TISIDB

Summary
Symbol	CCND1
Name	cyclin D1
Aliases	U21B31; parathyroid adenomatosis 1; B-cell CLL/lymphoma 1; G1/S-specific cyclin D1; BCL1; D11S287E; PRAD1; c ......
Chromosomal Location	11q13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway

> Subcellular Location, Domain and Function [ TOP ]
Subcellular Location	Nucleus Cytoplasm Membrane Note=Cyclin D-CDK4 complexes accumulate at the nuclear membrane and are then translocated to the nucleus through interaction with KIP/CIP family members.
Domain	PF02984 Cyclin PF00134 Cyclin
Function	Regulatory component of the cyclin D1-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. Also substrate for SMAD3, phosphorylating SMAD3 in a cell-cycle-dependent manner and repressing its transcriptional activity. Component of the ternary complex, cyclin D1/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex. Exhibits transcriptional corepressor activity with INSM1 on the NEUROD1 and INS promoters in a cell cycle-independent manner.

> Gene Ontology [ TOP ]
Biological Process	GO:0000075 cell cycle checkpoint GO:0000077 DNA damage checkpoint GO:0000079 regulation of cyclin-dependent protein serine/threonine kinase activity GO:0000082 G1/S transition of mitotic cell cycle GO:0000086 G2/M transition of mitotic cell cycle GO:0000320 re-entry into mitotic cell cycle GO:0001889 liver development GO:0006986 response to unfolded protein GO:0007050 cell cycle arrest GO:0007093 mitotic cell cycle checkpoint GO:0007346 regulation of mitotic cell cycle GO:0007548 sex differentiation GO:0007584 response to nutrient GO:0007589 body fluid secretion GO:0007595 lactation GO:0008406 gonad development GO:0008584 male gonad development GO:0009314 response to radiation GO:0009411 response to UV GO:0009416 response to light stimulus GO:0009991 response to extracellular stimulus GO:0010035 response to inorganic substance GO:0010038 response to metal ion GO:0010039 response to iron ion GO:0010165 response to X-ray GO:0010212 response to ionizing radiation GO:0010389 regulation of G2/M transition of mitotic cell cycle GO:0010948 negative regulation of cell cycle process GO:0010971 positive regulation of G2/M transition of mitotic cell cycle GO:0016055 Wnt signaling pathway GO:0030111 regulation of Wnt signaling pathway GO:0030178 negative regulation of Wnt signaling pathway GO:0030856 regulation of epithelial cell differentiation GO:0030857 negative regulation of epithelial cell differentiation GO:0030879 mammary gland development GO:0030968 endoplasmic reticulum unfolded protein response GO:0031099 regeneration GO:0031100 animal organ regeneration GO:0031570 DNA integrity checkpoint GO:0031571 mitotic G1 DNA damage checkpoint GO:0031667 response to nutrient levels GO:0031960 response to corticosteroid GO:0032026 response to magnesium ion GO:0032355 response to estradiol GO:0032941 secretion by tissue GO:0033197 response to vitamin E GO:0033273 response to vitamin GO:0033327 Leydig cell differentiation GO:0033598 mammary gland epithelial cell proliferation GO:0033599 regulation of mammary gland epithelial cell proliferation GO:0033601 positive regulation of mammary gland epithelial cell proliferation GO:0033674 positive regulation of kinase activity GO:0034620 cellular response to unfolded protein GO:0034976 response to endoplasmic reticulum stress GO:0035966 response to topologically incorrect protein GO:0035967 cellular response to topologically incorrect protein GO:0042493 response to drug GO:0043627 response to estrogen GO:0044321 response to leptin GO:0044770 cell cycle phase transition GO:0044772 mitotic cell cycle phase transition GO:0044773 mitotic DNA damage checkpoint GO:0044774 mitotic DNA integrity checkpoint GO:0044783 G1 DNA damage checkpoint GO:0044819 mitotic G1/S transition checkpoint GO:0044839 cell cycle G2/M phase transition GO:0044843 cell cycle G1/S phase transition GO:0045137 development of primary sexual characteristics GO:0045444 fat cell differentiation GO:0045471 response to ethanol GO:0045737 positive regulation of cyclin-dependent protein serine/threonine kinase activity GO:0045786 negative regulation of cell cycle GO:0045787 positive regulation of cell cycle GO:0045860 positive regulation of protein kinase activity GO:0045930 negative regulation of mitotic cell cycle GO:0045931 positive regulation of mitotic cell cycle GO:0046546 development of primary male sexual characteristics GO:0046661 male sex differentiation GO:0048545 response to steroid hormone GO:0048608 reproductive structure development GO:0048732 gland development GO:0050673 epithelial cell proliferation GO:0050678 regulation of epithelial cell proliferation GO:0050679 positive regulation of epithelial cell proliferation GO:0050878 regulation of body fluid levels GO:0051384 response to glucocorticoid GO:0051385 response to mineralocorticoid GO:0051412 response to corticosterone GO:0051592 response to calcium ion GO:0060070 canonical Wnt signaling pathway GO:0060749 mammary gland alveolus development GO:0061008 hepaticobiliary system development GO:0061180 mammary gland epithelium development GO:0061377 mammary gland lobule development GO:0061458 reproductive system development GO:0070141 response to UV-A GO:0071156 regulation of cell cycle arrest GO:0071157 negative regulation of cell cycle arrest GO:0071900 regulation of protein serine/threonine kinase activity GO:0071902 positive regulation of protein serine/threonine kinase activity GO:0090068 positive regulation of cell cycle process GO:0097305 response to alcohol GO:0097421 liver regeneration GO:0198738 cell-cell signaling by wnt GO:1901654 response to ketone GO:1901987 regulation of cell cycle phase transition GO:1901988 negative regulation of cell cycle phase transition GO:1901989 positive regulation of cell cycle phase transition GO:1901990 regulation of mitotic cell cycle phase transition GO:1901991 negative regulation of mitotic cell cycle phase transition GO:1901992 positive regulation of mitotic cell cycle phase transition GO:1902749 regulation of cell cycle G2/M phase transition GO:1902751 positive regulation of cell cycle G2/M phase transition GO:1902806 regulation of cell cycle G1/S phase transition GO:1902807 negative regulation of cell cycle G1/S phase transition GO:1904029 regulation of cyclin-dependent protein kinase activity GO:1904031 positive regulation of cyclin-dependent protein kinase activity GO:1990267 response to transition metal nanoparticle GO:2000045 regulation of G1/S transition of mitotic cell cycle GO:2000134 negative regulation of G1/S transition of mitotic cell cycle
Molecular Function	GO:0003714 transcription corepressor activity GO:0008134 transcription factor binding GO:0016538 cyclin-dependent protein serine/threonine kinase regulator activity GO:0019207 kinase regulator activity GO:0019887 protein kinase regulator activity GO:0042826 histone deacetylase binding GO:0070064 proline-rich region binding
Cellular Component	GO:0000307 cyclin-dependent protein kinase holoenzyme complex GO:0005923 bicellular tight junction GO:0017053 transcriptional repressor complex GO:0043296 apical junction complex GO:0061695 transferase complex, transferring phosphorus-containing groups GO:0070160 occluding junction GO:1902554 serine/threonine protein kinase complex GO:1902911 protein kinase complex

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04068 FoxO signaling pathway hsa04110 Cell cycle hsa04115 p53 signaling pathway hsa04151 PI3K-Akt signaling pathway hsa04152 AMPK signaling pathway hsa04310 Wnt signaling pathway hsa04340 Hedgehog signaling pathway hsa04390 Hippo signaling pathway hsa04510 Focal adhesion hsa04530 Tight junction hsa04630 Jak-STAT signaling pathway hsa04917 Prolactin signaling pathway hsa04919 Thyroid hormone signaling pathway hsa04921 Oxytocin signaling pathway
Reactome	R-HSA-1640170: Cell Cycle R-HSA-69278: Cell Cycle, Mitotic R-HSA-3247509: Chromatin modifying enzymes R-HSA-4839726: Chromatin organization R-HSA-69656: Cyclin A R-HSA-69231: Cyclin D associated events in G1 R-HSA-69202: Cyclin E associated events during G1/S transition R-HSA-1280215: Cytokine Signaling in Immune system R-HSA-69236: G1 Phase R-HSA-69206: G1/S Transition R-HSA-168256: Immune System R-HSA-6785807: Interleukin-4 and 13 signaling R-HSA-453279: Mitotic G1-G1/S phases R-HSA-8849470: PTK6 Regulates Cell Cycle R-HSA-1912422: Pre-NOTCH Expression and Processing R-HSA-1912408: Pre-NOTCH Transcription and Translation R-HSA-3214858: RMTs methylate histone arginines R-HSA-69242: S Phase R-HSA-187577: SCF(Skp2)-mediated degradation of p27/p21 R-HSA-162582: Signal Transduction R-HSA-449147: Signaling by Interleukins R-HSA-157118: Signaling by NOTCH R-HSA-8848021: Signaling by PTK6 R-HSA-75815: Ubiquitin-dependent degradation of Cyclin D R-HSA-69229: Ubiquitin-dependent degradation of Cyclin D1

> KEGG and Reactome Pathway

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KEGG

hsa04068 FoxO signaling pathway
hsa04110 Cell cycle
hsa04115 p53 signaling pathway
hsa04151 PI3K-Akt signaling pathway
hsa04152 AMPK signaling pathway
hsa04310 Wnt signaling pathway
hsa04340 Hedgehog signaling pathway
hsa04390 Hippo signaling pathway
hsa04510 Focal adhesion
hsa04530 Tight junction
hsa04630 Jak-STAT signaling pathway
hsa04917 Prolactin signaling pathway
hsa04919 Thyroid hormone signaling pathway
hsa04921 Oxytocin signaling pathway

Reactome

R-HSA-1640170: Cell Cycle
R-HSA-69278: Cell Cycle, Mitotic
R-HSA-3247509: Chromatin modifying enzymes
R-HSA-4839726: Chromatin organization
R-HSA-69656: Cyclin A
R-HSA-69231: Cyclin D associated events in G1
R-HSA-69202: Cyclin E associated events during G1/S transition
R-HSA-1280215: Cytokine Signaling in Immune system
R-HSA-69236: G1 Phase
R-HSA-69206: G1/S Transition
R-HSA-168256: Immune System
R-HSA-6785807: Interleukin-4 and 13 signaling
R-HSA-453279: Mitotic G1-G1/S phases
R-HSA-8849470: PTK6 Regulates Cell Cycle
R-HSA-1912422: Pre-NOTCH Expression and Processing
R-HSA-1912408: Pre-NOTCH Transcription and Translation
R-HSA-3214858: RMTs methylate histone arginines
R-HSA-69242: S Phase
R-HSA-187577: SCF(Skp2)-mediated degradation of p27/p21
R-HSA-162582: Signal Transduction
R-HSA-449147: Signaling by Interleukins
R-HSA-157118: Signaling by NOTCH
R-HSA-8848021: Signaling by PTK6
R-HSA-75815: Ubiquitin-dependent degradation of Cyclin D
R-HSA-69229: Ubiquitin-dependent degradation of Cyclin D1

Summary
Symbol	CCND1
Name	cyclin D1
Aliases	U21B31; parathyroid adenomatosis 1; B-cell CLL/lymphoma 1; G1/S-specific cyclin D1; BCL1; D11S287E; PRAD1; c ......
Chromosomal Location	11q13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between CCND1 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.

> Text Mining

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Literatures describing the relation between CCND1 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
19225534	Mantle cell lymphoma	Promote immunity; immnuotherapy target	These results indicate that these T cells are potent cytotoxic T cells and recognize cyclin D1 peptides naturally presented by patient lymphoma cells in the context of HLA-A(*)0201 molecules. Taken together, our work identifies cyclin D1 as a potentially important antigen for immunotherapy of MCL.

Summary
Symbol	CCND1
Name	cyclin D1
Aliases	U21B31; parathyroid adenomatosis 1; B-cell CLL/lymphoma 1; G1/S-specific cyclin D1; BCL1; D11S287E; PRAD1; c ......
Chromosomal Location	11q13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.

> High-throughput Screening

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Statistical results of CCND1 in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	CCND1
Name	cyclin D1
Aliases	U21B31; parathyroid adenomatosis 1; B-cell CLL/lymphoma 1; G1/S-specific cyclin D1; BCL1; D11S287E; PRAD1; c ......
Chromosomal Location	11q13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders

> Expression difference between responders and non-responders

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Points in the above scatter plot represent the expression difference of CCND1 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	0.261	0.536
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	1.023	0.731
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.3	0.895
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.215	0.625
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.14	0.953
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.316	0.912
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.424	0.439
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.267	0.904
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-1.184	0.628
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.125	0.955
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	0.526	0.867
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.632	0.00502

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of CCND1 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	0	1.4	-1.4	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	7.1	-7.1	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	0	0	0	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	5.9	-5.9	0.447
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	9.1	-9.1	0.458
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	11.1	0	11.1	0.36
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	20	0	20	0.357
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	5.3	0	5.3	0.507
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	9.1	0	9.1	0.519
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	CCND1
Name	cyclin D1
Aliases	U21B31; parathyroid adenomatosis 1; B-cell CLL/lymphoma 1; G1/S-specific cyclin D1; BCL1; D11S287E; PRAD1; c ......
Chromosomal Location	11q13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CCND1. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.

> Lymphocyte [ TOP ]

Summary
Symbol	CCND1
Name	cyclin D1
Aliases	U21B31; parathyroid adenomatosis 1; B-cell CLL/lymphoma 1; G1/S-specific cyclin D1; BCL1; D11S287E; PRAD1; c ......
Chromosomal Location	11q13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CCND1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CCND1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	CCND1
Name	cyclin D1
Aliases	U21B31; parathyroid adenomatosis 1; B-cell CLL/lymphoma 1; G1/S-specific cyclin D1; BCL1; D11S287E; PRAD1; c ......
Chromosomal Location	11q13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CCND1. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	CCND1
Name	cyclin D1
Aliases	U21B31; parathyroid adenomatosis 1; B-cell CLL/lymphoma 1; G1/S-specific cyclin D1; BCL1; D11S287E; PRAD1; c ......
Chromosomal Location	11q13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of CCND1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	CCND1
Name	cyclin D1
Aliases	U21B31; parathyroid adenomatosis 1; B-cell CLL/lymphoma 1; G1/S-specific cyclin D1; BCL1; D11S287E; PRAD1; c ......
Chromosomal Location	11q13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between CCND1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	CCND1
Name	cyclin D1
Aliases	U21B31; parathyroid adenomatosis 1; B-cell CLL/lymphoma 1; G1/S-specific cyclin D1; BCL1; D11S287E; PRAD1; c ......
Chromosomal Location	11q13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting CCND1 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting CCND1.

ID	Name	Drug Type	Targets	#Targets
DB01169	Arsenic trioxide	Small Molecule	AKT1, CCND1, CDKN1A, HDAC1, IKBKB, JUN, MAPK1, MAPK3, PML, TXNRD1	10

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