- Length
- 435 aa
- Mass
- 47.6 kDa
- Annotated
- 2026-06-13
43 papers in source corpus
14 papers cited in narrative
15 extracted findings
Mechanistic narrative
Synthesis pass · prose summary of the discoveries below
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Mechanism profile
Synthesis pass · controlled-vocabulary classification · explore literature graph →
No controlled-vocabulary terms were assigned to this entry.
Evidence
Reading pass · 15 per-paper findings extracted from the source corpus
| Year | Finding | Method | Journal | Conf | PMIDs |
|---|---|---|---|---|---|
| 2007 | Necl-3/SynCAM-2 (CADM2) localizes to myelinated axons at the interface between the axon shaft and the myelin sheath, binds selectively to oligodendrocytes, and engages in homo- and heterophilic interactions with other Necl family members (Necl-1, Necl-2), leading to cell aggregation, establishing it as a bona fide cell adhesion molecule in the nervous system. | Subcellular fractionation/immunolocalization, multiple independent cell adhesion assays (aggregation assays), binding assays with oligodendrocytes | BMC neuroscience | Medium | 17967169 |
| 2010 | CADM2a (a defined isoform with its own promoter, mapping to human chromosome 3p12.1) functions as a tumor suppressor in prostate cancer: adenovirus-mediated CADM2a expression suppressed DU145 cell proliferation in vitro and colony formation in soft agar. CADM2a expression is epigenetically silenced by promoter hypermethylation, and treatment with the demethylating agent 5-aza-2'-deoxycytidine alone or combined with the HDAC inhibitor trichostatin A reactivated its expression. | Adenovirus-mediated overexpression with proliferation/colony assays; bisulfite sequencing, methylation-specific PCR; pharmacological demethylation | Clinical cancer research | Medium | 21062931 |
| 2013 | CADM2 functions as a tumor suppressor in renal cell carcinoma: re-expression of CADM2 in the 786-O cancer cell line suppressed tumor cell growth in vitro and in mouse xenografts via G1 phase cell cycle arrest and induction of apoptosis, and inhibited anchorage-independent growth and invasion. Conversely, siRNA-mediated knockdown of endogenous CADM2 induced a tumorigenic phenotype in non-tumorigenic MDCK cells. CADM2 promoter hypermethylation and/or loss of heterozygosity accounts for its silencing. | Lentivirus-mediated overexpression, xenograft mouse model, siRNA knockdown, cell cycle analysis, apoptosis assay, methylation analysis | Biochemical and biophysical research communications | Medium | 23643812 |
| 2017 | Cadm2 deletion in obese mice (Cadm2/ob) reduced adiposity, systemic glucose levels, and improved insulin sensitivity, while increasing locomotor activity, energy expenditure rate, and core body temperature, establishing Cadm2 as a regulator of systemic energy homeostasis through the central nervous system. The risk variant rs13078960 was also associated with increased CADM2 expression in the human hypothalamus. | Cadm2 knockout mouse model (loss-of-function), metabolic phenotyping (glucose tolerance, insulin sensitivity, locomotor activity, energy expenditure, core temperature), brain region expression analysis | Molecular metabolism | High | 29217450 |
| 2018 | CADM2 is a direct target of miR-10b in hepatocellular carcinoma (HCC): miR-10b binds the 3'UTR of CADM2 (confirmed by dual-luciferase reporter assay), and the miR-10b/CADM2 axis modulates EMT, migration, and invasion via the FAK/AKT signaling pathway. Overexpression of CADM2 inhibited EMT and reduced migratory/invasive ability of HCC cells. | Dual-luciferase reporter assay, overexpression of CADM2, wound healing and Transwell migration/invasion assays, Western blotting for FAK/AKT pathway components | Journal of experimental & clinical cancer research | Medium | 29506532 |
| 2018 | CADM2 overexpression suppresses AKT signaling in esophageal squamous cell carcinoma (ESCC) cells, inhibiting proliferation and inducing apoptosis. CADM2 knockdown reverses the anti-proliferative/pro-apoptotic effect of miR-21-5p downregulation and restores p-AKT levels, placing CADM2 upstream of AKT in the miR-21-5p/CADM2/AKT axis. | CADM2 overexpression and siRNA knockdown, cell proliferation assays, apoptosis assays, Western blotting for p-AKT | Chemico-biological interactions | Medium | 29680210 |
| 2021 | CADM1 and CADM2 act as host factors enabling neuropathogenic measles virus (MeV) membrane fusion and transsynaptic spread between neurons. Uniquely, CADM1 and CADM2 interact in cis (on the same cell membrane as the viral attachment protein) with the MeV hemagglutinin (H) protein, triggering hyperfusogenic fusion protein (F)-mediated membrane fusion. Knockdown of CADM1 and CADM2 inhibited syncytium formation and virus transmission between neurons. | siRNA knockdown of CADM1/CADM2, cell-cell fusion assays (syncytium formation), virus transmission assays between neurons, co-localization/interaction studies | Journal of virology | High | 33910952 |
| 2021 | Only short-stalk isoforms of CADM2 (generated by alternative splicing and predominantly expressed in the brain) induce hyperfusogenic MeV F protein-mediated membrane fusion. These short-stalk isoforms interact in cis with the MeV H protein stalk domain (independently of the head domain), thereby triggering membrane fusion—distinct from conventional receptor-mediated trans interactions. | Splice isoform expression studies, cell-cell fusion assays with isoform-specific constructs, domain-deletion mutants of H protein | Journal of virology | Medium | 34788082 |
| 2023 | Alanine substitutions at positions 171–175 in the stalk region of the MeV H protein abolish CADM1/CADM2-triggered membrane fusion (but not SLAM-triggered fusion), and recombinant hyperfusogenic MeV carrying this H protein mutant cannot spread in primary mouse neurons or cause neurovirulence in suckling hamsters, establishing the H protein stalk region as the molecular interface for CADM1/CADM2-dependent MeV neuropathogenesis in vivo. | Site-directed mutagenesis (alanine substitution of H stalk residues 171–175), primary neuron spreading assay, in vivo neuropathogenicity model (suckling hamsters), cell-cell fusion assays | Journal of virology | High | 37166307 |
| 2019 | Overexpression of CADM2 in glioma cells inhibited proliferation in vitro and in vivo, and suppressed migration and invasion. CADM2 overexpression decreased expression of G1/S transition regulators (cyclin D1, cyclin E, CDK2, CDK4) and altered EMT markers (increased E-cadherin, altered β-catenin), placing CADM2 as a regulator of the cell cycle and EMT in glioma. | CADM2 overexpression, in vitro proliferation/migration/invasion assays, in vivo xenograft, Western blotting for cell cycle regulators and EMT markers | Oncology reports | Medium | 30816549 |
| 2023 | In Cadm2 mutant mice (MouseWAS), loss of Cadm2 recapitulated associations found in humans including impulsivity, cognition, and BMI, confirming a direct role for Cadm2 in these behavioral and metabolic phenotypes. | Cadm2 knockout/mutant mouse model with behavioral battery (impulsivity, cognition) and metabolic phenotyping (BMI) | Translational psychiatry | Medium | 37173343 |
| 2024 | CADM2 mediates the anti-inflammatory effect of the microbial metabolite acetyl L-carnitine (ALC) in colonic epithelial cells: gene silencing of CADM2 abolished ALC's inhibitory effect on the TLR-MyD88 signaling pathway, thereby reducing suppression of inflammatory factor release. This places CADM2 as a required intermediary between ALC and TLR-MyD88 pathway inhibition in intestinal epithelium. | Gene silencing (knockdown of CADM2), transcriptome sequencing, colitis mouse model (DSS-induced), cytokine measurement | Biochimica et biophysica acta. Molecular basis of disease | Medium | 38369215 |
| 2024 | Loss of CADM2 in zebrafish results in excessive sleepiness (hypersomnia phenotype), and this can be rescued by an NPY receptor agonist. In Drosophila, the CADM2 ortholog beat-Ia is required for synaptic elaboration of neuropeptide F (NPF, the fly homolog of NPY) neurites projecting to the suboesophageal zone (SEZ), where they synapse onto GABAergic neurons to stabilize arousal. | CADM2 knockout in zebrafish (loss-of-function sleep phenotyping), Drosophila neuronal knockdown of beat-Ia (sleep phenotyping), brain connectome analysis, NPY receptor agonist pharmacological rescue | Nature communications | High | 41526386 |
| 2025 | CADM2 contains a functional recursive splice site (RS1) in its first intron that regulates transcript abundance and isoform usage in neurons. CRISPR-mediated deletion of RS1 in human induced neurons decreased overall CADM2 expression, altered the gradient of RNA abundance across the first intron, changed transcript usage, and globally altered expression of genes involved in neuronal processes (synapse and axon development). Rat models with Cadm2 RS1 deletions showed significant changes in relevant behaviors and functional brain connectivity. | CRISPR modeling of patient deletions in human induced neurons and rats, transcriptome analysis (RNA-seq), behavioral assays, brain connectivity imaging | bioRxivpreprint | Medium | |
| 2026 | DNMT3B binds to the CADM2 promoter and mediates its epigenetic silencing in esophageal squamous cell carcinoma (ESCC). The lncRNA ADAMTS9-AS2 directly binds DNMT3B (confirmed by RIP and ChIP), preventing its occupancy at the CADM2 locus. Rescue experiments confirmed that CADM2 overexpression reversed the oncogenic phenotypes (proliferation, migration, invasion) induced by ADAMTS9-AS2 knockdown, placing DNMT3B-mediated CADM2 methylation downstream of ADAMTS9-AS2 loss. | RIP (RNA immunoprecipitation), ChIP (chromatin immunoprecipitation), pyrosequencing for methylation, CADM2 overexpression rescue experiments, gene knockdown | Frontiers in immunology | Medium | 41869309 |
Source papers
Stage 0 corpus · 43 papers · ranked by NIH iCite citations
| Year | Title | Journal | Citations | PMID |
|---|---|---|---|---|
| 2018 | Genome-wide association study of habitual physical activity in over 377,000 UK Biobank participants identifies multiple variants including CADM2 and APOE. | International journal of obesity (2005) | 309 | 29899525 |
| 2019 | Genome-Wide Association Studies of Impulsive Personality Traits (BIS-11 and UPPS-P) and Drug Experimentation in up to 22,861 Adult Research Participants Identify Loci in the CACNA1I and CADM2 genes. | The Journal of neuroscience : the official journal of the Society for Neuroscience | 116 | 30718321 |
| 2015 | GWAS for executive function and processing speed suggests involvement of the CADM2 gene. | Molecular psychiatry | 109 | 25869804 |
| 2023 | CADM2 is implicated in impulsive personality and numerous other traits by genome- and phenome-wide association studies in humans and mice. | Translational psychiatry | 66 | 37173343 |
| 2018 | CADM2, as a new target of miR-10b, promotes tumor metastasis through FAK/AKT pathway in hepatocellular carcinoma. | Journal of experimental & clinical cancer research : CR | 57 | 29506532 |
| 2019 | Genetic variation in CADM2 as a link between psychological traits and obesity. | Scientific reports | 48 | 31089183 |
| 2013 | Aberrant methylation and loss of CADM2 tumor suppressor expression is associated with human renal cell carcinoma tumor progression. | Biochemical and biophysical research communications | 48 | 23643812 |
| 2017 | Cadm2 regulates body weight and energy homeostasis in mice. | Molecular metabolism | 46 | 29217450 |
| 2010 | Hypoexpression and epigenetic regulation of candidate tumor suppressor gene CADM-2 in human prostate cancer. | Clinical cancer research : an official journal of the American Association for Cancer Research | 37 | 21062931 |
| 2007 | The adhesion molecule Necl-3/SynCAM-2 localizes to myelinated axons, binds to oligodendrocytes and promotes cell adhesion. | BMC neuroscience | 36 | 17967169 |
| 2021 | FOXO3a inhibits the EMT and metastasis of breast cancer by regulating TWIST-1 mediated miR-10b/CADM2 axis. | Translational oncology | 34 | 33882368 |
| 2017 | Replication and characterization of CADM2 and MSRA genes on human behavior. | Heliyon | 34 | 28795158 |
| 2018 | The CADM2/Akt pathway is involved in the inhibitory effect of miR-21-5p downregulation on proliferation and apoptosis in esophageal squamous cell carcinoma cells. | Chemico-biological interactions | 28 | 29680210 |
| 2020 | Long Noncoding MAGI2-AS3 Suppresses Several Cellular Processes of Lung Squamous Cell Carcinoma Cells by Regulating miR-374a/b-5p/CADM2 Axis. | Cancer management and research | 25 | 32021443 |
| 2020 | Copy number variation of CADM2 gene revealed its association with growth traits across Chinese Capra hircus (goat) populations. | Gene | 25 | 32126252 |
| 2022 | The CADM2 Gene and Behavior: A Phenome-Wide Scan in UK-Biobank. | Behavior genetics | 24 | 35867259 |
| 2021 | CADM1 and CADM2 Trigger Neuropathogenic Measles Virus-Mediated Membrane Fusion by Acting in cis. | Journal of virology | 24 | 33910952 |
| 2021 | Associations between the CADM2 gene, substance use, risky sexual behavior, and self-control: A phenome-wide association study. | Addiction biology | 23 | 33604983 |
| 2018 | Downregulation of microRNA‑182 inhibits cell viability, invasion and angiogenesis in retinoblastoma through inhibition of the PI3K/AKT pathway and CADM2 upregulation. | International journal of oncology | 22 | 30320366 |
| 2019 | CADM2 inhibits human glioma proliferation, migration and invasion. | Oncology reports | 20 | 30816549 |
| 2020 | Cell adhesion molecule 2 (CADM2) promotes brain metastasis by inducing epithelial-mesenchymal transition (EMT) in human non-small cell lung cancer. | Annals of translational medicine | 19 | 32395509 |
| 2013 | Low CADM2 expression predicts high recurrence risk of hepatocellular carcinoma patients after hepatectomy. | Journal of cancer research and clinical oncology | 19 | 24240726 |
| 2021 | Short-Stalk Isoforms of CADM1 and CADM2 Trigger Neuropathogenic Measles Virus-Mediated Membrane Fusion by Interacting with the Viral Hemagglutinin. | Journal of virology | 15 | 34788082 |
| 2024 | Quercetin inhibits the epithelial-mesenchymal transition and reverses CDK4/6 inhibitor resistance in breast cancer by regulating circHIAT1/miR-19a-3p/CADM2 axis. | PloS one | 14 | 38990915 |
| 2024 | The intestinal microbial metabolite acetyl l-carnitine improves gut inflammation and immune homeostasis via CADM2. | Biochimica et biophysica acta. Molecular basis of disease | 13 | 38369215 |
| 2019 | Copy Number Variation of the CADM2 Gene and Its Association with Growth Traits in Yak. | Animals : an open access journal from MDPI | 11 | 31766342 |
| 2022 | MiR-17-5p Targets and Downregulates CADM2, Activating the Malignant Phenotypes of Colon Cancer Cells. | Molecular biotechnology | 10 | 35696058 |
| 2017 | The CADM2 gene is associated with processing speed performance - evidence among elderly with type 2 diabetes. | The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry | 9 | 28797215 |
| 2022 | Long Non-Coding RNA HCG11 Inhibits Glioma Cells Proliferation and Migration through Decoying miR-590-3p and Up-Regulating CADM2. | Pathobiology : journal of immunopathology, molecular and cellular biology | 7 | 35279660 |
| 2023 | Interaction of the Hemagglutinin Stalk Region with Cell Adhesion Molecule (CADM) 1 and CADM2 Mediates the Spread between Neurons and Neuropathogenicity of Measles Virus with a Hyperfusogenic Fusion Protein. | Journal of virology | 6 | 37166307 |
| 2023 | Liver fibrosis-derived exosomal miR-106a-5p facilitates the malignancy by targeting SAMD12 and CADM2 in hepatocellular carcinoma. | PloS one | 6 | 37228062 |
| 2017 | MicroRNA-125a-3p is involved in early behavioral disorders in stroke-afflicted rats through the regulation of Cadm2. | International journal of molecular medicine | 6 | 29039453 |
| 2011 | A novel splicing variant of CADM2 as a protective transcript of psoriasis. | Biochemical and biophysical research communications | 6 | 21864505 |
| 2023 | LINC01354 enhances the metastatic ability of gastric cancer cells by adjusting miR-153-5p/CADM2 expression. | American journal of cancer research | 3 | 37424819 |
| 2022 | Long noncoding RNA WT1-AS regulates trophoblast proliferation, migration, and invasion via the microRNA-186-5p/CADM2 axis. | Open medicine (Warsaw, Poland) | 3 | 36561840 |
| 2026 | Cross-species evidence for a developmental origin of adult hypersomnia with loss of synaptic adhesion molecules beat-Ia/CADM2. | Nature communications | 2 | 41526386 |
| 2024 | CADM2 participates in endometriosis development by influencing the epithelial-mesenchymal transition. | Reproductive sciences (Thousand Oaks, Calif.) | 2 | 38767769 |
| 2024 | The lncRNA CADM2-AS1 promotes gastric cancer metastasis by binding with miR-5047 and activating NOTCH4 translation. | Frontiers in pharmacology | 2 | 39309008 |
| 2023 | CircDDX17 inhibits invasive progression of pituitary adenomas by sponging miR-1279 and regulating CADM2 expression. | Frontiers in oncology | 2 | 38023219 |
| 2018 | Investigation of the CADM2 polymorphism rs17518584 in memory and executive functions measures in a cohort of young healthy individuals. | Neurobiology of learning and memory | 1 | 30125698 |
| 2026 | ADAMTS9-AS2 acts as an epigenetic brake to constrain DNMT3B-mediated CADM2 silencing in esophageal squamous cell carcinoma metastasis. | Frontiers in immunology | 0 | 41869309 |
| 2025 | LncRNA ADAMTS9-AS1 regulates the proliferation, migration, and invasion of esophageal cancer cells via miR-575/ CADM2. | Discover oncology | 0 | 40887541 |
| 2024 | Cross-species evidence for a developmental origin of adult hypersomnia with loss of synaptic adhesion molecules beat-Ia/CADM2. | bioRxiv : the preprint server for biology | 0 | 39386457 |
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