On this page
L1CAM
L1 cell adhesion molecule
The L1CAM gene provides instructions for the L1 cell adhesion molecule, a protein critical for the proper development and function of the nervous system. The L1CAM gene encodes a protein called L1 cell adhesion molecule, which is primarily found on the surface of nerve cells.
L1CAM is located on the long (q) arm of chromosome X, at band Xq28. Arm ratio per GRCh38 - banding schematic.
Explore chromosome X in the library →Available at Jeen Health
Clinical tests that include this
Overview
The L1CAM gene, also known as L1 cell adhesion molecule, provides the genetic blueprint for producing the L1 protein. This protein is predominantly located on the surface of neurons throughout the nervous system, where it mediates cell-to-cell interactions.
Its functions are fundamental to processes such as brain development, cognitive abilities, memory, and motor control, making it an important gene in human genetics.
What the gene does
The L1 protein spans the cell membrane, allowing one part of the protein to reside inside the cell and another to project outwards. This unique positioning enables the L1 protein to bind with other proteins, including other L1 proteins, on adjacent neurons. This binding facilitates cell-cell adhesion, helping nerve cells to connect effectively.
Beyond adhesion, the L1 protein is crucial for the movement and organisation of neurons during development. It also supports the outgrowth of axons, which are specialised extensions that transmit nerve impulses. The protein additionally contributes to the formation of myelin, a protective sheath around certain neurons, and the establishment of synapses, the junctions where nerve cells communicate.
Video: Genetics 101
Chromosome location
The L1CAM gene is situated on the long arm of the X chromosome at position 28, denoted as Xq28. This chromosomal location indicates that L1CAM follows an X-linked inheritance pattern.
Protein structure
The L1CAM protein is comprised of 1257 amino acids and features a complex domain architecture. It contains six Ig-like C2-type domains: Ig-like C2-type 1 (amino acids 35-125), Ig-like C2-type 2 (amino acids 139-226), Ig-like C2-type 3 (amino acids 240-328), Ig-like C2-type 4 (amino acids 333-420), Ig-like C2-type 5 (amino acids 425-507), and Ig-like C2-type 6 (amino acids 518-607). A Cell attachment site motif is found between amino acids 554-556. Following these, there are five Fibronectin type-III domains: Fibronectin type-III 1 (amino acids 615-712), Fibronectin type-III 2 (amino acids 717-810), Fibronectin type-III 3 (amino acids 814-916), Fibronectin type-III 4 (amino acids 920-1015), and Fibronectin type-III 5 (amino acids 1016-1115). Additionally, there are Disordered regions at amino acids 698-725, 1176-1207, and 1226-1257.
Key variants
Over 350 different genetic changes, referred to as mutations or variants, have been identified within the L1CAM gene. These variants can lead to alterations in the L1 protein, affecting its structure and function. The specific impact of a variant can vary significantly, resulting in a range of clinical presentations.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.1375C>T | p.Gln459Ter | Pathogenic | ★★☆☆ | X-linked complicated corpus callosum dysgenesis |
c.1528del | p.Ala510fs | Pathogenic/Likely pathogenic | ★★☆☆ | L1CAM-related disorder |
c.2596_2597del | p.Ile866fs | Pathogenic/Likely pathogenic | ★★☆☆ | X-linked hydrocephalus syndrome |
c.2701C>T | p.Arg901Ter | Pathogenic | ★★☆☆ | L1CAM-related disorders |
c.2872+1G>A | - | Pathogenic/Likely pathogenic | ★★☆☆ | Spastic paraplegia |
c.3166+1G>A | - | Pathogenic | ★★☆☆ | L1 syndrome |
c.3453_3456del | p.Lys1150_Tyr1151insTer | Pathogenic | ★★☆☆ | Spastic paraplegia |
c.3496C>T | p.Arg1166Ter | Pathogenic | ★★☆☆ | MASA syndrome |
c.3531-12G>A | - | Pathogenic/Likely pathogenic | ★★☆☆ | Spastic paraplegia |
c.3671C>T | p.Ser1224Leu | Pathogenic/Likely pathogenic | ★★☆☆ | Inborn genetic diseases |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Variants in the L1CAM gene are primarily associated with L1 syndrome, a group of X-linked conditions that predominantly affect males and impact the nervous system. Individuals with L1 syndrome often experience brain abnormalities, intellectual disability, and difficulties with movement. Rarely, L1CAM variants have also been linked to hydrocephalus (fluid build-up in the brain) co-occurring with Hirschsprung disease, an intestinal disorder characterised by a lack of nerve cells in parts of the bowel.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic L1CAM variants typically follow X-linked inheritance.
Carrier frequency by population How common is heterozygous L1CAM carrier status across ancestry groups?UK clinical status
L1CAM is listed on several NHS Genomic Medicine Service national test panels. These include DDG2P, Familial Hirschsprung Disease, Foetal anomalies (R21), Hereditary spastic paraplegia, Hereditary spastic paraplegia, childhood onset (R61), Hydrocephalus (R86), Intellectual disability, and Paediatric pseudo-obstruction syndrome (R438). Its inclusion on these panels highlights its significance in diagnosing these conditions within the UK healthcare system.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the primary role of the L1CAM gene?
The L1CAM gene provides instructions for the L1 cell adhesion molecule, a protein essential for nerve cell adhesion, migration, and the proper development and function of the nervous system.
What is L1 syndrome?
L1 syndrome is a group of conditions caused by variants in the L1CAM gene, primarily affecting males. It is characterised by neurological issues such as brain abnormalities, intellectual disability, and motor problems.
Why is the L1CAM gene considered X-linked?
The L1CAM gene is located on the X chromosome (Xq28), meaning that conditions associated with its variants follow an X-linked inheritance pattern, often presenting differently in males and females.
References
- Christaller WA, Vos Y, Gebre-Medhin S. L1 syndrome diagnosis complemented with functional analysis of L1CAM variants located to the two N-terminal Ig-like domains. Clinical genetics. 2017. PMID: 26891472
- Ferese R, Zampatti S, Griguoli AM. A New Splicing Mutation in the L1CAM Gene Responsible for X-Linked Hydrocephalus (HSAS). Journal of molecular neuroscience : MN. 2016. PMID: 27207492
- Marín R, Ley-Martos M, Gutiérrez G. Three cases with L1 syndrome and two novel mutations in the L1CAM gene. European journal of pediatrics. 2015. PMID: 25948108
- Weller S, Gärtner J. Genetic and clinical aspects of X-linked hydrocephalus (L1 disease): Mutations in the L1CAM gene. Human mutation. 2001. PMID: 11438988
- Kenwrick S, Watkins A, De Angelis E. Neural cell recognition molecule L1: relating biological complexity to human disease mutations. Human molecular genetics. 2000. PMID: 10767310
- Finckh U, Schröder J, Ressler B. Spectrum and detection rate of L1CAM mutations in isolated and familial cases with clinically suspected L1-disease. American journal of medical genetics. 2000. PMID: 10797421