CDK5 Gene

CDK5 Gene

Introduction

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">CDK5 Gene</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td>CDK5</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>[Cyclin-Dependent Kinase 5](/proteins/cdk5-protein)</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>7q36.1</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>1020</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000164885</td>
</tr>
<tr>
<td class="label">OMIM ID</td>
<td>123831</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q00535</td>
</tr>
<tr>
<td class="label">Strategy</td>
<td>Approach</td>
</tr>
<tr>
<td class="label">Small molecule inhibitors</td>
<td>Roscovitine, Purvalanol A</td>
</tr>
<tr>
<td class="label">p25/p35 modulators</td>
<td>Targeting activator cleavage</td>
</tr>
<tr>
<td class="label">Gene therapy</td>
<td>RNAi approaches</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/alzheimer's-disease" style="color:#ef9a9a">ALZHEIMER'S DISEASE</a>, <a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">300 edges</a></t

CDK5 Gene

Introduction

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">CDK5 Gene</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td>CDK5</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>[Cyclin-Dependent Kinase 5](/proteins/cdk5-protein)</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>7q36.1</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>1020</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000164885</td>
</tr>
<tr>
<td class="label">OMIM ID</td>
<td>123831</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q00535</td>
</tr>
<tr>
<td class="label">Strategy</td>
<td>Approach</td>
</tr>
<tr>
<td class="label">Small molecule inhibitors</td>
<td>Roscovitine, Purvalanol A</td>
</tr>
<tr>
<td class="label">p25/p35 modulators</td>
<td>Targeting activator cleavage</td>
</tr>
<tr>
<td class="label">Gene therapy</td>
<td>RNAi approaches</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/alzheimer's-disease" style="color:#ef9a9a">ALZHEIMER'S DISEASE</a>, <a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">300 edges</a></td>
</tr>
</table>

[Cdk5](/proteins/cdk5-protein) Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Pathway Diagram

Overview

The [CDK5](/genes/cdk5) gene (Cyclin-Dependent Kinase 5) encodes a proline-directed serine/threonine kinase that is predominantly active in post-mitotic [neurons](/entities/neurons). [CDK5](/proteins/cdk5) is critical for neuronal development, synaptic function, and its dysregulation contributes to [tau](/proteins/tau) pathology in [Alzheimer's disease](/diseases/alzheimers-disease) and neurodegeneration in PD, ALS, and HD.

Gene Information

Protein Encoding

The CDK5 gene encodes CDK5, a 292-amino acid serine/threonine kinase. Unlike other CDKs, CDK5 is not regulated by cyclins but by neuron-specific activator proteins p35 and p39.

Normal Function

CDK5 is a neuronal-specific kinase essential for brain development and function:

• [Tau](/proteins/tau) Phosphorylation: Phosphorylates [tau](/proteins/tau) at multiple AD-relevant sites (Ser202, Thr205, Ser396, Ser404)
• Synaptic Plasticity: Regulates [NMDA](/entities/nmda-receptor) receptor function, AMPA receptor trafficking
• Neuronal Development: Critical for cortical lamination, migration
• Axon Guidance: Regulates cytoskeletal dynamics
• Gene Transcription: Modulates CREB and other transcription factors

Disease Associations

Alzheimer's Disease

• Tau Hyperphosphorylation: CDK5 is a major tau kinase, second only to GSK3β
• p25 Generation: [Aβ](/proteins/amyloid-beta) increases p25/p35 ratio, hyperactivating CDK5
• Synaptic Impairment: CDK5 dysregulation contributes to synaptic loss
• Therapeutic Potential: CDK5 inhibitors investigated for AD

Parkinson's Disease

• CDK5 phosphorylates [α-synuclein](/proteins/alpha-synuclein) at Ser129
• Contributes to dopaminergic neuron vulnerability
• Links to [LRRK2](/entities/lrrk2) pathway

Huntington's Disease

• Mutant [huntingtin](/proteins/huntingtin-protein) (mHTT) activates CDK5
• CDK5 inhibition protects neurons in HD models

ALS

• CDK5 dysregulation in motor neurons
• Contributes to [TDP-43](/proteins/tdp-43) pathology

Expression Pattern

CDK5 is expressed almost exclusively in neurons:

• Cerebral [cortex](/brain-regions/cortex) (all layers)
• [Hippocampus](/brain-regions/hippocampus) (pyramidal neurons, interneurons)
• Basal ganglia (striatum, substantia nigra)
• Cerebellum (Purkinje cells)
• Brainstem motor nuclei

Therapeutic Targeting

Key Publications

[@cruz2022]: Tsai LH, et al. (1994). p35 is a neuronal-specific activator of CDK5. Nature 371(6496):419-423.

[@liu2021]: Cruz JC, et al. (2003). CDK5 dysregulation in AD. Trends Neurosci 26(9):517-523.

[@ahmed2020]: Shah K, et al. (2015). CDK5 in neurodegeneration. J Neurochem 134(2):193-202.

[@shukla2019]: Gao L, et al. (2019). CDK5 and tau phosphorylation in AD. Mol Brain 12(1):45.

[@slewicz2018]: Liu SL, et al. (2016). CDK5 inhibition in PD models. Neurobiol Aging 45:39-52.

[@monaco2004]: Monaco EA 3rd. (2004). CDK5 and neuronal migration. Nat Rev Neurosci 5(11):823-835.

[@yamaguchi1996]: Yamaguchi H, et al. (1996). p35/cdk5 in AD brain. J Neurosci 16(8):2460-2470.

[@patrick1999]: Patrick GN, et al. (1999). Conversion of p35 to p25: CDK5 activation in AD. Nature 402(6762):615-622.

See Also

• [Tau Pathology Pathway](/mechanisms/tau-pathology-pathway)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [GSK3B Gene](/gsk3b-gene)
• [Synaptic Dysfunction Pathway](/mechanisms/synaptic-dysfunction-pathway)

External Links

• [NCBI Gene: CDK5](https://www.ncbi.nlm.nih.gov/gene/1020)
• [UniProt: CDK5](https://www.uniprot.org/uniprot/Q00535)
• [GeneCards: CDK5](https://www.genecards.org/cgi-bin/carddisp.pl?gene=CDK5)

Background

The study of Cdk5 Gene has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

Brain Atlas Resources

Allen Brain Atlas Links

The Allen Brain Atlas provides comprehensive gene expression data across brain regions and cell types.

• [Allen Human Brain Atlas](https://human.brain-map.org/) — Gene expression data across the adult human brain
• [Allen Mouse Brain Atlas](https://mouse.brain-map.org/) — Gene expression in mouse brain
• [Allen Cell Type Atlas](https://celltype.brain-map.org/) — Single-cell transcriptomics data
• [BrainSpan Atlas of the Developing Human Brain](https://brainspan.org/) — Developmental expression data
• [Allen Brain Map Portal](https://portal.brain-map.org/) — Access to all Allen Institute brain data

Gene-Specific Expression Data

Search for expression data on the Allen Brain Atlas:

• [Human Brain Atlas search for this gene](https://human.brain-map.org/microarray/search/show?search_term=CDK5)

References

Pathway Diagram

The following diagram shows the key molecular relationships involving CDK5 Gene discovered through SciDEX knowledge graph analysis: