of the aqueduct of Sylvius (Strong), mode of inheritance: XL
- X-linked hydrocephalus with stenosis of the aqueduct of Sylvius (Supportive), mode of inheritance: XL
- MASA syndrome (Supportive), mode of inheritance: XL
- X-linked complicated corpus callosum dysgenesis (Supportive), mode of inheritance: XL
- X-linked complicated spastic paraplegia type 1 (Supportive), mode of inheritance: XL
- X-linked hydrocephalus with stenosis of the aqueduct of Sylvius (Definitive), mode of inheritance: XL
- X-linked complicated corpus callosum dysgenesis (Strong), mode of inheritance: XL
- L1 syndrome (Definitive), mode of inheritance: XL
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Hydrocephalus due to congenital stenosis of aqueduct of Sylvius; MASA syndrome; CRASH syndrome; Corpus callosum, partial agenesis of; Spastic paraplegia-1 | XL | 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 | Gastrointestinal; Musculoskeletal; Neurologic | 4855169; 7070456; 6702900; 2737668; 2277384; 1870106; 1303258; 7920659; 8062435; 7920660; 8556302; 7562969; 9279760; 15368500; 16650080; 21271669; 21644943; 21839187; 21961551; 22222883; 22344793; 22354677 |
| Individuals may be at risk for findings including Hirschsprung disease as well as hydrocephalus |
ClinVar
This is a list of variants' phenotypes submitted to
- Spastic_paraplegia (994 variants)
- not_provided (340 variants)
- Inborn_genetic_diseases (121 variants)
- not_specified (81 variants)
- X-linked_hydrocephalus_syndrome (72 variants)
- L1CAM-related_disorder (59 variants)
- MASA_syndrome (51 variants)
- X-linked_complicated_corpus_callosum_dysgenesis (33 variants)
- Hereditary_spastic_paraplegia (26 variants)
- L1_syndrome (23 variants)
- Hydrocephalus_due_to_aqueductal_stenosis (6 variants)
- Intellectual_disability (3 variants)
- L1CAM-related_disorders (3 variants)
- See_cases (2 variants)
- Peripheral_neuropathy (1 variants)
- Hereditary_ataxia (1 variants)
- Aganglionic_megacolon (1 variants)
- History_of_neurodevelopmental_disorder (1 variants)
- Muscular_dystrophy,_limb-girdle,_autosomal_recessive_23 (1 variants)
- Global_developmental_delay (1 variants)
- Hydrops_fetalis (1 variants)
- Cerebellar_ataxia (1 variants)
- Hydrocephalus,_X-linked,_with_congenital_idiopathic_intestinal_pseudoobstruction (1 variants)
- Congenital_cerebellar_hypoplasia (1 variants)
- Severe_hydrocephalus (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the L1CAM gene is commonly pathogenic or not. These statistics are base on transcript: NM_001278116.2. 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 | 279 | 67 | 354 | |||
| missense | 16 | 25 | 257 | 152 | 56 | 506 |
| nonsense | 38 | 47 | ||||
| start loss | 2 | 2 | ||||
| frameshift | 33 | 16 | 49 | |||
| splice donor/acceptor (+/-2bp) | 18 | 23 | 43 | |||
| Total | 105 | 77 | 264 | 432 | 123 |
Highest pathogenic variant AF is 0.000008941424
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| L1CAM | protein_coding | protein_coding | ENST00000370060 | 28 | 47709 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 5.37e-7 | 125737 | 1 | 1 | 125739 | 0.00000795 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.84 | 373 | 562 | 0.663 | 0.0000500 | 8251 |
| Missense in Polyphen | 106 | 240.9 | 0.44002 | 3609 | ||
| Synonymous | -0.659 | 257 | 244 | 1.05 | 0.0000229 | 2479 |
| Loss of Function | 6.22 | 2 | 49.0 | 0.0408 | 0.00000372 | 734 |
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) | 0.0000244 | 0.0000176 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- 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}.;
- Disease
- DISEASE: Hydrocephalus due to stenosis of the aqueduct of Sylvius (HSAS) [MIM:307000]: Hydrocephalus is a condition in which abnormal accumulation of cerebrospinal fluid in the brain causes increased intracranial pressure inside the skull. This is usually due to blockage of cerebrospinal fluid outflow in the brain ventricles or in the subarachnoid space at the base of the brain. In children is typically characterized by enlargement of the head, prominence of the forehead, brain atrophy, mental deterioration, and convulsions. In adults the syndrome includes incontinence, imbalance, and dementia. HSAS is characterized by mental retardation and enlarged brain ventricles. {ECO:0000269|PubMed:10797421, ECO:0000269|PubMed:11857550, ECO:0000269|PubMed:12435569, ECO:0000269|PubMed:12514225, ECO:0000269|PubMed:19846429, ECO:0000269|PubMed:20621658, ECO:0000269|PubMed:22344793, ECO:0000269|PubMed:22973895, ECO:0000269|PubMed:24155914, ECO:0000269|PubMed:7562969, ECO:0000269|PubMed:7762552, ECO:0000269|PubMed:7881431, ECO:0000269|PubMed:7920659, ECO:0000269|PubMed:8401576, ECO:0000269|PubMed:8556302, ECO:0000269|PubMed:8929944, ECO:0000269|PubMed:9118141, ECO:0000269|PubMed:9195224, ECO:0000269|PubMed:9268105, ECO:0000269|PubMed:9521424, ECO:0000269|PubMed:9744477, ECO:0000269|PubMed:9832035}. Note=The disease is caused by mutations affecting the gene represented in this entry. L1CAM mutations have also been found in few patients affected by hydrocephalus with Hirschsprung disease, suggesting a role of this gene acting either in a direct or indirect way in the pathogenesis of Hirschsprung disease (PubMed:22344793). {ECO:0000269|PubMed:22344793}.; DISEASE: Mental retardation, aphasia, shuffling gait, and adducted thumbs syndrome (MASA) [MIM:303350]: An X-linked recessive syndrome with a highly variable clinical spectrum. Main clinical features include spasticity and hyperreflexia of lower limbs, shuffling gait, mental retardation, aphasia and adducted thumbs. The features of spasticity have been referred to as complicated spastic paraplegia type 1 (SPG1). Some patients manifest corpus callosum hypoplasia and hydrocephalus. Inter- and intrafamilial variability is very wide, such that patients with hydrocephalus, MASA, SPG1, and agenesis of corpus callosum can be present within the same family. {ECO:0000269|PubMed:10797421, ECO:0000269|PubMed:10805190, ECO:0000269|PubMed:11857550, ECO:0000269|PubMed:16816908, ECO:0000269|PubMed:19846429, ECO:0000269|PubMed:22344793, ECO:0000269|PubMed:22973895, ECO:0000269|PubMed:24155914, ECO:0000269|PubMed:26891472, ECO:0000269|PubMed:7562969, ECO:0000269|PubMed:7762552, ECO:0000269|PubMed:7881431, ECO:0000269|PubMed:7920659, ECO:0000269|PubMed:7920660, ECO:0000269|PubMed:8556302, ECO:0000269|PubMed:9268105, ECO:0000269|PubMed:9300653, ECO:0000269|PubMed:9452110, ECO:0000269|PubMed:9521424, ECO:0000269|PubMed:9744477, ECO:0000269|PubMed:9832035}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=Defects in L1CAM may contribute to Hirschsprung disease by modifying the effects of Hirschsprung disease- associated genes to cause intestinal aganglionosis. {ECO:0000269|PubMed:11857550}.; DISEASE: Agenesis of the corpus callosum, X-linked, partial (ACCPX) [MIM:304100]: A syndrome characterized by partial corpus callosum agenesis, hypoplasia of inferior vermis and cerebellum, mental retardation, seizures and spasticity. Other features include microcephaly, unusual facies, and Hirschsprung disease in some patients. {ECO:0000269|PubMed:16650080}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=Defects in L1CAM are associated with a wide phenotypic spectrum which varies from severe hydrocephalus and prenatal death (HSAS) to a milder phenotype (MASA). These variations may even occur within the same family. Due to the overlap of phenotypes between HSAS and MASA, many authors use the general concept of L1 syndrome which covers both ends of the spectrum. {ECO:0000269|PubMed:19846429, ECO:0000269|PubMed:22222883, ECO:0000269|PubMed:26891472}.;
- Pathway
- Cell adhesion molecules (CAMs) - Homo sapiens (human);Axon guidance - Homo sapiens (human);Developmental Biology;Recycling pathway of L1;Beta3 integrin cell surface interactions;Interaction between L1 and Ankyrins;Cell surface interactions at the vascular wall;Hemostasis;Signal transduction by L1;L1CAM interactions;Axon guidance;Basigin interactions
(Consensus)
Intolerance Scores
- loftool
- 0.0181
- rvis_EVS
- -1.3
- rvis_percentile_EVS
- 4.92
Haploinsufficiency Scores
- pHI
- 0.367
- hipred
- Y
- hipred_score
- 0.631
- ghis
- 0.575
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.843
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- L1cam
- Phenotype
- growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); cellular phenotype; craniofacial phenotype; vision/eye phenotype; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); pigmentation phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton 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
- l1cama
- Affected structure
- medial longitudinal fasciculus
- Phenotype tag
- abnormal
- Phenotype quality
- defasciculated
Gene ontology
- Biological process
- chemotaxis;cell adhesion;homophilic cell adhesion via plasma membrane adhesion molecules;cell-matrix adhesion;nervous system development;axon guidance;cell migration;neuron projection development;positive regulation of axon extension;synapse organization;leukocyte migration;axon development
- Cellular component
- plasma membrane;focal adhesion;cell surface;integral component of membrane;axon;dendrite;neuronal cell body;axonal growth cone;collagen-containing extracellular matrix
- Molecular function
- protein binding;axon guidance receptor activity;protein domain specific binding