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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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CCNE2
cyclin E2
Chromosome 8 · 8q22.1
NCBI Gene: 9134Ensembl: ENSG00000175305.19HGNC: HGNC:1590UniProt: O96020
79PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingcyclin-dependent protein serine/threonine kinase regulator activitycytoplasmpositive regulation of G1/S transition of mitotic cell cycleneurodegenerative diseaseneurodevelopmental disorder with cerebellar hypoplasia and spasticitytype 2 diabetes mellitusbreast cancer
✦AI Summary

CCNE2 encodes cyclin E2, a regulatory protein essential for cell cycle control at the G1/S transition 1. The protein functions by forming a complex with CDK2 to phosphorylate specific substrates that promote DNA replication and cell cycle progression 1. CCNE2 is subject to post-translational modifications including lactylation, which promotes hepatocellular carcinoma (HCC) cell growth, while SIRT3-mediated delactylation suppresses HCC development 2. The protein plays significant roles in cancer biology, with oncogenic activation leading to replication stress and genomic instability 1. CCNE2 overexpression contributes to trastuzumab resistance in HER2+ breast cancer, where miR-26a and miR-30b normally regulate its expression 3. Additionally, CCNE2 alterations confer resistance to CDK4/6 inhibitors in hormone receptor-positive breast cancer 4. The gene is also transcriptionally suppressed by E2F2 degradation pathways 5 and represents a potential therapeutic target in visceral adipose tissue for type 2 diabetes 6. These findings highlight CCNE2's dual role in normal cell cycle regulation and cancer pathogenesis, making it a clinically relevant target for therapeutic intervention.

Sources cited
1
CCNE2 forms complex with CDK2 for G1/S transition and DNA replication control
PMID: 34901021
2
CCNE2 lactylation promotes HCC growth while SIRT3-mediated delactylation suppresses it
PMID: 36896611
3
CCNE2 overexpression contributes to trastuzumab resistance in HER2+ breast cancer
PMID: 28120942
4
CCNE2 alterations confer resistance to CDK4/6 inhibitors in breast cancer
PMID: 32404308
5
CCNE2 is transcriptionally suppressed by E2F2 degradation pathways
PMID: 36375317
6
CCNE2 represents potential therapeutic target for type 2 diabetes in visceral adipose tissue
PMID: 37540242
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.53Moderate
neurodevelopmental disorder with cerebellar hypoplasia and spasticityOpen Targets
0.33Weak
type 2 diabetes mellitusOpen Targets
0.11Weak
breast cancerOpen Targets
0.11Weak
azoospermiaOpen Targets
0.10Suggestive
non-small cell lung carcinomaOpen Targets
0.09Suggestive
partial chromosome Y deletionOpen Targets
0.09Suggestive
spermatogenic failure 25Open Targets
0.08Suggestive
spermatogenic failure, X-linked, 2Open Targets
0.08Suggestive
spermatogenic failure 57Open Targets
0.08Suggestive
head and neck squamous cell carcinomaOpen Targets
0.08Suggestive
spermatogenic failure 50Open Targets
0.08Suggestive
gliomaOpen Targets
0.08Suggestive
isochromosomy YpOpen Targets
0.08Suggestive
spermatogenic failure 63Open Targets
0.07Suggestive
spermatogenic failure 71Open Targets
0.07Suggestive
spinocerebellar ataxia type 32Open Targets
0.07Suggestive
spermatogenic failure 48Open Targets
0.07Suggestive
isochromosomy YqOpen Targets
0.07Suggestive
spermatogenic failure 54Open Targets
0.07Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
MCM4Protein interaction100%ORC3Protein interaction100%CCNA2Protein interaction100%SKP1Protein interaction100%CUL1Protein interaction100%FBXW7Protein interaction100%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
34%
Ovary
6%
Lung
5%
Liver
4%
Heart
4%
Gene Interaction Network
Click a node to explore
CCNE2MCM4ORC3CCNA2SKP1CUL1FBXW7
PROTEIN STRUCTURE
Preparing viewer…
PDB8HN9 · 3.70 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.54Moderately Constrained
pLIⓘ
0.95Intolerant
Observed/Expected LoF0.31 [0.18–0.54]
RankingsWhere CCNE2 stands among ~20K protein-coding genes
  • #5,983of 20,598
    Most Researched79
  • #3,382of 17,882
    Most Constrained (LOEUF)0.54 · top quartile
Genes detectedCCNE2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
SIRT3-dependent delactylation of cyclin E2 prevents hepatocellular carcinoma growth.
PMID: 36896611
EMBO Rep · 2023
1.00
2
Cyclin E/CDK2: DNA Replication, Replication Stress and Genomic Instability.
PMID: 34901021
Front Cell Dev Biol · 2021
0.90
3
Atypical E3 ligase ZFP91 promotes small-molecule-induced E2F2 transcription factor degradation for cancer therapy.
PMID: 36375317
EBioMedicine · 2022
0.80
4
Transcriptome-wide association study-derived genes as potential visceral adipose tissue-specific targets for type 2 diabetes.
PMID: 37540242
Diabetologia · 2023
0.70
5
Combining PARP with ATR inhibition overcomes PARP inhibitor and platinum resistance in ovarian cancer models.
PMID: 32709856
Nat Commun · 2020
0.60