CDK9: Cyclin-Dependent Kinase 9
A key regulator of transcriptional elongation and therapeutic target in cancer and HIV
Gene Information Card
| Symbol | CDK9 |
|---|---|
| Full Name | Cyclin-dependent kinase 9 |
| Gene Type | Protein coding |
| Chromosomal Location | 9q34.11 |
| NCBI Gene ID | 1025 ncbi.nlm.nih.gov/gene/1025 |
| Ensembl ID | ENSG00000136807 |
| UniProt ID | P50750 |
| OMIM ID | 603251 |
| HGNC ID | 1780 |
| Aliases | C-2k, CTK1, PITALRE, TAK |
Description
CDK9 encodes a member of the cyclin-dependent kinase (CDK) family that is a catalytic subunit of the positive transcription elongation factor b (P-TEFb). P-TEFb is required for RNA polymerase II transcriptional elongation and regulates the transition from abortive to productive elongation. CDK9 activity is essential for the expression of many genes, including those involved in cell cycle, apoptosis, and differentiation. It is also a key host factor for HIV-1 Tat-mediated transactivation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | CDK9 overexpression or hyperactivation drives oncogenic transcription programs, including MYC and MCL1 expression | PMID: 31723249, PMID: 30266990 |
| HIV-1 infection | CDK9 is required for HIV-1 Tat-dependent transcriptional elongation of the viral genome | PMID: 10629003, PMID: 11390644 |
| Cardiac hypertrophy | CDK9 activity is implicated in pathological cardiac remodeling | PMID: 20089852 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone marrow | 12.5 | Medium |
| Lymph node | 10.8 | Medium |
| Spleen | 9.2 | Medium |
| Testis | 8.1 | Medium |
| Brain | 4.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.2 | High expression |
| K562 | 14.8 | High expression |
| HEK293 | 12.1 | Medium expression |
| HepG2 | 11.5 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.832C>T (p.Arg278Cys) | Missense | <0.1% | Reduced kinase activity in vitro |
| c.1015G>A (p.Glu339Lys) | Missense | <0.1% | Unknown functional effect |
Mutation functional classification
Loss of Function (LOF)
Rare missense variants (e.g., p.Arg278Cys) show reduced kinase activity in cellular assays.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported in CDK9.
Dominant Negative (DN)
Not described for CDK9.
View complete mutation data：
Gene Ontology (GO)
Pathways
• HIV-1 Tat-mediated transactivation (KEGG: hsa05170)
• Transcriptional regulation by P-TEFb (Reactome: R-HSA-112382)
• RNA polymerase II transcription elongation (Reactome: R-HSA-75955)
Protein Summary
CDK9 is a 42 kDa serine/threonine protein kinase that forms the catalytic core of P-TEFb. It contains an N-terminal kinase domain and a C-terminal region involved in cyclin binding (cyclin T1, T2, or K). CDK9 phosphorylates the RNA polymerase II C-terminal domain (CTD) at Ser2, as well as negative elongation factors (NELF, DSIF), promoting productive elongation. Its activity is tightly regulated by association with cyclins and by inhibitory factors such as HEXIM1/7SK snRNA. CDK9 is a validated drug target in cancer and HIV.
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