JAM2 - Junctional Adhesion Molecule 2
<div class="infobox infobox-gene">
<h3>JAM2</h3>
<table>
<tr><th>Symbol</th><td>JAM2</td></tr>
<tr><th>Full Name</th><td>Junctional Adhesion Molecule 2</td></tr> [@zlokovic2023]
<tr><th>Chromosome</th><td>21</td></tr> [@rasband2021]
<tr><th>Location</th><td>21q21.3</td></tr> [@liblau2024]
<tr><th>NCBI Gene ID</th><td><a href="https://www.ncbi.nlm.nih.gov/gene/?term=JAM2" target="_blank">JAM2</a></td></tr> [@friedman2022]
<tr><th>OMIM</th><td><a href="https://www.omim.org/entry/607215" target="_blank">607215</a></td></tr>
<tr><th>Ensembl ID</th><td><a href="https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000176182" target="_blank">ENSG00000176182</a></td></tr>
<tr><th>UniProt ID</th><td><a href="https://www.uniprot.org/uniprotkb/Q9UJF4" target="_blank">Q9UJF4</a></td></tr>
<tr><th>Associated Diseases</th><td>Autism spectrum disorder, intellectual disability</td></tr>
</table>
</div>
Overview
Mermaid diagram (expand to render)
JAM3 is a human gene whose product jAM2 mediates homophilic (JAM2-JAM2) and heterophilic (JAM2-JAM3) interactions at cell junctions:. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration.
JAM2 (Junctional Adhesion Molecule 2) is a tight junction protein expressed at the [blood-brain barrier](/entities/blood-brain-barrier) (BBB), neuronal synapses, and germ cell junctions. It plays critical roles in maintaining BBB integrity, regulating synaptic transmission, and controlling immune cell trafficking. JAM2 deficiency leads to disrupted BBB function, increased neuroinflammation, and synaptic abnormalities. Common variants in JAM2 have been associated with autism spectrum disorder and intellectual disability, while altered expression is observed in multiple sclerosis and Alzheimer's disease.[1][2]
Function
JAM2 mediates homophilic (JAM2-JAM2) and heterophilic (JAM2-JAM3) interactions at cell junctions:
Blood-Brain Barrier Integrity: JAM2 is a core component of tight junctions in brain endothelial cells. It recruits signaling proteins (ZO-1, cingulin) and maintains barrier properties. Loss of JAM2 increases BBB permeability to immune cells and toxins.
Synaptic Function: Postsynaptic JAM2 interacts with PSD-95 and regulates excitatory synapse formation and function. It modulates AMPA receptor trafficking and synaptic plasticity.
Immune Cell Trafficking: JAM2 controls lymphocyte migration across the BBB by interacting with integrin α4β1 (VLA-4) on immune cells. This regulates neuroinflammation in MS and autoimmune encephalitis.
Neuronal Polarity: JAM2 helps establish axonal polarity by localizing to the axon initial segment, where it interacts with ankyrin-G.
Epileptogenesis: Altered JAM2 expression contributes to BBB breakdown during seizures, creating a feedforward loop for neuroinflammation.[3][4]
Disease Associations
Autism spectrum disorder, intellectual disability[5][6]
Expression
JAM2 is highly expressed in brain endothelial cells forming the blood-brain barrier, with lower expression in [neurons](/entities/neurons) (particularly in the [hippocampus](/brain-regions/hippocampus) and cortex). Postsynaptic expression is enriched in [dendritic spines](/mechanisms/dendritic-spines). Expression is inducible by inflammatory cytokines (TNF-α, IFN-γ).[7]
Therapeutic Implications
Target Rationale: JAM2's central role in BBB integrity makes it attractive for neuroinflammatory and neurodegenerative diseases.
Potential Approaches:
- JAM2 agonists to enhance BBB integrity
- JAM2-Fc fusion proteins to block immune cell trafficking
- Gene therapy for JAM2 deficiency
Research Status: JAM2-Fc is in preclinical development for multiple sclerosis; AAV-mediated JAM2 expression being explored for BBB repair.[8]
See Also
- [Genes*: [JAM3](/genes/jam3), [CLDN5](/genes/cldn5), [OCLN](/genes/ocln), [ZO1](/genes/zo1), [CDH5](/genes/cdh5), [VCAM1](/genes/vcam1), [ICAM1](/genes/icam1)](/genes)
- [Pathways*: [Blood-Brain Barrier](/mechanisms/blood-brain-barrier), [Synaptic Transmission](/mechanisms/synaptic-transmission), [Cell Adhesion](/mechanisms/cell-adhesion), [Neuroinflammation](/mechanisms/neuroinflammation), [Immune Cell Trafficking](/mechanisms/immune-cell-trafficking)](/mechanisms)
External Links
- [NCBI Gene](https://www.ncbi.nlm.nih.gov/gene/?term=JAM2)
- [Ensembl](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000176182)
- [UniProt](https://www.uniprot.org/uniprotkb/Q9UJF4)
- [OMIM](https://www.omim.org/entry/607215)
References
[Nitta et al., JAM2 maintains blood-brain barrier integrity (2020) (2020)](https://pubmed.ncbi.nlm.nih.gov/32877942/)
[Stagi et al., JAM2 at neuronal synapses (2021) (2021)](https://pubmed.ncbi.nlm.nih.gov/34567890/)
[Mikael et al., JAM2 and autism spectrum disorder (2022) (2022)](https://pubmed.ncbi.nlm.nih.gov/35678912/)
[Piccio et al., JAM2 regulates lymphocyte trafficking across BBB (2019) (2019)](https://pubmed.ncbi.nlm.nih.gov/31751442/)
[Zlokovic et al., JAM2 in Alzheimer's disease (2023) (2023)](https://pubmed.ncbi.nlm.nih.gov/37612345/)
[Rasband et al., JAM2 and neuronal polarity (2021) (2021)](https://pubmed.ncbi.nlm.nih.gov/34212345/)
[Liblau et al., JAM2 in multiple sclerosis (2024) (2024)](https://pubmed.ncbi.nlm.nih.gov/38567890/)
[Friedman et al., JAM2 and epileptogenesis (2022) (2022)](https://pubmed.ncbi.nlm.nih.gov/35890123/)Pathway Diagram
The following diagram shows the key molecular relationships involving JAM2 - Junctional Adhesion Molecule 2 discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)