CCND1
CCND1 (G1/S-specific cyclin-D1) is a protein that switches other genes on and off. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor, a biomarker, a fusion partner and a DNA repair gene, and an approved or late-stage drug is recorded against it. Tied to Breast cancer, Skin cancer, Multiple myeloma and 5 more.
Overview
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.
CIViC holds 23 clinical evidence items and 0 assertions across 5 variants, naming Palbociclib, Tamoxifen, Ribociclib and Sorafenib and others. Open Targets scores its association with cancer at 0.86 (direct and indirect evidence; datatypes clinical 0.97, genetic literature 0.61, affected pathway 0.80, literature 1.00, genetic association 0.70, somatic mutation 0.93, animal model 0.56). IntOGen calls it a driver in 4 cohorts (2 activating, 2 loss-of-function), covering Head and Neck Squamous Cell Carcinoma, Plasma Cell Myeloma, Endometrial Carcinoma.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · CCND1 (G1/S-specific cyclin-D1) is a protein that switches other genes on and off. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor, a biomarker, a fusion partner and a DNA repair gene, and an approved or late-stage drug is recorded against it. Tied to Breast cancer, Skin cancer, Multiple myeloma and 5 more.
- 1 · What it is
CCND1 (G1/S-specific cyclin-D1) is a protein that switches other genes on and off. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor, a biomarker, a fusion partner and a DNA repair gene, and an approved or late-stage drug is recorded against it. Tied to Breast cancer, Skin cancer, Multiple myeloma and 5 more.
- 2 · What goes wrong in cancer
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.
- 3 · How drugs use it
No product in this corpus aims at CCND1 yet. Transcription factors have no pocket to plug, so drugs either degrade them or block the partner protein they need to dock on DNA.
External identifiers
Sources: HGNC HGNC:1582 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt P24385 (protein name, function text, keywords and locations (REST API)); CIViC gene CCND1 (23 evidence items, 0 assertions, 5 variants; diseases: Breast Cancer, Lung Non-small Cell Carcinoma, Mantle Cell Lymphoma, Cancer, Ovarian Cancer and 8 more (GraphQL API, CC0)); Open Targets ENSG00000110092 (association with cancer (MONDO_0004992) 0.86; per-cancer scores at or above 0.5: colorectal cancer 0.58, prostate cancer 0.54, endometrial cancer 0.51, melanoma 0.63, plasma cell myeloma 0.53, non-Hodgkin lymphoma 0.57 (GraphQL API, CC0)); IntOGen CCND1 (driver in 4 cohorts (Act 2, LoF 2); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Biology
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 a 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. Location: Nucleus; Cytoplasm; Nucleus membrane (UniProt). Locus 11q13.3 (HGNC).
- Breast cancer: Open Targets association 0.75 with breast cancer (MONDO_0007254); CIViC evidence names this disease
- Skin cancer: Open Targets association 0.64 with skin cancer (MONDO_0002898)
- Multiple myeloma: Open Targets association 0.53 with plasma cell myeloma (MONDO_0009693); CIViC evidence names this disease
- Ovarian cancer: CIViC evidence names this disease
- Head and neck squamous cell carcinoma: CIViC evidence names this disease; IntOGen driver in 1 cohort (HNSC)
- Renal cell carcinoma: CIViC evidence names this disease
Notes
top- Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: Open Targets known-drug datatype score 0.97; IntOGen calls it an activating (Act) driver in 2 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 2 cohorts; CIViC holds 23 clinical evidence items on its variants; UniProt disease notes describe a translocation or gene fusion involving the gene; UniProt keyword "DNA damage". Evidence tier "approved-drug" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.
- Diseases the sources name that have no OnCo cancer page yet, so they are not linked: Childhood B-cell Acute Lymphoblastic Leukaemia; Anaplastic Thyroid Carcinoma.
Latest papers
topQuery for this target: (TITLE:"CCND1" OR ABSTRACT:"CCND1" OR TITLE:"cyclin D1" OR ABSTRACT:"cyclin D1" OR TITLE:"G1/S-specific cyclin-D1" OR ABSTRACT:"G1/S-specific cyclin-D1" OR TITLE:"U21B31" OR ABSTRACT:"U21B31" OR TITLE:"BCL1" OR ABSTRACT:"BCL1" OR TITLE:"D11S287E" OR ABSTRACT:"D11S287E") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about CCND1, not a curated reading list.