CADM2: Cell Adhesion Molecule 2 – A Key Regulator of Neural Connectivity and Metabolic Traits
Comprehensive genomic and functional analysis of CADM2, a synaptic adhesion molecule implicated in neurodevelopmental disorders, obesity, and cancer.
Gene Information Card
| Symbol | CADM2 |
|---|---|
| Full Name | Cell Adhesion Molecule 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 3p12.1 |
| NCBI Gene ID | 253559 ncbi.nlm.nih.gov/gene/253559 |
| Ensembl ID | ENSG00000175161 |
| UniProt ID | Q8N6J6 |
| OMIM ID | 609936 |
| HGNC ID | 29849 |
| Aliases | IGSF4D, NECL3, SynCAM2, TSLC2 |
Description
CADM2 (Cell Adhesion Molecule 2) encodes a member of the immunoglobulin superfamily that functions as a homophilic and heterophilic cell adhesion molecule. It is predominantly expressed in the brain, where it localizes to synapses and plays a critical role in synaptic organization, neurite outgrowth, and neural circuit formation. CADM2 has also been implicated in metabolic regulation, with genome-wide association studies linking variants to body mass index, obesity, and type 2 diabetes. Additionally, altered expression is observed in several cancers, suggesting a role in tumor suppression or progression.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Obesity | GWAS variants (e.g., rs13078960) near CADM2 are associated with increased BMI and waist circumference; the gene may influence energy homeostasis via hypothalamic expression. | GWAS meta-analysis (PMID: 25673413, 30239722) |
| Autism Spectrum Disorder | Rare copy number variants and common variants in CADM2 have been linked to autism risk; synaptic adhesion deficits may impair neural connectivity. | Case-control studies (PMID: 22495306, 30559424) |
| Schizophrenia | CADM2 expression is altered in postmortem brain tissue from schizophrenia patients; synaptic dysfunction is a proposed mechanism. | Expression analysis (PMID: 26754917) |
| Colorectal Cancer | Promoter hypermethylation and reduced CADM2 expression are observed in colorectal tumors; loss of adhesion may promote invasion. | Methylation and expression studies (PMID: 20628086) |
| Lung Cancer | Downregulation of CADM2 in non-small cell lung cancer correlates with poor prognosis; re-expression suppresses tumor growth. | Functional studies (PMID: 21573173) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 38.5 | High |
| Brain (cerebellum) | 22.1 | Medium |
| Adipose tissue | 12.3 | Medium |
| Testis | 8.7 | Low |
| Lung | 4.2 | Low |
| Colon | 3.1 | Low |
| Liver | 1.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 45.2 | Neuronal model; high CADM2 expression |
| U-87 MG (glioblastoma) | 28.6 | Glial tumor line; moderate expression |
| HEK293 (embryonic kidney) | 12.1 | Low endogenous expression; used for recombinant studies |
| HCT116 (colorectal carcinoma) | 3.4 | Low expression; promoter hypermethylation reported |
| A549 (lung carcinoma) | 2.8 | Low expression; correlates with tumor suppression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs13078960 | SNV (intergenic) | 0.15 (European) | Associated with increased BMI and obesity risk |
| rs9841829 | SNV (intronic) | 0.22 (European) | Linked to waist-hip ratio |
| c.1015C>T (p.Arg339*) | Nonsense | Rare | Premature truncation; loss of adhesion domain; reported in autism cohort |
| c.1423G>A (p.Gly475Arg) | Missense | Rare | Located in Ig-like domain; may impair homophilic binding |
| Promoter hypermethylation | Epigenetic | Frequent in colorectal cancer | Transcriptional silencing; loss of tumor suppressor function |
Mutation functional classification
Loss of Function (LOF)
Nonsense mutations (e.g., p.Arg339*) and promoter hypermethylation lead to reduced or absent CADM2 protein, impairing cell adhesion and synaptic organization. Loss-of-function is associated with neurodevelopmental phenotypes and tumor progression.
Gain of Function (GOF)
No well-characterized gain-of-function mutations have been reported for CADM2. Overexpression in some cancers may paradoxically promote metastasis in specific contexts, but this is not classified as a classic gain-of-function mutation.
Dominant Negative (DN)
Missense mutations in the extracellular Ig-like domains (e.g., p.Gly475Arg) may disrupt homophilic trans-interactions, potentially exerting a dominant-negative effect on wild-type CADM2 at the synapse.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Cell adhesion molecules (CAMs) – KEGG hsa04514
• Synaptic vesicle cycle – KEGG hsa04721
• Neurexin–neuroligin signaling – Reactome R-HSA-6794362
Protein Summary
CADM2 (SynCAM2) is a single-pass type I membrane protein belonging to the nectin-like family. It contains three extracellular immunoglobulin-like domains (one V-type, two C2-type) and a short cytoplasmic tail with a PDZ-binding motif. The protein mediates homophilic and heterophilic (with CADM1, CADM3, and nectins) cell adhesion at synapses, contributing to synaptic assembly and plasticity. CADM2 is also involved in cell–cell interactions in non-neuronal tissues, where it can act as a tumor suppressor by maintaining epithelial integrity. Post-translational modifications include N-glycosylation, which is essential for proper trafficking and adhesion.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CADM2 Knockout HEK293 Cell Line | EDJ-KQ11735 | Human | 253559 | Details Get a Quote |
| CADM2 Knockout HeLa Cell Line | EDJ-KQ59242 | Human | 253559 | Details Get a Quote |
| CADM2 Knockout A-549 Cell Line | EDJ-KQ67710 | Human | 253559 | Details Get a Quote |
| CADM2 Knockout HCT 116 Cell Line | EDJ-KQ76092 | Human | 253559 | Details Get a Quote |
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