CCNE2

Summary

CCNE2 (cyclin E2, HGNC:1590) is a protein-coding gene on chromosome 8q22.1, encoding G1/S-specific cyclin-E2 (O96020). Essential for the control of the cell cycle at the late G1 and early S phase.

The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through the cell cycle. Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. This cyclin forms a complex with and functions as a regulatory subunit of CDK2. This cyclin has been shown to specifically interact with CIP/KIP family of CDK inhibitors, and plays a role in cell cycle G1/S transition. The expression of this gene peaks at the G1-S phase and exhibits a pattern of tissue specificity distinct from that of cyclin E1. A significantly increased expression level of this gene was observed in tumor-derived cells.

Source: NCBI Gene 9134 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 56 total — 5 pathogenic, 2 likely-pathogenic
• Druggable target: yes — 12 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_057749

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1590
Approved symbol	CCNE2
Name	cyclin E2
Location	8q22.1
Locus type	gene with protein product
Status	Approved
Aliases	CYCE2
Ensembl gene	ENSG00000175305
Ensembl biotype	protein_coding
OMIM	603775
Entrez	9134

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 13 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000308108, ENST00000396133, ENST00000517487, ENST00000519889, ENST00000520509, ENST00000521809, ENST00000523476, ENST00000524224, ENST00000860224, ENST00000860225, ENST00000860226, ENST00000860227, ENST00000860228, ENST00000918118, ENST00000918119, ENST00000918120, ENST00000944866

RefSeq mRNA: 1 — MANE Select: NM_057749 NM_057749

CCDS: CCDS6264

Canonical transcript exons

ENST00000308108 — 12 exons

Exon	Start	End
ENSE00001203872	94885067	94885201
ENSE00001289861	94882132	94882289
ENSE00001322769	94882781	94882892
ENSE00001343008	94880224	94881745
ENSE00001343055	94893891	94893944
ENSE00002097112	94895177	94895201
ENSE00002703798	94894208	94894247
ENSE00003475609	94892818	94892969
ENSE00003576419	94894023	94894119
ENSE00003600370	94885463	94885558
ENSE00003632426	94887927	94888073
ENSE00003636416	94890415	94890550

Expression profiles

Bgee: expression breadth ubiquitous, 233 present calls, max score 89.54.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.7774 / max 142.7542, expressed in 1089 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
93995	4.5710	1053
93997	0.2064	87

Top tissues by expression

287 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
endometrium epithelium	UBERON:0004811	89.54	gold quality
corpus callosum	UBERON:0002336	88.58	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	87.13	gold quality
inferior vagus X ganglion	UBERON:0005363	86.63	gold quality
spinal cord	UBERON:0002240	86.16	gold quality
bone marrow	UBERON:0002371	84.97	gold quality
ganglionic eminence	UBERON:0004023	84.47	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.78	gold quality
ventricular zone	UBERON:0003053	83.01	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.24	gold quality
bone marrow cell	CL:0002092	81.98	gold quality
subthalamic nucleus	UBERON:0001906	81.85	gold quality
rectum	UBERON:0001052	78.84	gold quality
buccal mucosa cell	CL:0002336	78.80	gold quality
cranial nerve II	UBERON:0000941	78.23	gold quality
medulla oblongata	UBERON:0001896	77.54	gold quality
pons	UBERON:0000988	77.14	gold quality
monocyte	CL:0000576	76.65	gold quality
calcaneal tendon	UBERON:0003701	76.21	gold quality
mononuclear cell	CL:0000842	76.05	gold quality
vermiform appendix	UBERON:0001154	75.91	gold quality
cerebellar hemisphere	UBERON:0002245	75.73	gold quality
right hemisphere of cerebellum	UBERON:0014890	75.53	gold quality
cerebellar cortex	UBERON:0002129	75.51	gold quality
stromal cell of endometrium	CL:0002255	75.45	gold quality
substantia nigra	UBERON:0002038	75.27	gold quality
trabecular bone tissue	UBERON:0002483	75.20	gold quality
leukocyte	CL:0000738	75.17	gold quality
colonic epithelium	UBERON:0000397	74.95	gold quality
midbrain	UBERON:0001891	74.91	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-7052	yes	287.46
E-MTAB-6911	no	174.52
E-ANND-3	no	3.71

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BACH1, CHD8, CUX1, E2F1, EZH2, FOXM1, MYCT1, NEUROG2

miRNA regulators (miRDB)

128 targeting CCNE2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-5688	99.96	73.23	4504

Literature-anchored findings (GeneRIF, showing 39)

• expression is deregulated in primary breast tumors (PMID:12466974)
• The CCNE2 qualify as independent prognostic markers for lymph node-negative breast cancer patients. (PMID:16740753)
• Since SCF(Fbxw7/hCdc4) is functionally inactivated in several cancer types, alteration of this molecular pathway could contribute to the deregulation of cyclin E2 in tumorigenesis. (PMID:19084516)
• A hypothetical model whereby PTEN loss upregulates cell cycle genes such as cdc6 and cyclin E2 that in turn promote metastatic colonization at distant sites. (PMID:19107233)
• Data indicate that cyclin E2-Cdk2 activation by estrogen occurs via E2F- and CHD8-mediated transcription of cyclin E2 downstream of cyclin D1, and does not require c-myc. (PMID:19564413)
• Investigated downregulation of coronary vascular smooth muscle cell growth by siRNA against E2F1, cyclins E1 and E2. Data shows reduction in the phosphorylation levels of the retinoblastoma protein pRB and a decrease in the amount of cyclin A2. (PMID:19603101)
• Loss of cyclin D1 in ovarian cancer cells treated with SHetA2 is sufficient to induce G(1) cell cycle arrest and this strategy is not impeded by the presence of cyclin E2. (PMID:19638577)
• Tamoxifen resistant tumors displayed enriched expression of genes related to cell cycle and proliferation, as well as elevated activity of E2F transcription factors. (PMID:21789246)
• protein and mRNA expressions of Cyclin E2 in nasopharyngeal carcinoma (PMID:22394640)
• In cancer cells Fbw7, fails to effectively target cyclin E2 for proteosomal degradation. (PMID:23324394)
• Cyclin E2 induction of genomic instability by a mechanism distinct from cyclin E1 indicates that these two proteins have unique functions in a cancer setting. (PMID:23324395)
• Data indicate that miR-26a overexpression inhibited pancreatic cancer cell growth by the downregulation of cyclin E2 expression. (PMID:24116110)
• data suggests the potential role of monomorphic morphology, high cyclin E2 and Ki67 expression as adverse prognostic factors for TNKLPD (PMID:25475054)
• Our study shows miR-25 is overexpressed in small cell lung cancer and acting as oncogenic regulator by regulating cyclin E2. (PMID:25550809)
• Results suggest that the miR-30d-5p/CCNE2 axis may contribute to NSCLC cell proliferation and motility. (PMID:25843294)
• miR-144-5p functions as tumour suppressor in BC cells. CCNE1 and CCNE2 were directly regulated by miR-144-5p and might be good prognostic markers for survival of bladder cancer patients (PMID:26057453)
• In breast cancer patients, high levels of HMGA1 and CCNE2 expression are associated with the YAP/TAZ signature. (PMID:26265440)
• Survivin and cyclin E2 genes expression may have clinical relevance and can be considered as molecular risk factors for AL. Also they may be useful as predictive markers for treatment outcome in leukemic patients. (PMID:26600399)
• Combinatorial PX-866 and Raloxifene Decrease Rb Phosphorylation, Cyclin E2 Transcription, and Proliferation of MCF-7 Breast Cancer Cells (PMID:26660119)
• miR-26a regulated mouse hepatocyte proliferation by directly targeting the 3’ untranslated regions of cyclin D2/cyclin E2. (PMID:26818545)
• Overexpression of cyclin E2 is an early event in gastric carcinogenesis. (PMID:27034264)
• The results suggest that miR30a may function as a novel tumor suppressor in CRPC. Its antioncogenic activity may occur by the reduced expression of a distinct cell cycle protein, CCNE2. (PMID:27431942)
• the molecular mechanism of trastuzumab action in BT474 cell line may be regulated by miR-26a and miR-30b and CCNE2 overexpression might play an important role in acquired trastuzumab resistance in HER2+ breast cancer. (PMID:28120942)
• cyclin E2 participates in regulating viral replication through the CDK2/SAMHD1 phosphorylation pathway in an HBV infection system. (PMID:29782647)
• Knockdown of CCNE2 promoted MCF7 cell apoptosis and G2-stage cell cycle arrest. (PMID:30157476)
• Cyclin A2 or E1 alterations define a homogenous entity of aggressive hepatocellular carcinoma (HCC) subgroup. (PMID:30531861)
• Up-regulation of cyclin E2 was observed in gastric cancer tissues.Cyclin E2 was a target of miR-383 in gastric cancer cells. (PMID:31170011)
• The overexpression of MNX1 promoted cervical cancer cells proliferation, migration, and invasion. Moreover, MNX1 upregulated 2 critical cell cycle regulators, CCNE1 and CCNE2. (PMID:31436258)
• Nicotine-upregulated miR-30a arrests cell cycle in G1 phase by directly targeting CCNE2 in human periodontal ligament cells. (PMID:31689122)
• Circular RNA CircCCNB1 sponges micro RNA-449a to inhibit cellular senescence by targeting CCNE2. (PMID:31767812)
• Antibiotic tigecycline inhibits cell proliferation, migration and invasion via down-regulating CCNE2 in pancreatic ductal adenocarcinoma. (PMID:32141702)
• CARM1 promotes non-small cell lung cancer progression through upregulating CCNE2 expression. (PMID:32487779)
• Clinical significance of CCNE2 protein and mRNA expression in thyroid cancer tissues. (PMID:33059229)
• SP1-induced overexpression of LINC00520 facilitates non-small cell lung cancer progression through miR-577/CCNE2 pathway and predicts poor prognosis. (PMID:33728585)
• Vascular endothelial cell-derived exosomal miR-30a-5p inhibits lung adenocarcinoma malignant progression by targeting CCNE2. (PMID:34128973)
• E2F transcription factor 1 (E2F1) promotes the transforming growth factor TGF-beta1 induced human cardiac fibroblasts differentiation through promoting the transcription of CCNE2 gene. (PMID:34521301)
• Screening Differential CircRNAs Expression Profiles Reveals the Regulatory Role of the has_circTPT1_003-has-miR-218-5p-CCNE2/SMC4 Signaling Axis in Bladder Carcinoma Progression. (PMID:35005988)
• Genome-wide chromatin contacts of super-enhancer-associated lncRNA identify LINC01013 as a regulator of fibrosis in the aortic valve. (PMID:35041643)
• Downregulation of miR-503-5p Promotes the Development of Pancreatic Cancer by Targeting Cyclin E2. (PMID:38505921)

Cross-species orthologs

15 orthologs

Organism	Symbol	Gene ID
danio_rerio	ccne2	ENSDARG00000098529
mus_musculus	Ccne2	ENSMUSG00000028212
rattus_norvegicus	Ccne2	ENSRNOG00000008055
drosophila_melanogaster	CycA	FBGN0000404
drosophila_melanogaster	CycB	FBGN0000405
drosophila_melanogaster	CycD	FBGN0010315
drosophila_melanogaster	CycE	FBGN0010382
caenorhabditis_elegans		WBGENE00000863
caenorhabditis_elegans		WBGENE00000864
caenorhabditis_elegans		WBGENE00000865
caenorhabditis_elegans		WBGENE00000866
caenorhabditis_elegans	cyb-2.2	WBGENE00000867
caenorhabditis_elegans		WBGENE00000870
caenorhabditis_elegans	cye-1	WBGENE00000871
caenorhabditis_elegans		WBGENE00017259

Paralogs (18): CCNE1 (ENSG00000105173), CCNP (ENSG00000105219), CCNJ (ENSG00000107443), CCND1 (ENSG00000110092), CCND3 (ENSG00000112576), CCNG1 (ENSG00000113328), CCNI (ENSG00000118816), CCND2 (ENSG00000118971), CCNA1 (ENSG00000133101), CCNB1 (ENSG00000134057), CCNJL (ENSG00000135083), CCNG2 (ENSG00000138764), CCNA2 (ENSG00000145386), CCNB3 (ENSG00000147082), CCNO (ENSG00000152669), CCNB2 (ENSG00000157456), CCNF (ENSG00000162063), CCNI2 (ENSG00000205089)

Protein

Protein identifiers

G1/S-specific cyclin-E2 — O96020 (reviewed: O96020)

All UniProt accessions (5): E5RHN2, O96020, E5RK20, H0YBQ2, Q8WUE3

UniProt curated annotations — full annotation on UniProt →

Function. Essential for the control of the cell cycle at the late G1 and early S phase.

Subunit / interactions. Interacts with the CDK2 (in vivo) and CDK3 (in vitro) protein kinases to form a serine/threonine kinase holoenzyme complex. The cyclin subunit imparts substrate specificity to the complex.

Subcellular location. Nucleus.

Tissue specificity. According to PubMed:9858585, highest levels of expression in adult testis, thymus and brain. Lower levels in placenta, spleen and colon. Consistently elevated levels in tumor-derived cells compared to non-transformed proliferating cells. According to PubMed:9840927: low levels in thymus, prostate, brain, skeletal muscle, and kidney. Elevated levels in lung. According to PubMed:9840943 highly expressed in testis, placenta, thymus and brain. In a lesser extent in small intestine and colon.

Post-translational modifications. Phosphorylation by CDK2 triggers its release from CDK2 and degradation via the ubiquitin proteasome pathway. Lactylated at Lys-348. Delactylated by SIRT3.

Induction. Activated by papilloma viral oncoproteins E6 and E7 which bind to and inactivate p53 and Rb, respectively.

Similarity. Belongs to the cyclin family. Cyclin E subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
O96020-1	Long	yes
O96020-2	Short, SV

RefSeq proteins (1): NP_477097* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004367	Cyclin_C-dom	Domain
IPR006671	Cyclin_N	Domain
IPR013763	Cyclin-like_dom	Domain
IPR036915	Cyclin-like_sf	Homologous_superfamily
IPR039361	Cyclin	Family
IPR048258	Cyclins_cyclin-box	Conserved_site

Pfam: PF00134, PF02984

UniProt features (11 total): modified residue 4, compositionally biased region 2, chain 1, region of interest 1, mutagenesis site 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8HN9	X-RAY DIFFRACTION	3.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O96020-F1	77.80	0.61

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (4): 21, 348, 383, 392

Mutagenesis-validated functional residues (1):

Position	Phenotype
392	increase of steady state level.

Function

Pathways and Gene Ontology

Reactome pathways

39 pathways

ID	Pathway
R-HSA-1538133	G0 and Early G1
R-HSA-187577	SCF(Skp2)-mediated degradation of p27/p21
R-HSA-2559586	DNA Damage/Telomere Stress Induced Senescence
R-HSA-390471	Association of TriC/CCT with target proteins during biosynthesis
R-HSA-6804116	TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest
R-HSA-69017	CDK-mediated phosphorylation and removal of Cdc6
R-HSA-69200	Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 complexes
R-HSA-69202	Cyclin E associated events during G1/S transition
R-HSA-69231	Cyclin D associated events in G1
R-HSA-69563	p53-Dependent G1 DNA Damage Response
R-HSA-9661069	Defective binding of RB1 mutants to E2F1,(E2F2, E2F3)
R-HSA-1640170	Cell Cycle
R-HSA-1643685	Disease
R-HSA-212436	Generic Transcription Pathway
R-HSA-2262752	Cellular responses to stress
R-HSA-2559583	Cellular Senescence
R-HSA-3700989	Transcriptional Regulation by TP53
R-HSA-390466	Chaperonin-mediated protein folding
R-HSA-391251	Protein folding
R-HSA-392499	Metabolism of proteins
R-HSA-453279	Mitotic G1 phase and G1/S transition
R-HSA-6791312	TP53 Regulates Transcription of Cell Cycle Genes
R-HSA-69052	Switching of origins to a post-replicative state
R-HSA-69206	G1/S Transition
R-HSA-69236	G1 Phase
R-HSA-69239	Synthesis of DNA
R-HSA-69242	S Phase
R-HSA-69278	Cell Cycle, Mitotic
R-HSA-69306	DNA Replication
R-HSA-69580	p53-Dependent G1/S DNA damage checkpoint

MSigDB gene sets: 381 (showing top): GOBP_MEIOTIC_CHROMOSOME_SEGREGATION, GOBP_CHROMOSOME_ORGANIZATION, REACTOME_DNA_REPLICATION, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_REGULATION_OF_PHOSPHORYLATION, FISCHER_G1_S_CELL_CYCLE, GCANCTGNY_MYOD_Q6, REACTOME_SCF_SKP2_MEDIATED_DEGRADATION_OF_P27_P21, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_POSITIVE_REGULATION_OF_MITOTIC_CELL_CYCLE, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, TATTATA_MIR374, GOBP_TELOMERE_ORGANIZATION, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY

GO Biological Process (10): regulation of cyclin-dependent protein serine/threonine kinase activity (GO:0000079), G1/S transition of mitotic cell cycle (GO:0000082), telomere maintenance (GO:0000723), DNA replication initiation (GO:0006270), homologous chromosome pairing at meiosis (GO:0007129), regulation of protein localization (GO:0032880), cell division (GO:0051301), positive regulation of G1/S transition of mitotic cell cycle (GO:1900087), regulation of cell cycle (GO:0051726), chromosome organization involved in meiotic cell cycle (GO:0070192)

GO Molecular Function (3): cyclin-dependent protein serine/threonine kinase regulator activity (GO:0016538), protein kinase binding (GO:0019901), protein binding (GO:0005515)

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), microtubule organizing center (GO:0005815), cytosol (GO:0005829), cyclin E1-CDK2 complex (GO:0097134), cyclin E2-CDK2 complex (GO:0097135)

Reactome top-level categories

Rollup of top-17 pathways:

Category	Pathways
Cyclin E associated events during G1/S transition	2
Mitotic G1 phase and G1/S transition	1
Cyclin A:Cdk2-associated events at S phase entry	1
Cellular Senescence	1
Chaperonin-mediated protein folding	1
TP53 Regulates Transcription of Cell Cycle Genes	1
Switching of origins to a post-replicative state	1
G1/S Transition	1
G1 Phase	1
p53-Dependent G1/S DNA damage checkpoint	1
Aberrant regulation of mitotic G1/S transition in cancer due to RB1 defects	1
RNA Polymerase II Transcription	1
Cellular responses to stimuli	1
Cellular responses to stress	1
Generic Transcription Pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cyclin-dependent protein serine/threonine kinase activity	2
DNA metabolic process	2
cyclin-dependent protein kinase holoenzyme complex	2
regulation of protein serine/threonine kinase activity	1
mitotic cell cycle	1
mitotic cell cycle phase transition	1
cell cycle G1/S phase transition	1
telomere organization	1
DNA-templated DNA replication	1
homologous chromosome segregation	1
chromosome organization involved in meiotic cell cycle	1
intracellular protein localization	1
regulation of localization	1
cellular process	1
G1/S transition of mitotic cell cycle	1
positive regulation of mitotic cell cycle phase transition	1
positive regulation of cell cycle G1/S phase transition	1
regulation of G1/S transition of mitotic cell cycle	1
cell cycle	1
regulation of cellular process	1
chromosome organization	1
meiotic cell cycle	1
meiotic cell cycle process	1
cyclin-dependent protein kinase regulator activity	1
kinase binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
microtubule cytoskeleton	1
cytoplasm	1

Protein interactions and networks

STRING

2234 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCNE2	CDK2	P24941	997
CCNE2	CDK4	P11802	922
CCNE2	CDKN1B	P46527	815
CCNE2	CCNL2	Q96S94	794
CCNE2	CDKN1A	P38936	792
CCNE2	TP53	P04637	763
CCNE2	CDC25A	P30304	759
CCNE2	CDC6	Q99741	755
CCNE2	E2F1	Q01094	754
CCNE2	CDK6	Q00534	716
CCNE2	CHEK1	O14757	677
CCNE2	CDK1	P06493	658
CCNE2	CDK3	Q00526	652
CCNE2	E2F3	O00716	651
CCNE2	MCM10	Q7L590	651

IntAct

63 interactions, top by confidence:

A	B	Type	Score
CDK2	CCNE2	psi-mi:“MI:0914”(association)	0.940
CCNE2	CDK2	psi-mi:“MI:0915”(physical association)	0.940
CDK2	CCNE2	psi-mi:“MI:0915”(physical association)	0.940
CDK2	CCNE2	psi-mi:“MI:0407”(direct interaction)	0.940
CDKN1A	CCNE2	psi-mi:“MI:0915”(physical association)	0.890
CCNE2	CDKN1A	psi-mi:“MI:0915”(physical association)	0.890
CDKN1A	CCNE2	psi-mi:“MI:0407”(direct interaction)	0.890
CDKN1A	CCNE2	psi-mi:“MI:0914”(association)	0.890
CDK2	CCNB2	psi-mi:“MI:0914”(association)	0.860
CDK1	CCNB2	psi-mi:“MI:0914”(association)	0.840
CDKN1B	CCNE2	psi-mi:“MI:0915”(physical association)	0.790
CCNE2	CDKN1B	psi-mi:“MI:0915”(physical association)	0.790
CDKN1B	CCNE2	psi-mi:“MI:0914”(association)	0.790
CDKN1A	CDK14	psi-mi:“MI:0914”(association)	0.770
CDKN1B	CCNB2	psi-mi:“MI:0914”(association)	0.670
CCNE2	CDK3	psi-mi:“MI:0915”(physical association)	0.660
CDK2	GMNN	psi-mi:“MI:0914”(association)	0.640
CCNE2	WFS1	psi-mi:“MI:0915”(physical association)	0.560
CCNE2	HTT	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (77): CCNE2 (Two-hybrid), CCNE2 (Affinity Capture-MS), CCNE2 (Affinity Capture-MS), CCNE2 (Affinity Capture-MS), CDKN1A (Affinity Capture-MS), CCNE2 (Affinity Capture-MS), CCNE2 (Affinity Capture-MS), CCNE2 (Affinity Capture-MS), CCNE2 (Affinity Capture-MS), CCNE2 (Affinity Capture-MS), CDKN1A (Affinity Capture-MS), CCNE2 (Affinity Capture-MS), CCNE2 (Affinity Capture-MS), CCNE2 (Affinity Capture-MS), CCNE2 (Affinity Capture-MS)

ESM2 similar proteins: A5PK16, O08918, O42575, O96020, P24385, P24864, P25322, P30279, P30280, P30282, P39948, P39949, P39950, P41002, P47794, P48961, P49706, P49707, P50755, P50756, P51944, P51945, P51959, P53782, P55169, Q04827, Q0P5D3, Q16589, Q2KI22, Q32NJ2, Q32NM1, Q52QT8, Q5E9I1, Q5E9K7, Q5R5D0, Q5R6J5, Q5SRT8, Q5T5M9, Q5XGG5, Q61457

Diamond homologs: A0MEB5, A2YH60, A5PK16, C4YR54, O15995, O48790, O77689, O95067, O96020, P04962, P07818, P0CY18, P10815, P13351, P13365, P15206, P18063, P20248, P20437, P20438, P20439, P24860, P24861, P24862, P24864, P24868, P24869, P24870, P24871, P25009, P25010, P25011, P25012, P29332, P30183, P30274, P30276, P30277, P30278, P30283

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
CCNE2	“form complex”	CyclinE/CDK2	binding
MYCT1	“down-regulates quantity by repression”	CCNE2	“transcriptional regulation”
CHD8	“up-regulates quantity by expression”	CCNE2	“transcriptional regulation”
“Cullin 1-RBX1-Skp1”	“down-regulates quantity by destabilization”	CCNE2	polyubiquitination
FBXW7	“down-regulates quantity by destabilization”	CCNE2	binding
SCF-SKP2	“down-regulates quantity by destabilization”	CCNE2	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 28 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
TP53 Regulates Transcription of Cell Cycle Genes	7	181.3×	8e-13
Defective binding of RB1 mutants to E2F1,(E2F2, E2F3)	6	181.3×	2e-11
TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest	5	143.1×	4e-09
Aberrant regulation of mitotic cell cycle due to RB1 defects	6	116.5×	4e-10
G1 Phase	6	112.5×	4e-10
Diseases of mitotic cell cycle	6	112.5×	4e-10
G0 and Early G1	5	104.6×	2e-08
Cyclin D associated events in G1	8	88.8×	2e-12

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of DNA replication	5	111.8×	1e-07
G1/S transition of mitotic cell cycle	8	61.7×	1e-10
cell division	8	14.2×	5e-06

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

56 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	2
Uncertain significance	37
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
147309	GRCh38/hg38 8q22.1(chr8:93038175-95667782)x1	Pathogenic
563556	GRCh37/hg19 8q21.2-23.3(chr8:86841154-116518125)x3	Pathogenic
60383	GRCh38/hg38 8q21.3-22.1(chr8:92283179-95786443)x1	Pathogenic
60386	GRCh38/hg38 8q21.3-22.1(chr8:92287062-95786443)x1	Pathogenic
60387	GRCh38/hg38 8q22.1(chr8:92755532-97792132)x1	Pathogenic
441773	GRCh37/hg19 8q22.1(chr8:93391781-96572606)x1	Likely pathogenic
979843	GRCh37/hg19 8q22.1(chr8:95803280-97802022)x3	Likely pathogenic

SpliceAI

1795 predictions. Top by Δscore:

Variant	Effect	Δscore
8:94880112:T:TA	acceptor_gain	1.0000
8:94880113:G:A	acceptor_gain	1.0000
8:94885089:T:TA	donor_gain	1.0000
8:94887921:ACTT:A	donor_loss	1.0000
8:94887922:CTT:C	donor_loss	1.0000
8:94887923:TTA:T	donor_loss	1.0000
8:94887924:TA:T	donor_loss	1.0000
8:94887925:A:C	donor_loss	1.0000
8:94887926:CCT:C	donor_gain	1.0000
8:94890546:CCCAG:C	acceptor_gain	1.0000
8:94890547:CCAG:C	acceptor_gain	1.0000
8:94890547:CCAGC:C	acceptor_gain	1.0000
8:94890548:CAG:C	acceptor_gain	1.0000
8:94890548:CAGC:C	acceptor_gain	1.0000
8:94892812:TCTTA:T	donor_loss	1.0000
8:94892813:CTTAC:C	donor_loss	1.0000
8:94892814:TTAC:T	donor_loss	1.0000
8:94892815:TA:T	donor_loss	1.0000
8:94892816:A:C	donor_loss	1.0000
8:94892965:CAATT:C	acceptor_gain	1.0000
8:94892968:TT:T	acceptor_gain	1.0000
8:94892970:C:CC	acceptor_gain	1.0000
8:94892974:C:CT	acceptor_gain	1.0000
8:94892975:A:C	acceptor_gain	1.0000
8:94893417:A:C	donor_gain	1.0000
8:94893889:AC:A	donor_gain	1.0000
8:94893890:CC:C	donor_gain	1.0000
8:94893902:A:AC	donor_gain	1.0000
8:94893903:C:CC	donor_gain	1.0000
8:94893941:CATC:C	acceptor_gain	1.0000

AlphaMissense

2684 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:94890424:C:A	W148C	1.000
8:94890424:C:G	W148C	1.000
8:94890426:A:G	W148R	1.000
8:94890426:A:T	W148R	1.000
8:94885190:C:A	W236C	0.999
8:94885190:C:G	W236C	0.999
8:94885192:A:G	W236R	0.999
8:94885192:A:T	W236R	0.999
8:94885479:T:A	E227V	0.999
8:94885521:A:T	V213D	0.999
8:94887933:T:A	K198N	0.999
8:94887933:T:G	K198N	0.999
8:94887940:G:T	A196D	0.999
8:94887961:C:T	G189E	0.999
8:94887962:C:G	G189R	0.999
8:94887962:C:T	G189R	0.999
8:94887969:T:A	Q186H	0.999
8:94887969:T:G	Q186H	0.999
8:94888031:C:G	A166P	0.999
8:94888068:A:C	C153W	0.999
8:94890422:A:G	L149P	0.999
8:94890425:C:G	W148S	0.999
8:94890442:C:A	R142S	0.999
8:94890442:C:G	R142S	0.999
8:94890443:C:A	R142M	0.999
8:94890443:C:G	R142T	0.999
8:94882885:T:A	D280V	0.998
8:94887934:T:A	K198I	0.998
8:94887967:A:G	L187P	0.998
8:94887973:A:G	L185P	0.998

dbSNP variants (sampled 300 via entrez): RS1000142631 (8:94892139 GA>G,GAA), RS1000355678 (8:94891054 C>T), RS1000370794 (8:94897888 A>G), RS1000636233 (8:94884416 G>A), RS1000989360 (8:94896365 C>T), RS1001394005 (8:94883497 C>T), RS1001735003 (8:94896660 G>C), RS1002223994 (8:94897100 G>C), RS1002473510 (8:94884808 C>T), RS1002745881 (8:94885297 A>G), RS1002971577 (8:94882405 A>G), RS1003251877 (8:94889273 C>T), RS1003374614 (8:94895301 C>A,T), RS1003407342 (8:94895622 A>C), RS1003494899 (8:94895374 G>A,T)

Disease associations

OMIM: gene MIM:603775 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90013442_10	Keratoconus	3.000000e-10

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (5): CHEMBL2094126 (PROTEIN COMPLEX), CHEMBL2111444 (PROTEIN COMPLEX GROUP), CHEMBL4523633 (PROTEIN COMPLEX), CHEMBL4523635 (PROTEIN COMPLEX), CHEMBL5483189 (PROTEIN COMPLEX GROUP)

Molecules with ChEMBL bioactivity

12 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 57,850 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL189963	PALBOCICLIB	4	13,102
CHEMBL3301610	ABEMACICLIB	4	7,045
CHEMBL2103840	DINACICLIB	3	2,257
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL14762	SELICICLIB	2	3,787
CHEMBL2347597	ASNUCICLIB	2	100
CHEMBL4446357	EBVACICLIB	2	599
CHEMBL575448	BMS-754807	2	406
CHEMBL4277900	CROZBACICLIB	2	18
CHEMBL296468	BMS-387032	1	2,075
CHEMBL3545083	RGB-286638	1	551
CHEMBL4439321	ATUVECICLIB	1	129

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

748 potent at pChembl≥5 of 802 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.00	Ki	1	nM	DINACICLIB
9.00	Ki	1	nM	EBVACICLIB
9.00	Ki	1	nM	CHEMBL5286090
9.00	IC50	1	nM	CHEMBL328406
8.70	IC50	2	nM	CHEMBL126997
8.70	IC50	2	nM	CHEMBL355631
8.70	Ki	2	nM	CHEMBL298445
8.70	IC50	2	nM	CHEMBL575888
8.70	IC50	2	nM	CHEMBL420463
8.70	IC50	2	nM	CHEMBL430653
8.67	IC50	2.13	nM	CHEMBL1684800
8.52	IC50	3	nM	CHEMBL424207
8.52	IC50	3	nM	CHEMBL126549
8.52	IC50	3	nM	CHEMBL300936
8.52	IC50	3	nM	CHEMBL354634
8.52	IC50	3	nM	CHEMBL340904
8.52	IC50	3	nM	RGB-286638
8.52	Ki	3	nM	ASNUCICLIB
8.52	IC50	3	nM	CHEMBL100012
8.52	IC50	3	nM	CHEMBL317953
8.40	IC50	4	nM	CHEMBL354995
8.40	IC50	4	nM	CHEMBL126328
8.40	IC50	4	nM	CHEMBL170130
8.40	IC50	4	nM	CHEMBL412267
8.40	IC50	4	nM	CHEMBL172640
8.40	IC50	4	nM	CHEMBL170752
8.40	IC50	4	nM	CHEMBL318564
8.40	IC50	4	nM	CHEMBL306856
8.30	IC50	5	nM	CHEMBL171439
8.30	IC50	5	nM	CHEMBL353182
8.30	IC50	5	nM	CHEMBL295136
8.30	IC50	5	nM	CHEMBL126993
8.30	IC50	5	nM	CHEMBL129396
8.30	IC50	5	nM	CHEMBL126630
8.30	Ki	5	nM	CHEMBL5195030
8.30	IC50	5	nM	CHEMBL103714
8.30	IC50	5	nM	CHEMBL358102
8.22	IC50	6	nM	CHEMBL129471
8.22	IC50	6	nM	CHEMBL536029
8.22	IC50	6	nM	CHEMBL2111846
8.22	IC50	6	nM	CHEMBL74637
8.15	IC50	7	nM	CHEMBL171297
8.15	Ki	7	nM	CHEMBL5281179
8.15	IC50	7	nM	CHEMBL148580
8.15	IC50	7	nM	CHEMBL346164
8.10	IC50	8	nM	CHEMBL422738
8.10	Ki	8	nM	CHEMBL5285230
8.10	IC50	8	nM	CHEMBL148889
8.10	IC50	8	nM	CHEMBL346184
8.10	IC50	8	nM	CHEMBL306748

PubChem BioAssay actives

636 with measured affinity, of 1675 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
6-(difluoromethyl)-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	1940562: Inhibition of CDK2/cyclin E (unknown origin) assessed as inhibition constant	ki	0.0010	uM
4-[[5-chloro-4-(1-methylpyrazol-4-yl)pyrimidin-2-yl]amino]benzenesulfonamide	1940570: Inhibition of CDK2/cyclin E (unknown origin) assessed as inhibition constant incubated for 30 to 60 mins presence of dithiothreitol by Cheng-Prusoff equation analysis	ki	0.0010	uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	1247623: Inhibition of CDK2/cyclin E (unknown origin) after 40 mins by scintillation counting analysis	ic50	0.0010	uM
5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-N-pyridin-4-yl-1,3-thiazol-2-amine	53837: Inhibition of Cyclin-dependent kinase 2-cyclin E	ic50	0.0010	uM
2-[(2S)-1-[3-ethyl-7-[(1-oxidopyridin-1-ium-3-yl)methylamino]pyrazolo[1,5-a]pyrimidin-5-yl]piperidin-2-yl]ethanol	1940562: Inhibition of CDK2/cyclin E (unknown origin) assessed as inhibition constant	ki	0.0010	uM
(3Z)-5-fluoro-3-[(3-methoxy-1H-pyrrol-2-yl)methylidene]-4-[2-[(2S)-pyrrolidin-2-yl]ethynyl]-1H-indol-2-one	53857: In vitro inhibition of recombinant Cyclin Dependent Kinase-2/Cyclin E.	ic50	0.0020	uM
(2S)-1-[4-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]pyrrolo[2,1-f][1,2,4]triazin-2-yl]pyrrolidine-2-carboxamide	440837: Inhibition of CDK2/Cyclin E after 60 mins by fluorescence electrophoresis	ic50	0.0020	uM
4-methyl-5-[2-(3-nitroanilino)pyrimidin-4-yl]-1,3-thiazol-2-amine	53995: Inhibition of protein kinase Cyclin-dependent kinase 2-cyclin E	ki	0.0020	uM
1-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]-3-(2,6-difluorophenyl)urea	55525: Inhibitory activity against baculovirus expressed Cyclin dependent kinase 2-cyclinE	ic50	0.0020	uM
5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-N-pyridin-2-yl-1,3-thiazol-2-amine	53837: Inhibition of Cyclin-dependent kinase 2-cyclin E	ic50	0.0020	uM
4-[[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]amino]-N-(2-hydroxyethyl)benzenesulfonamide	53837: Inhibition of Cyclin-dependent kinase 2-cyclin E	ic50	0.0020	uM
N-[5-amino-1-[(4-methoxyphenyl)methyl]pyrazol-4-yl]-5-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino]-2-methylbenzamide	578725: Inhibition of CDK2/cyclin E	ic50	0.0021	uM
1-[3-[4-[[4-(2-methoxyethyl)piperazin-1-yl]methyl]phenyl]-4-oxo-1H-indeno[2,1-d]pyrazol-5-yl]-3-morpholin-4-ylurea	1921507: Inhibition of CDK2/cyclin E (unknown origin)	ic50	0.0030	uM
(3Z)-4-[(3S)-3-amino-4-hydroxybut-1-ynyl]-5-fluoro-3-[(3-methoxy-1H-pyrrol-2-yl)methylidene]-1H-indol-2-one	53857: In vitro inhibition of recombinant Cyclin Dependent Kinase-2/Cyclin E.	ic50	0.0030	uM
N-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]-2-[4-[(1,3-dihydroxypropan-2-ylamino)methyl]phenyl]acetamide	55525: Inhibitory activity against baculovirus expressed Cyclin dependent kinase 2-cyclinE	ic50	0.0030	uM
(3Z)-4-[(3R,4S,5R)-4-amino-3,5-dihydroxyhex-1-ynyl]-5-fluoro-3-[(3-methoxy-1H-pyrrol-2-yl)methylidene]-1H-indol-2-one	53857: In vitro inhibition of recombinant Cyclin Dependent Kinase-2/Cyclin E.	ic50	0.0030	uM
1-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]-3-(2,6-dichlorophenyl)urea	55525: Inhibitory activity against baculovirus expressed Cyclin dependent kinase 2-cyclinE	ic50	0.0030	uM
N-[5-[(2-tert-butyl-1,3-oxazol-5-yl)methylsulfanyl]-1,3-thiazol-2-yl]-2-phenylacetamide	55525: Inhibitory activity against baculovirus expressed Cyclin dependent kinase 2-cyclinE	ic50	0.0030	uM
5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-N-pyridin-3-yl-1,3-thiazol-2-amine	53837: Inhibition of Cyclin-dependent kinase 2-cyclin E	ic50	0.0030	uM
3-[[6-[[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]amino]-3-pyridinyl]methylamino]-2,2-dimethylpropan-1-ol	53837: Inhibition of Cyclin-dependent kinase 2-cyclin E	ic50	0.0030	uM
3-[[5-fluoro-4-[4-methyl-2-(methylamino)-1,3-thiazol-5-yl]pyrimidin-2-yl]amino]benzenesulfonamide	1940562: Inhibition of CDK2/cyclin E (unknown origin) assessed as inhibition constant	ki	0.0030	uM
(3Z)-5-fluoro-4-[(3S)-4-hydroxy-3-(methylamino)but-1-ynyl]-3-[(3-methoxy-1H-pyrrol-2-yl)methylidene]-1H-indol-2-one	53857: In vitro inhibition of recombinant Cyclin Dependent Kinase-2/Cyclin E.	ic50	0.0040	uM
(3Z)-5-fluoro-4-[2-(4-hydroxyoxan-4-yl)ethynyl]-3-[(3-methoxy-1H-pyrrol-2-yl)methylidene]-1H-indol-2-one	53857: In vitro inhibition of recombinant Cyclin Dependent Kinase-2/Cyclin E.	ic50	0.0040	uM
(3Z)-5-fluoro-3-[(3-methoxy-1H-pyrrol-2-yl)methylidene]-4-[3-(methylamino)prop-1-ynyl]-1H-indol-2-one	53857: In vitro inhibition of recombinant Cyclin Dependent Kinase-2/Cyclin E.	ic50	0.0040	uM
(3Z)-4-(4-amino-3-hydroxybut-1-ynyl)-5-fluoro-3-[(3-methoxy-1H-pyrrol-2-yl)methylidene]-1H-indol-2-one	53857: In vitro inhibition of recombinant Cyclin Dependent Kinase-2/Cyclin E.	ic50	0.0040	uM
(3Z)-5-fluoro-4-[2-[(2S,4R)-4-hydroxypyrrolidin-2-yl]ethynyl]-3-[(3-methoxy-1H-pyrrol-2-yl)methylidene]-1H-indol-2-one	53857: In vitro inhibition of recombinant Cyclin Dependent Kinase-2/Cyclin E.	ic50	0.0040	uM
N-[5-[[5-(cyclohexylmethyl)-1,3-oxazol-2-yl]methylsulfanyl]-1,3-thiazol-2-yl]acetamide	55525: Inhibitory activity against baculovirus expressed Cyclin dependent kinase 2-cyclinE	ic50	0.0040	uM
5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-N-phenyl-1,3-thiazol-2-amine	53837: Inhibition of Cyclin-dependent kinase 2-cyclin E	ic50	0.0040	uM
3-[3-(4-hydroxypiperidin-1-yl)propyl]-6-methoxy-18-methyl-3,13,18-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,21]tricosa-1(16),2(10),4(9),5,7,11(15),17(21),19,22-nonaene-12,14-dione	55503: Inhibitory activity against Cyclin E-cyclin-dependent kinase 2 in enzymatic assay by measuring phosphorylation of RbING	ic50	0.0040	uM
(2S,3R)-3-[[6-[(4,6-dimethyl-3-pyridinyl)methylamino]-9-propan-2-ylpurin-2-yl]amino]pentan-2-ol	1940562: Inhibition of CDK2/cyclin E (unknown origin) assessed as inhibition constant	ki	0.0050	uM
(3Z)-4-[(3R)-3-amino-4-hydroxybut-1-ynyl]-5-fluoro-3-[(3-methoxy-1H-pyrrol-2-yl)methylidene]-1H-indol-2-one	53857: In vitro inhibition of recombinant Cyclin Dependent Kinase-2/Cyclin E.	ic50	0.0050	uM
(3Z)-5-fluoro-4-[2-[(2S,4S)-4-hydroxypyrrolidin-2-yl]ethynyl]-3-[(3-methoxy-1H-pyrrol-2-yl)methylidene]-1H-indol-2-one	53857: In vitro inhibition of recombinant Cyclin Dependent Kinase-2/Cyclin E.	ic50	0.0050	uM
N-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]acetamide	53837: Inhibition of Cyclin-dependent kinase 2-cyclin E	ic50	0.0050	uM
N-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]-2-methylpropanamide	55525: Inhibitory activity against baculovirus expressed Cyclin dependent kinase 2-cyclinE	ic50	0.0050	uM
N-[5-[(5-ethyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]-2-methylpropanamide	55525: Inhibitory activity against baculovirus expressed Cyclin dependent kinase 2-cyclinE	ic50	0.0050	uM
N-[5-[(5-ethyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]-2-pyridin-3-ylacetamide	55525: Inhibitory activity against baculovirus expressed Cyclin dependent kinase 2-cyclinE	ic50	0.0050	uM
N-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]-2-pyridin-3-ylacetamide	53837: Inhibition of Cyclin-dependent kinase 2-cyclin E	ic50	0.0050	uM
1-(dimethylamino)-3-[3-(4-methoxyphenyl)-4-oxo-1H-indeno[2,1-d]pyrazol-5-yl]urea	53699: Inhibition of Cyclin-dependent kinase 2-cyclin E	ic50	0.0050	uM
N-[5-[(5-propan-2-yl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]acetamide	55525: Inhibitory activity against baculovirus expressed Cyclin dependent kinase 2-cyclinE	ic50	0.0060	uM
(2R)-N-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]-2-phenylpropanamide	55525: Inhibitory activity against baculovirus expressed Cyclin dependent kinase 2-cyclinE	ic50	0.0060	uM
6-hydroxy-3,13,18-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,21]tricosa-1(16),2(10),4(9),5,7,11(15),17(21),19,22-nonaene-12,14-dione	55503: Inhibitory activity against Cyclin E-cyclin-dependent kinase 2 in enzymatic assay by measuring phosphorylation of RbING	ic50	0.0060	uM
(3Z)-5-fluoro-4-[2-(4-hydroxypiperidin-4-yl)ethynyl]-3-[(3-methoxy-1H-pyrrol-2-yl)methylidene]-1H-indol-2-one;hydrochloride	53857: In vitro inhibition of recombinant Cyclin Dependent Kinase-2/Cyclin E.	ic50	0.0060	uM
(3Z)-5-fluoro-4-[(3R,4R)-4-hydroxy-3-(methylamino)pent-1-ynyl]-3-[(3-methoxy-1H-pyrrol-2-yl)methylidene]-1H-indol-2-one	53857: In vitro inhibition of recombinant Cyclin Dependent Kinase-2/Cyclin E.	ic50	0.0070	uM
5-chloro-4-(1-methylpyrazol-4-yl)-N-(4-methylsulfonylphenyl)pyrimidin-2-amine	1940570: Inhibition of CDK2/cyclin E (unknown origin) assessed as inhibition constant incubated for 30 to 60 mins presence of dithiothreitol by Cheng-Prusoff equation analysis	ki	0.0070	uM
2-(4-carbamimidoylpiperazin-1-yl)-N-[3-(4-methoxyphenyl)-4-oxo-1H-indeno[2,1-d]pyrazol-5-yl]acetamide	53700: Compound was evaluated for inhibition of Cyclin-dependent kinase 2-cyclin E	ic50	0.0070	uM
[3-(4-methoxyphenyl)-4-oxo-1H-indeno[2,1-d]pyrazol-5-yl]urea	53700: Compound was evaluated for inhibition of Cyclin-dependent kinase 2-cyclin E	ic50	0.0070	uM
5-chloro-4-(1-methylpyrazol-4-yl)-N-(1-methylsulfonylpiperidin-4-yl)pyrimidin-2-amine	1940570: Inhibition of CDK2/cyclin E (unknown origin) assessed as inhibition constant incubated for 30 to 60 mins presence of dithiothreitol by Cheng-Prusoff equation analysis	ki	0.0080	uM
(3Z)-5-fluoro-4-[(3R)-4-hydroxy-3-(methylamino)but-1-ynyl]-3-[(3-methoxy-1H-pyrrol-2-yl)methylidene]-1H-indol-2-one	53857: In vitro inhibition of recombinant Cyclin Dependent Kinase-2/Cyclin E.	ic50	0.0080	uM
1-[2-[[3-(4-methoxyphenyl)-4-oxo-1H-indeno[2,1-d]pyrazol-5-yl]amino]-2-oxoethyl]piperidine-4-carboxamide	53700: Compound was evaluated for inhibition of Cyclin-dependent kinase 2-cyclin E	ic50	0.0080	uM
4-[2-[[3-(4-methoxyphenyl)-4-oxo-1H-indeno[2,1-d]pyrazol-5-yl]amino]-2-oxoethyl]piperazine-1-carboxamide	53700: Compound was evaluated for inhibition of Cyclin-dependent kinase 2-cyclin E	ic50	0.0080	uM

CTD chemical–gene interactions

158 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects expression, decreases expression, increases expression, decreases reaction	8
sodium arsenite	affects cotreatment, increases abundance, decreases reaction, increases expression, decreases expression	7
Benzo(a)pyrene	increases expression	5
bisphenol A	increases expression, decreases reaction, affects expression, decreases expression	4
Valproic Acid	affects expression, decreases expression	4
trichostatin A	affects cotreatment, decreases expression	3
palbociclib	decreases expression	3
Cyclosporine	decreases expression, increases expression	3
Aflatoxin B1	affects expression, increases expression	3
arsenite	affects expression, decreases expression	2
cobaltous chloride	decreases expression	2
entinostat	decreases expression, affects cotreatment	2
monomethylarsonous acid	decreases expression	2
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression, decreases expression	2
Resveratrol	increases expression, decreases expression, affects cotreatment	2
Zoledronic Acid	decreases expression, increases expression	2
Fulvestrant	affects cotreatment, decreases expression	2
Air Pollutants	decreases expression, increases abundance	2
Arsenic	decreases expression, affects cotreatment, increases abundance	2
Cadmium	decreases expression, increases expression	2
Cisplatin	increases expression	2
Endosulfan	increases expression, decreases expression, affects cotreatment	2
Nickel	affects cotreatment, increases expression	2
Niclosamide	decreases expression, decreases reaction, increases expression	2
Oxygen	decreases expression	2
Quercetin	decreases expression, increases expression	2
Tretinoin	decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression, increases expression	2
Lithium Chloride	increases expression, decreases expression	2
Cadmium Chloride	affects expression, decreases expression	2

ChEMBL screening assays

159 unique, capped per target: 159 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1039187	Binding	Inhibition of CDK2/Cyclin E at 100 nM by radiometric protein kinase assay	N3-arylmalonamides: a new series of thieno[3,2-b]pyridine based inhibitors of c-Met and VEGFR2 tyrosine kinases. — Bioorg Med Chem Lett

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D7LY	Ubigene A-549 CCNE2 KO	Cancer cell line	Male
CVCL_SH39	HAP1 CCNE2 (-) 1	Cancer cell line	Male
CVCL_SH40	HAP1 CCNE2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.