CCND2

Summary

CCND2 (cyclin D2, HGNC:1583) is a protein-coding gene on chromosome 12p13.32, encoding G1/S-specific cyclin-D2 (P30279). Regulatory component of the cyclin D2-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition. In precision oncology, CCND1 Amplification OR CCND2 Amplification OR CCND3 Amplification confers sensitivity to Palbociclib in Cancer (CIViC Level B).

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 CDK4 or CDK6 and functions as a regulatory subunit of the complex, whose activity is required for cell cycle G1/S transition. This protein has been shown to interact with and be involved in the phosphorylation of tumor suppressor protein Rb. Knockout studies of the homologous gene in mouse suggest the essential roles of this gene in ovarian granulosa and germ cell proliferation. High level expression of this gene was observed in ovarian and testicular tumors. Mutations in this gene are associated with megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3 (MPPH3).

Source: NCBI Gene 894 — RefSeq curated summary.

At a glance

• Gene–disease (curated): megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3 (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 56
• Clinical variants (ClinVar): 175 total — 9 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 25
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 1 curated variant–drug association
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 2 cancer types
• MANE Select transcript: NM_001759

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1583
Approved symbol	CCND2
Name	cyclin D2
Location	12p13.32
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000118971
Ensembl biotype	protein_coding
OMIM	123833
Entrez	894

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 10 protein_coding, 2 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000261254, ENST00000536537, ENST00000536795, ENST00000541542, ENST00000675468, ENST00000675880, ENST00000676279, ENST00000676411, ENST00000862873, ENST00000862874, ENST00000929292, ENST00000929293, ENST00000929294, ENST00000943418

RefSeq mRNA: 1 — MANE Select: NM_001759 NM_001759

CCDS: CCDS8524

Canonical transcript exons

ENST00000261254 — 5 exons

Exon	Start	End
ENSE00000802837	4273762	4274235
ENSE00000802838	4276005	4276220
ENSE00000802839	4278760	4278919
ENSE00000802840	4288842	4288990
ENSE00000802841	4299860	4305353

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 99.05.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 52.8838 / max 1171.3717, expressed in 1371 samples.

FANTOM5 promoters (23 alternative TSS)

Promoter ID	TPM avg	Samples expressed
123526	20.0361	1292
123528	14.5721	1019
123527	12.9433	1194
123515	0.6124	146
206537	0.5498	286
206538	0.5240	255
123514	0.4950	168
123534	0.4949	120
123533	0.4611	165
206540	0.4045	124

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	99.05	gold quality
seminal vesicle	UBERON:0000998	99.03	gold quality
cauda epididymis	UBERON:0004360	98.97	gold quality
ventricular zone	UBERON:0003053	98.91	gold quality
ganglionic eminence	UBERON:0004023	98.88	gold quality
embryo	UBERON:0000922	98.66	gold quality
cardiac muscle of right atrium	UBERON:0003379	98.27	gold quality
left ventricle myocardium	UBERON:0006566	98.26	gold quality
corpus epididymis	UBERON:0004359	98.16	gold quality
myocardium	UBERON:0002349	98.10	gold quality
colonic epithelium	UBERON:0000397	98.06	gold quality
caput epididymis	UBERON:0004358	98.04	gold quality
tendon of biceps brachii	UBERON:0008188	97.99	gold quality
mucosa of sigmoid colon	UBERON:0004993	97.93	gold quality
blood vessel layer	UBERON:0004797	97.50	gold quality
vena cava	UBERON:0004087	97.41	gold quality
Brodmann (1909) area 46	UBERON:0006483	97.11	gold quality
urethra	UBERON:0000057	96.90	gold quality
heart right ventricle	UBERON:0002080	96.89	gold quality
colonic mucosa	UBERON:0000317	96.81	gold quality
cartilage tissue	UBERON:0002418	96.64	gold quality
ileal mucosa	UBERON:0000331	96.43	gold quality
jejunal mucosa	UBERON:0000399	96.32	gold quality
superficial temporal artery	UBERON:0001614	96.22	gold quality
postcentral gyrus	UBERON:0002581	96.19	gold quality
parietal lobe	UBERON:0001872	95.97	gold quality
decidua	UBERON:0002450	95.58	gold quality
apex of heart	UBERON:0002098	95.53	gold quality
right adrenal gland cortex	UBERON:0035827	95.46	gold quality
saphenous vein	UBERON:0007318	95.38	gold quality

Single-cell (SCXA)

Detected in 15 experiment(s), a significant marker in 11.

Experiment	Marker?	Max mean expression
E-ENAD-21	yes	823.19
E-MTAB-9435	yes	559.83
E-CURD-7	yes	472.05
E-MTAB-6701	yes	64.42
E-HCAD-1	yes	42.69
E-MTAB-6678	yes	27.47
E-GEOD-84465	yes	23.84
E-HCAD-9	yes	17.35
E-CURD-122	yes	13.45
E-ANND-3	yes	12.82
E-CURD-112	yes	9.05
E-GEOD-75140	no	3278.12
E-MTAB-8894	no	923.07
E-MTAB-11121	no	266.89
E-GEOD-93593	no	7.31

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ABL1, ASCL1, BACH1, BCL6, CEBPG, CREB1, CUX1, EGR1, ELF5, ERP29, ESR1, ETV4, FOS, FOXL2, FOXM1, FOXO1, FOXO3, FUBP1, GATA1, GATA4, GLI1, GLI2, GTF2I, HDAC1, HNF4A, IRF9, JUN, KLF4, MAF, MAFB, MAX, MNT, MXD1, MYBL2, MYC, MYCN, MYCT1, NANOG, NFIA, NFKB1

miRNA regulators (miRDB)

337 targeting CCND2, 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-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-150-5P	99.99	66.69	1976
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790

Literature-anchored findings (GeneRIF, showing 40)

• Activation of cyclin D1 and D2 promoters by human T-cell leukemia virus type I tax protein is associated with IL-2-independent growth of T cells (PMID:11992406)
• Overexpression of cyclin D2 is associated with increased in vivo invasiveness of human squamous carcinoma cells. (PMID:12112307)
• cyclin d2 hypermethylation associated with loss of cyclin d2 expression in subset of gastric cancer (PMID:12771922)
• results show that cyclin D2 is complexed with p27, leading to a model for testicular germ cell tumors whereby the overexpression of cyclin D2 leads to the functional sequestration of p27 in the presence of CCNE and CCND2, favoring cell proliferation (PMID:12777997)
• methylation of Cyclin D2 in prostate cancers correlates with clinicopathological features of poor prognosis (PMID:14581343)
• hypermethylated in invasive and in in situ lobular breast cancer (PMID:14601057)
• DNA hypomethylation is a mechanism underlying the increased expression of cyclin D2 in cancer cells and demethylation of cyclin D2 may be involved in development and progression of gastric carcinoma (PMID:14612939)
• p21/cyclin D2/cdk4 complex is not an inhibitory complex for the cyclin D2/cdk4 complex in HTLV-1 infected cells. (PMID:15169570)
• E2 may stimulate the growth of keratinocytes by inducing cyclin D2 expression via CREB phosphorylation by protein kinase A, dependent on cAMP. (PMID:15245432)
• conditional activation of FoxO3a leads to accumulation of BCL6 and down-regulation of cyclin D2 at protein and mRNA levels (PMID:15509806)
• Cyclin D1, D2, or D3 expression appears to be increased and/or dysregulated in virtually all MM tumors despite their low proliferative capacity (PMID:15755896)
• This suggests that dysregulation of CCND2 and CDK4 plays a specific role in WT tumorigenesis. (PMID:15797629)
• the recurrent T-ALL-associated t(12;14) results in overexpression of cyclin D2 (PMID:16548914)
• Cyclin D2 promoter methylation and gene silencing may play an important functional role in prostate carcinogenesis. (PMID:17016690)
• cyclin D2 expression in normal and malignant hematopoietic cells is regulated by ubiquitin/proteasome-dependent degradation triggered by Thr280 phosphorylation by GSK3beta or p38, which is induced by inhibition of the PI3K pathway (PMID:17486076)
• Responsible for neoplastic cell transformation when coexpressed with an activated Ras protein. (PMID:17873913)
• role for D-type cyclins in the excessive basal-cell proliferation and perturbed keratinocyte differentiation in the psoriatic epidermis (PMID:17882269)
• cyclin E expression in 2 t(11;14)-negative mantle cell lymphomas characterized by a cryptic t(2;14)(p24;q32) and identification of MYCN as a new lymphoma oncogene associated with a blastoid mantle cell lymphoma (PMID:18391076)
• Data demonstrate that RNA interference of genes encoding cyclin D1 and cyclin D2 (CCND1 and CCND2, respectively) inhibits proliferation and is progressively cytotoxic in human myeloma cells. (PMID:18431519)
• Forty one percent of breast cancers were associated with methylation of cyclin d2. (PMID:18483325)
• Tax-induced cell-cycle progression in T cells is mediated, at least in part, through cell-type-specific activation of the cyclin D2 and cdk6 genes through NF-kappaB and may be important for the cell-type-specific oncogenesis. (PMID:18504428)
• All three D-type cyclins promoted robust hepatocyte proliferation and marked liver growth, although cyclin D3 stimulated less DNA synthesis than D1 or D2. (PMID:18635970)
• in response to cellular activation in T cells and B cells, a PTB-containing stability complex forms that contains binding sites for Rab8A and cyclin D(2) transcripts and increases their mRNA half-lifes (PMID:18714005)
• a pattern of translocalization suggests a spatial separation of the cyclin D-Cdk complex from pRb and DNA in the nucleus to regulate the G1-S transition (PMID:18827403)
• These results suggest that miR-302b plays an important role in maintaining the pluripotency of embryonal carcinoma cells and probably embryonic stem cells , by post-transcriptional regulation of Cyclin D2 expression. (PMID:18930031)
• Valproic acid could down-regulate mRNA expression of cyclin D2 in the kasumi-1 leukemic cell line. (PMID:19379567)
• study suggests that downstream signaling components of the PI3K/Akt pathway, GSK3 & cyclin D2 as well as the significant interaction between PTEN-PDK and between pAkt-pGSK3beta, are involved in the survival and proliferation of leiomyomas. (PMID:19464003)
• In colorectal adenocarcinoma expression of cyclin D2 at the margin was associated with vascular invasion, lymph node metastasis and liver metastasis (PMID:19508551)
• restoration of CCND2 expression potentially prevents the carcinogenesis of prostate cancer, which is mostly androgen receptor -dependent in the initial settings. (PMID:19577536)
• As a result of the mantle cell lymphoma translocation, cycD2 mRNA was highly over-expressed when compared with normal lymphoid tissue and other B-cell non-Hodgkin’s lymphomas (PMID:19608671)
• Data show that methylation of CCND-2, p16, RAR-beta and RASSF-1a was significantly more prevalent in tumor than in normal tissue specimens. (PMID:19618401)
• data presented here indicate that cD2 is not necessary for cortical intermediate progenitor cells (IPCs) to emerge but that cD2 is used in progenitors as they transition into and expand their IPC numbers (PMID:19641124)
• the knockdown of cyclin D1 is compensated by the upregulation of cyclin D2, a more powerful strategy would be to inhibit both cyclin D1 and cyclin D2. (PMID:19679881)
• Cyclin D2 and the CDK substrate p220(NPAT) are required for self-renewal of human embryonic stem cells. (PMID:19890848)
• hypermethylation in tumors from non-small cell lung cancer patients is associated with gender and histologic type (PMID:19945765)
• cyclin D2+ cells represent a pool of leukemic cells with the potential to enter the dividing compartment. (PMID:20066902)
• High cyclin D2 is associated with higher grade (III and IV) of astrocytoma. (PMID:20077038)
• One common polymorphism in the 5’-untranslated region (that is, rs1049606) and the most common haplotype (CCND-ht1 [T-C-T-A-T]), however, were significantly associated with hepatatis B virus clearance. (PMID:20414251)
• the 3’UTR of E2F2 and CCND2 were directly bound to let-7a and let-7a down-regulated the expression of E2F2 and CCND2, suppressing prostate cancer cell proliferation in culture (PMID:20418948)
• High level of CCND2 expression is associated with nasopharyngeal carcinoma. (PMID:20473882)

Cross-species orthologs

12 orthologs

Organism	Symbol	Gene ID
danio_rerio	ccnd2a	ENSDARG00000051748
danio_rerio	ccnd2b	ENSDARG00000070408
mus_musculus	Ccnd2	ENSMUSG00000000184
rattus_norvegicus	Ccnd2	ENSRNOG00000076926
drosophila_melanogaster	CycB	FBGN0000405
drosophila_melanogaster	CycD	FBGN0010315
drosophila_melanogaster	CycE	FBGN0010382
caenorhabditis_elegans		WBGENE00000865
caenorhabditis_elegans		WBGENE00000866
caenorhabditis_elegans	cyb-2.2	WBGENE00000867
caenorhabditis_elegans		WBGENE00000870
caenorhabditis_elegans	cye-1	WBGENE00000871

Paralogs (18): CCNE1 (ENSG00000105173), CCNP (ENSG00000105219), CCNJ (ENSG00000107443), CCND1 (ENSG00000110092), CCND3 (ENSG00000112576), CCNG1 (ENSG00000113328), CCNI (ENSG00000118816), CCNA1 (ENSG00000133101), CCNB1 (ENSG00000134057), CCNJL (ENSG00000135083), CCNG2 (ENSG00000138764), CCNA2 (ENSG00000145386), CCNB3 (ENSG00000147082), CCNO (ENSG00000152669), CCNB2 (ENSG00000157456), CCNF (ENSG00000162063), CCNE2 (ENSG00000175305), CCNI2 (ENSG00000205089)

Protein

Protein identifiers

G1/S-specific cyclin-D2 — P30279 (reviewed: P30279)

All UniProt accessions (2): A0A6Q8PGZ3, P30279

UniProt curated annotations — full annotation on UniProt →

Function. Regulatory component of the cyclin D2-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complex and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase. Hypophosphorylates RB1 in early G(1) phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals.

Subunit / interactions. Interacts with either CDK4 or CDK6 protein kinase to form a serine/threonine kinase holoenzyme complex. The cyclin subunit imparts substrate specificity to the complex.

Subcellular location. Nucleus. Cytoplasm. Nucleus membrane Cytoplasm.

Post-translational modifications. Phosphorylation at Thr-280 by MAP kinases is required for ubiquitination and degradation by the DCX(AMBRA1) complex. Ubiquitinated by the DCX(AMBRA1) complex during the transition from G1 to S cell phase, leading to its degradation: ubiquitination is dependent on Thr-280 phosphorylation. The DCX(AMBRA1) complex represents the major regulator of CCND2 stability during the G1/S transition. Polyubiquitinated by the SCF(FBXL2) complex, leading to proteasomal degradation.

Disease relevance. Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3 (MPPH3) [MIM:615938] A syndrome characterized by megalencephaly, ventriculomegaly that may lead to hydrocephalus, and polymicrogyria; polydactyly may also be seen. There is considerable phenotypic similarity between this disorder and the megalencephaly-capillary malformation syndrome. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. Acts as a proto-oncogene. Retains ability to bind CDK4, but unable to catalyze efficiently RB phosphorylation and inactivation.

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

Isoforms (2)

UniProt ID	Names	Canonical?
P30279-1	1	yes
P30279-2	2, Truncated

RefSeq proteins (1): NP_001750* (*=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 (15 total): sequence variant 6, sequence conflict 2, modified residue 2, splice variant 2, chain 1, domain 1, region of interest 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6EI2	X-RAY DIFFRACTION	1.61

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P30279-F1	87.98	0.72

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 (2): 271, 280

Function

Pathways and Gene Ontology

Reactome pathways

16 pathways

ID	Pathway
R-HSA-69231	Cyclin D associated events in G1
R-HSA-8934593	Regulation of RUNX1 Expression and Activity
R-HSA-9661069	Defective binding of RB1 mutants to E2F1,(E2F2, E2F3)
R-HSA-9754119	Drug-mediated inhibition of CDK4/CDK6 activity
R-HSA-1640170	Cell Cycle
R-HSA-1643685	Disease
R-HSA-212436	Generic Transcription Pathway
R-HSA-453279	Mitotic G1 phase and G1/S transition
R-HSA-69236	G1 Phase
R-HSA-69278	Cell Cycle, Mitotic
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-8878171	Transcriptional regulation by RUNX1
R-HSA-9659787	Aberrant regulation of mitotic G1/S transition in cancer due to RB1 defects
R-HSA-9675126	Diseases of mitotic cell cycle
R-HSA-9687139	Aberrant regulation of mitotic cell cycle due to RB1 defects

MSigDB gene sets: 752 (showing top): GOBP_MEMORY, TGGTGCT_MIR29A_MIR29B_MIR29C, RNGTGGGC_UNKNOWN, VERHAAK_AML_WITH_NPM1_MUTATED_DN, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, GOBP_RESPONSE_TO_IONIZING_RADIATION, IIZUKA_LIVER_CANCER_EARLY_RECURRENCE, GOBP_COGNITION, GRUETZMANN_PANCREATIC_CANCER_DN, GOBP_BEHAVIOR, YAGI_AML_WITH_INV_16_TRANSLOCATION, BASSO_B_LYMPHOCYTE_NETWORK, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, TTCCGTT_MIR191, GCANCTGNY_MYOD_Q6

GO Biological Process (11): G1/S transition of mitotic cell cycle (GO:0000082), long-term memory (GO:0007616), positive regulation of cell population proliferation (GO:0008284), adult locomotory behavior (GO:0008344), negative regulation of apoptotic process (GO:0043066), cell division (GO:0051301), cellular response to X-ray (GO:0071481), positive regulation of G1/S transition of mitotic cell cycle (GO:1900087), regulation of cell cycle (GO:0051726), positive regulation of mitotic cell cycle phase transition (GO:1901992), regulation of G1/S transition of mitotic cell cycle (GO:2000045)

GO Molecular Function (5): cyclin-dependent protein serine/threonine kinase regulator activity (GO:0016538), protein kinase binding (GO:0019901), protein serine/threonine kinase activator activity (GO:0043539), cyclin-dependent protein serine/threonine kinase activator activity (GO:0061575), protein binding (GO:0005515)

GO Cellular Component (11): cyclin-dependent protein kinase holoenzyme complex (GO:0000307), chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), microtubule organizing center (GO:0005815), cytosol (GO:0005829), nuclear membrane (GO:0031965), cyclin D2-CDK4 complex (GO:0097129), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
G1 Phase	1
Transcriptional regulation by RUNX1	1
Aberrant regulation of mitotic G1/S transition in cancer due to RB1 defects	1
Cyclin D associated events in G1	1
RNA Polymerase II Transcription	1
Cell Cycle, Mitotic	1
Mitotic G1 phase and G1/S transition	1
Cell Cycle	1
Gene expression (Transcription)	1
Generic Transcription Pathway	1
Aberrant regulation of mitotic cell cycle due to RB1 defects	1
Disease	1
Diseases of mitotic cell cycle	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
mitotic cell cycle phase transition	2
G1/S transition of mitotic cell cycle	2
regulation of mitotic cell cycle phase transition	2
cyclin-dependent protein serine/threonine kinase activity	2
nuclear lumen	2
mitotic cell cycle	1
cell cycle G1/S phase transition	1
memory	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
locomotory behavior	1
adult behavior	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
cellular process	1
response to X-ray	1
cellular response to ionizing radiation	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
positive regulation of mitotic cell cycle	1
positive regulation of cell cycle phase transition	1
regulation of cell cycle G1/S phase transition	1
cyclin-dependent protein kinase regulator activity	1
kinase binding	1
protein serine/threonine kinase activity	1
protein kinase activator activity	1
cyclin-dependent protein serine/threonine kinase regulator activity	1
protein serine/threonine kinase activator activity	1
binding	1
serine/threonine protein kinase complex	1
chromosome	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

3244 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCND2	CDK4	P11802	997
CCND2	CDK6	Q00534	997
CCND2	BCL2	P10415	883
CCND2	CCNL2	Q96S94	865
CCND2	LMO2	P25791	848
CCND2	BCL6	P41182	846
CCND2	DMTF1	Q9Y222	844
CCND2	CDK2	P24941	811
CCND2	CDKN1A	P38936	787
CCND2	CDKN2A	P42771	780
CCND2	CDK1	P06493	721
CCND2	CDKN1B	P46527	708
CCND2	MYC	P01106	699
CCND2	CCL3	P10147	698
CCND2	E2F2	Q14209	680

IntAct

88 interactions, top by confidence:

A	B	Type	Score
CDK5	CCND2	psi-mi:“MI:0915”(physical association)	0.960
CCND2	CDK5	psi-mi:“MI:0915”(physical association)	0.960
CCND2	CDK4	psi-mi:“MI:0915”(physical association)	0.960
CDK4	CCND2	psi-mi:“MI:0915”(physical association)	0.960
CCND2	CDK4	psi-mi:“MI:0914”(association)	0.960
CCND2	CDKN1A	psi-mi:“MI:0915”(physical association)	0.950
CDKN1A	CCND2	psi-mi:“MI:0915”(physical association)	0.950

BioGRID (237): CCND2 (Reconstituted Complex), CDK5 (Two-hybrid), CDKN1A (Two-hybrid), CDK2 (Affinity Capture-MS), CDK4 (Affinity Capture-MS), RBL2 (Affinity Capture-MS), CDKN1B (Affinity Capture-MS), CDK5 (Affinity Capture-MS), CDKN1C (Affinity Capture-MS), CDKN1A (Affinity Capture-MS), CDKN1A (Two-hybrid), CDKN1B (Two-hybrid), CDKN1A (Co-localization), CCND2 (Two-hybrid), DTNBP1 (Affinity Capture-Western)

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: O08918, P13351, P24868, P24869, P25011, P25012, P25322, P30183, P30278, P30279, P30280, P39950, P46277, P46278, P51945, P51959, Q04827, Q0JIF2, Q0P5D3, Q14094, Q16589, Q39068, Q39069, Q52QT8, Q5E9I1, Q5R5D0, Q61456, Q6AY13, Q6ZMN8, Q8WNW2, Q92161, Q95TJ9, Q9Z2V9, A0MEB5, O01501, O15995, O42575, O77689, O95067, O96020

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
GSK3B	down-regulates	CCND2	phosphorylation
ROBO	down-regulates	CCND2	phosphorylation
palbociclib	down-regulates	CCND2	“chemical inhibition”
FOXL2	“down-regulates quantity by repression”	CCND2	“transcriptional regulation”
FUBP1	“up-regulates quantity by expression”	CCND2	“transcriptional regulation”
MYCT1	“down-regulates quantity by repression”	CCND2	“transcriptional regulation”
MYC	“up-regulates quantity by expression”	CCND2	“transcriptional regulation”
hsa-miR-1-5p	“down-regulates quantity by repression”	CCND2	“post transcriptional regulation”
FBXL2	“down-regulates quantity by destabilization”	CCND2	binding
“Cullin 1-RBX1-Skp1”	“down-regulates quantity by destabilization”	CCND2	polyubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 24 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
Defective binding of RB1 mutants to E2F1,(E2F2, E2F3)	5	151.1×	2e-08
Aberrant regulation of mitotic cell cycle due to RB1 defects	5	97.1×	9e-08
G1 Phase	5	93.8×	9e-08
Diseases of mitotic cell cycle	5	93.8×	9e-08
Cyclin E associated events during G1/S transition	5	68.0×	4e-07
G1/S Transition	6	66.6×	3e-08
Cyclin A:Cdk2-associated events at S phase entry	5	63.2×	5e-07
Mitotic G1 phase and G1/S transition	7	61.4×	4e-09

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of DNA replication	5	121.1×	1e-07
G1/S transition of mitotic cell cycle	7	58.5×	1e-08
epidermal growth factor receptor signaling pathway	5	51.6×	5e-06
regulation of cell cycle	5	15.5×	7e-04
cell division	7	13.5×	5e-05
positive regulation of gene expression	5	8.1×	6e-03

Disease & clinical

Cancer significance

From CIViC — curated cancer-variant interpretation:

Cyclin D has been shown in many cancer types to be misregulated. Well established for their oncogenic properties, the cyclins and the cyclin-dependent kinases (CDK’s) they activate have been the focus of major research and development efforts over the past decade. The methods by which the cyclins are misregulated are widely variable, ranging from genomic amplification to changes in promoter methylation. While Cyclin D2 has only been found to be significantly deregulated in glioma, Cyclin D1 in particular seems to be a pan-cancer actor. Cyclin D misregulation has been shown to lead to poorer outcomes in a number of studies, and currently there are no FDA-approved targeted therapies.

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 2 cancer types — AML, CLLSLL.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	9
Likely pathogenic	3
Uncertain significance	71
Likely benign	50
Benign	14

Top pathogenic / likely-pathogenic (12)

Variant ID	HGVS	Classification
143981	NM_001759.4(CCND2):c.838A>G (p.Thr280Ala)	Pathogenic
143982	NM_001759.4(CCND2):c.808A>T (p.Lys270Ter)	Pathogenic
143984	NM_001759.4(CCND2):c.841C>T (p.Pro281Ser)	Pathogenic
143986	NM_001759.4(CCND2):c.842C>T (p.Pro281Leu)	Pathogenic
3997605	NM_001759.4(CCND2):c.643C>T (p.Gln215Ter)	Pathogenic
4528281	NM_001759.4(CCND2):c.416_419dup (p.Leu141fs)	Pathogenic
520663	NM_001759.4(CCND2):c.841C>G (p.Pro281Ala)	Pathogenic
872569	NM_001759.4(CCND2):c.793C>T (p.Gln265Ter)	Pathogenic
985457	NM_001759.4(CCND2):c.814G>T (p.Glu272Ter)	Pathogenic
2504114	NM_001759.4(CCND2):c.812C>A (p.Ser271Ter)	Likely pathogenic
3775676	NM_001759.4(CCND2):c.802G>T (p.Gly268Ter)	Likely pathogenic
4607569	NM_001759.4(CCND2):c.806_818dup (p.Glu274fs)	Likely pathogenic

SpliceAI

1243 predictions. Top by Δscore:

Variant	Effect	Δscore
12:4274232:GGAG:G	donor_gain	1.0000
12:4274233:GAGG:G	donor_gain	1.0000
12:4274234:AGG:A	donor_loss	1.0000
12:4276002:TA:T	acceptor_loss	1.0000
12:4276004:GGT:G	acceptor_gain	1.0000
12:4276004:GGTCT:G	acceptor_gain	1.0000
12:4276217:GCTG:G	donor_gain	1.0000
12:4276221:G:GC	donor_loss	1.0000
12:4276221:G:GG	donor_gain	1.0000
12:4276222:T:G	donor_loss	1.0000
12:4278745:T:A	acceptor_gain	1.0000
12:4278756:CCAG:C	acceptor_loss	1.0000
12:4278757:CAGGA:C	acceptor_loss	1.0000
12:4278759:GGA:G	acceptor_gain	1.0000
12:4278919:GGTA:G	donor_loss	1.0000
12:4278920:G:A	donor_loss	1.0000
12:4278920:G:GG	donor_gain	1.0000
12:4278921:T:G	donor_loss	1.0000
12:4288840:A:AG	acceptor_gain	1.0000
12:4288841:G:GG	acceptor_gain	1.0000
12:4288925:G:GT	donor_gain	1.0000
12:4300011:G:GT	donor_gain	1.0000
12:4274233:GAG:G	donor_gain	0.9900
12:4274236:G:GG	donor_gain	0.9900
12:4276001:A:AG	acceptor_gain	0.9900
12:4276001:ATAG:A	acceptor_gain	0.9900
12:4276002:T:G	acceptor_gain	0.9900
12:4276003:A:AG	acceptor_gain	0.9900
12:4276003:AG:A	acceptor_gain	0.9900
12:4276004:G:GG	acceptor_gain	0.9900

AlphaMissense

1889 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:4274206:C:A	R56S	1.000
12:4274219:C:A	A60D	1.000
12:4274224:T:A	W62R	1.000
12:4274224:T:C	W62R	1.000
12:4274226:G:C	W62C	1.000
12:4274226:G:T	W62C	1.000
12:4276063:A:T	D85V	1.000
12:4276066:G:C	R86P	1.000
12:4276113:G:C	G102R	1.000
12:4276114:G:A	G102D	1.000
12:4276122:T:C	C105R	1.000
12:4276123:G:A	C105Y	1.000
12:4276124:C:G	C105W	1.000
12:4276141:A:T	K111I	1.000
12:4276142:A:C	K111N	1.000
12:4276142:A:T	K111N	1.000
12:4276177:T:C	L123P	1.000
12:4278793:T:A	W149R	1.000
12:4278793:T:C	W149R	1.000
12:4288878:C:A	A203E	1.000
12:4274129:T:C	L30P	0.999
12:4274205:G:A	M55I	0.999
12:4274205:G:C	M55I	0.999
12:4274205:G:T	M55I	0.999
12:4274218:G:C	A60P	0.999
12:4274225:G:C	W62S	0.999
12:4274225:G:T	W62L	0.999
12:4274228:T:A	M63K	0.999
12:4274228:T:G	M63R	0.999
12:4274231:T:C	L64P	0.999

dbSNP variants (sampled 300 via entrez): RS1000007977 (12:4295512 C>G), RS1000011224 (12:4278461 G>A), RS1000042678 (12:4290233 C>T), RS1000067705 (12:4283713 C>A), RS1000084604 (12:4283972 G>C), RS1000237934 (12:4279577 A>G), RS1000415205 (12:4290054 G>A), RS1000472058 (12:4273785 G>A,C), RS1000545381 (12:4290898 G>A), RS1000684123 (12:4285414 A>G), RS1000746354 (12:4291209 G>C), RS1000908719 (12:4296571 A>G), RS1000954408 (12:4303044 G>A), RS1001048090 (12:4279831 A>T), RS1001070560 (12:4302642 G>A,T)

Disease associations

OMIM: gene MIM:123833 | disease phenotypes: MIM:615938, MIM:603387, MIM:618733

GenCC curated gene-disease

Disease	Classification	Inheritance
megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3	Definitive	Autosomal dominant
megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3	Definitive	AD

Mondo (4): megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3 (MONDO:0014408), megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 (MONDO:0011313), neuromuscular disease and ocular or auditory anomalies with or without seizures (MONDO:0032890), megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome (MONDO:0019375)

Orphanet (1): Megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome (Orphanet:83473)

HPO phenotypes

25 total (25 of 25 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000160	Narrow mouth
HP:0000238	Hydrocephalus
HP:0000256	Macrocephaly
HP:0000316	Hypertelorism
HP:0000348	High forehead
HP:0000506	Telecanthus
HP:0001159	Syndactyly
HP:0001162	Postaxial hand polydactyly
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001344	Absent speech
HP:0001355	Megalencephaly
HP:0001629	Ventricular septal defect
HP:0001653	Mitral regurgitation
HP:0001671	Abnormal cardiac septum morphology
HP:0002119	Ventriculomegaly
HP:0002126	Polymicrogyria
HP:0003577	Congenital onset
HP:0005105	Abnormal nasal morphology
HP:0005280	Depressed nasal bridge
HP:0007074	Thick corpus callosum
HP:0010864	Severe intellectual disability
HP:0011220	Prominent forehead
HP:0100542	Abnormal localization of kidney

GWAS associations

56 associations (top):

Study	Trait	p-value
GCST000304_1	Major depressive disorder	6.000000e-06
GCST000588_2	Red blood cell count	6.000000e-09
GCST001762_589	Obesity-related traits	9.000000e-06
GCST001765_23	Red blood cell traits	8.000000e-12
GCST001787_8	Colorectal cancer	6.000000e-08
GCST001787_9	Colorectal cancer	3.000000e-07
GCST001792_1	Colorectal cancer	3.000000e-08
GCST001792_2	Colorectal cancer	5.000000e-10
GCST001850_1	Major depressive disorder	9.000000e-06
GCST001890_10	QT interval (drug interaction)	4.000000e-06
GCST002454_18	Colorectal cancer	1.000000e-10
GCST003017_18	Colorectal cancer	2.000000e-06
GCST003084_8	Glucocorticoid-induced osteonecrosis	6.000000e-06
GCST004004_57	Mean corpuscular volume	1.000000e-08
GCST004006_35	Mean corpuscular hemoglobin	1.000000e-08
GCST004008_18	Red blood cell count	1.000000e-07
GCST004008_2	Red blood cell count	3.000000e-11
GCST004212_28	Height	3.000000e-08
GCST004894_112	Type 2 diabetes	3.000000e-08
GCST004894_8	Type 2 diabetes	2.000000e-08
GCST005047_101	Type 2 diabetes	1.000000e-09
GCST005047_20	Type 2 diabetes	3.000000e-07
GCST005413_20	Type 2 diabetes	2.000000e-10
GCST006867_103	Type 2 diabetes	2.000000e-10
GCST006988_50	Blond vs. brown/black hair color	4.000000e-08
GCST006989_8	Brown vs. black hair color	2.000000e-09
GCST007096_149	Pulse pressure	1.000000e-08
GCST007269_313	Pulse pressure	1.000000e-12
GCST007552_14	Colorectal cancer	3.000000e-09
GCST007856_28	Colorectal cancer or advanced adenoma	4.000000e-19

EFO canonical traits (15, from GWAS)

EFO ID	Trait name
EFO:0004305	erythrocyte count
EFO:0004627	IGF-1 measurement
EFO:0004527	mean corpuscular hemoglobin
EFO:0004682	QT interval
EFO:0007916	response to tricyclic antidepressant
EFO:0003924	hair color
EFO:0005763	pulse pressure measurement
EFO:0004344	birth weight
EFO:0005939	parental genotype effect measurement
EFO:0006525	cigarettes per day measurement
EFO:0004530	triglyceride measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004468	glucose measurement
EFO:0004980	appendicular lean mass
EFO:0004736	aspartate aminotransferase measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C566381	Megalancephaly Polymicrogyria-Polydactyly Hydrocephalus Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2095942 (PROTEIN COMPLEX GROUP), CHEMBL3301385 (PROTEIN COMPLEX), CHEMBL3301386 (PROTEIN COMPLEX), CHEMBL5483183 (PROTEIN COMPLEX GROUP)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 42,958 (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
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL296468	BMS-387032	1	2,075

Clinical evidence (CIViC)

Drug × variant × indication: 1 predictive associations from 1 curated evidence items; also 4 prognostic, 1 diagnostic.

Variant	Therapy	Indication	Effect	Level	CIViC
CCND1 Amplification OR CCND2 Amplification OR CCND3 Amplification	Palbociclib	Cancer	Sensitivity/Response	CIViC B	EID11673

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

ChEMBL bioactivities

156 potent at pChembl≥5 of 161 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.15	IC50	0.7	nM	CHEMBL142619
8.70	IC50	2	nM	CHEMBL365847
8.70	IC50	2	nM	CHEMBL190281
8.40	IC50	4	nM	CHEMBL426818
8.40	IC50	4	nM	CHEMBL370295
8.40	IC50	4	nM	CHEMBL141018
8.40	IC50	4	nM	CHEMBL140808
8.30	IC50	5	nM	CHEMBL189937
8.30	IC50	5	nM	CHEMBL190460
8.30	IC50	5	nM	CHEMBL190627
8.30	IC50	5	nM	CHEMBL193167
8.22	IC50	6	nM	CHEMBL364317
8.22	IC50	6	nM	CHEMBL190096
8.22	IC50	6	nM	CHEMBL143534
8.15	IC50	7	nM	CHEMBL358057
8.10	IC50	8	nM	CHEMBL139653
8.05	IC50	9	nM	PALBOCICLIB
8.05	IC50	9	nM	CHEMBL430653
8.05	IC50	9	nM	CHEMBL358057
8.00	IC50	10	nM	CHEMBL191046
8.00	IC50	10	nM	CHEMBL372207
7.96	IC50	11	nM	PALBOCICLIB
7.96	IC50	11	nM	CHEMBL421763
7.92	IC50	12	nM	CHEMBL193177
7.89	IC50	13	nM	CHEMBL373300
7.89	IC50	13	nM	CHEMBL192827
7.89	IC50	13	nM	CHEMBL189011
7.89	IC50	13	nM	PALBOCICLIB
7.89	IC50	13	nM	CHEMBL445126
7.85	IC50	14	nM	CHEMBL360675
7.85	IC50	14	nM	CHEMBL193184
7.82	IC50	15	nM	CHEMBL192060
7.82	IC50	15	nM	PALBOCICLIB
7.80	IC50	16	nM	CHEMBL370237
7.80	IC50	16	nM	CHEMBL192308
7.80	IC50	15.85	nM	PALBOCICLIB
7.75	IC50	18	nM	CHEMBL190684
7.75	IC50	18	nM	CHEMBL371198
7.72	IC50	19	nM	CHEMBL366211
7.72	IC50	19	nM	CHEMBL415773
7.68	IC50	21	nM	CHEMBL372712
7.66	IC50	22	nM	CHEMBL190061
7.60	IC50	25	nM	CHEMBL192945
7.58	IC50	26	nM	CHEMBL317953
7.57	IC50	27	nM	CHEMBL189099
7.55	IC50	28	nM	CHEMBL192059
7.52	IC50	30	nM	CHEMBL190200
7.52	IC50	30	nM	CHEMBL191511
7.52	IC50	30	nM	CHEMBL328406
7.51	IC50	31	nM	CHEMBL189543

PubChem BioAssay actives

154 with measured affinity, of 176 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
8-cyclopentyl-2-[4-[2-(diethylamino)ethoxy]anilino]pyrido[2,3-d]pyrimidin-7-one	54016: Inhibition of Cyclin-dependent kinase 4-cyclin D	ic50	0.0007	uM
6-bromo-8-cyclopentyl-2-(4-piperazin-1-ylanilino)pyrido[2,3-d]pyrimidin-7-one	240709: Inhibition of Cyclin-dependent kinase 4-cyclinD	ic50	0.0020	uM
6-acetyl-8-cyclopentyl-5-methyl-2-(4-piperazin-1-ylanilino)pyrido[2,3-d]pyrimidin-7-one	240709: Inhibition of Cyclin-dependent kinase 4-cyclinD	ic50	0.0020	uM
8-cycloheptyl-2-[4-[2-(diethylamino)ethoxy]anilino]pyrido[2,3-d]pyrimidin-7-one	54016: Inhibition of Cyclin-dependent kinase 4-cyclin D	ic50	0.0040	uM
8-cyclohexyl-2-[4-(4-methylpiperazin-1-yl)anilino]pyrido[2,3-d]pyrimidin-7-one	54016: Inhibition of Cyclin-dependent kinase 4-cyclin D	ic50	0.0040	uM
6-acetyl-8-cyclopentyl-5-methyl-2-[(5-morpholin-4-yl-2-pyridinyl)amino]pyrido[2,3-d]pyrimidin-7-one	240709: Inhibition of Cyclin-dependent kinase 4-cyclinD	ic50	0.0040	uM
methyl 8-cyclopentyl-5-methyl-7-oxo-2-(4-piperazin-1-ylanilino)pyrido[2,3-d]pyrimidine-6-carboxylate	241660: Inhibition of [32P]ATP binding to Cyclin dependant kinase 4-cyclin D	ic50	0.0040	uM
6-bromo-8-cyclopentyl-5-methyl-2-(4-piperazin-1-ylanilino)pyrido[2,3-d]pyrimidin-7-one	240709: Inhibition of Cyclin-dependent kinase 4-cyclinD	ic50	0.0050	uM
6-acetyl-8-cyclopentyl-5-methyl-2-[[5-(4-methylpiperazin-1-yl)-2-pyridinyl]amino]pyrido[2,3-d]pyrimidin-7-one	240709: Inhibition of Cyclin-dependent kinase 4-cyclinD	ic50	0.0050	uM
6-acetyl-8-cyclopentyl-5-methyl-2-[(5-piperidin-1-yl-2-pyridinyl)amino]pyrido[2,3-d]pyrimidin-7-one	240709: Inhibition of Cyclin-dependent kinase 4-cyclinD	ic50	0.0050	uM
8-cyclopentyl-6-iodo-5-methyl-2-(4-piperazin-1-ylanilino)pyrido[2,3-d]pyrimidin-7-one	241660: Inhibition of [32P]ATP binding to Cyclin dependant kinase 4-cyclin D	ic50	0.0050	uM
8-(2-bicyclo[2.2.1]heptanyl)-2-[4-(4-methylpiperazin-1-yl)anilino]pyrido[2,3-d]pyrimidin-7-one	54016: Inhibition of Cyclin-dependent kinase 4-cyclin D	ic50	0.0060	uM
ethyl 8-cyclopentyl-5-methyl-7-oxo-2-(4-piperazin-1-ylanilino)pyrido[2,3-d]pyrimidine-6-carboxylate	240709: Inhibition of Cyclin-dependent kinase 4-cyclinD	ic50	0.0060	uM
8-cyclopentyl-2-(4-piperazin-1-ylanilino)pyrido[2,3-d]pyrimidin-7-one	241660: Inhibition of [32P]ATP binding to Cyclin dependant kinase 4-cyclin D	ic50	0.0060	uM
8-cyclopentyl-2-[4-(4-methylpiperazin-1-yl)anilino]pyrido[2,3-d]pyrimidin-7-one	241660: Inhibition of [32P]ATP binding to Cyclin dependant kinase 4-cyclin D	ic50	0.0070	uM
8-(2-bicyclo[2.2.1]heptanyl)-2-[4-[4-(3-hydroxypropyl)piperidin-1-yl]anilino]pyrido[2,3-d]pyrimidin-7-one	54016: Inhibition of Cyclin-dependent kinase 4-cyclin D	ic50	0.0080	uM
5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-N-pyridin-2-yl-1,3-thiazol-2-amine	54020: Inhibition of Cyclin-dependent kinase 4-cyclin D	ic50	0.0090	uM
Palbociclib	1239753: Inhibition of CDK6/cyclin D2 (unknown origin) expressed in baculovirus infected insect cells using GST-fused pRb (792 to 928) as substrate preincubated for 2 mins followed by [gamma-32P]-ATP addition measured after 15 mins by beta plate counting analysis	ic50	0.0090	uM
8-cyclopentyl-2-(4-morpholin-4-ylanilino)pyrido[2,3-d]pyrimidin-7-one	241660: Inhibition of [32P]ATP binding to Cyclin dependant kinase 4-cyclin D	ic50	0.0100	uM
8-cyclopentyl-2-(4-piperidin-1-ylanilino)pyrido[2,3-d]pyrimidin-7-one	241660: Inhibition of [32P]ATP binding to Cyclin dependant kinase 4-cyclin D	ic50	0.0100	uM
8-cyclohexyl-2-[4-[2-(diethylamino)ethoxy]anilino]pyrido[2,3-d]pyrimidin-7-one	54016: Inhibition of Cyclin-dependent kinase 4-cyclin D	ic50	0.0110	uM
6-acetyl-8-cyclopentyl-2-[[5-(1,4-diazepan-1-yl)-2-pyridinyl]amino]-5-methylpyrido[2,3-d]pyrimidin-7-one	240709: Inhibition of Cyclin-dependent kinase 4-cyclinD	ic50	0.0120	uM
8-(3-methylbutyl)-2-[4-(4-methylpiperazin-1-yl)anilino]pyrido[2,3-d]pyrimidin-7-one	54016: Inhibition of Cyclin-dependent kinase 4-cyclin D	ic50	0.0130	uM
8-cyclohexyl-2-[(5-piperazin-1-yl-2-pyridinyl)amino]pyrido[2,3-d]pyrimidin-7-one	240709: Inhibition of Cyclin-dependent kinase 4-cyclinD	ic50	0.0130	uM
8-cyclopentyl-6-(hydroxymethyl)-2-[(5-piperazin-1-yl-2-pyridinyl)amino]pyrido[2,3-d]pyrimidin-7-one	240709: Inhibition of Cyclin-dependent kinase 4-cyclinD	ic50	0.0130	uM
8-cyclopentyl-6-(methoxymethyl)-2-[(5-piperazin-1-yl-2-pyridinyl)amino]pyrido[2,3-d]pyrimidin-7-one	240709: Inhibition of Cyclin-dependent kinase 4-cyclinD	ic50	0.0130	uM
6-acetyl-2-[[5-(3-aminopyrrolidin-1-yl)-2-pyridinyl]amino]-8-cyclopentyl-5-methylpyrido[2,3-d]pyrimidin-7-one	240709: Inhibition of Cyclin-dependent kinase 4-cyclinD	ic50	0.0140	uM
8-cyclopentyl-5-methyl-2-(4-piperazin-1-ylanilino)pyrido[2,3-d]pyrimidin-7-one	241660: Inhibition of [32P]ATP binding to Cyclin dependant kinase 4-cyclin D	ic50	0.0140	uM
8-cyclopentyl-2-[(5-piperazin-1-yl-2-pyridinyl)amino]pyrido[2,3-d]pyrimidin-7-one	240709: Inhibition of Cyclin-dependent kinase 4-cyclinD	ic50	0.0150	uM
6-bromo-8-cyclopentyl-2-[(5-piperazin-1-yl-2-pyridinyl)amino]pyrido[2,3-d]pyrimidin-7-one	240709: Inhibition of Cyclin-dependent kinase 4-cyclinD	ic50	0.0160	uM
6-chloro-8-cyclopentyl-5-methyl-2-(4-piperazin-1-ylanilino)pyrido[2,3-d]pyrimidin-7-one	241660: Inhibition of [32P]ATP binding to Cyclin dependant kinase 4-cyclin D	ic50	0.0160	uM
8-cyclopentyl-6-(ethoxymethyl)-2-[(5-piperazin-1-yl-2-pyridinyl)amino]pyrido[2,3-d]pyrimidin-7-one	240709: Inhibition of Cyclin-dependent kinase 4-cyclinD	ic50	0.0180	uM
8-cyclopentyl-5-methyl-2-[4-(4-methylpiperazin-1-yl)anilino]pyrido[2,3-d]pyrimidin-7-one	241660: Inhibition of [32P]ATP binding to Cyclin dependant kinase 4-cyclin D	ic50	0.0180	uM
6-amino-8-cyclopentyl-2-[(5-piperazin-1-yl-2-pyridinyl)amino]pyrido[2,3-d]pyrimidin-7-one	240709: Inhibition of Cyclin-dependent kinase 4-cyclinD	ic50	0.0190	uM
6-acetyl-8-cyclopentyl-2-[[5-(4-hydroxypiperidin-1-yl)-2-pyridinyl]amino]-5-methylpyrido[2,3-d]pyrimidin-7-one	240709: Inhibition of Cyclin-dependent kinase 4-cyclinD	ic50	0.0190	uM
6-acetyl-8-cyclopentyl-2-[[5-(3,3-dimethylpiperazin-1-yl)-2-pyridinyl]amino]-5-methylpyrido[2,3-d]pyrimidin-7-one	240709: Inhibition of Cyclin-dependent kinase 4-cyclinD	ic50	0.0210	uM
8-cyclopentyl-6-ethyl-2-[(5-piperazin-1-yl-2-pyridinyl)amino]pyrido[2,3-d]pyrimidin-7-one	240709: Inhibition of Cyclin-dependent kinase 4-cyclinD	ic50	0.0220	uM
8-cyclopentyl-6-ethyl-5-methyl-2-(4-piperazin-1-ylanilino)pyrido[2,3-d]pyrimidin-7-one	241660: Inhibition of [32P]ATP binding to Cyclin dependant kinase 4-cyclin D	ic50	0.0250	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	54020: Inhibition of Cyclin-dependent kinase 4-cyclin D	ic50	0.0260	uM
8-cyclopentyl-6-methyl-2-[(5-piperazin-1-yl-2-pyridinyl)amino]pyrido[2,3-d]pyrimidin-7-one	240709: Inhibition of Cyclin-dependent kinase 4-cyclinD	ic50	0.0270	uM
2-(3-chloro-4-piperazin-1-ylanilino)-8-cyclopentyl-5-methylpyrido[2,3-d]pyrimidin-7-one	241660: Inhibition of [32P]ATP binding to Cyclin dependant kinase 4-cyclin D	ic50	0.0280	uM
5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-N-pyridin-4-yl-1,3-thiazol-2-amine	54020: Inhibition of Cyclin-dependent kinase 4-cyclin D	ic50	0.0300	uM
6-acetyl-8-cyclopentyl-2-[[5-(3,5-dimethylmorpholin-4-yl)-2-pyridinyl]amino]-5-methylpyrido[2,3-d]pyrimidin-7-one	240709: Inhibition of Cyclin-dependent kinase 4-cyclinD	ic50	0.0300	uM
8-cyclopentyl-6-fluoro-5-methyl-2-(4-piperazin-1-ylanilino)pyrido[2,3-d]pyrimidin-7-one	241660: Inhibition of [32P]ATP binding to Cyclin dependant kinase 4-cyclin D	ic50	0.0300	uM
8-cyclopentyl-6-(2-methoxyethoxymethyl)-2-[(5-piperazin-1-yl-2-pyridinyl)amino]pyrido[2,3-d]pyrimidin-7-one	240709: Inhibition of Cyclin-dependent kinase 4-cyclinD	ic50	0.0310	uM
2-[4-(4-methylpiperazin-1-yl)anilino]-8-propan-2-ylpyrido[2,3-d]pyrimidin-7-one	54016: Inhibition of Cyclin-dependent kinase 4-cyclin D	ic50	0.0320	uM
8-cyclopentyl-5-methyl-7-oxo-2-(4-piperazin-1-ylanilino)pyrido[2,3-d]pyrimidine-6-carboxylic acid	241660: Inhibition of [32P]ATP binding to Cyclin dependant kinase 4-cyclin D	ic50	0.0320	uM
8-cyclopentyl-2-[4-[4-(3-hydroxypropyl)piperidin-1-yl]anilino]pyrido[2,3-d]pyrimidin-7-one	241660: Inhibition of [32P]ATP binding to Cyclin dependant kinase 4-cyclin D	ic50	0.0340	uM
8-cyclopentyl-2-[4-[4-(2-hydroxyethyl)piperazin-1-yl]anilino]-5-methylpyrido[2,3-d]pyrimidin-7-one	241660: Inhibition of [32P]ATP binding to Cyclin dependant kinase 4-cyclin D	ic50	0.0350	uM
6-acetyl-8-cyclopentyl-2-[[5-(3,5-dimethylpiperazin-1-yl)-2-pyridinyl]amino]-5-methylpyrido[2,3-d]pyrimidin-7-one	240709: Inhibition of Cyclin-dependent kinase 4-cyclinD	ic50	0.0370	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, decreases methylation, increases expression, affects cotreatment	7
Valproic Acid	affects expression, decreases expression, increases expression	6
sodium arsenite	decreases expression, increases expression	4
Particulate Matter	increases abundance, increases expression, affects cotreatment, decreases expression	4
trichostatin A	increases expression, decreases expression	3
bisphenol S	decreases expression, decreases methylation, increases expression	3
(+)-JQ1 compound	affects binding, decreases reaction, decreases expression	3
Air Pollutants	increases abundance, increases expression, decreases expression	3
Calcitriol	decreases expression	3
Cisplatin	affects cotreatment, decreases expression, increases expression	3
Quercetin	affects cotreatment, increases expression, decreases expression	3
Tobacco Smoke Pollution	decreases expression, decreases methylation, increases expression	3
Tretinoin	increases expression	3
methylmercuric chloride	increases expression	2
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	decreases reaction, increases expression, decreases methylation, affects cotreatment	2
chloropicrin	decreases expression	2
belinostat	decreases expression, affects cotreatment	2
Acetaminophen	decreases expression, increases expression	2
Ethanol	increases abundance, increases expression, decreases expression, decreases reaction, affects cotreatment	2
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	2
Copper	affects expression, decreases expression, affects binding	2
Dexamethasone	decreases expression, affects cotreatment, increases expression	2
Doxorubicin	affects response to substance, decreases expression	2
Drugs, Chinese Herbal	increases expression, decreases expression	2
Estradiol	affects cotreatment, increases expression	2
Fluorouracil	affects response to substance, increases expression, affects reaction, decreases expression	2
Indomethacin	affects cotreatment, increases expression, decreases expression	2
Niclosamide	decreases expression, increases expression	2
Cyclosporine	decreases expression, increases expression	2
Ritonavir	decreases expression	2

ChEMBL screening assays

28 unique, capped per target: 28 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4887807	Binding	CDK4/cyclinD Millipore kinase panel	Data for DCP probe BAY-091

Cellosaurus cell lines

7 cell lines: 5 cancer cell line, 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2TL	Abcam HEK293T CCND2 KO	Transformed cell line	Female
CVCL_B8CK	Abcam HCT 116 CCND2 KO	Cancer cell line	Male
CVCL_B8TE	Abcam MCF-7 CCND2 KO	Cancer cell line	Female
CVCL_B9ET	Abcam A-549 CCND2 KO	Cancer cell line	Male
CVCL_D9BC	Ubigene HEK293 CCND2 KO	Transformed cell line	Female
CVCL_SH35	HAP1 CCND2 (-) 1	Cancer cell line	Male
CVCL_SH36	HAP1 CCND2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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