CADM1: Cell Adhesion Molecule 1 – Tumor Suppressor and Synaptic Organizer
Comprehensive genomic and proteomic overview of CADM1 (IGSF4, TSLC1), a member of the immunoglobulin superfamily involved in cell adhesion, tumor suppression, and neuronal synapse formation.
Gene Information Card
| Symbol | CADM1 |
|---|---|
| Full Name | Cell adhesion molecule 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 11q23.3 |
| NCBI Gene ID | 23705 ncbi.nlm.nih.gov/gene/23705 |
| Ensembl ID | ENSG00000182985 |
| UniProt ID | Q9BY67 |
| OMIM ID | 605686 |
| HGNC ID | 5951 |
| Aliases | IGSF4, TSLC1, NECL2, SynCAM1, RA175, BL2, ST17 |
Description
CADM1 (Cell Adhesion Molecule 1) encodes a transmembrane glycoprotein of the immunoglobulin superfamily. It mediates homophilic and heterophilic cell-cell adhesion, acts as a tumor suppressor in multiple epithelial cancers, and is essential for synapse organization in the nervous system. Loss of CADM1 expression is frequently observed in lung, esophageal, and breast cancers due to promoter methylation or genomic deletion.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Non-small cell lung cancer | Loss of CADM1 expression via promoter hypermethylation reduces cell adhesion and promotes invasion. | PMID: 15696293; NCBI GeneRIF |
| Esophageal squamous cell carcinoma | Frequent allelic loss and methylation silencing of CADM1 correlate with poor prognosis. | PMID: 16189552; COSMIC |
| Breast cancer | Reduced CADM1 expression is associated with metastasis and shorter survival. | PMID: 19662633; ClinVar |
| Autism spectrum disorder | Rare missense variants in CADM1 disrupt synaptic adhesion and neuronal connectivity. | PMID: 23453885; OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 28.5 | Medium |
| Esophagus | 22.1 | Medium |
| Brain (cerebellum) | 35.7 | High |
| Breast | 12.3 | Low |
| Testis | 40.2 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (lung carcinoma) | 18.4 | Reduced expression vs normal lung |
| HCT116 (colorectal carcinoma) | 25.1 | Moderate expression |
| SH-SY5Y (neuroblastoma) | 42.6 | High expression; neuronal model |
| MCF7 (breast carcinoma) | 8.9 | Low expression; promoter methylated |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense/Start loss | <0.1% | Loss of translation initiation; likely loss-of-function |
| c.325C>T (p.Arg109Trp) | Missense | 0.2% | Disrupts Ig-like domain; reduced adhesion |
| c.1018C>T (p.Arg340*) | Nonsense | <0.1% | Premature stop; truncation of cytoplasmic domain |
| Promoter hypermethylation | Epigenetic | Frequent in NSCLC | Transcriptional silencing; loss of tumor suppression |
Mutation functional classification
Loss of Function (LOF)
Nonsense, frameshift, and start-loss mutations that abolish protein expression or truncate functional domains. Promoter hypermethylation also leads to loss of function.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in CADM1.
Dominant Negative (DN)
Missense mutations in the extracellular Ig domains (e.g., p.Arg109Trp) may interfere with homophilic adhesion in a dominant-negative manner.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Cell adhesion molecules (CAMs) – KEGG hsa04514
• Adherens junction – KEGG hsa04520
• Synaptic adhesion pathway – Reactome R-HSA-6794362
Protein Summary
CADM1 is a 442-amino-acid type I transmembrane protein with three extracellular immunoglobulin-like domains (one V-set, two C2-set) and a short cytoplasmic tail containing a PDZ-binding motif. It forms homodimers and heterodimers with CADM3 and NECTIN3 to mediate intercellular adhesion. In epithelia, it suppresses tumor growth by maintaining cell polarity and contact inhibition. In neurons, it localizes to synapses and promotes presynaptic differentiation. The protein is N-glycosylated and undergoes proteolytic shedding.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CADM1 Knockout HEK293 Cell Line | EDJ-KQ3881 | Human | 23705 | Details Get a Quote |
| CADM1 Knockout A-549 Cell Line | EDJ-KQ26090 | Human | 23705 | Details Get a Quote |
| CADM1 Knockout HeLa Cell Line | EDJ-KQ26091 | Human | 23705 | Details Get a Quote |
| CADM1 Knockout MDCK Cell Line | EDJ-KZ127 | Dog | 479432 | Details Get a Quote |
| CADM1 Knockout HCT 116 Cell Line | EDJ-KQ72740 | Human | 23705 | Details Get a Quote |
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