CDK5R2 Gene (Cyclin Dependent Kinase 5 Regulatory Subunit 2)
Neuron-specific activator of CDK5, essential for neuronal migration and synaptic plasticity
Gene Information Card
| Symbol | CDK5R2 |
|---|---|
| Full Name | Cyclin Dependent Kinase 5 Regulatory Subunit 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 2q33.1 |
| NCBI Gene ID | 8941 ncbi.nlm.nih.gov/gene/8941 |
| Ensembl ID | ENSG00000171450 |
| UniProt ID | Q13319 |
| OMIM ID | 603764 |
| HGNC ID | 1775 |
| Aliases | p39, NCK5A, CDK5R2 |
Description
CDK5R2 encodes p39, a neuron-specific regulatory subunit that binds and activates cyclin-dependent kinase 5 (CDK5). Unlike cyclins, p39 and its homolog p35 are essential for CDK5 activity in post-mitotic neurons. CDK5R2 is critical for neuronal migration, cortical lamination, and synaptic plasticity. Mutations in CDK5R2 are associated with lissencephaly and intellectual disability.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Lissencephaly 7 (LIS7) | Loss-of-function mutations in CDK5R2 impair CDK5 activation, disrupting neuronal migration and cortical layering. | OMIM #616342; PMID: 27545674 |
| Intellectual disability | Homozygous truncating variants cause severe developmental delay and seizures. | ClinVar; PMID: 27545674 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 27.8 | High |
| Cerebral cortex | 32.1 | High |
| Cerebellum | 25.4 | High |
| Hippocampus | 30.0 | High |
| Testis | 1.2 | Low |
| Other tissues | <0.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.2 | Neuronal model |
| U-87 MG (glioblastoma) | 8.7 | Glial expression |
| HEK293 (embryonic kidney) | 0.3 | No significant expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.457C>T (p.Arg153*) | Nonsense | Rare | Loss of function; truncation of p39 |
| c.1A>G (p.Met1?) | Start loss | Rare | Loss of function; no protein translation |
| c.632G>A (p.Arg211Gln) | Missense | Rare | Impaired CDK5 binding and activation |
Mutation functional classification
Loss of Function (LOF)
Nonsense and start-loss mutations lead to truncated or absent p39, abolishing CDK5 activation in neurons.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
Not described; all pathogenic variants are recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• CDK5 signaling in neurons (Reactome: R-HSA-8862803)
• Signaling by NGF (Reactome: R-HSA-166520)
• Neuronal system (Reactome: R-HSA-112316)
Protein Summary
p39 (UniProt Q13319) is a 367-amino acid protein with a myristoylation signal at the N-terminus that targets it to the plasma membrane. It contains a CDK5-binding domain and a cyclin-like fold. p39 activates CDK5 specifically in post-mitotic neurons, regulating cytoskeletal dynamics, neuronal migration, and synaptic function. Unlike p35 (CDK5R1), p39 is expressed later in development and in specific brain regions.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CDK5R2 Knockout HEK293 Cell Line | EDJ-KQ6411 | Human | 8941 | Details Get a Quote |
| CDK5R2 Knockout HeLa Cell Line | EDJ-KQ55042 | Human | 8941 | Details Get a Quote |
| CDK5R2 Knockout A-549 Cell Line | EDJ-KQ63526 | Human | 8941 | Details Get a Quote |
| CDK5R2 Knockout HCT 116 Cell Line | EDJ-KQ71992 | Human | 8941 | Details Get a Quote |
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