L1CAM Gene: Structure, Function, and Clinical Significance
A comprehensive overview of the L1CAM gene, its protein product, associated diseases, expression patterns, and mutations.
Gene Information Card
| Symbol | L1CAM |
|---|---|
| Full Name | L1 cell adhesion molecule |
| Gene Type | protein coding |
| Chromosomal Location | Xq28 |
| NCBI Gene ID | 3897 ncbi.nlm.nih.gov/gene/3897 |
| Ensembl ID | ENSG00000198910 |
| UniProt ID | P32004 |
| OMIM ID | 308840 |
| HGNC ID | 6471 |
| Aliases | CAML1, CD171, HSAS, HSAS1, MASA, MIC5, N-CAM-L1, S10, SPG1 |
Description
The L1CAM gene encodes the L1 cell adhesion molecule, a transmembrane glycoprotein of the immunoglobulin superfamily. It plays a critical role in nervous system development, including neuronal migration, axon outgrowth, fasciculation, and myelination. Mutations in L1CAM are associated with a spectrum of X-linked neurological disorders known as L1 syndrome, which includes hydrocephalus, agenesis of the corpus callosum, spastic paraplegia, and intellectual disability.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| L1 syndrome (CRASH syndrome) | Loss-of-function mutations in L1CAM disrupt neuronal adhesion and signaling, leading to impaired brain development. | ClinVar, OMIM |
| X-linked hydrocephalus (HSAS) | Mutations impair L1CAM-mediated axon guidance and cerebrospinal fluid flow, causing ventricular dilation. | OMIM, PubMed |
| MASA syndrome | Reduced L1CAM function affects neuronal migration and axonal growth, resulting in intellectual disability and spasticity. | OMIM |
| Spastic paraplegia type 1 (SPG1) | Mutations in L1CAM lead to corticospinal tract dysfunction, causing progressive spasticity. | OMIM |
| Corpus callosum agenesis | L1CAM deficiency disrupts callosal axon guidance, leading to partial or complete absence of the corpus callosum. | OMIM |
| Colorectal cancer (prognostic marker) | Overexpression of L1CAM in tumor cells promotes invasion and metastasis via enhanced cell motility and signaling. | COSMIC, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | High |
| Peripheral nervous system | 8.2 | Medium |
| Adrenal gland | 3.1 | Low |
| Kidney | 2.0 | Low |
| Liver | 0.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.3 | High expression; used in neuronal differentiation studies |
| U87 (glioblastoma) | 10.1 | Moderate expression; associated with invasive phenotype |
| HCT116 (colorectal carcinoma) | 7.8 | Elevated expression linked to metastasis |
| MCF7 (breast cancer) | 2.2 | Low expression; not typically expressed in normal breast |
| HEK293 (embryonic kidney) | 1.0 | Low endogenous expression; often used for recombinant L1CAM studies |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1648C>T (p.Arg550Ter) | Nonsense | Rare (found in L1 syndrome families) | Truncated protein lacking cytoplasmic domain; loss of function |
| c.2266G>A (p.Gly756Arg) | Missense | Rare (reported in HSAS) | Disrupts fibronectin type III domain; impairs cell adhesion |
| c.2944C>T (p.Arg982Cys) | Missense | Rare (in MASA syndrome) | Alters extracellular domain; reduces ligand binding |
| c.3572delA (p.Asn1191fs) | Frameshift | Rare (in SPG1) | Premature stop; loss of function |
| c.1A>G (p.Met1Val) | Start codon loss | Rare (in L1 syndrome) | No protein synthesis; complete loss of function |
Mutation functional classification
Loss of Function (LOF)
Most L1CAM mutations are loss-of-function, leading to reduced or absent protein expression or impaired adhesion/signaling. These cause L1 syndrome phenotypes.
Gain of Function (GOF)
In certain cancers, L1CAM overexpression (not mutation) acts as a gain-of-function, promoting tumor progression and metastasis.
Dominant Negative (DN)
Some missense mutations may exert a dominant-negative effect by forming nonfunctional dimers with wild-type L1CAM, though this is less common.
View complete mutation data：
Gene Ontology (GO)
| • cell adhesion | • axon guidance |
| • neuron projection development | • homophilic cell adhesion via plasma membrane adhesion molecules |
| • signal transduction | • nervous system development |
| • cell migration | • extracellular matrix binding |
Pathways
• Axon guidance
• Cell adhesion molecules (CAMs)
• Signaling by Rho GTPases
• MAPK signaling pathway
• PI3K-Akt signaling pathway
Protein Summary
The L1CAM protein is a type I membrane glycoprotein consisting of six immunoglobulin-like domains and five fibronectin type III repeats in the extracellular region, a single transmembrane domain, and a highly conserved cytoplasmic tail. It mediates homophilic and heterophilic cell adhesion, interacting with integrins, neurocan, and other ligands. Intracellularly, it links to the actin cytoskeleton via ankyrin and ezrin, and activates signaling cascades such as MAPK and PI3K, crucial for neuronal migration and axon growth. Proteolytic cleavage of L1CAM releases a soluble ectodomain that can modulate cell behavior. In cancer, L1CAM expression correlates with poor prognosis and metastatic potential.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| L1CAM Knockout HEK293 Cell Line | EDJ-KQ5103 | Human | 3897 | Details Get a Quote |
| L1CAM Knockout A-549 Cell Line | EDJ-KQ28054 | Human | 3897 | Details Get a Quote |
| L1CAM Knockout HCT 116 Cell Line | EDJ-KQ28055 | Human | 3897 | Details Get a Quote |
| L1CAM Knockout HeLa Cell Line | EDJ-KQ28056 | Human | 3897 | Details Get a Quote |
| L1CAM Knockout MDCK Cell Line | EDJ-KZ321 | Dog | 492244 | Details Get a Quote |
Displaying Records 1 To 5 Of 5 Records
