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 (top 2% of genes corpus-wide)
• Clinical variants (ClinVar): 185 total — 8 pathogenic, 3 likely-pathogenic
• GTEx eGene: eQTL in 27 tissues, sQTL in 22 (q < 0.05)
• Phenotypes (HPO): 25
• ChEMBL bioactivity: 3 clinical-phase molecules tested; no curated mechanism-of-action drug
• Precision-oncology evidence (CIViC): 1 curated variant–drug association
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 2 cancer types (inferred from mutation patterns)
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.39 (moderately constrained)
• MANE Select transcript: NM_001759
• Interaction hub: 2,724 STRING partners (top 3% of genes corpus-wide)

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: 18 — 14 protein_coding, 2 protein_coding_CDS_not_defined, 2 retained_intron

MANE Select: ENST00000261254

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 3: 2, TSL 5: 1

ENST00000261254, ENST00000536537, ENST00000536795, ENST00000541542, ENST00000675468, ENST00000675880, ENST00000676279, ENST00000676411, ENST00000862873, ENST00000862874, ENST00000929292, ENST00000929293, ENST00000929294, ENST00000943418, ENST00001114510, ENST00001117593, ENST00001127939, ENST00001136252

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
ENSE00004788402	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.

Highest expression (Bgee): adrenal tissue, seminal vesicle, cauda epididymis, ventricular zone, ganglionic eminence.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CCND2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 27 tissues and its splicing (sQTL) in 22 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 49 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells EBV-transformed lymphocytes	sqtl	2.9e-40	-1.06	12:4278918:C:G
Brain Cerebellar Hemisphere	eqtl	1.9e-25	+1.94	12:4275678:T:G
Adipose Visceral Omentum	sqtl	4.5e-22	-0.68	12:4278918:C:G
Brain Cerebellum	eqtl	5.2e-19	+1.61	12:4275678:T:G
Skin Not Sun Exposed Suprapubic	sqtl	7.5e-16	-0.55	12:4278918:C:G
Nerve Tibial	sqtl	1.1e-15	+0.56	12:4278918:C:G
Thyroid	sqtl	2.0e-15	-0.54	12:4278918:C:G
Heart Atrial Appendage	sqtl	6.0e-15	+0.71	12:4278918:C:G
Artery Tibial	eqtl	1.2e-14	+0.91	12:4275678:T:G
Artery Tibial	sqtl	3.4e-14	-0.52	12:4278918:C:G
Esophagus Muscularis	sqtl	1.6e-12	+0.55	12:4278918:C:G
Colon Transverse	sqtl	8.7e-12	-0.59	12:4278918:C:G
Adipose Subcutaneous	eqtl	3.4e-11	+1.03	12:4275678:T:G
Colon Sigmoid	sqtl	6.2e-11	+0.74	12:4278918:C:G
Adipose Subcutaneous	sqtl	2.3e-10	-0.46	12:4278918:C:G
Muscle Skeletal	eqtl	4.6e-10	+0.60	12:4275678:T:G
Nerve Tibial	eqtl	5.3e-10	+0.68	12:4275678:T:G
Whole Blood	eqtl	1.3e-09	-0.14	12:4289183:CG:C
Pancreas	sqtl	3.1e-09	+0.61	12:4278918:C:G
Cells Cultured fibroblasts	eqtl	1.2e-08	+1.04	12:4275678:T:G

FANTOM5 promoters

showing 10 of 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

showing 100 of 300 tissues 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
olfactory bulb	UBERON:0002264	95.31	gold quality
lower lobe of lung	UBERON:0008949	95.16	gold quality
pericardium	UBERON:0002407	95.12	gold quality
adrenal gland	UBERON:0002369	95.02	gold quality
orbitofrontal cortex	UBERON:0004167	94.92	gold quality
cranial nerve II	UBERON:0000941	94.90	gold quality
right adrenal gland	UBERON:0001233	94.90	gold quality
adrenal cortex	UBERON:0001235	94.71	gold quality
layer of synovial tissue	UBERON:0007616	94.71	gold quality
medial globus pallidus	UBERON:0002477	94.63	gold quality
cardiac ventricle	UBERON:0002082	94.41	gold quality
type B pancreatic cell	CL:0000169	94.39	silver quality
synovial joint	UBERON:0002217	94.37	gold quality
left adrenal gland	UBERON:0001234	94.32	gold quality
heart left ventricle	UBERON:0002084	94.31	gold quality
cortical plate	UBERON:0005343	94.27	gold quality
tendon	UBERON:0000043	94.25	gold quality
trigeminal ganglion	UBERON:0001675	94.18	gold quality
left adrenal gland cortex	UBERON:0035825	94.17	gold quality
sigmoid colon	UBERON:0001159	93.80	gold quality
heart	UBERON:0000948	93.76	gold quality
skin of hip	UBERON:0001554	93.75	gold quality
superior frontal gyrus	UBERON:0002661	93.59	gold quality
upper leg skin	UBERON:0004262	93.54	gold quality
cardiac atrium	UBERON:0002081	93.46	gold quality
mammary duct	UBERON:0001765	93.42	gold quality
dorsal root ganglion	UBERON:0000044	93.41	gold quality
placenta	UBERON:0001987	93.23	gold quality
calcaneal tendon	UBERON:0003701	93.15	gold quality
myometrium	UBERON:0001296	93.10	gold quality
right atrium auricular region	UBERON:0006631	92.99	gold quality
muscle layer of sigmoid colon	UBERON:0035805	92.88	gold quality
entorhinal cortex	UBERON:0002728	92.85	gold quality
bone marrow cell	CL:0002092	92.83	gold quality
penis	UBERON:0000989	92.82	gold quality
duodenum	UBERON:0002114	92.67	gold quality
mammalian vulva	UBERON:0000997	92.62	gold quality
globus pallidus	UBERON:0001875	92.46	gold quality
epithelium of mammary gland	UBERON:0003244	92.38	gold quality
large intestine	UBERON:0000059	92.34	gold quality
colon	UBERON:0001155	92.25	gold quality
urinary bladder	UBERON:0001255	92.07	gold quality
CA1 field of hippocampus	UBERON:0003881	92.04	gold quality
oviduct epithelium	UBERON:0004804	91.95	gold quality
bone marrow	UBERON:0002371	91.86	gold quality
intestine	UBERON:0000160	91.84	gold quality
parotid gland	UBERON:0001831	91.75	gold quality
mucosa of urinary bladder	UBERON:0001259	91.73	gold quality
trachea	UBERON:0003126	91.71	gold quality
periodontal ligament	UBERON:0008266	91.50	gold quality
germinal epithelium of ovary	UBERON:0001304	91.36	gold quality
nipple	UBERON:0002030	91.34	gold quality
mucosa of stomach	UBERON:0001199	91.28	gold quality
uterus	UBERON:0000995	91.26	gold quality
parietal pleura	UBERON:0002400	91.23	gold quality
upper arm skin	UBERON:0004263	91.22	gold quality
superior surface of tongue	UBERON:0007371	91.18	gold quality
cardia of stomach	UBERON:0001162	91.16	gold quality
endometrium	UBERON:0001295	91.10	gold quality
pons	UBERON:0000988	90.96	gold quality
secondary oocyte	CL:0000655	90.92	gold quality
ascending aorta	UBERON:0001496	90.89	gold quality
thoracic aorta	UBERON:0001515	90.80	gold quality
thoracic mammary gland	UBERON:0005200	90.72	gold quality
pylorus	UBERON:0001166	90.70	gold quality
bone element	UBERON:0001474	90.69	gold quality
right coronary artery	UBERON:0001625	90.64	gold quality
mammary gland	UBERON:0001911	90.51	gold quality
mucosa of transverse colon	UBERON:0004991	90.45	gold quality
pleura	UBERON:0000977	90.42	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

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Putamen	tissue	238.4
Cerebral cortex	tissue	235.6	low
Somatosensory cortex	tissue	235.6
Motor cortex	tissue	231.3
Occipital cortex	tissue	219.2
Prefrontal cortex	tissue	209.0
Hippocampal formation	tissue	208.4
Entorhinal cortex	tissue	208.4
Basal ganglia	tissue	205.7	not detected
Temporal cortex	tissue	195.2
Retrosplenial and cingulate cortex	tissue	182.0
Insular cortex	tissue	176.8
Retrosplenial cortex	tissue	175.2
Ventral forebrain	tissue	147.1
Septum	tissue	137.6
Amygdala	tissue	134.0
Spinal cord	tissue	133.7
Thalamus	tissue	125.2
Olfactory bulb	tissue	121.8
Superior colliculi	tissue	121.0
Medulla oblongata	tissue	104.6
Midbrain	tissue	100.7
Substantia nigra	tissue	91.3
Pons	tissue	85.8
Cerebellum	tissue	82.3	not detected
Postcentral gyrus	tissue	80.5
Corpus callosum	tissue	80.4
Hypothalamus	tissue	70.7
Periaqueductal gray	tissue	66.5
Hippocampus	tissue	61.2	not detected
Caudate putamen	tissue	55.9
Nucleus accumbens	tissue	39.4
Frontal cortex	tissue	31.9
Heart muscle	tissue	27.8	medium
Locus coeruleus	tissue	23.8
Choroid plexus	tissue	21.0
Bone marrow	tissue	19.2	not detected
Duodenum	tissue	16.4	low
Pancreas	tissue	15.4	low
Adrenal gland	tissue	15.3	low
Placenta	tissue	12.1	not detected
Rectum	tissue	9.8	medium
Parathyroid gland	tissue	9.3	not detected
Colon	tissue	9.3	low
Smooth muscle	tissue	9.2	not detected
Thyroid gland	tissue	9.2	medium
Small intestine	tissue	9.1	low
Seminal vesicle	tissue	8.6	not detected
Appendix	tissue	8.3	low
Endometrium 1	tissue	7.6	low
Spleen	tissue	7.4	not detected
Fallopian tube	tissue	7.2	not detected
Epididymis	tissue	7.1	medium
Cervix	tissue	5.6	low
Vagina	tissue	5.5	low
Urinary bladder	tissue	5.4	low
Prostate	tissue	5.1	not detected
Lymph node	tissue	5.0	not detected
Tonsil	tissue	4.8	low
Esophagus	tissue	4.4	low

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Dorsal hippocampus (198.9), Ventral hippocampus (169.4), Subiculum (154.4), Dorsal spinal cord (133.7), Ventral spinal cord (132.7).

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)

Targeting CCND2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 337 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 0.999, LOEUF 0.385, missense Z 2.88 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000261254 splits into 2 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
12:4,274,041–4,299,897	178 / 322.8	0.55	no
12:4,299,898–4,300,006	57 / 50.7	1.12	no

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:88314) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 33 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal response to cardiac infarction	1
abnormal cranium morphology	1
enlarged spleen	1
abnormal cerebellum morphology	1
small cerebellum	1
abnormal cerebellar foliation	1
abnormal cerebellum external granule cell layer morphology	1
thin external granule cell layer	1
abnormal Purkinje cell morphology	1
abnormal cerebellar granule layer morphology	1
abnormal cerebellar molecular layer	1
abnormal ovarian folliculogenesis	1
small testis	1
hyperactivity	1
trunk curl	1
increased circulating phosphate level	1
female infertility	1
abnormal ovulation	1
oligozoospermia	1
increased heart weight	1
increased circulating alkaline phosphatase level	1
decreased myocardial infarct size	1
increased lean body mass	1
abnormal spine curvature	1
abnormal myocardial fiber physiology	1

+8 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Xenopus laevis	P50756	99.8%	Diamond
Pongo abelii	Q5R6J5	99.3%	Diamond
Bos taurus	Q0P5D3	98.3%	Diamond
Sus scrofa	Q8WNW2	98.3%	Diamond
Canis lupus familiaris	Q64HP0	95.9%	Diamond
Gallus gallus	P49706	91.4%	Diamond
Arabidopsis thaliana	Q0WQN9	73.2%	Diamond
Caenorhabditis briggsae	Q8MUK3	65.2%	Diamond
Oryza sativa Japonica Group	Q6YXH8	56.8%	Diamond
Human herpesvirus 8 strain GK18	Q77Q36	35.3%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
CCND2-AS1	ncRNA	103752584
LINC03141	ncRNA	105369611
FGF6	protein-coding	2251
TIGAR	protein-coding	57103
FGF23	protein-coding	8074
FERRY3	protein-coding	57102

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 by resolution:

PDB	Title	Method	Resolution (Å)
6EI2	Crystal Structure of HLA-A68 presenting a C-terminally extended peptide	X-RAY DIFFRACTION	1.61

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Predicted intracellular proteins, Cancer-related genes, Candidate cancer biomarkers, Disease related genes, Human disease related genes, Congenital malformations, Other congenital malformations

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm

Antibody reliability (HPA): IH approved · IF enhanced

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)

Type	Positions
Phosphoserine	271
Phosphothreonine	280

Function

Pathways and Gene Ontology

Reactome pathways

4 curated (TAS) of 16; 5 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

16 pathways:

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

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 (7): G1/S transition of mitotic cell cycle (GO:0000082), positive regulation of cell population proliferation (GO:0008284), negative regulation of apoptotic process (GO:0043066), cell division (GO:0051301), positive regulation of G1/S transition of mitotic cell cycle (GO:1900087), 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 (10): 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)

Reactome top-level categories

13 top-level categories:

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

39 GO namespaces:

Category	Terms
cellular anatomical structure	5
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
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
cellular process	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
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
microtubule cytoskeleton	1
cytoplasm	1
nucleus	1
nuclear envelope	1
organelle membrane	1
cyclin-dependent protein kinase holoenzyme complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 14 of 22 annotations. The rest are phylogenetic / computational / electronic (IEA).

14 experimentally-supported GO terms:

GO term	NS	Evidence
G1/S transition of mitotic cell cycle	BP	direct assay
negative regulation of apoptotic process	BP	mutant phenotype
positive regulation of G1/S transition of mitotic cell cycle	BP	mutant phenotype
positive regulation of cell population proliferation	BP	mutant phenotype
chromatin	CC	direct assay
cyclin-dependent protein kinase holoenzyme complex	CC	direct assay
cytosol	CC	direct assay
nuclear membrane	CC	direct assay
nucleolus	CC	direct assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
cyclin-dependent protein serine/threonine kinase activator activity	MF	direct assay
protein kinase binding	MF	physical interaction
protein serine/threonine kinase activator activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 2,724 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCND2	CCNL2	Q96S94	831
CCND2	CDK2	P24941	803
CCND2	CDK4	P11802	791
CCND2	CDK6	Q00534	785
CCND2	CDKN2A	P42771	746
CCND2	BCL2	P10415	743
CCND2	BCL6	P41182	732
CCND2	LMO2	P25791	730
CCND2	MYC	P01106	706
CCND2	CDKN1B	P46527	700
CCND2	CDKN1A	P38936	673
CCND2	TP53	P04637	620
CCND2	CDKN2D	P55273	619
CCND2	DMTF1	Q9Y222	613
CCND2	DDX1	Q92499	590

IntAct

Human interaction partners of CCND2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

17 partners by confidence:

Partner	Interaction type	MIscore	Records
CDK4	physical association	0.960	18
CDK5	physical association	0.960	12
CDKN1A	physical association	0.950	16
CDKN1B	physical association	0.820	5
CDK2	physical association	0.740	1
PCGF2	physical association	0.590	4
BRAF	proximity	0.470	2
AKAP8	physical association	0.400	1
ADRB2	physical association	0.370	1
CDK1	association	0.350	1
FBXW7	proximity	0.270	4
SMAD4	proximity	0.270	4
SMARCA4	proximity	0.270	4
SPOP	proximity	0.270	4
AKT1	proximity	0.270	1
EGFR	proximity	0.270	1
PTPN11	proximity	0.270	1

BioGRID (242 interactions; top human partners by supporting records): CDKN1A (Two-hybrid; 20 records), CDK4 (Affinity Capture-MS; 18 records), CDK5 (Two-hybrid; 11 records), CDK6 (Two-hybrid; 8 records), CDKN1B (Affinity Capture-MS; 6 records), CDK2 (Affinity Capture-MS; 5 records), RNF6 (Affinity Capture-MS; 5 records), RB1 (Biochemical Activity; 4 records), CDKN1C (Affinity Capture-MS; 3 records), CDKN2A (Reconstituted Complex; 3 records), PCGF2 (Affinity Capture-Western; 3 records), RBL2 (Affinity Capture-MS; 3 records), AMBRA1 (Affinity Capture-Western; 2 records), DMP1 (Reconstituted Complex; 2 records), FBXL2 (Affinity Capture-Western; 2 records)

SIGNOR signaling

10 signaling 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

Protein complexes (CORUM) (4)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

4 complexes by size:

Complex	Subunits	Members
★ p16-cyclin D2-CDK4 complex	3	CCND2, CDK4, CDKN2A
★ p34(SEI-1)-CDK4-CyclinD2 complex	3	CCND2, CDK4, SERTAD1
★ CCND2-CDK4 complex	2	CCND2, CDK4
★ CCND2-CDK6 complex	2	CCND2, CDK6

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 17 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
Cyclin E associated events during G1/S transition	5	89.2×	2e-07
G1/S Transition	6	87.4×	2e-08
Cyclin A:Cdk2-associated events at S phase entry	5	83.0×	2e-07
Transcriptional regulation by RUNX2	5	79.3×	2e-07
Mitotic G1 phase and G1/S transition	6	69.1×	3e-08
S Phase	5	56.6×	6e-07
Transcriptional Regulation by TP53	6	23.3×	3e-06
PIP3 activates AKT signaling	5	20.9×	4e-05

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of DNA replication	5	170.9×	4e-08
G1/S transition of mitotic cell cycle	5	59.0×	4e-06

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.

intOGen’s role is a computational inference from cohort mutation patterns and may diverge from the gene’s curated/literature role; read it alongside the evidence above.

Genetic variants

Variant evidence for CCND2: 185 ClinVar records (11 pathogenic / likely pathogenic); 3 CIViC cancer variants; 56 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	3
Uncertain significance	76
Likely benign	55
Benign	14

Top pathogenic / likely-pathogenic (11)

Showing all 11 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
143981	NM_001759.4(CCND2):c.838A>G (p.Thr280Ala)	Pathogenic	criteria provided, multiple submitters, no conflicts	8
520663	NM_001759.4(CCND2):c.841C>G (p.Pro281Ala)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
2504114	NM_001759.4(CCND2):c.812C>A (p.Ser271Ter)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
143982	NM_001759.4(CCND2):c.808A>T (p.Lys270Ter)	Pathogenic	criteria provided, single submitter	3
143986	NM_001759.4(CCND2):c.842C>T (p.Pro281Leu)	Pathogenic	criteria provided, single submitter	3
872569	NM_001759.4(CCND2):c.793C>T (p.Gln265Ter)	Pathogenic	criteria provided, single submitter	1
985457	NM_001759.4(CCND2):c.814G>T (p.Glu272Ter)	Pathogenic	criteria provided, single submitter	1
3997605	NM_001759.4(CCND2):c.643C>T (p.Gln215Ter)	Pathogenic	criteria provided, single submitter	1
4528281	NM_001759.4(CCND2):c.416_419dup (p.Leu141fs)	Pathogenic	criteria provided, single submitter	1
3775676	NM_001759.4(CCND2):c.802G>T (p.Gly268Ter)	Likely pathogenic	criteria provided, single submitter	1
4607569	NM_001759.4(CCND2):c.806_818dup (p.Glu274fs)	Likely pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore CCND2’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 24 predictions of 605):

Position(s)	Effect	Δscore	Sites
12:4274236–4274237	donor_loss	1.0000	4
12:4276003–4276004	acceptor_loss	1.0000	3
12:4276221–4276222	donor_loss	1.0000	4
12:4278745	acceptor_gain	1.0000
12:4278758–4278759	acceptor_loss	1.0000	3
12:4278920–4278921	donor_loss	1.0000	5
12:4274236	donor_loss	0.9900
12:4276002	acceptor_gain	0.9900
12:4276003	acceptor_loss	0.9900
12:4276221	donor_loss	0.9900

AlphaMissense

999 missense substitutions predicted likely pathogenic (of 1,889 scored), across 214 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M55	9	0.976	0.999
M63	9	0.945	0.999
D85	8	0.998	1.000
H180	8	0.989	0.996
F77	8	0.981	0.999
D128	8	0.979	0.995
D158	8	0.978	0.988
F194	8	0.960	0.996
F159	8	0.956	0.999
F184	8	0.956	0.996
F44	8	0.954	0.993
D17	8	0.953	0.972
D283	8	0.933	0.979
F107	8	0.931	0.996
M201	8	0.907	0.986
D191	8	0.893	0.971
D241	8	0.846	0.951
D23	8	0.800	0.916
W62	7	0.999	1.000
W149	7	0.998	1.000

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Testicular Germ Cell Tumor)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Breast Invasive Carcinoma (validation)	favorable	0.000756
Pancreatic Adenocarcinoma (TCGA)	favorable	0.00098

Disease associations

OMIM: gene MIM:123833 | disease phenotypes: MIM:603387, MIM:615938, MIM:606369

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3	Definitive	Autosomal dominant	4
megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity

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

1 validity classifications:

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

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (13 panels, 13 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

13 panels:

Panel	Rating
Cerebral malformation	green
DDG2P	green
Fetal anomalies	green
Hydrocephalus	green
Hypotonic infant	green
Intellectual disability	green
Leukodystrophy, childhood onset	green
Limb disorders	green
Malformations of cortical development	green
Neurological segmental overgrowth	green
Paediatric disorders	green
Segmental overgrowth disorders - Deep sequencing	green
Severe microcephaly	green

Mondo (4): megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 (MONDO:0011313), megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3 (MONDO:0014408), Lennox-Gastaut syndrome (MONDO:0016532), megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome (MONDO:0019375)

Orphanet (2): Megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome (Orphanet:83473), Lennox-Gastaut syndrome (Orphanet:2382)

HPO phenotypes

25 phenotypes (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

showing 30 of 56 associations:

Study	Trait	p-value
GCST90000025_518	Appendicular lean mass	8e-112
GCST009379_257	Type 2 diabetes	1e-69
GCST010244_72	Triglyceride levels	8e-30
GCST009379_256	Type 2 diabetes	3e-21
GCST009869_61	Colorectal cancer	2e-19
GCST007856_26	Colorectal cancer or advanced adenoma	4e-19
GCST007856_24	Colorectal cancer or advanced adenoma	1e-17
GCST010661_8	Blood glucose levels	1e-16
GCST010173_53	Triglyceride levels	2e-16
GCST90000025_519	Appendicular lean mass	6e-14
GCST008362_215	Birth weight	2e-13
GCST010660_19	Triglyceride levels	4e-13
GCST007269_232	Pulse pressure	1e-12
GCST010118_169	Type 2 diabetes	1e-12
GCST001765_3	Red blood cell traits	8e-12
GCST007856_28	Colorectal cancer or advanced adenoma	2e-11
GCST004008_2	Red blood cell count	3e-11
GCST009379_255	Type 2 diabetes	3e-11
GCST009379_254	Type 2 diabetes	9e-11
GCST010204_154	Low density lipoprotein cholesterol levels	9e-11
GCST002454_18	Colorectal cancer	1e-10
GCST010659_17	Waist circumference	1e-10
GCST005413_20	Type 2 diabetes	2e-10
GCST006867_112	Type 2 diabetes	2e-10
GCST001792_2	Colorectal cancer	5e-10
GCST90013663_1	Alanine aminotransferase levels	5e-10
GCST005047_66	Type 2 diabetes	1e-9
GCST90013664_98	Aspartate aminotransferase levels	1e-9
GCST006989_8	Brown vs. black hair color	2e-9
GCST007552_39	Colorectal cancer	3e-9

EFO canonical traits (from GWAS)

15 canonical traits:

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

2 disease descriptors:

Descriptor	Name	Tree numbers
D065768	Lennox Gastaut Syndrome	C10.228.140.490.493.750; C16.320.495
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

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 44,068 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

3 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL189963	PALBOCICLIB	4	13,796
CHEMBL428690	ALVOCIDIB	3	28,145
CHEMBL296468	BMS-387032	1	2,127

Clinical evidence (CIViC)

Drug × variant × indication, from 1 curated evidence items; also 4 prognostic, 1 diagnostic. CIViC evidence level: A (validated) → B (clinical) → C (case study) → D (preclinical) → E (inferential).

1 predictive associations by evidence level:

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

CIViC curated variants (3)

Named clinical variants curated in CIViC for this gene (the catalogue beneath the predictive evidence above):

OVEREXPRESSION, PROMOTER DEMETHYLATION, Amplification.

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

40 measured of 44 human assays (44 total across all organisms); most potent 40 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
4-(3,3-diethyl-7-fluoro-2-methyl-3H-indol-5-yl)-5-fluoro-N-(5-(1-methylpiperidin-4-yl)pyridin-2-yl)pyrimidine-2-amino	IC50	0.2 nM	US-11091476: Protein kinase inhibitors, preparation method and medical use thereof
5-Fluoro-4-(7′-fluoro-2′-methylspiro[cyclopentane-1,3′-indol]-5′-yl)-N-(5-((4-methylpiperazin-1-yl)methyl)pyridin-2-yl)pyrimidine-2-amino	IC50	0.9 nM	US-11091476: Protein kinase inhibitors, preparation method and medical use thereof
4-(3-ethyl-7-fluoro-2,3-dimethyl-3H-indol-5-yl)-5-fluoro-N-(5-((4-methylpiperazin-1-yl)methyl)pyridin-2-yl)pyrimidine-2-amino	IC50	2.33 nM	US-11091476: Protein kinase inhibitors, preparation method and medical use thereof
1-(2-((4-(3-Ethyl-7-fluoro-2,3-dimethyl-3H-indol-5-yl)-5-fluoropyrimidin-2-yl)amino)-7,8-dihydro-1,6-naphthyridine-6 (5H)-yl)-2-hydroxyacetamide	IC50	5.65 nM	US-11091476: Protein kinase inhibitors, preparation method and medical use thereof
5-Fluoro-N-(5-(1-methylpiperidin-4-yl)pyridin-2-yl)-4-(2,3,3-trimethyl-3H-indol-5-yl)pyrimidine-2-amino	IC50	22.9 nM	US-11091476: Protein kinase inhibitors, preparation method and medical use thereof
1-(2-((5-fluoro-4-(7′-fluoro-2′-methylspiro[cyclopentane-1,3′-indol]-5′-yl) pyrimidin-2-yl)amino)-7,8-dihydro-1,6-naphthyridine-6 (5H)-yl)-2-hydroxyacetamide	IC50	25 nM	US-11091476: Protein kinase inhibitors, preparation method and medical use thereof
5-fluoro-4-(2’-methylspiro[cyclopentane-1,3’-indole]-5’-yl)-N-(5-piperidin-4-yl-2-pyridinyl)pyrimidin-2-amine	IC50	27 nM	US-11091476: Protein kinase inhibitors, preparation method and medical use thereof
5-fluoro-N-[5-(1-methylpiperidin-4-yl)-2-pyridinyl]-4-(2’-methylspiro[cyclopentane-1,3’-indole]-5’-yl)pyrimidin-2-amine	IC50	50 nM	US-11091476: Protein kinase inhibitors, preparation method and medical use thereof
4-(3-ethyl-2,3-dimethylindol-5-yl)-5-fluoro-N-[5-(1-methylpiperidin-4-yl)-2-pyridinyl]pyrimidin-2-amine	IC50	54 nM	US-11091476: Protein kinase inhibitors, preparation method and medical use thereof
4-(3-ethyl-7-fluoro-2,3-dimethylindol-5-yl)-N-[5-(4-ethylpiperazin-1-yl)-2-pyridinyl]-5-fluoropyrimidin-2-amine	IC50	65 nM	US-11091476: Protein kinase inhibitors, preparation method and medical use thereof
4-(3,3-diethyl-7-fluoro-2-methylindol-5-yl)-5-fluoro-N-(5-piperazin-1-yl-2-pyridinyl)pyrimidin-2-amine	IC50	82 nM	US-11091476: Protein kinase inhibitors, preparation method and medical use thereof
4-(3-ethyl-7-fluoro-2,3-dimethylindol-5-yl)-5-fluoro-N-(5-piperazin-1-yl-2-pyridinyl)pyrimidin-2-amine	IC50	84 nM	US-11091476: Protein kinase inhibitors, preparation method and medical use thereof
4-(3,3-diethyl-7-fluoro-2-methylindol-5-yl)-5-fluoro-N-[5-(4-methylpiperazin-1-yl)-2-pyridinyl]pyrimidin-2-amine	IC50	96 nM	US-11091476: Protein kinase inhibitors, preparation method and medical use thereof
3-(9-oxo-9H-fluoren-4-yl)-1-pyridin-2-ylurea	IC50	100 nM
4-(3-ethyl-2,3-dimethylindol-5-yl)-N-[5-(4-ethylpiperazin-1-yl)-2-pyridinyl]-5-fluoropyrimidin-2-amine	IC50	101 nM	US-11091476: Protein kinase inhibitors, preparation method and medical use thereof
4-(3-ethyl-7-fluoro-2,3-dimethylindol-5-yl)-5-fluoro-N-(5-piperidin-4-yl-2-pyridinyl)pyrimidin-2-amine	IC50	110 nM	US-11091476: Protein kinase inhibitors, preparation method and medical use thereof
4-(3-ethyl-2,3-dimethylindol-5-yl)-5-fluoro-N-[5-(4-methylpiperazin-1-yl)-2-pyridinyl]pyrimidin-2-amine	IC50	112 nM	US-11091476: Protein kinase inhibitors, preparation method and medical use thereof
4-(3-ethyl-7-fluoro-2,3-dimethylindol-5-yl)-5-fluoro-N-[5-(1-methylpiperidin-4-yl)-2-pyridinyl]pyrimidin-2-amine	IC50	131 nM	US-11091476: Protein kinase inhibitors, preparation method and medical use thereof
N-[5-(1-ethylpiperidin-4-yl)-2-pyridinyl]-5-fluoro-4-(2’-methylspiro[cyclopentane-1,3’-indole]-5’-yl)pyrimidin-2-amine	IC50	135 nM	US-11091476: Protein kinase inhibitors, preparation method and medical use thereof
4-(3-ethyl-2,3-dimethylindol-5-yl)-5-fluoro-N-(5-piperazin-1-yl-2-pyridinyl)pyrimidin-2-amine	IC50	142 nM	US-11091476: Protein kinase inhibitors, preparation method and medical use thereof
5-fluoro-4-(7’-fluoro-2’-methylspiro[cyclopentane-1,3’-indole]-5’-yl)-N-(5-piperazin-1-yl-2-pyridinyl)pyrimidin-2-amine	IC50	152 nM	US-11091476: Protein kinase inhibitors, preparation method and medical use thereof
4-(3-ethyl-7-fluoro-2,3-dimethylindol-5-yl)-5-fluoro-N-[5-(4-methylpiperazin-1-yl)-2-pyridinyl]pyrimidin-2-amine	IC50	153 nM	US-11091476: Protein kinase inhibitors, preparation method and medical use thereof
4-(3-ethyl-2,3-dimethylindol-5-yl)-5-fluoro-N-(5-piperidin-4-yl-2-pyridinyl)pyrimidin-2-amine	IC50	166 nM	US-11091476: Protein kinase inhibitors, preparation method and medical use thereof
2-[4-[6-[[5-fluoro-4-(7’-fluoro-2’-methylspiro[cyclopentane-1,3’-indole]-5’-yl)pyrimidin-2-yl]amino]-3-pyridinyl]piperidin-1-yl]ethanol	IC50	176 nM	US-11091476: Protein kinase inhibitors, preparation method and medical use thereof
4-(3-ethyl-7-fluoro-2,3-dimethylindol-5-yl)-N-[5-(1-ethylpiperidin-4-yl)-2-pyridinyl]-5-fluoropyrimidin-2-amine	IC50	216 nM	US-11091476: Protein kinase inhibitors, preparation method and medical use thereof
5-fluoro-4-(2’-methylspiro[cyclopentane-1,3’-indole]-5’-yl)-N-(5-piperazin-1-yl-2-pyridinyl)pyrimidin-2-amine	IC50	234 nM	US-11091476: Protein kinase inhibitors, preparation method and medical use thereof
N-[5-[(4-ethylpiperazin-1-yl)methyl]-2-pyridinyl]-5-fluoro-4-(2’-methylspiro[cyclopentane-1,3’-indole]-5’-yl)pyrimidin-2-amine	IC50	268 nM	US-11091476: Protein kinase inhibitors, preparation method and medical use thereof
5-fluoro-4-(7’-fluoro-2’-methylspiro[cyclopentane-1,3’-indole]-5’-yl)-N-(5-piperidin-4-yl-2-pyridinyl)pyrimidin-2-amine	IC50	327 nM	US-11091476: Protein kinase inhibitors, preparation method and medical use thereof
2-[4-[6-[[5-fluoro-4-(7’-fluoro-2’-methylspiro[cyclopentane-1,3’-indole]-5’-yl)pyrimidin-2-yl]amino]-3-pyridinyl]piperazin-1-yl]ethanol	IC50	328 nM	US-11091476: Protein kinase inhibitors, preparation method and medical use thereof
5-fluoro-N-[5-(4-methylpiperazin-1-yl)-2-pyridinyl]-4-(2’-methylspiro[cyclopentane-1,3’-indole]-5’-yl)pyrimidin-2-amine	IC50	417 nM	US-11091476: Protein kinase inhibitors, preparation method and medical use thereof
4-(3,3-diethyl-7-fluoro-2-methylindol-5-yl)-N-[5-[(4-ethylpiperazin-1-yl)methyl]-2-pyridinyl]-5-fluoropyrimidin-2-amine	IC50	436 nM	US-11091476: Protein kinase inhibitors, preparation method and medical use thereof
N-[5-(4-ethylpiperazin-1-yl)-2-pyridinyl]-5-fluoro-4-(2’-methylspiro[cyclopentane-1,3’-indole]-5’-yl)pyrimidin-2-amine	IC50	915 nM	US-11091476: Protein kinase inhibitors, preparation method and medical use thereof
4-(3-ethyl-7-fluoro-2,3-dimethylindol-5-yl)-N-[5-[(4-ethylpiperazin-1-yl)methyl]-2-pyridinyl]-5-fluoropyrimidin-2-amine	IC50	966 nM	US-11091476: Protein kinase inhibitors, preparation method and medical use thereof
N-[5-(1-ethylpiperidin-4-yl)-2-pyridinyl]-5-fluoro-4-(7’-fluoro-2’-methylspiro[cyclopentane-1,3’-indole]-5’-yl)pyrimidin-2-amine	IC50	1070 nM	US-11091476: Protein kinase inhibitors, preparation method and medical use thereof
N-[5-(4-ethylpiperazin-1-yl)-2-pyridinyl]-5-fluoro-4-(7’-fluoro-2’-methylspiro[cyclopentane-1,3’-indole]-5’-yl)pyrimidin-2-amine	IC50	1160 nM	US-11091476: Protein kinase inhibitors, preparation method and medical use thereof
5-fluoro-4-(7’-fluoro-2’-methylspiro[cyclopentane-1,3’-indole]-5’-yl)-N-[5-(4-methylpiperazin-1-yl)-2-pyridinyl]pyrimidin-2-amine	IC50	1440 nM	US-11091476: Protein kinase inhibitors, preparation method and medical use thereof
5-fluoro-4-(7-fluoro-2,3,3-trimethylindol-5-yl)-N-(5-piperazin-1-yl-2-pyridinyl)pyrimidin-2-amine	IC50	2220 nM	US-11091476: Protein kinase inhibitors, preparation method and medical use thereof
N-[5-[(4-ethylpiperazin-1-yl)methyl]-2-pyridinyl]-5-fluoro-4-(7’-fluoro-2’-methylspiro[cyclopentane-1,3’-indole]-5’-yl)pyrimidin-2-amine	IC50	2240 nM	US-11091476: Protein kinase inhibitors, preparation method and medical use thereof
5-fluoro-4-(7’-fluoro-2’-methylspiro[cyclopentane-1,3’-indole]-5’-yl)-N-[5-(1-methylpiperidin-4-yl)-2-pyridinyl]pyrimidin-2-amine	IC50	2710 nM	US-11091476: Protein kinase inhibitors, preparation method and medical use thereof
(Z)-Hymenialdisine	IC50	7000 nM

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

155 with measured affinity, of 177 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

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, decreases expression, decreases methylation, increases expression	7
Valproic Acid	affects expression, decreases expression, increases expression	6
sodium arsenite	decreases expression, increases expression	4
Air Pollutants	increases abundance, increases expression, decreases expression	4
Particulate Matter	affects cotreatment, decreases expression, increases abundance, increases expression	4
trichostatin A	decreases expression, increases expression	3
bisphenol S	decreases methylation, increases expression, decreases expression	3
(+)-JQ1 compound	affects binding, decreases reaction, decreases expression	3
Calcitriol	decreases expression	3
Cisplatin	decreases expression, increases expression, affects cotreatment	3
Quercetin	increases expression, decreases expression, affects cotreatment	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	increases expression, decreases expression	2
Ethanol	decreases expression, decreases reaction, affects cotreatment, increases abundance, increases expression	2
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	2
Copper	affects binding, affects expression, decreases expression	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	increases expression, decreases expression	2
Cyclosporine	increases expression, decreases 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)

Via MONDO — disease-level, not drug-specific.

56 trials:

NCT	Phase	Status	Title
NCT01370486	Phase 4	WITHDRAWN	Melatonin Versus Placebo in the Lennox-Gastaut Syndrome: Neurophysiological and Neuropsychological Effects
NCT02731300	Phase 4	COMPLETED	Transcranial Direct Current Stimulation, Treatment of Childhood Drug-Resistant Lennox-Gastaut Syndrome, A Pilot Study
NCT04133480	Phase 4	WITHDRAWN	Investigation of Cognitive Outcomes With Cannabidiol Oral Solution
NCT05044819	Phase 4	ACTIVE_NOT_RECRUITING	Assessment of Potential for Chronic Liver Injury in Participants Treated With Epidiolex (Cannabidiol) Oral Solution
NCT06924827	Phase 4	NOT_YET_RECRUITING	A Study to Investigate the Transition of Children From ‘Artisanal Cannabidiol (CBD) to Epidiolex
NCT07728097	Phase 4	NOT_YET_RECRUITING	A Study to Investigate the Effect of Gradual Titration to Optimize Cannabidiol Treatment in Adults With LGS
NCT00004776	Phase 3	COMPLETED	Phase III Randomized, Double-Blind, Placebo-Controlled Study of Oral Topiramate for Lennox-Gastaut Syndrome
NCT01146951	Phase 3	COMPLETED	A Placebo-Controlled, Double-Blind Comparative Study of E2080 in Lennox-Gastaut Syndrome Patients (Study E2080-J081-304)
NCT01151540	Phase 3	COMPLETED	A Long Term Extension Study of E2080 in Lennox-Gastaut Patients
NCT01160770	Phase 3	COMPLETED	Safety and Effectiveness of Open-Label Clobazam in Subjects With Lennox-Gastaut Syndrome
NCT01405053	Phase 3	COMPLETED	Study of Rufinamide in Pediatric Subjects 1 to Less Than 4 Years of Age With Lennox-Gastaut Syndrome Inadequately Controlled With Other Anti-epileptic Drugs
NCT02224560	Phase 3	COMPLETED	Efficacy and Safety of GWP42003-P for Seizures Associated With Lennox-Gastaut Syndrome in Children and Adults
NCT02224573	Phase 3	COMPLETED	An Open Label Extension Study of Cannabidiol (GWP42003-P) in Children and Adults With Dravet or Lennox-Gastaut Syndromes
NCT02224690	Phase 3	COMPLETED	A Study to Investigate the Efficacy and Safety of Cannabidiol (GWP42003-P; CBD) as Adjunctive Treatment for Seizures Associated With Lennox-Gastaut Syndrome in Children and Adults
NCT02318537	Phase 3	WITHDRAWN	Cannabidiol Oral Solution as an Adjunctive Therapy for Treatment of Participants With Inadequately Controlled Lennox-Gastaut Syndrome
NCT02834793	Phase 3	TERMINATED	Study of Perampanel as Adjunctive Treatment for Inadequately Controlled Seizures Associated With Lennox-Gastaut Syndrome
NCT03355209	Phase 3	COMPLETED	A Study to Investigate the Efficacy and Safety of ZX008 (Fenfluramine Hydrochloride) as an Adjunctive Therapy in Children and Adults With Lennox-Gastaut Syndrome
NCT03936777	Phase 3	COMPLETED	A Study to Investigate the Long-Term Safety of ZX008 (Fenfluramine Hydrochloride) Oral Solution in Children and Adults With Epileptic Encephalopathy Including Dravet Syndrome and Lennox-Gastaut Syndrome
NCT04611438	Phase 3	UNKNOWN	Research on Cognitive Effect of Cannabidiol on Dravet Syndrome and Lennox-Gastaut SyndromeGastaut Syndrome
NCT04938427	Phase 3	COMPLETED	A Study of Soticlestat as an Add-on Therapy in Children, Teenagers, and Adults With Lennox-Gastaut Syndrome
NCT05066217	Phase 3	RECRUITING	An Efficacy and Safety Study of Clemizole HCl in Patients With Lennox-Gastaut Syndrome
NCT05163314	Phase 3	TERMINATED	A Study of Soticlestat as an Add-on Therapy in Children and Adults With Dravet Syndrome or Lennox-Gastaut Syndrome
NCT05219617	Phase 3	RECRUITING	Investigate Efficacy and Safety of Carisbamate as Adjunctive Treatment for Seizures Associated With LGS in Children and Adults
NCT06422377	Phase 3	TERMINATED	A Study Evaluating Soticlestat in Participants With Dravet Syndrome or Lennox-Gastaut Syndrome Who Have Been Exposed to Fenfluramine
NCT02655198	Phase 2	UNKNOWN	Add-on Therapy With Low Dose Fenfluramine in Lennox Gastaut Epilepsy
NCT03635073	Phase 2	TERMINATED	A Study of Soticlestat in Adults and Children With Rare Epilepsies
NCT03650452	Phase 2	COMPLETED	A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of TAK-935 (OV935) as an Adjunctive Therapy in Pediatric Participants With Developmental and/or Epileptic Encephalopathies
NCT05339126	Phase 2	ACTIVE_NOT_RECRUITING	RNS System LGS Feasibility Study
NCT05626634	Phase 2	COMPLETED	Open-label, Long-term Safety Study of LP352 in Subjects With Developmental and Epileptic Encephalopathy
NCT06401538	Phase 2	RECRUITING	BMB-101 in Absence Epilepsy and DEE
NCT03467113	Phase 1	COMPLETED	A Study to Assess the Safety and Tolerability of ZX008 in Children and Young Adults With Dravet Syndrome or Lennox Gastaut Syndrome Currently Taking Cannabidiol
NCT03731715	Phase 1	COMPLETED	Carisbamate in Adult & Pediatric Subjects With Lennox-Gastaut Syndrome
NCT04062981	Phase 1	COMPLETED	Carisbamate Safety Study in Adult and Pediatric Subjects With Lennox-Gastaut Syndrome
NCT02815540	Phase 1/2	TERMINATED	The Effects of Cannabidiol (CBD) on Electrical and Autonomic Cardiac Function in Children With Severe Epilepsy
NCT05364021	Phase 1/2	COMPLETED	Study to Investigate LP352 in Subjects With Developmental and Epileptic Encephalopathies
NCT06738732	Phase 1/2	NOT_YET_RECRUITING	CBD Delivery with the A-Synaptic GT4 Transdermal Delivery System in with Dravet Syndrome And/or Lennox-Gastaut Syndrome
NCT02632149	Early Phase 1	UNKNOWN	Trial to Assess Vagus Nerve Stimulation Therapy in Children With Lennox-Gastaut Syndrome
NCT00004729	Not specified	COMPLETED	Ketogenic Diet for Child Epilepsy and Seizure Control
NCT00552045	Not specified	COMPLETED	Epilepsy Phenome/Genome Project
NCT01991041	Not specified	COMPLETED	European Registry of Anti-Epileptic Drug Use in Patients With Lennox-Gastaut Syndrome (LGS)
NCT02175173	Not specified	COMPLETED	Post-marketing Surveillance of Long-term Administration of Inovelon Tablets in Patients With Lennox-Gastaut Syndrome
NCT02307578	Not specified	NO_LONGER_AVAILABLE	An Extended Access Program (EAP) for Perampanel
NCT02910297	Not specified	WITHDRAWN	The Pharmacokinetics of Cannabidiol (CBD) and Its Effects in Children With Severe Epilepsy
NCT03254680	Not specified	WITHDRAWN	Turmeric as Treatment in Epilepsy
NCT03778424	Not specified	AVAILABLE	An Extended Access Program (EAP) for Participants Who Have Completed Rufinamide Study E2080-G000-303
NCT03955432	Not specified	TERMINATED	Long-term Cardiac Monitoring in Epilepsy
NCT05374824	Not specified	RECRUITING	Comparative Effectiveness of Palliative Surgery Versus Additional Anti-Seizure Medications for Lennox-Gastaut Syndrome
NCT05485831	Not specified	ACTIVE_NOT_RECRUITING	Epidyolex® in Lennox Gastaut, Dravet Syndrome and Tuberous Sclerosis Complex: an Observational Study in ITALY
NCT05982717	Not specified	COMPLETED	A Study to Gather Information About Overall Occurrence and New Cases of Dravet and Lennox-Gastaut Syndromes in Children, Teenagers and Adults in Spain
NCT06149663	Not specified	AVAILABLE	Intermediate-Size Expanded Access Protocol (EAP) for LP352
NCT06395792	Not specified	WITHDRAWN	A Study on Dravet Syndrome (DS) and Lennox-Gastaut Syndrome (LGS) in Children, Teenagers and Adults in Portugal
NCT06464653	Not specified	ACTIVE_NOT_RECRUITING	Pallidothalamic Tracts Electrical Stimulation for Lennox-Gastaut Syndrome
NCT06924086	Not specified	RECRUITING	The Children’s Adaptive Deep Brain Stimulation for Epilepsy Trial
NCT07225231	Not specified	NOT_YET_RECRUITING	Clinical Utility of Reduced EEG Home Monitoring in Fenfluramine Titration for Dravet and LGS
NCT07555171	Not specified	ENROLLING_BY_INVITATION	EEG Dynamics in Lennox-Gastaut Syndrome Patients Undergoing Fenfluramine Treatment
NCT07568860	Not specified	NOT_YET_RECRUITING	Sleep-Driven Adaptive Neuromodulation in Lennox-Gastaut Syndrome

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for CCND2 across ~30M SureChEMBL compounds — explore on Sugi Predict.