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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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NCAM2
neural cell adhesion molecule 2
Chromosome 21 · 21q21.1
NCBI Gene: 4685Ensembl: ENSG00000154654.15HGNC: HGNC:7657UniProt: O15394
38PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
plasma membraneidentical protein bindingneuron projectionmembranesmoking initiationattention deficit hyperactivity disordersubstance abusevenous thromboembolism
✦AI Summary

NCAM2 is a neural cell adhesion molecule primarily expressed in the brain that functions as a key regulator of neuronal morphogenesis and cytoskeletal organization 1. Unlike its paralog NCAM1, NCAM2 contains five immunoglobulin modules and two fibronectin type III domains but lacks polysialic acid glycosylation, suggesting distinct functional mechanisms 1. NCAM2 regulates dendritic and axonal differentiation through interactions with cytoskeletal proteins MAP2 and 14-3-3, promoting neurite outgrowth and neuronal polarization 2. During development, NCAM2 controls dendritic architecture formation, axonal compartmentalization, and cortical migration 23. In the adult brain, NCAM2 is highly expressed in dendritic spines where it regulates synaptic plasticity, learning, and memory formation 3. NCAM2 also regulates adult neurogenesis by controlling radial glial progenitor differentiation in the hippocampus 4. Clinically, NCAM2 is implicated in Alzheimer's disease pathogenesis: amyloid-β binding induces NCAM2 removal from synapses and cleavage of its extracellular domain, contributing to synapse loss 5. Additionally, NCAM2 promotes APP targeting to BACE1-containing recycling endosomes, increasing amyloidogenic processing and amyloid-β production 6. These findings suggest NCAM2 involvement in neurodevelopmental disorders and neurodegeneration.

Sources cited
1
NCAM2 structure (immunoglobulin and fibronectin domains), lack of polysialic acid modification, and role in neurite outgrowth and neuronal compartmentalization
PMID: 22155300
2
NCAM2 regulates dendritic and axonal differentiation through MAP2 and 14-3-3 interaction, controls neuronal polarization and cortical migration
PMID: 32043120
3
NCAM2 role in neuronal morphogenesis, axodendritic architecture, neuronal differentiation, synaptogenesis, memory formation, and synaptic plasticity in adult brain
PMID: 34576185
4
NCAM2 regulates radial glial progenitor differentiation and young-adult neurogenesis in the hippocampus
PMID: 37724425
5
Amyloid-β induces NCAM2 removal from synapses and cleavage, contributing to synapse loss in Alzheimer's disease
PMID: 26611261
6
NCAM2 binds APP and promotes its targeting to BACE1-containing recycling endosomes, increasing amyloidogenic processing and amyloid-β production
PMID: 40721030
Disease Associationsⓘ20
smoking initiationOpen Targets
0.43Moderate
attention deficit hyperactivity disorderOpen Targets
0.33Weak
substance abuseOpen Targets
0.33Weak
venous thromboembolismOpen Targets
0.32Weak
parasitic infectionOpen Targets
0.31Weak
hemiplegiaOpen Targets
0.29Weak
response to stimulusOpen Targets
0.28Weak
severe acute respiratory syndromeOpen Targets
0.28Weak
COVID-19Open Targets
0.28Weak
Abnormality of the integumentOpen Targets
0.27Weak
frozen shoulderOpen Targets
0.27Weak
mathematical abilityOpen Targets
0.26Weak
sign or symptomOpen Targets
0.26Weak
schizophreniaOpen Targets
0.25Weak
Paralytic ileusOpen Targets
0.24Weak
infectious meningitisOpen Targets
0.23Weak
Abnormality of the immune systemOpen Targets
0.23Weak
blood coagulation diseaseOpen Targets
0.23Weak
pericarditisOpen Targets
0.23Weak
preeclampsiaOpen Targets
0.23Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
PRNPProtein interaction94%L1CAMProtein interaction92%NCAM1Protein interaction92%SIGLEC14Shared pathway50%SIGLEC11Shared pathway50%MUC16Shared pathway50%
Tissue Expression6 tissues
Brain
100%
Heart
15%
Lung
9%
Bone Marrow
3%
Liver
2%
Ovary
1%
Gene Interaction Network
Click a node to explore
NCAM2PRNPL1CAMNCAM1SIGLEC14SIGLEC11MUC16
PROTEIN STRUCTURE
Preparing viewer…
PDB2XY2 · 1.77 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.41Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.29 [0.21–0.41]
RankingsWhere NCAM2 stands among ~20K protein-coding genes
  • #10,522of 20,598
    Most Researched38
  • #2,145of 17,882
    Most Constrained (LOEUF)0.41 · top quartile
Genes detectedNCAM2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
NCAM2/OCAM/RNCAM: cell adhesion molecule with a role in neuronal compartmentalization.
PMID: 22155300
Int J Biochem Cell Biol · 2012
1.00
2
NCAM2 Regulates Dendritic and Axonal Differentiation through the Cytoskeletal Proteins MAP2 and 14-3-3.
PMID: 32043120
Cereb Cortex · 2020
0.90
3
The Hidden Side of NCAM Family: NCAM2, a Key Cytoskeleton Organization Molecule Regulating Multiple Neural Functions.
PMID: 34576185
Int J Mol Sci · 2021
0.80
4
Cloning of a novel human neural cell adhesion molecule gene (NCAM2) that maps to chromosome region 21q21 and is potentially involved in Down syndrome.
PMID: 9226371
Genomics · 1997
0.70
5
Regulation of young-adult neurogenesis and neuronal differentiation by neural cell adhesion molecule 2 (NCAM2).
PMID: 37724425
Cereb Cortex · 2023
0.60