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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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CADM3
cell adhesion molecule 3
Chromosome 1 · 1q23.2
NCBI Gene: 57863Ensembl: ENSG00000162706.14HGNC: HGNC:17601UniProt: Q8N126
35PubMed Papers
21Diseases
0Drugs
1Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingplasma membranecell-cell junctionhomophilic cell-cell adhesionCharcot-Marie-Tooth disease, axonal, type 2FFneurodegenerative diseaseasthmamathematical ability
✦AI Summary

CADM3 (cell adhesion molecule 3) is a calcium-independent cell adhesion protein mediating both homophilic and heterophilic cell-cell adhesion interactions 1. In the peripheral nervous system, CADM3 functions as the primary axonal ligand for glial Cadm4, where it regulates myelinated axon organization and the distribution of ion channels like Kv1 potassium channels; this interaction can be partially compensated by Cadm1 and Cadm2 1. CADM3 is associated with Charcot-Marie-Tooth disease, axonal type 2FF, a hereditary motor neuropathy where CADM3 mutations were identified through whole exome/genome sequencing as causative genetic factors 2. Beyond neurological functions, CADM3 serves as a biomarker in multiple contexts: it is significantly correlated with colorectal cancer prognosis 3, is downregulated in amyotrophic lateral sclerosis cerebrospinal fluid suggesting neuropathological significance 4, and is highly expressed in superficial CD34-positive fibroblastic tumors where it aids diagnostic classification 5. In fibroblast biology, CADM3 participates in a regulatory axis controlling collagen I synthesis and skin thickness through AKT/ERK pathway activation 6. Additionally, CADM3 suppression by miR-140-5p inhibits retinoblastoma cell proliferation and invasion 7, indicating tumor-suppressive potential in certain cancer contexts.

Sources cited
1
CADM3 is the main axonal ligand for glial Cadm4 in peripheral myelinated axons and regulates axonal organization
PMID: 33397712
2
CADM3 mutations were identified as causative genes in hereditary motor neuropathies through whole exome/genome sequencing
PMID: 32796276
3
CADM3 expression is significantly correlated with prognosis in colorectal cancer patients
PMID: 37446311
4
CADM3-derived peptides are downregulated in amyotrophic lateral sclerosis cerebrospinal fluid compared to controls
PMID: 40681694
5
CADM3 is highly expressed in superficial CD34-positive fibroblastic tumors and aids in their diagnosis
PMID: 34969957
6
CADM3 participates in the circ0044633-miR-23b-CADM3/MAP4K4 axis regulating fibroblast proliferation and collagen I synthesis via AKT/ERK activation
PMID: 36502948
7
CADM3 is targeted by miR-140-5p to suppress retinoblastoma cell proliferation, migration, and invasion
PMID: 29808799
Disease Associationsⓘ21
Charcot-Marie-Tooth disease, axonal, type 2FFOpen Targets
0.62Moderate
neurodegenerative diseaseOpen Targets
0.46Moderate
asthmaOpen Targets
0.46Moderate
mathematical abilityOpen Targets
0.45Moderate
HypercholesterolemiaOpen Targets
0.32Weak
joint diseaseOpen Targets
0.32Weak
ProptosisOpen Targets
0.22Weak
genetic disorderOpen Targets
0.19Weak
prostate cancerOpen Targets
0.11Weak
Familial prostate cancerOpen Targets
0.11Weak
microscopic polyangiitisOpen Targets
0.10Weak
breast cancerOpen Targets
0.08Suggestive
chronic inflammatory demyelinating polyneuropathyOpen Targets
0.07Suggestive
Pelizeaus-Merzbacher spectrum disorderOpen Targets
0.04Suggestive
autosomal dominant slowed nerve conduction velocityOpen Targets
0.04Suggestive
gliomaOpen Targets
0.04Suggestive
adult-onset autosomal dominant demyelinating leukodystrophyOpen Targets
0.04Suggestive
colorectal cancerOpen Targets
0.03Suggestive
gastric carcinomaOpen Targets
0.03Suggestive
neoplasmOpen Targets
0.02Suggestive
Charcot-Marie-Tooth disease, axonal, type 2FFUniProt
Pathogenic Variants1
NM_001127173.3(CADM3):c.413A>G (p.Tyr138Cys)Likely pathogenic
Charcot-Marie-Tooth disease, axonal, type 2FF|not provided
★★☆☆2024→ Residue 138
View on ClinVar ↗
Related Genes
CEACAM19Shared pathway100%CEACAM18Shared pathway100%NECTIN1Protein interaction96%DLG3Protein interaction95%MPP3Protein interaction95%PALS2Protein interaction86%
Tissue Expression6 tissues
Brain
100%
Heart
12%
Lung
3%
Ovary
1%
Liver
1%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
CADM3CEACAM19CEACAM18NECTIN1DLG3MPP3PALS2
PROTEIN STRUCTURE
Preparing viewer…
PDB1Z9M · 2.40 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.38Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.22 [0.14–0.38]
RankingsWhere CADM3 stands among ~20K protein-coding genes
  • #10,927of 20,598
    Most Researched35
  • #5,210of 5,498
    Most Pathogenic Variants1
  • #1,846of 17,882
    Most Constrained (LOEUF)0.38 · top quartile
Genes detectedCADM3
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Using Machine Learning Methods to Study Colorectal Cancer Tumor Micro-Environment and Its Biomarkers.
PMID: 37446311
Int J Mol Sci · 2023
1.00
2
Hereditary motor neuropathies.
PMID: 32796276
Curr Opin Neurol · 2020
0.90
3
Clinicopathologic and molecular study of superficial CD34-positive fibroblastic tumours mimicking atypical fibrous histiocytoma (dermatofibroma).
PMID: 39044682
Histopathology · 2024
0.80
4
Peptidomic analysis of CSF reveals new biomarker candidates for amyotrophic lateral sclerosis.
PMID: 40681694
EMBO Mol Med · 2025
0.70
5
Circ004463 promotes fibroblast proliferation and collagen I synthesis by sponging miR-23b and regulating CADM3/MAP4K4 via activation of AKT/ERK pathways.
PMID: 36502948
Int J Biol Macromol · 2023
0.60