CDK12 Gene: Cyclin Dependent Kinase 12
A key regulator of transcription, RNA splicing, and genomic stability, frequently altered in cancer.
Gene Information Card
| Symbol | CDK12 |
|---|---|
| Full Name | Cyclin Dependent Kinase 12 |
| Gene Type | Protein coding |
| Chromosomal Location | 17q12 |
| NCBI Gene ID | 51755 ncbi.nlm.nih.gov/gene/51755 |
| Ensembl ID | ENSG00000167258 |
| UniProt ID | Q9NYV4 |
| OMIM ID | 615514 |
| HGNC ID | 24224 |
| Aliases | CRKRS, CRK7, KIAA0904 |
Description
CDK12 encodes a cyclin-dependent kinase that phosphorylates the C-terminal domain of RNA polymerase II, regulating transcription elongation and co-transcriptional RNA processing. It is essential for the expression of genes involved in DNA damage response, including homologous recombination repair genes such as BRCA1. CDK12 also plays roles in alternative splicing and genomic stability. Alterations in CDK12, particularly loss-of-function mutations, are common in various cancers and are associated with specific molecular and clinical features.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | Loss-of-function mutations lead to defective DNA repair and genomic instability, promoting tumorigenesis. | COSMIC, ClinVar, literature |
| Ovarian cancer | Recurrent somatic mutations and copy-number alterations; associated with homologous recombination deficiency. | COSMIC, ClinVar, literature |
| Prostate cancer | Biallelic loss and mutations; linked to aggressive disease and potential sensitivity to PARP inhibitors. | COSMIC, ClinVar, literature |
| Breast cancer | Mutations and copy-number changes; contribute to genomic instability and poor prognosis. | COSMIC, ClinVar, literature |
| Endometrial cancer | Frequent mutations; role in tumor progression. | COSMIC, ClinVar, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 22.5 | High |
| Bone marrow | 15.3 | Medium |
| Lymph node | 12.8 | Medium |
| Spleen | 11.9 | Medium |
| Brain | 8.7 | Low |
| Liver | 6.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K562 (leukemia) | 18.4 | High expression |
| HeLa (cervical cancer) | 15.2 | Medium |
| A549 (lung cancer) | 12.1 | Medium |
| MCF7 (breast cancer) | 10.5 | Medium |
| HepG2 (liver cancer) | 7.8 | Low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2386C>T (p.Arg796Ter) | Nonsense | ~2% in ovarian cancer | Loss of function, truncation |
| c.1045C>T (p.Arg349Ter) | Nonsense | ~1% in prostate cancer | Loss of function, truncation |
| c.1567_1568del (p.Glu523fs) | Frameshift | ~1% in breast cancer | Loss of function, frameshift |
| c.2041A>G (p.Lys681Glu) | Missense | Rare | Unknown; potential impact on kinase activity |
Mutation functional classification
Loss of Function (LOF)
Most CDK12 mutations are loss-of-function, leading to reduced kinase activity, impaired DNA repair, and genomic instability.
Gain of Function (GOF)
Gain-of-function mutations are rare and not well characterized; some missense variants may alter substrate specificity but evidence is limited.
Dominant Negative (DN)
Dominant-negative effects have been suggested for some missense mutations that interfere with dimerization or complex formation, but evidence is not conclusive.
View complete mutation data：
Gene Ontology (GO)
| • protein kinase activity | • ATP binding |
| • RNA polymerase II C-terminal domain binding | • regulation of transcription by RNA polymerase II |
| • DNA damage response | • mRNA splicing |
| • cell cycle |
Pathways
• RNA polymerase II transcription
• Homologous recombination repair
• DNA damage response
• mRNA splicing
Protein Summary
CDK12 is a serine/threonine kinase that phosphorylates the C-terminal domain of RNA polymerase II, facilitating transcription elongation and co-transcriptional splicing. It is critical for the expression of DNA damage response genes, including BRCA1, and maintains genomic stability. The protein contains a kinase domain, an arginine/serine-rich region, and a proline-rich region, and interacts with cyclin K. CDK12 is implicated in cancer pathogenesis, where loss-of-function mutations lead to defective DNA repair and increased sensitivity to PARP inhibitors.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CDK12 Knockout HAP1 Cell Line | EDJ-KQ78109 | Human | 51755 | Details Get a Quote |
| CDK12 Knockout HEK293T Cell Line | EDJ-KQ78140 | Human | 51755 | Details Get a Quote |
| CDK12 Knockout HCT 116 Cell Line | EDJ-KQ78141 | Human | 51755 | Details Get a Quote |
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