CCND1 Gene

HGNC Family	Cyclins (CCN)
Name	cyclin D1
Description	The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance throughout the cell cycle. Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. This cyclin forms a complex with and functions as a regulatory subunit of CDK4 or CDK6, whose activity is required for cell cycle G1/S transition. This protein has been shown to interact with tumor suppressor protein Rb and the expression of this gene is regulated positively by Rb. Mutations, amplification and overexpression of this gene, which alters cell cycle progression, are observed frequently in a variety of human cancers. [provided by RefSeq, Dec 2019]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Cyclin D1 (CCND1) is a pivotal regulator of cell‐cycle progression, acting primarily to drive the G1/S transition through activation of cyclin‐dependent kinases 4 and 6. Its expression is tightly controlled by a variety of upstream signals and transcriptional mechanisms that couple extracellular cues to proliferative responses. For example, osteoblast‐derived signals such as osteocalcin can stimulate cyclin D1 expression in pancreatic β‐cells, thereby linking bone metabolism to energy homeostasis and cell proliferation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In breast cancer, CCND1 is frequently amplified and serves as both a marker for aggressive, estrogen receptor–positive tumors and a therapeutic target for CDK4/6 inhibitors, underscoring its role in tumor cell proliferation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Moreover, regulatory networks controlling CCND1 transcription are diverse: circadian regulators such as mPer2 help maintain proper timing of cyclin D1 expression, while nuclear epidermal growth factor receptor (EGFR) can act as a direct transcriptional activator at the CCND1 promoter."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In addition, non‐metabolic functions of pyruvate kinase M2 (PKM2) include its nuclear translocation where it facilitates β‐catenin–mediated transcription of CCND1 by promoting chromatin remodeling"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "and."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Similarly, RNA‐binding proteins such as TLS, modulated by damage‐induced noncoding RNAs, can repress CCND1 transcription in response to genotoxic stress."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " In renal cell carcinoma, selective signaling via HIF‐2α upregulates cyclin D1 to promote tumorigenesis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ", whereas metformin has been shown to reduce cyclin D1 levels in prostate cancer, contributing to cell‐cycle arrest."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Finally, activation of STAT3 also drives cyclin D1 expression, consolidating its role as a convergence point for multiple oncogenic pathways"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ", and enhanced β‐catenin signaling—such as that triggered by ADAM10‐mediated E‐cadherin shedding—further reinforces cyclin D1 transcription."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " Collectively, these findings highlight how dysregulation of CCND1 expression, whether by amplification or aberrant upstream signaling, promotes unrestrained cell proliferation and tumor progression.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Na Kyung Lee, Hideaki Sowa, Eiichi Hinoi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Endocrine regulation of energy metabolism by the skeleton."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2007.05.047"}], "href": "https://doi.org/10.1016/j.cell.2007.05.047"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17693256"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17693256"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Richard S Finn, John P Crown, Istvan Lang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Lancet Oncol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/S1470-2045(14)71159-3"}], "href": "https://doi.org/10.1016/S1470-2045(14"}, {"type": "t", "text": "71159-3) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25524798"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25524798"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Loning Fu, Helene Pelicano, Jinsong Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The circadian gene Period2 plays an important role in tumor suppression and DNA damage response in vivo."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0092-8674(02)00961-3"}], "href": "https://doi.org/10.1016/s0092-8674(02"}, {"type": "t", "text": "00961-3) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12372299"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12372299"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "S Y Lin, K Makino, W Xia, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nuclear localization of EGF receptor and its potential new role as a transcription factor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2001)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncb0901-802"}], "href": "https://doi.org/10.1038/ncb0901-802"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11533659"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11533659"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Weiwei Yang, Yan Xia, Haitao Ji, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nuclear PKM2 regulates β-catenin transactivation upon EGFR activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature10598"}], "href": "https://doi.org/10.1038/nature10598"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22056988"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22056988"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Weiwei Yang, Yan Xia, David Hawke, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PKM2 phosphorylates histone H3 and promotes gene transcription and tumorigenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2012.07.018"}], "href": "https://doi.org/10.1016/j.cell.2012.07.018"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22901803"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22901803"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Xiangting Wang, Shigeki Arai, Xiaoyuan Song, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Induced ncRNAs allosterically modify RNA-binding proteins in cis to inhibit transcription."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature06992"}], "href": "https://doi.org/10.1038/nature06992"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18509338"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18509338"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Raju R Raval, Kah Weng Lau, Maxine G B Tran, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Contrasting properties of hypoxia-inducible factor 1 (HIF-1) and HIF-2 in von Hippel-Lindau-associated renal cell carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.25.13.5675-5686.2005"}], "href": "https://doi.org/10.1128/MCB.25.13.5675-5686.2005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15964822"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15964822"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "I Ben Sahra, K Laurent, A Loubat, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The antidiabetic drug metformin exerts an antitumoral effect in vitro and in vivo through a decrease of cyclin D1 level."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.onc.1211024"}], "href": "https://doi.org/10.1038/sj.onc.1211024"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18212742"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18212742"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Khandaker Siddiquee, Shumin Zhang, Wayne C Guida, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Selective chemical probe inhibitor of Stat3, identified through structure-based virtual screening, induces antitumor activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0609757104"}], "href": "https://doi.org/10.1073/pnas.0609757104"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17463090"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17463090"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Thorsten Maretzky, Karina Reiss, Andreas Ludwig, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ADAM10 mediates E-cadherin shedding and regulates epithelial cell-cell adhesion, migration, and beta-catenin translocation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0500918102"}], "href": "https://doi.org/10.1073/pnas.0500918102"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15958533"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15958533"}]}]}]}
Synonyms	BCL1, PRAD1, U21B31, D11S287E
Proteins	CCND1_HUMAN
NCBI Gene ID	595
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

CCND1 has 27,001 functional associations with biological entities spanning 9 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 131 datasets.

Click the + buttons to view associations for CCND1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

CCND1 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by CCND1 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of CCND1 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of CCND1 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of CCND1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of CCND1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of CCND1 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving CCND1 protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of CCND1 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of CCND1 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of CCND1 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of CCND1 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of CCND1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with CCND1 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with CCND1 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with CCND1 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of CCND1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of CCND1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of CCND1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of CCND1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing CCND1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing CCND1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing CCND1 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with CCND1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with CCND1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing CCND1 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of CCND1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with CCND1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with CCND1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with CCND1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of CCND1 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving CCND1 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving CCND1 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with CCND1 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with CCND1 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with CCND1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with CCND1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with CCND1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with CCND1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for CCND1 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at CCND1 gene from the ENCODE Histone Modification Site Profiles dataset.