CDK5R1 Gene (Cyclin Dependent Kinase 5 Regulatory Subunit 1)
Neuronal-specific activator of CDK5; key regulator of neuronal migration, synaptic plasticity, and cytoskeletal dynamics.
Gene Information Card
| Symbol | CDK5R1 |
|---|---|
| Full Name | Cyclin Dependent Kinase 5 Regulatory Subunit 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 17q11.2 |
| NCBI Gene ID | 8851 ncbi.nlm.nih.gov/gene/8851 |
| Ensembl ID | ENSG00000176749 |
| UniProt ID | P49759 |
| OMIM ID | 603460 |
| HGNC ID | 1775 |
| Aliases | p35, CDK5R, NCK5A |
Description
CDK5R1 encodes p35, a neuron-specific activator of cyclin-dependent kinase 5 (CDK5). p35 binding is essential for CDK5 kinase activity. The CDK5/p35 complex regulates neuronal migration, axon guidance, synaptic plasticity, and cytoskeletal organization. Dysregulation of CDK5R1 is implicated in neurodegenerative disorders and lissencephaly.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Lissencephaly 7 (LIS7) | Loss-of-function mutations in CDK5R1 impair CDK5 activation, disrupting neuronal migration during cortical development. | OMIM #603460; PMID: 25220019 |
| Alzheimer Disease | p35 cleavage to p25 leads to aberrant CDK5 hyperactivation, causing tau hyperphosphorylation and neurofibrillary tangle formation. | PMID: 10531052; PMID: 12872122 |
| Prostate Cancer | CDK5R1 overexpression correlates with increased CDK5 activity, promoting androgen receptor signaling and tumor progression. | PMID: 29784789 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 48.2 | High |
| Cerebral cortex | 52.1 | High |
| Cerebellum | 45.6 | High |
| Testis | 2.3 | Low |
| Liver | 0.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 35.1 | Neuronal model; high CDK5R1 expression |
| U-87 MG (glioblastoma) | 28.4 | Moderate expression |
| HeLa (cervical carcinoma) | 1.2 | Very low expression |
| HEK293 (embryonic kidney) | 0.8 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.172C>T (p.Arg58*) | Nonsense | <0.01% | Loss of function; associated with lissencephaly 7 |
| c.479G>A (p.Arg160Gln) | Missense | <0.01% | Impaired CDK5 binding; reduced kinase activity |
| c.1A>G (p.Met1?) | Start loss | <0.01% | Complete loss of p35 protein; severe neuronal migration defect |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg58*) produce truncated p35 unable to activate CDK5, leading to lissencephaly.
Gain of Function (GOF)
Not well documented; p25 generation from calpain cleavage is a post-translational gain-of-function mechanism, not a mutation.
Dominant Negative (DN)
Missense mutations (e.g., p.Arg160Gln) may produce p35 that binds CDK5 but fails to activate it, competing with wild-type p35.
View complete mutation data：
Gene Ontology (GO)
Pathways
• CDK5-mediated neuronal migration (Reactome R-HSA-8862803)
• Tau phosphorylation in Alzheimer disease (KEGG hsa05010)
• p35/CDK5 signaling (WikiPathways WP179)
Protein Summary
The CDK5R1 gene encodes p35, a 307-amino acid protein (UniProt P49759) that acts as a neuron-specific regulatory subunit of cyclin-dependent kinase 5 (CDK5). p35 contains a myristoylation signal at its N-terminus that targets the CDK5/p35 complex to the plasma membrane. Proteolytic cleavage of p35 by calpain generates p25, which lacks the membrane-targeting domain and causes aberrant CDK5 hyperactivation, contributing to neurodegeneration. p35 is essential for proper cortical lamination and synaptic function.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CDK5R1 Knockout HEK293 Cell Line | EDJ-KQ5696 | Human | 8851 | Details Get a Quote |
| CDK5R1 Knockout A-549 Cell Line | EDJ-KQ30386 | Human | 8851 | Details Get a Quote |
| CDK5R1 Knockout HCT 116 Cell Line | EDJ-KQ30388 | Human | 8851 | Details Get a Quote |
| CDK5R1 Knockout HeLa Cell Line | EDJ-KQ30389 | Human | 8851 | Details Get a Quote |
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