Calsyntenin 1

Calsyntenin 1

Overview

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">Calsyntenin 1</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td>CLSTN1</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Calsyntenin 1</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>1p36.21</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>[64085](https://www.ncbi.nlm.nih.gov/gene/64085)</td>
</tr>
<tr>
<td class="label">OMIM</td>
<td>[611295](https://www.omim.org/entry/611295)</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000171603</td>
</tr>
<tr>
<td class="label">UniProt</td>
<td>[Q9BZZ5](https://www.uniprot.org/uniprot/Q9BZZ5)</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

Calsyntenin 1

Overview

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">Calsyntenin 1</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td>CLSTN1</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Calsyntenin 1</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>1p36.21</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>[64085](https://www.ncbi.nlm.nih.gov/gene/64085)</td>
</tr>
<tr>
<td class="label">OMIM</td>
<td>[611295](https://www.omim.org/entry/611295)</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000171603</td>
</tr>
<tr>
<td class="label">UniProt</td>
<td>[Q9BZZ5](https://www.uniprot.org/uniprot/Q9BZZ5)</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

Calsyntenin 1 (CLSTN1) is a type I transmembrane protein enriched in excitatory synapses. It interacts with the [amyloid precursor protein](/entities/app-protein) (APP) and may regulate [amyloid-beta](/proteins/amyloid-beta) production. CLSTN1 mediates synaptic plasticity by interacting with the postsynaptic density and is cleaved by [gamma-secretase](/entities/gamma-secretase), releasing an intracellular domain that may regulate gene expression. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration. It interacts with the amyloid precursor protein (APP) and may regulate amyloid-beta production. CLSTN1 mediates synaptic plasticity by interacting with the postsynaptic density and is cleaved by gamma-secretase, releasing a intracellular domain that may regulate gene expression. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration.

Gene Summary

CLSTN1 (Calsyntenin 1) is a neuronal transmembrane protein that functions as a synaptic adhesion molecule. It is involved in synaptic plasticity, learning, and memory, and has been implicated in [Alzheimer disease](/diseases/alzheimers-disease) pathogenesis. [@moranteredolat2002]

Gene Information

Function

Normal Function

CLSTN1: Calsyntenin 1 is a type I transmembrane protein enriched in excitatory synapses. It interacts with the amyloid precursor protein (APP) and may regulate amyloid-beta production. CLSTN1 mediates synaptic plasticity by interacting with the postsynaptic density and is cleaved by gamma-secretase, releasing a intracellular domain that may regulate gene expression. [@maljevic2011]

LGI1: Leucine-rich glioma inactivated 1 is a secreted protein that binds to ADAM22 and ADAM23 receptors on postsynaptic [neurons](/entities/neurons). It regulates AMPA receptor trafficking and synaptic transmission. LGI1 is essential for normal brain development and synaptic function.

NRCAM: Neuronal cell adhesion molecule is an immunoglobulin superfamily member that mediates cell-cell adhesion through homophilic and heterophilic interactions. It plays critical roles in axonal guidance, synapse formation, and myelination. NRCAM is expressed in developing and mature neurons.

ATP1A3: The Na+/K+ ATPase alpha-3 subunit is expressed primarily in neurons and maintains the electrochemical gradient essential for neuronal excitability. It uses ATP to transport 3 Na+ out and 2 K+ in, maintaining the resting membrane potential. This subunit is critical for fast-spiking neurons.

KCNQ2: KCNQ2 forms voltage-gated potassium channels (Kv7.2) that generate the M-current, a slowly activating and deactivating K+ current that dampens neuronal excitability. Channels composed of KCNQ2/KCNQ3 subunits are critical for regulating action potential firing, particularly in hippocampal and cortical neurons.

Disease Associations

• CLSTN1: [Alzheimer disease](/diseases/alzheimers-disease) - CLSTN1 polymorphisms are associated with AD risk. It interacts with APP and may influence amyloid pathology. [1](https://pubmed.ncbi.nlm.nih.gov/23453810/)
• LGI1: [Autosomal dominant lateral temporal lobe epilepsy](/diseases/epilepsy) - Heterozygous mutations cause ADLTE characterized by auditory seizures. [2](https://pubmed.ncbi.nlm.nih.gov/11781378/)
• NRCAM: [Autism spectrum disorder](/diseases/autism) - NRCAM variants are associated with ASD risk. It plays roles in neural circuit formation. [3](https://pubmed.ncbi.nlm.nih.gov/19248075/)
• ATP1A3: [Rapid-onset dystonia parkinsonism](/diseases/rapid-onset-dystonia-parkinsonism) - Dominant mutations cause RDP, a severe movement disorder. Also causes [alternating hemiplegia of childhood](/diseases/alternating-hemiplegia). [4](https://pubmed.ncbi.nlm.nih.gov/17460021/)
• KCNQ2: [Benign familial neonatal seizures](/diseases/benign-familial-neonatal-seizures) - Mutations cause self-limited neonatal seizures. Severe mutations cause early infantile epileptic encephalopathy. [5](https://pubmed.ncbi.nlm.nih.gov/11572950/)

Expression Pattern

• CLSTN1: High expression in [cortex](/brain-regions/cortex), [hippocampus](/brain-regions/hippocampus), and cerebellum. Enriched in postsynaptic densities. [6](https://pubmed.ncbi.nlm.nih.gov/12629553/)
• LGI1: Broad expression in brain, particularly hippocampus and cerebral cortex. Expressed in neurons and glia. [7](https://pubmed.ncbi.nlm.nih.gov/14534157/)
• NRCAM: Expressed in developing nervous system, particularly in axon tracts. In adults, expression persists in specific brain regions. [8](https://pubmed.ncbi.nlm.nih.gov/10835640/)
• ATP1A3: High expression in motor neurons, thalamus, and brainstem. Enriched in fast-spiking neurons. [9](https://pubmed.ncbi.nlm.nih.gov/12019208/)
• KCNQ2: Broad expression in brain, especially hippocampus, cortex, and cerebellum. Predominant in pyramidal neurons. [10](https://pubmed.ncbi.nlm.nih.gov/10572054/)

Therapeutic Implications

• CLSTN1: Modulating CLSTN1-APP interaction may provide therapeutic benefit in AD. Gene therapy approaches to enhance synaptic CLSTN1 are being explored.
• LGI1: Antisense oligonucleotides and small molecules to restore LGI1 function are under investigation for ADLTE.
• NRCAM: Targeting NRCAM-mediated adhesion may benefit neurodevelopmental disorders. Cell adhesion molecule therapies are in development.
• ATP1A3: Gene therapy with wild-type ATP1A3 is being developed for RDP. Small molecule sodium pump modulators show promise. [11](https://pubmed.ncbi.nlm.nih.gov/28986526/)
• KCNQ2: Retigabine and other KCNQ2/KCNQ3 channel openers are used to treat epilepsy. Precision medicine approaches for specific KCNQ2 mutations are in development. [12](https://pubmed.ncbi.nlm.nih.gov/21454897/)

See Also

• [Synaptic plasticity](/mechanisms/synaptic-plasticity)
• [Alzheimer disease](/diseases/alzheimers-disease)
• [Parkinson disease](/diseases/parkinsons-disease)
• [Epilepsy](/diseases/epilepsy)
• [Ion channel dysfunction in neurodegeneration](/mechanisms/ion-channel-dysfunction-neurodegeneration)
• [Sodium channels](/proteins/sodium-channels)
• [Potassium channels](/proteins/potassium-channels)
• [Synaptic adhesion molecules](/proteins/synaptic-adhesion-molecules)

External Links

• [NCBI Gene](https://www.ncbi.nlm.nih.gov/gene/64085)
• [UniProt](https://www.uniprot.org/uniprot/Q9BZZ5)
• [Ensembl](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000171603)
• [GeneCards](https://www.genecards.org/cgi-bin/carddisp.pl?gene=CLSTN1)

Brain Atlas Resources

• [Allen Human Brain Atlas search: Calsyntenin 1](https://human.brain-map.org/search?searchText=Calsyntenin 1)
• [Allen Mouse Brain Atlas search: Calsyntenin 1](https://mouse.brain-map.org/search/index.html?query=Calsyntenin 1)
• [Allen Brain Map portal search: Calsyntenin 1](https://portal.brain-map.org/search?query=Calsyntenin 1)
• [BrainSpan developmental transcriptome search: Calsyntenin 1](https://www.brainspan.org/search/index.html?search=Calsyntenin 1)

References