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L1CAM (L1 cell adhesion molecule)

Written2008-12Heiner Schäfer, Susanne Sebens Müerköster
Laboratory of Molecular Gastroenterology, 1st Dept. of Medicine, UKSH Campus Kiel, Schittenhelmstr. 12, 24105 Kiel, Germany

(Note : for Links provided by Atlas : click)


antigen identified by monoclonal antibody R1
Alias_symbol (synonym)CD171
Other aliasCAML1
LocusID (NCBI) 3897
Atlas_Id 44110
Location Xq28  [Link to chromosome band Xq28]
Location_base_pair Starts at 153861514 and ends at 153875944 bp from pter ( according to hg19-Feb_2009)  [Mapping L1CAM.png]
  Picture from Genetics Home Reference; Reviewed March 2008.
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
L1CAM (Xq28) / FLNA (Xq28)L1CAM (Xq28) / L1CAM (Xq28)


Description The L1CAM gene is 24,657 bp in length, consisting of 28 exons according to Ensembl and Entrez-gene.
Transcription There are 7 transcripts of the gene according to Ensembl.


  Protein domain structure (left) and cleavage sites (right) of L1CAM. NTF, 200 kDa N-terminal cleavage product; CTF1, 32 kDa C-terminal cleavage product; Ig, immunoglobulin like domain; FN, fibronectin like domain (From Fogel et al., 2003 and Maretzky et al., 2005).
Description L1CAM (L1) is a 200-220 kD glycoprotein and a member of the immunoglobulin superfamily. This type-1 transmembrane protein consists of six immunoglobulin like domains at the amino terminal end of the molecule followed by five fibronectin type III homologous repeats, a single transmembrane region and a short intracellular domain (Moos et al., 1988). Two splicing variants are known encoding for 1257 and 1253 amino acids proteins.
Expression Neural, hematopoietic and transformed epithelial cells.
Localisation Cell surface, extracellular matrix and nucleus (C-terminal fragment).
Function L1 plays a critical role in axon outgrowth and fasciculation, neuronal migration and survival, synaptic plasticity and regeneration after trauma (Maness et al., 2007). L1 can interact with itself (homophilic) but also with a variety of heterophilic ligands such as integrins, CD24, neurocan, neuropilin-1 and other members of the neural cell adhesion family. In many incidences the binding sites in the L1 molecule have been mapped. The RGD site in the sixth Ig domain supports α5β1, αvβ3,5 integrin-mediated cell binding and the first Ig domain can bind to the proteoglycan neurocan or the VEGF-R2-coreceptor neuropilin-1.
Beside its cell surface localization, L1CAM can also be cleaved by several proteases, i.e. the matrix metalloproteinases ADAM10 and ADAM17, metalloprotease PC5A proprotein convertase or by γ-secretases (Maretzky et al., 2005). Soluble L1CAM has been reported to be important for migration of neuronal as well as of tumor cells (Maretzky et al., 2005; Mechtersheimer et al., 2001), and several studies support a role for L1CAM in tumor growth (Arlt et al., 2006), tumor cell invasion, metastasis of melanoma, ovarial and colon cancer (Mechtersheimer et al., 2001; Gavert et al., 2005; Fogel et al., 2003) and chemoresistance (Sebens Müerköster et al., 2007; Stoeck et al., 2007).
L1 transiently activates pp60c-src, phosphoinositide 3-kinase (PI3 kinase), the VAV2 guanine nucleotide exchange factor, the RAC1 GTPase and p21-activated kinase (PAK1) in a pathway culminating in MEK and ERK activation.
Homology NrCAM/BRABO, CHL1, neurofascin; in invertebrates, neuroglian and sax-7.


Germinal Numerous mutations in the L1CAM gene are known (De Angelis et al., 1999) accounting for X-linked neurological syndromes (corpus callosum hypoplasia, retardation, aphasia, spastic paraplegia and hydrocephalus). Alternative splicing of a neuron-specific exon is thought to be functionally relevant.

Implicated in

Note Various cancers
Disease Overexpression of L1 has been reported in ovarian cancer, colon cancer, glioma, renal cell cancer, neuroblastoma, endometrial cancer, melanoma, pancreatic cancer. L1 expression promotes invasiveness of the tumor as well as chemoresistance. Thus, L1 expression is mainly found in the invasive front of coloretal cancer and blockade of L1 reduces tumor growth in mouse models. Blockade of L1 dimishes resistance of ovarian and pancreatic cancer towards anti-cancer drugs.
Prognosis In ovarian cancer, L1 expression associates with poor prognosis. Other L1 expressing tumor entities include those with extremely poor prognosis, i.e. pancreatic or renal cell cancer.
Entity Various diseases
Disease L1 mutations associate with X-linked mental retardation (=L1 syndrome: mental retardation, hydrocephalus, aphasia, spastic paraplegia, agenesis of corpus callosum, optic nerve atrophy), Hirschprung's disease and schizophrenia in some populations.


Efficient inhibition of intra-peritoneal tumor growth and dissemination of human ovarian carcinoma cells in nude mice by anti-L1-cell adhesion molecule monoclonal antibody treatment.
Arlt MJ, Novak-Hofer I, Gast D, Gschwend V, Moldenhauer G, Grunberg J, Honer M, Schubiger PA, Altevogt P, Kruger A.
Cancer Res. 2006 Jan 15;66(2):936-43.
PMID 16424028
Pathological missense mutations of neural cell adhesion molecule L1 affect homophilic and heterophilic binding activities.
De Angelis E, MacFarlane J, Du J-S, Yeo G, Hicks R, Rathjen FG, Kenwrick S, Brummendorf T.
EMBO J. 1999 Sep 1;18(17):4744-53.
PMID 10469653
L1 expression as a predictor of progression and survival in patients with uterine and ovarian carcinomas.
Fogel M, Gutwein P, Mechtersheimer S, Riedle S, Stoeck A, Smirnov A, Edler L, Ben-Arie A, Huszar M, Altevogt P.
Lancet. 2003 Sep 13;362(9387):869-75.
PMID 13678974
L1, a novel target of beta-catenin signaling, transforms cells and is expressed at the invasive front of colon cancers.
Gavert N, Conacci-Sorrell M, Gast D, Schneider A, Altevogt P, Brabletz T, Ben-Ze'ev A.
J Cell Biol. 2005 Feb 14;168(4):633-42.
PMID 15716380
Neural recognition molecules of the immunoglobulin superfamily: signaling transducers of axon guidance and neuronal migration.
Maness PF, Schachner M.
Nat Neurosci. 2007 Jan;10(1):19-26. (REVIEW)
PMID 17189949
L1 is sequentially processed by two differently activated metalloproteases and presenilin/gamma-secretase and regulates neural cell adhesion, cell migration, and neurite outgrowth.
Maretzky T, Schulte M, Ludwig A, Rose-John S, Blobel C, Hartmann D, Altevogt P, Saftig P, Reiss K.
Mol Cell Biol. 2005 Oct;25(20):9040-53.
PMID 16199880
Ectodomain shedding of L1 adhesion molecule promotes cell migration by autocrine binding to integrins.
Mechtersheimer S, Gutwein P, Agmon-Levin N, Stoeck A, Oleszewski M, Riedle S, Postina R, Fahrenholz F, Fogel M, Lemmon V, Altevogt P.
J Cell Biol. 2001 Nov 12;155(4):661-73.
PMID 11706054
Neural adhesion molecule L1 as a member of the immunoglobulin superfamily with binding domains similar to fibronectin.
Moos M, Tacke R, Scherer H, Teplow D, Fruh K, Schachner M.
Nature. 1988 Aug 25;334(6184):701-3.
PMID 3412448
Drug-induced expression of the cellular adhesion molecule L1CAM confers anti-apoptotic protection and chemoresistance in pancreatic ductal adenocarcinoma cells.
Sebens Muerkoster S, Werbing V, Sipos B, Debus MA, Witt M, Grossmann M,Leisner D, Kotteritzsch J, Kappes H, Kloppel G, Altevogt P, Folsch UR, Schafer H.
Oncogene. 2007 Apr 26;26(19):2759-68.
PMID 17086212
L1-CAM in a membrane-bound or soluble form augments protection from apoptosis in ovarian carcinoma cells.
Stoeck A, Gast D, Sanderson MP, Issa Y, Gutwein P, Altevogt P.
Gynecol Oncol. 2007 Feb;104(2):461-9.
PMID 17030349


This paper should be referenced as such :
Schè_fer, H ; Sebens, Möerköster S
L1CAM (L1 cell adhesion molecule)
Atlas Genet Cytogenet Oncol Haematol. 2009;13(11):847-849.
Free journal version : [ pdf ]   [ DOI ]
On line version :

External links

HGNC (Hugo)L1CAM   6470
LRG (Locus Reference Genomic)LRG_14
Entrez_Gene (NCBI)L1CAM  3897  L1 cell adhesion molecule
AliasesCAML1; CD171; HSAS; HSAS1; 
GeneCards (Weizmann)L1CAM
Ensembl hg19 (Hinxton)ENSG00000198910 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000198910 [Gene_View]  ENSG00000198910 [Sequence]  chrX:153861514-153875944 [Contig_View]  L1CAM [Vega]
ICGC DataPortalENSG00000198910
TCGA cBioPortalL1CAM
Genatlas (Paris)L1CAM
SOURCE (Princeton)L1CAM
Genetics Home Reference (NIH)L1CAM
Genomic and cartography
GoldenPath hg38 (UCSC)L1CAM  -     chrX:153861514-153875944 -  Xq28   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)L1CAM  -     Xq28   [Description]    (hg19-Feb_2009)
EnsemblL1CAM - Xq28 [CytoView hg19]  L1CAM - Xq28 [CytoView hg38]
Mapping of homologs : NCBIL1CAM [Mapview hg19]  L1CAM [Mapview hg38]
OMIM303350   304100   307000   308840   
Gene and transcription
Genbank (Entrez)AB102653 AI361399 AK289754 AY927629 BC025843
RefSeq transcript (Entrez)NM_000425 NM_001143963 NM_001278116 NM_024003
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)L1CAM
Cluster EST : UnigeneHs.522818 [ NCBI ]
CGAP (NCI)Hs.522818
Alternative Splicing GalleryENSG00000198910
Gene ExpressionL1CAM [ NCBI-GEO ]   L1CAM [ EBI - ARRAY_EXPRESS ]   L1CAM [ SEEK ]   L1CAM [ MEM ]
Gene Expression Viewer (FireBrowse)L1CAM [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevestigatorExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)3897
GTEX Portal (Tissue expression)L1CAM
Human Protein AtlasENSG00000198910-L1CAM [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP32004   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP32004  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP32004
Splice isoforms : SwissVarP32004
Domaine pattern : Prosite (Expaxy)FN3 (PS50853)    IG_LIKE (PS50835)   
Domains : Interpro (EBI)FN3_dom    Ig-like_dom    Ig-like_fold    Ig_I-set    Ig_sub    Ig_sub2    Neurofascin/L1/NrCAM_C   
Domain families : Pfam (Sanger)Bravo_FIGEY (PF13882)    fn3 (PF00041)    I-set (PF07679)   
Domain families : Pfam (NCBI)pfam13882    pfam00041    pfam07679   
Domain families : Smart (EMBL)FN3 (SM00060)  IG (SM00409)  IGc2 (SM00408)  
Conserved Domain (NCBI)L1CAM
DMDM Disease mutations3897
Blocks (Seattle)L1CAM
Human Protein Atlas [tissue]ENSG00000198910-L1CAM [tissue]
Peptide AtlasP32004
IPIIPI00871467   IPI00334532   IPI01013306   IPI01016031   IPI01011905   IPI00643864   IPI00646281   IPI00853275   IPI00853066   IPI00927501   IPI00927755   IPI00924481   
Protein Interaction databases
IntAct (EBI)P32004
Ontologies - Pathways
Ontology : AmiGOprotein binding  plasma membrane  plasma membrane  focal adhesion  chemotaxis  cell adhesion  cell-matrix adhesion  nervous system development  axon guidance  axon guidance  cell surface  cell surface  integral component of membrane  cell migration  protein domain specific binding  axon  dendrite  extracellular matrix  neuron projection development  neuronal cell body  axonal growth cone  positive regulation of axon extension  synapse organization  leukocyte migration  axon development  
Ontology : EGO-EBIprotein binding  plasma membrane  plasma membrane  focal adhesion  chemotaxis  cell adhesion  cell-matrix adhesion  nervous system development  axon guidance  axon guidance  cell surface  cell surface  integral component of membrane  cell migration  protein domain specific binding  axon  dendrite  extracellular matrix  neuron projection development  neuronal cell body  axonal growth cone  positive regulation of axon extension  synapse organization  leukocyte migration  axon development  
Pathways : KEGGCell adhesion molecules (CAMs)    Axon guidance   
REACTOMEP32004 [protein]
REACTOME PathwaysR-HSA-445144 [pathway]   
NDEx NetworkL1CAM
Atlas of Cancer Signalling NetworkL1CAM
Wikipedia pathwaysL1CAM
Orthology - Evolution
GeneTree (enSembl)ENSG00000198910
Phylogenetic Trees/Animal Genes : TreeFamL1CAM
Homologs : HomoloGeneL1CAM
Homology/Alignments : Family Browser (UCSC)L1CAM
Gene fusions - Rearrangements
Fusion : QuiverL1CAM
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerL1CAM [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)L1CAM
Exome Variant ServerL1CAM
ExAC (Exome Aggregation Consortium)ENSG00000198910
GNOMAD BrowserENSG00000198910
Genetic variants : HAPMAP3897
Genomic Variants (DGV)L1CAM [DGVbeta]
DECIPHERL1CAM [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisL1CAM 
ICGC Data PortalL1CAM 
TCGA Data PortalL1CAM 
Broad Tumor PortalL1CAM
OASIS PortalL1CAM [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICL1CAM  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDL1CAM
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
LOVD (Leiden Open Variation Database)NGRL, Manchester LOVD
BioMutasearch L1CAM
DgiDB (Drug Gene Interaction Database)L1CAM
DoCM (Curated mutations)L1CAM (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)L1CAM (select a term)
NCG5 (London)L1CAM
Cancer3DL1CAM(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
OMIM303350    304100    307000    308840   
Orphanet164    541    1668    21239   
Genetic Testing Registry L1CAM
NextProtP32004 [Medical]
Target ValidationL1CAM
Huge Navigator L1CAM [HugePedia]
snp3D : Map Gene to Disease3897
BioCentury BCIQL1CAM
ClinGenL1CAM (curated)
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD3897
Chemical/Pharm GKB GenePA30259
Clinical trialL1CAM
canSAR (ICR)L1CAM (select the gene name)
PubMed246 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Mon Jul 16 09:51:54 CEST 2018

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