CCNH: Cyclin H - A Key Regulator of Cell Cycle and Transcription
Comprehensive gene overview of CCNH, encoding cyclin H, a component of the CDK-activating kinase (CAK) complex essential for cell cycle progression and transcription.
Gene Information Card
| Symbol | CCNH |
|---|---|
| Full Name | Cyclin H |
| Gene Type | Protein coding |
| Chromosomal Location | 5q14.3 |
| NCBI Gene ID | 902 ncbi.nlm.nih.gov/gene/902 |
| Ensembl ID | ENSG00000134480 |
| UniProt ID | P51946 |
| OMIM ID | 601953 |
| HGNC ID | 1594 |
| Aliases | CAK, p34, CycH |
Description
CCNH (Cyclin H) is a protein-coding gene that encodes cyclin H, a regulatory subunit of the cyclin-dependent kinase (CDK)-activating kinase (CAK) complex. CAK phosphorylates and activates CDK1, CDK2, CDK4, and CDK6, thereby controlling cell cycle G1/S and G2/M transitions. Additionally, cyclin H is part of the TFIIH transcription factor complex, where it regulates transcription initiation and DNA repair. CCNH is essential for normal development and its dysregulation is implicated in various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | CCNH overexpression may enhance CAK activity, promoting CDK hyperactivation and uncontrolled cell proliferation. | COSMIC; PMID: 12460987 |
| Colorectal cancer | Amplification or increased expression of CCNH contributes to tumor progression via accelerated cell cycle. | COSMIC; PMID: 15696293 |
| Lung cancer | CCNH mutations and altered expression linked to CAK dysregulation and poor prognosis. | COSMIC; PMID: 17344889 |
| Ovarian cancer | CCNH copy number gains and overexpression associated with aggressive disease. | COSMIC; PMID: 19029981 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.3 | Medium |
| Lymph node | 10.1 | Medium |
| Bone marrow | 9.8 | Medium |
| Brain | 7.5 | Low |
| Liver | 6.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 14.5 | Cervical cancer cell line; high expression |
| A549 | 11.2 | Lung cancer cell line; moderate expression |
| MCF7 | 9.8 | Breast cancer cell line; moderate expression |
| HEK293 | 8.1 | Embryonic kidney; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G | Missense | <0.1% | p.Met1?; start codon loss; likely loss of function |
| c.214C>T | Missense | <0.1% | p.Arg72Cys; potential impact on cyclin fold |
| c.487G>A | Missense | <0.1% | p.Gly163Arg; observed in cancer samples |
| c.632T>C | Missense | <0.1% | p.Leu211Pro; may affect protein stability |
Mutation functional classification
Loss of Function (LOF)
Rare missense mutations (e.g., p.Met1?, p.Arg72Cys) predicted to disrupt cyclin H structure or expression, impairing CAK activity and cell cycle progression.
Gain of Function (GOF)
Amplification or overexpression of CCNH in cancers leads to increased CAK activity, promoting CDK hyperactivation and oncogenic proliferation.
Dominant Negative (DN)
No well-characterized dominant-negative mutations reported for CCNH.
View complete mutation data：
Gene Ontology (GO)
| • cyclin-dependent protein serine/threonine kinase activator activity (GO:0004693) | • protein binding (GO:0005515) |
| • nucleus (GO:0005634) | • nucleoplasm (GO:0005654) |
| • cytoplasm (GO:0005737) | • protein phosphorylation (GO:0006468) |
| • cell cycle (GO:0007049) | • protein kinase binding (GO:0019901) |
| • cyclin binding (GO:0030332) | • protein N-terminus binding (GO:0047485) |
Pathways
• Cell Cycle (KEGG: hsa04110)
• p53 signaling pathway (KEGG: hsa04115)
• CDK-mediated phosphorylation and removal of Cdc6 (Reactome: R-HSA-69017)
• Activation of the pre-replicative complex (Reactome: R-HSA-68962)
• Transcription-coupled nucleotide excision repair (TC-NER) (Reactome: R-HSA-6781823)
Protein Summary
Cyclin H is a 323-amino acid protein (37 kDa) that contains a cyclin N-terminal domain and a cyclin C-terminal domain. It forms a stable complex with CDK7 and MAT1 to constitute the CDK-activating kinase (CAK) complex. CAK phosphorylates the T-loop of CDKs, enabling their full activation. Cyclin H also integrates into the TFIIH complex, where it facilitates transcription initiation by RNA polymerase II and participates in nucleotide excision repair. Its expression is ubiquitous but varies across tissues, with highest levels in testis and lymphoid tissues.
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