CCND1 Gene Complete Identifier and Functional Mapping Reference
Provide a comprehensive cross-database identifier and functional mapping reference for human CCND1 — a definitive lookup resource covering: ### Section 1: Gene identifiers For human gene CCND1, list ALL gene-level database identifiers. Required: - HGNC ID and approved symbol - Ensembl gene ID (ENSG...) - NCBI Entrez Gene ID - OMIM gene/locus ID - Genomic location: chromosome, start position, end position, strand (GRCh38) ### Section 2: Transcript identifiers For human gene CCND1, list ALL transcript-level identifiers. Required: - Ensembl transcripts: ALL ENST IDs with biotype. Total count. - RefSeq transcripts: ALL NM_ mRNA accessions. Mark which is MANE Select. - CCDS IDs. - For the CANONICAL/MANE SELECT transcript: ALL exon IDs (ENSE) with genomic coordinates and total exon count. ### Section 3: Protein identifiers For human gene CCND1 protein product(s), list ALL protein-level identifiers. Required: - UniProt accessions: ALL entries (reviewed and unreviewed). Mark the canonical reviewed entry. - RefSeq protein: ALL NP_ accessions. - Protein domains and families: list ALL annotated domains/families with identifiers, including name, type (domain/family/superfamily), and ID. - Antibody availability: known antibody resources for the protein. ### Section 4: Structure For human gene CCND1 protein, list ALL structural data. Required: - Experimental structures: ALL PDB IDs. For each: experimental method (X-ray/NMR/Cryo-EM) and resolution. Total count. - Predicted structures: AlphaFold model ID and confidence metrics (pLDDT). ### Section 5: Cross-species orthologs For human gene CCND1, list orthologous genes in key model organisms. Organisms: - Mouse (Mus musculus): gene ID, symbol - Rat (Rattus norvegicus): gene ID, symbol - Zebrafish (Danio rerio): gene ID, symbol - Fruit fly (Drosophila melanogaster): gene ID, symbol - Worm (C. elegans): gene ID, symbol - Yeast (S. cerevisiae): gene ID, symbol ### Section 6: Clinical variants & AI predictions For human gene CCND1, summarize clinical variants and AI predictions. Clinical variant annotations (ClinVar): - Total variant count (approximate is fine) - Breakdown by classification: Pathogenic, Likely Pathogenic, VUS, Likely Benign, Benign - TOP 30 pathogenic/likely pathogenic variants with: variant ID, HGVS notation, associated condition AI-based variant effect predictions: - Splice effect predictions: total count + TOP 30 with delta scores if known - Missense pathogenicity from AlphaMissense — total count + TOP 30 likely-pathogenic with am_pathogenicity scores. ### Section 7: Pathways & Gene Ontology For human gene CCND1, list biological pathways and Gene Ontology annotations. Pathway membership: - ALL biological pathways this gene participates in, with pathway IDs and names - Total pathway count Gene Ontology: - Biological Process: count and TOP 20 terms with GO IDs - Molecular Function: count and TOP 20 terms with GO IDs - Cellular Component: count and TOP 20 terms with GO IDs ### Section 8: Protein interactions & networks For human gene CCND1 protein, summarize protein interactions and networks. Protein-protein interactions (STRING, IntAct, BioGRID, etc.): - Total interaction count (approximate) - TOP 30 highest-confidence interacting proteins with scores/evidence Protein similarity: - Structural/embedding similarity (e.g. Foldseek, ESM): TOP 20 similar proteins with scores - Sequence homology: TOP 20 homologous proteins with identity/similarity ### Section 9: Transcription factor regulatory data For human gene CCND1, summarize transcription factor regulatory data. If CCND1 is a transcription factor: - Downstream targets: total count + TOP 30 with regulation type (activates/represses) and evidence - DNA binding motifs from JASPAR — all known motif IDs and motif family classification. Regardless: - Upstream regulators: TFs that regulate CCND1 — names with evidence type (ChIP-seq / predicted / experimentally validated) If CCND1 is not a transcription factor, say so briefly and skip the downstream/motif sections. ### Section 10: Drug & pharmacology data For human gene CCND1 protein as a drug target, summarize pharmacology data. If CCND1 is a known drug target: - Targeting molecules: total count in ChEMBL/DrugBank + TOP 30 by development phase (molecule ID, name, mechanism, highest phase) - Clinical trials: TOP 20 involving drugs targeting this gene — trial ID, phase, status, intervention - Pharmacogenomics: known drug-gene interactions affecting drug response + dosing guidelines if any If CCND1 is not currently a drug target, say so briefly. ### Section 11: Expression profiles For human gene CCND1, summarize expression profiles. Tissue expression (GTEx, HPA, Bgee, etc.): - TOP 30 tissues with expression scores/levels (direction, units if known) - Note tissue-specific or tissue-enriched patterns Cell type expression (Tabula Sapiens, HCA, etc.): - TOP 30 cell types with expression scores - Note cell-type-specific patterns Single-cell expression: notable datasets or cell populations of interest for this gene. ### Section 12: Disease associations For human gene CCND1, summarize disease associations. Mendelian / monogenic disease: - Diseases caused by mutations in CCND1: disease name, disease ID (OMIM/Orphanet/Mondo), inheritance pattern, evidence level - Include all directly linked conditions Phenotype associations: - Clinical phenotypes associated with the gene (HPO terms where known) - TOP 30 phenotype terms with HPO IDs Complex-disease / GWAS: - Traits and diseases significantly associated via GWAS: trait name, variant, effect size, study where known - TOP 30 GWAS associations
Executive summary
CCND1 (cyclin D1, HGNC:1582) encodes a core G1/S-phase cell cycle regulator that drives progression through the restriction point by forming active complexes with CDK4 and CDK6; its overexpression is a well-established oncogenic driver. Mapped to chromosome 11q13 (GRCh38: 69,641,143–69,654,474), the gene produces a reviewed canonical protein (UniProt P24385) with 11 experimental crystal and cryo-EM structures and a high-confidence AlphaFold model (global pLDDT 87.31). Its interaction network is exceptionally broad — over 7,500 STRING interactions — anchored by CDK4, CDK2, CDK6, CDKN1A, and RB1, and regulated by 141 upstream transcription factors including E2F1, TP53, NF-κB, and ESR1. Three FDA-approved CDK4/6 inhibitors (palbociclib, ribociclib, abemaciclib) directly target the CCND1–CDK4/6 axis, with over 300 molecules in development and hundreds of clinical trials, predominantly in HR+/HER2− breast cancer. GWAS data link the 11q13 locus to breast cancer risk (p = 4.0e-95) and multiple myeloma.
CCND1 — Reference
Cross-database identifier and functional mapping reference for CCND1.
Gene identifiers
| Identifier | Value |
|---|---|
| HGNC ID | HGNC:1582 |
| Approved symbol | CCND1 |
| Ensembl gene ID | ENSG00000110092 |
| Entrez Gene ID | 595 |
| OMIM ID | 168461 |
| Chromosome | 11 |
| Start position (GRCh38) | 69,641,143 |
| End position (GRCh38) | 69,654,474 |
| Strand | + |
Transcript identifiers
| Ensembl Transcript | Biotype |
|---|---|
| ENST00000227507 | protein_coding |
| ENST00000535993 | retained_intron |
| ENST00000536559 | protein_coding |
| ENST00000539241 | retained_intron |
| ENST00000542367 | retained_intron |
| ENST00000545484 | retained_intron |
| ENST00000913508 | protein_coding |
Total Ensembl transcripts: 7
| RefSeq mRNA | Status | MANE Select |
|---|---|---|
| NM_001379248 | VALIDATED | — |
| NM_007631 | VALIDATED | — |
| NM_053056 | REVIEWED | ✓ |
| NM_131025 | VALIDATED | — |
| NM_171992 | VALIDATED | — |
Total RefSeq mRNA: 5
CCDS ID: CCDS8191
Canonical/MANE Select Transcript: ENST00000913508
| Exon ID | Start | End | Coordinates |
|---|---|---|---|
| ENSE00004381384 | 69641143 | 69641511 | chr11:69641143-69641511 |
| ENSE00000737399 | 69643832 | 69643991 | chr11:69643832-69643991 |
| ENSE00000894874 | 69647994 | 69648142 | chr11:69647994-69648142 |
| ENSE00000894873 | 69651118 | 69654474 | chr11:69651118-69654474 |
Total exons: 4
Protein identifiers
UniProt Accessions (3 total)
- P24385 (reviewed - canonical entry) - G1/S-specific cyclin-D1
- F5H437 (unreviewed)
- Q6FI00 (unreviewed)
RefSeq Protein Accessions (NP_ - 5 total)
- NP_001366177
- NP_031657
- NP_444284 (REVIEWED/MANE select - canonical)
- NP_571100
- NP_741989
Protein Domains and Families
Annotated domains are found exclusively in the canonical reviewed UniProt entry (P24385):
InterPro domains/families:
| Name | Type | Identifier |
|---|---|---|
| Cyclin, C-terminal domain | Domain | IPR004367 |
| Cyclin, N-terminal | Domain | IPR006671 |
| Cyclin-like domain | Domain | IPR013763 |
| Cyclin-like superfamily | Homologous_superfamily | IPR036915 |
| Cyclin | Family | IPR039361 |
| Cyclins, cyclin-box | Conserved_site | IPR048258 |
Pfam domains:
| Identifier |
|---|
| PF00134 |
| PF02984 |
SMART domains:
| Identifier |
|---|
| SM00385 |
| SM01332 |
PANTHER:
| Identifier |
|---|
| PTHR10177 |
Antibody Availability
Biobtree antibody dataset chain: No direct entries found via >>uniprot>>antibody mapping.
Antibody resources via Human Protein Atlas (HPA): P24385 links to ENSG00000110092 in HPA, which provides antibody information and protein detection data. HPA is a primary resource for CCND1 antibodies and protein localization studies.
Structure
Experimental Structures (11 PDB entries)
X-ray Crystallography (10 entries):
- 2W96: 2.3 Å resolution
- 2W99: 2.8 Å resolution
- 2W9F: 2.85 Å resolution
- 2W9Z: 2.45 Å resolution
- 5VZU: 2.7 Å resolution
- 6P8E: 2.3 Å resolution
- 6P8F: 2.89 Å resolution
- 6P8G: 2.8 Å resolution
- 6P8H: 3.19 Å resolution
- 9CSK: 2.253 Å resolution
Cryo-EM (1 entry):
- 9IVD: 3.55 Å resolution
Total count: 11 experimental structures
Predicted Structures
AlphaFold:
- Model ID: P24385
- Global pLDDT: 87.31
- Fraction of residues with pLDDT ≥ 90: 0.73 (73%)
Cross-species orthologs
| Organism | Gene ID | Symbol |
|---|---|---|
| Mouse (Mus musculus) | 12443 | Ccnd1 |
| Rat (Rattus norvegicus) | 58919 | Ccnd1 |
| Zebrafish (Danio rerio) | 30222 | ccnd1 |
| Fruit fly (Drosophila melanogaster) | 32551 | CycD |
| Worm (C. elegans) | 171993 | cyb-2.2 |
| Yeast (S. cerevisiae) | none | none |
Clinical variants & AI predictions
ClinVar Summary
| Classification | Count |
|---|---|
| Benign | 7 |
| Likely benign | 7 |
| Uncertain significance | 19 |
| Likely pathogenic | 1 |
| Unclassified/no assertion | 16 |
| Total | 50 |
TOP Pathogenic/Likely Pathogenic Variants (ClinVar)
| Variant ID | HGVS | Classification | Condition |
|---|---|---|---|
| 442080 | GRCh37/hg19 11q13.2-13.4(chr11:67799160-70701268)x1 | Likely pathogenic | Copy number loss |
Note: Only 1 likely pathogenic variant in ClinVar for CCND1. Remaining 49 variants are benign, likely benign, VUS, or unclassified.
AlphaMissense Missense Predictions
Total likely_pathogenic predictions: 100
TOP 30 High-Confidence Pathogenic Missense Variants (sorted by am_pathogenicity score)
| Position | Variant | Protein Change | am_pathogenicity | am_class |
|---|---|---|---|---|
| 11:69641443 | T:G | Y44D | 0.994 | likely_pathogenic |
| 11:69641443 | T:C | Y44H | 0.992 | likely_pathogenic |
| 11:69641360 | C:A | A16E | 0.992 | likely_pathogenic |
| 11:69641408 | T:C | L32P | 0.981 | likely_pathogenic |
| 11:69641356 | C:A | R15S | 0.979 | likely_pathogenic |
| 11:69641368 | G:C | D19H | 0.975 | likely_pathogenic |
| 11:69641334 | C:G | C7W | 0.973 | likely_pathogenic |
| 11:69641416 | G:A | E35K | 0.969 | likely_pathogenic |
| 11:69641378 | T:C | L22P | 0.966 | likely_pathogenic |
| 11:69641396 | T:C | L28P | 0.966 | likely_pathogenic |
| 11:69641418 | G:C | E35D | 0.956 | likely_pathogenic |
| 11:69641418 | G:T | E35D | 0.956 | likely_pathogenic |
| 11:69641359 | G:C | A16P | 0.954 | likely_pathogenic |
| 11:69641444 | A:G | Y44C | 0.954 | likely_pathogenic |
| 11:69641360 | C:T | A16V | 0.958 | likely_pathogenic |
| 11:69641333 | G:A | C7Y | 0.955 | likely_pathogenic |
| 11:69641368 | G:A | D19N | 0.946 | likely_pathogenic |
| 11:69641369 | A:G | D19G | 0.945 | likely_pathogenic |
| 11:69641456 | T:A | V48E | 0.945 | likely_pathogenic |
| 11:69641368 | G:T | D19Y | 0.964 | likely_pathogenic |
| 11:69641369 | A:T | D19V | 0.949 | likely_pathogenic |
| 11:69641338 | G:A | E9K | 0.949 | likely_pathogenic |
| 11:69641332 | T:A | C7S | 0.959 | likely_pathogenic |
| 11:69641333 | G:C | C7S | 0.959 | likely_pathogenic |
| 11:69641357 | G:C | R15P | 0.959 | likely_pathogenic |
| 11:69641392 | G:A | V27M | 0.779 | likely_pathogenic |
| 11:69641370 | T:A | D19E | 0.929 | likely_pathogenic |
| 11:69641370 | T:G | D19E | 0.929 | likely_pathogenic |
| 11:69641413 | G:C | A34P | 0.925 | likely_pathogenic |
| 11:69641359 | G:A | A16T | 0.924 | likely_pathogenic |
SpliceAI Splice Effect Predictions
Total variants: 854
TOP Splice-Affecting Variants (sample of high-confidence predictions from available data)
| Position | Variant | Gene | Effect Type | Delta Score |
|---|---|---|---|---|
| 11:69641513 | T:A | CCND1 | donor_loss | 0.9900 |
| 11:69641510 | AGG:A | CCND1 | donor_loss | 0.9900 |
| 11:69641511 | GGTGC:G | CCND1 | donor_loss | 0.9900 |
| 11:69641512 | GTGCG:G | CCND1 | donor_loss | 0.9900 |
| 11:69641508 | GGAGG:G | CCND1 | donor_loss | 0.9900 |
| 11:69641509 | G:GT | CCND1 | donor_gain | 1.0000 |
| 11:69641464 | G:GT | CCND1 | donor_gain | 1.0000 |
| 11:69641509 | G:T | CCND1 | donor_gain | 0.9400 |
| 11:69641484 | G:GT | CCND1 | donor_gain | 0.9900 |
| 11:69641502 | G:GT | CCND1 | donor_gain | 0.9600 |
| 11:69641508 | GGAG:G | CCND1 | donor_gain | 0.9400 |
| 11:69641509 | GAG:G | CCND1 | donor_gain | 0.9300 |
| 11:69641535 | T:TG | CCND1 | donor_gain | 0.9600 |
| 11:69641535 | T:G | CCND1 | donor_gain | 0.9500 |
| 11:69641672 | T:TG | CCND1 | donor_gain | 0.8200 |
| 11:69641673 | T:G | CCND1 | donor_gain | 0.7800 |
| 11:69641512 | G:GG | CCND1 | donor_gain | 0.7800 |
| 11:69641300 | G:GT | CCND1 | donor_gain | 0.7400 |
| 11:69641525 | G:GT | CCND1 | donor_gain | 0.7500 |
| 11:69641667 | G:A | CCND1 | donor_gain | 0.6600 |
| 11:69641226 | T:TA | CCND1 | donor_gain | 0.6200 |
| 11:69641282 | G:GT | CCND1 | donor_gain | 0.6000 |
| 11:69641105 | G:T | CCND1 | donor_gain | 0.6000 |
| 11:69641640 | G:T | CCND1 | donor_gain | 0.5900 |
| 11:69641579 | C:G | CCND1 | donor_gain | 0.5800 |
| 11:69641118 | T:TA | CCND1 | donor_gain | 0.5700 |
| 11:69641119 | A:AA | CCND1 | donor_gain | 0.5700 |
| 11:69641682 | G:GT | CCND1 | donor_gain | 0.5600 |
| 11:69641953 | GCC:G | CCND1 | donor_gain | 0.5600 |
| 11:69641685 | G:GT | CCND1 | donor_gain | 0.5300 |
Pathways & Gene Ontology
Reactome Pathways
| ID | Pathway Name |
|---|---|
| R-HSA-187577 | SCF(Skp2)-mediated degradation of p27/p21 |
| R-HSA-1912408 | Pre-NOTCH Transcription and Translation |
| R-HSA-3214858 | RMTs methylate histone arginines |
| R-HSA-6785807 | Interleukin-4 and Interleukin-13 signaling |
| R-HSA-69231 | Cyclin D associated events in G1 |
| R-HSA-75815 | Ubiquitin-dependent degradation of Cyclin D |
| R-HSA-8849470 | PTK6 Regulates Cell Cycle |
| R-HSA-8853884 | Transcriptional Regulation by VENTX |
| R-HSA-8878166 | Transcriptional regulation by RUNX2 |
| R-HSA-8934593 | Regulation of RUNX1 Expression and Activity |
| R-HSA-8951430 | RUNX3 regulates WNT signaling |
| R-HSA-8951936 | RUNX3 regulates p14-ARF |
| R-HSA-9018519 | Estrogen-dependent gene expression |
| R-HSA-9634638 | Estrogen-dependent nuclear events downstream of ESR-membrane signaling |
| R-HSA-9661069 | Defective binding of RB1 mutants to E2F1,(E2F2, E2F3) |
| R-HSA-9754119 | Drug-mediated inhibition of CDK4/CDK6 activity |
| R-HSA-9825892 | Regulation of MITF-M-dependent genes involved in cell cycle and proliferation |
| R-HSA-9929491 | SPOP-mediated proteasomal degradation of PD-L1(CD274) |
Total Reactome pathways: 18
MSigDB Gene Sets
Total MSigDB gene sets: 100
Gene Ontology Annotations
Biological Process (41 terms)
| Rank | GO ID | Term |
|---|---|---|
| 1 | GO:0000082 | G1/S transition of mitotic cell cycle |
| 2 | GO:0000122 | Negative regulation of transcription by RNA polymerase II |
| 3 | GO:0000320 | Re-entry into mitotic cell cycle |
| 4 | GO:0001889 | Liver development |
| 5 | GO:0006974 | DNA damage response |
| 6 | GO:0007595 | Lactation |
| 7 | GO:0008283 | Cell population proliferation |
| 8 | GO:0008284 | Positive regulation of cell population proliferation |
| 9 | GO:0009410 | Response to xenobiotic stimulus |
| 10 | GO:0010039 | Response to iron ion |
| 11 | GO:0010165 | Response to X-ray |
| 12 | GO:0010971 | Positive regulation of G2/M transition of mitotic cell cycle |
| 13 | GO:0016055 | Wnt signaling pathway |
| 14 | GO:0030182 | Neuron differentiation |
| 15 | GO:0030857 | Negative regulation of epithelial cell differentiation |
| 16 | GO:0030968 | Endoplasmic reticulum unfolded protein response |
| 17 | GO:0031100 | Animal organ regeneration |
| 18 | GO:0031571 | Mitotic G1 DNA damage checkpoint signaling |
| 19 | GO:0032026 | Response to magnesium ion |
| 20 | GO:0032355 | Response to estradiol |
Molecular Function (12 terms)
| Rank | GO ID | Term |
|---|---|---|
| 1 | GO:0003714 | Transcription corepressor activity |
| 2 | GO:0004672 | Protein kinase activity |
| 3 | GO:0005515 | Protein binding |
| 4 | GO:0016301 | Kinase activity |
| 5 | GO:0016538 | Cyclin-dependent protein serine/threonine kinase regulator activity |
| 6 | GO:0019899 | Enzyme binding |
| 7 | GO:0019901 | Protein kinase binding |
| 8 | GO:0042826 | Histone deacetylase binding |
| 9 | GO:0043539 | Protein serine/threonine kinase activator activity |
| 10 | GO:0044877 | Protein-containing complex binding |
| 11 | GO:0061575 | Cyclin-dependent protein serine/threonine kinase activator activity |
| 12 | GO:0070064 | Proline-rich region binding |
Cellular Component (12 terms)
| Rank | GO ID | Term |
|---|---|---|
| 1 | GO:0000307 | Cyclin-dependent protein kinase holoenzyme complex |
| 2 | GO:0005634 | Nucleus |
| 3 | GO:0005654 | Nucleoplasm |
| 4 | GO:0005737 | Cytoplasm |
| 5 | GO:0005815 | Microtubule organizing center |
| 6 | GO:0005829 | Cytosol |
| 7 | GO:0005923 | Bicellular tight junction |
| 8 | GO:0016020 | Membrane |
| 9 | GO:0017053 | Transcription repressor complex |
| 10 | GO:0031965 | Nuclear membrane |
| 11 | GO:0097128 | Cyclin D1-CDK4 complex |
| 12 | GO:0097131 | Cyclin D1-CDK6 complex |
Protein interactions & networks
Protein-Protein Interactions (STRING, IntAct, BioGRID)
Total interaction count (approximate):
- STRING: 7,562 interactions
- BioGRID: 567 interactions
- IntAct: 196 interactions
TOP 30 highest-confidence interacting proteins:
| Rank | UniProt ID | Protein | STRING Score | IntAct Confidence |
|---|---|---|---|---|
| 1 | P11802 | CDK4 (Cyclin-dependent kinase 4) | 999 | 0.990 |
| 2 | P24941 | CDK2 (Cyclin-dependent kinase 2) | 998 | 0.880 |
| 3 | Q00534 | CDK6 (Cyclin-dependent kinase 6) | 998 | 0.880 |
| 4 | P38936 | CDKN1A (CDK inhibitor 1) | 996 | 0.960 |
| 5 | P46527 | CDKN1B (CDK inhibitor 1B) | 992 | 0.910 |
| 6 | P06493 | CDK1 (Cyclin-dependent kinase 1) | 984 | 0.640 |
| 7 | P03372 | ESR1 (Estrogen receptor) | 972 | N/A |
| 8 | P10415 | BCL2 (Apoptosis regulator Bcl-2) | 958 | N/A |
| 9 | P01106 | MYC (Myc proto-oncogene) | 951 | N/A |
| 10 | Q96S94 | CCNL2 (Cyclin-L2) | 950 | N/A |
| 11 | P42771 | CDKN2A (CDK inhibitor 2A) | 947 | N/A |
| 12 | P04637 | TP53 (Tumor antigen p53) | 928 | N/A |
| 13 | P35222 | CTNNB1 (Catenin beta-1) | 926 | N/A |
| 14 | P31749 | AKT1 (RAC-alpha serine/threonine kinase) | 919 | N/A |
| 15 | P0DP08 | IGHV4-38-2 (Immunoglobulin heavy variable) | 909 | N/A |
| 16 | P40763 | STAT3 (Signal transducer and activator of transcription 3) | 899 | N/A |
| 17 | Q00987 | MDM2 (E3 ubiquitin-protein ligase) | 898 | N/A |
| 18 | P11142 | HSPA8 (Heat shock cognate 71 kDa protein) | 891 | N/A |
| 19 | Q01094 | E2F1 (Transcription factor E2F1) | 877 | N/A |
| 20 | P15056 | BRAF (Serine/threonine-protein kinase B-raf) | 864 | N/A |
| 21 | P04626 | ERBB2 (Receptor tyrosine-protein kinase) | 863 | N/A |
| 22 | Q9UJU2 | LEF1 (Lymphoid enhancer-binding factor 1) | 862 | N/A |
| 23 | P60484 | PTEN (Phosphatase and dual-specificity protein phosphatase) | 851 | N/A |
| 24 | P38398 | BRCA1 (Breast cancer type 1 susceptibility protein) | 848 | 0.460 |
| 25 | Q92831 | KAT2B (Histone acetyltransferase) | 848 | N/A |
| 26 | P42574 | CASP3 (Caspase-3) | 845 | N/A |
| 27 | P55211 | CASP9 (Caspase-9) | 842 | N/A |
| 28 | P06400 | RB1 (Retinoblastoma-associated protein) | 831 | 0.730 |
| 29 | P10275 | AR (Androgen receptor) | 831 | 0.540 |
| 30 | Q07820 | MCL1 (Induced myeloid leukemia cell differentiation protein) | 829 | N/A |
Common experimental evidence (BioGRID): Affinity Capture-Western, Two-hybrid, Affinity Capture-MS, Co-localization, Biochemical Activity, Reconstituted Complex, Affinity Capture-RNA
Protein Similarity
Structural/embedding similarity (ESM2 - top 20 with scores):
| Rank | UniProt ID | Protein Name | Top Similarity | Avg Similarity |
|---|---|---|---|---|
| 1 | P50756 | G1/S-specific cyclin-D1 (paralog) | 1.0000 | 0.9802 |
| 2 | Q91780 | G1/S-specific cyclin-D1 (paralog) | 1.0000 | 0.9801 |
| 3 | Q04827 | G1/S-specific cyclin | 0.9999 | 0.9810 |
| 4 | P25322 | G1/S-specific cyclin-D2 | 0.9999 | 0.9817 |
| 5 | P30280 | G1/S-specific cyclin-D2 | 0.9999 | 0.9814 |
| 6 | P39948 | G1/S-specific cyclin-E1 | 0.9999 | 0.9817 |
| 7 | Q5R5D0 | Cyclin-D related protein | 0.9999 | 0.9722 |
| 8 | Q5R6J5 | G1/S-specific cyclin-D1 | 0.9999 | 0.9818 |
| 9 | Q0P5D3 | Cyclin-D homolog | 0.9997 | 0.9806 |
| 10 | Q2KI22 | Cyclin-D protein | 0.9997 | 0.9817 |
| 11 | P30281 | CCND3 (G1/S-specific cyclin-D3) | 0.9995 | 0.9694 |
| 12 | P30282 | G1/S-specific cyclin-D variant | 0.9994 | 0.9700 |
| 13 | Q5E9K7 | Cyclin-E homolog | 0.9996 | 0.9774 |
| 14 | Q3MHH5 | Cyclin-D related protein | 0.9995 | 0.9666 |
| 15 | Q52QT8 | Cyclin protein | 0.9995 | 0.9717 |
| 16 | P39950 | Cyclin-E variant | 0.9996 | 0.9735 |
| 17 | P51945 | Cyclin-related protein | 0.9996 | 0.9742 |
| 18 | O96020 | CCNE2 (G1/S-specific cyclin-E2) | 0.9996 | 0.9767 |
| 19 | O42575 | Cyclin-D homolog | 0.9993 | 0.9812 |
| 20 | P53782 | Cyclin-related protein | 0.9987 | 0.9811 |
Sequence homology (DIAMOND - top 20 with identity % and bitscore):
| Rank | UniProt ID | Protein Name | Identity % | Bitscore |
|---|---|---|---|---|
| 1 | Q91780 | G1/S-specific cyclin-D1 | 99.80% | 825 |
| 2 | P50756 | G1/S-specific cyclin-D1 | 99.80% | 825 |
| 3 | O96020 | CCNE2 (Cyclin-E2) | 95.00% | 769 |
| 4 | Q5E9K7 | Cyclin-E homolog | 95.00% | 771 |
| 5 | O42575 | Cyclin-D homolog | 91.40% | 761 |
| 6 | P25322 | CCND2 (Cyclin-D2) | 99.00% | 583 |
| 7 | P39948 | CCNE1 (Cyclin-E1) | 99.00% | 583 |
| 8 | P24385 | CCND1 (self) | 99.30% | 565 |
| 9 | P39949 | Cyclin-E variant | 99.10% | 566 |
| 10 | P47794 | Cyclin protein | 64.60% | 493 |
| 11 | P30280 | CCND2 (Cyclin-D2) | 98.30% | 572 |
| 12 | P55169 | Cyclin-related protein | 86.80% | 502 |
| 13 | P49706 | Cyclin homolog | 91.40% | 540 |
| 14 | P30281 | CCND3 (Cyclin-D3) | 97.90% | 561 |
| 15 | P48961 | Cyclin-D variant | 98.30% | 557 |
| 16 | P50755 | Cyclin protein | 84.80% | 480 |
| 17 | Q3MHH5 | Cyclin-D related protein | 97.90% | 561 |
| 18 | Q2KI22 | Cyclin-D protein | 95.90% | 548 |
| 19 | Q64HP0 | Cyclin-D homolog | 95.90% | 548 |
| 20 | Q14094 | CCNI (Cyclin-I) | 93.90% | 706 |
Transcription factor regulatory data
CCND1 is not a transcription factor. It encodes cyclin D1, a cell cycle regulatory protein. Therefore, downstream targets and DNA binding motif sections are not applicable.
Upstream regulators (transcription factors regulating CCND1)
Total regulators: 141 transcription factors (from CollecTRI database)
Top regulators with high-confidence evidence:
| Transcription Factor | Regulation Type | Evidence |
|---|---|---|
| E2F1 | Activation | High (ChIP-seq) |
| TP53 | Repression | High (ChIP-seq) |
| JUN | Activation | High (ChIP-seq) |
| JUND | Activation | High (ChIP-seq) |
| NFKB1 | Activation | High (ChIP-seq) |
| NFKB | Activation | High (ChIP-seq) |
| RELA | Activation | High (ChIP-seq) |
| RELB | Activation | High (ChIP-seq) |
| AP1 | Activation | High (ChIP-seq) |
| EGR1 | Activation | High (ChIP-seq) |
| ESR1 | Activation | High (ChIP-seq) |
| ETS1 | Activation | High (ChIP-seq) |
| ETS2 | Activation | High (ChIP-seq) |
| EWSR1 | Activation | High (ChIP-seq) |
| FLI1 | Activation | High (ChIP-seq) |
| FOSB | Activation | High (ChIP-seq) |
| IRF1 | Activation | High (ChIP-seq) |
| KLF4 | Activation | High (ChIP-seq) |
| KLF5 | Activation | High (ChIP-seq) |
| NCOA3 | Activation | High (ChIP-seq) |
| NR4A1 | Activation | High (ChIP-seq) |
| NR4A3 | Activation | High (ChIP-seq) |
| NR2C2 | Activation | High (ChIP-seq) |
| SP1 | Activation | High (ChIP-seq) |
| STAT3 | Activation | High (ChIP-seq) |
| TAF1 | Activation | High (ChIP-seq) |
| ZIC1 | Activation | High (ChIP-seq) |
| CTNNB1 | Activation | High (ChIP-seq) |
| BHLHE41 | Repression | High (ChIP-seq) |
| CDX1 | Repression | High (ChIP-seq) |
| CDX2 | Repression | High (ChIP-seq) |
| ESR2 | Repression | High (ChIP-seq) |
| ELK3 | Repression | High (ChIP-seq) |
| FOXO1 | Repression | High (ChIP-seq) |
| FOS | Repression | High (ChIP-seq) |
| HBP1 | Repression | High (ChIP-seq) |
| HIF1A | Repression | High (ChIP-seq) |
| HOXB13 | Repression | High (ChIP-seq) |
| HTATIP2 | Repression | High (ChIP-seq) |
| ID1 | Repression | High (ChIP-seq) |
| PPARG | Repression | High (ChIP-seq) |
| SOX6 | Repression | High (ChIP-seq) |
| SOX9 | Repression | High (ChIP-seq) |
Additional regulators (141 total): Include ATF2, ATF4, BCL3, EGR1, ENO1, E2F4, FOXA1, FOXM1, GATA3, GLI1, ISL1, MEIS1, MYBL2, NFATC1, NFIC, NFKB2, NR0B2, NR2F2, NR3C1, POU2F1, POU5F1, SIX1, SOX17, SP2, SP3, SP4, STAT1, STAT5A, STAT5B, TCF7, TCF7L2, and others with varying confidence levels (High/Low/Moderate).
Drug & pharmacology data
CCND1 is a well-established drug target, particularly as part of the CDK4/6 complex central to cell cycle regulation. Drug development for CCND1 predominantly focuses on CDK4/6 inhibitors used in cancer therapy.
Targeting Molecules Summary
Total count: ~300+ molecules in ChEMBL targeting CDK4/cyclin D1 and CDK6/cyclin D complexes across all development phases.
TOP 30 MOLECULES BY DEVELOPMENT PHASE
Phase 4 (FDA Approved - 3 drugs):
- CHEMBL189963 | PALBOCICLIB (Ibrance) | CDK4/6 inhibitor | Phase 4
- CHEMBL3545110 | RIBOCICLIB (Kisqali) | CDK4/6 inhibitor | Phase 4
- CHEMBL3301610 | ABEMACICLIB (Verzenio) | CDK4/6 inhibitor | Phase 4
Phase 2 (12 drugs): 4. CHEMBL14762 | SELICICLIB | CDK inhibitor (CDK2, CDK4, CDK6) | Phase 2 5. CHEMBL3115681 | NARAZACICLIB | CDK4/6 inhibitor | Phase 2 6. CHEMBL4446357 | EBVACICLIB | CDK4/6 inhibitor | Phase 2 7. CHEMBL5095060 | ECIRUCICLIB | CDK4/6 inhibitor | Phase 2 8. CHEMBL5095094 | CULMERCICLIB | CDK4/6 inhibitor | Phase 2 9. CHEMBL5199065 | ISTISOCICLIB | CDK4/6 inhibitor | Phase 2 10. CHEMBL5201870 | TEGTOCICLIB | CDK4/6 inhibitor | Phase 2 11. CHEMBL1276127 | INDIRUBIN | CDK inhibitor | Phase 2 12. CHEMBL1738757 | REBASTINIB | Multi-kinase inhibitor (includes CDK) | Phase 2 13-30. Additional phase 2 candidates with limited data
Phase 1 (2 drugs):
- CHEMBL1230607 | PHA-793887 | CDK4/6 inhibitor | Phase 1
- CHEMBL296468 | BMS-387032 | CDK inhibitor | Phase 1
Clinical Trials: TOP 20 TRIALS
PALBOCICLIB (304 total trials):
- NCT02679755 | Palbociclib + Letrozole for HR+/HER2- breast cancer | Phase 4 | COMPLETED
- NCT01740427 | PALOMA-2: Palbociclib + Letrozole vs. Letrozole | Phase 3 | COMPLETED
- NCT01942135 | PALOMA-3: Palbociclib + Fulvestrant | Phase 3 | COMPLETED
- NCT02028507 | Palbociclib vs. Capecitabine in AI-resistant breast cancer | Phase 3 | COMPLETED
- NCT02297438 | PALOMA-4: Asian postmenopausal women with HR+/HER2- breast cancer | Phase 3 | COMPLETED
- NCT04862663 | Capivasertib + CDK4/6i + Fulvestrant (CAPItello-292) | Phase 3 | RECRUITING
- NCT06065748 | Giredestrant vs. Fulvestrant + CDK4/6i | Phase 3 | RECRUITING
- NCT04546009 | Giredestrant + Palbociclib vs. Letrozole + Palbociclib | Phase 3 | ACTIVE_NOT_RECRUITING
- NCT05909397 | Vepdegestrant + Palbociclib vs. Letrozole + Palbociclib | Phase 3 | ACTIVE_NOT_RECRUITING
- NCT06377852 | CDK4/6 Inhibitor Dosing Knowledge (CDK) Study | Phase 3 | RECRUITING
RIBOCICLIB (161 total trials): 11. NCT01958021 | LEE011 in postmenopausal women with advanced breast cancer | Phase 3 | COMPLETED 12. NCT02278120 | LEE011 in premenopausal women with HR+/HER2- breast cancer | Phase 3 | COMPLETED 13. NCT02422615 | LEE011 in men and postmenopausal women with advanced breast cancer | Phase 3 | COMPLETED 14. NCT02941926 | Ribociclib + Letrozole for HR+ HER2- advanced breast cancer | Phase 3 | COMPLETED 15. NCT03701334 | Ribociclib adjuvant with endocrine therapy in early breast cancer | Phase 3 | ACTIVE_NOT_RECRUITING 16. NCT05827081 | Ribociclib + ET in early breast cancer | Phase 3 | RECRUITING 17. NCT07085767 | Palazestrant + Ribociclib for first-line ER+/HER2- breast cancer | Phase 3 | RECRUITING 18. NCT04964934 | AZD9833 + CDK4/6i in HR+/HER2- breast cancer with ESR1m | Phase 3 | ACTIVE_NOT_RECRUITING
ABEMACICLIB (208 total trials): 19. NCT02107703 | Abemaciclib + Fulvestrant in HR+/HER2- breast cancer | Phase 3 | ACTIVE_NOT_RECRUITING 20. NCT02246621 | Aromatase inhibitors + Abemaciclib in postmenopausal women | Phase 3 | ACTIVE_NOT_RECRUITING
Pharmacogenomics
Known CCND1 associations:
- CCND1 is classified as a VIP (Very Important Pharmacogene) in PharmGKB with documented variant annotations
- CCND1 amplification/overexpression is a known biomarker for CDK4/6 inhibitor sensitivity; tumors with CCND1 amplification or high expression show improved response to CDK4/6 inhibitors
- CCND1 variants and copy number alterations affect response to non-CDK4/6 drugs: cetuximab, pemetrexed, lapatinib, and panitumumab show pharmacogenetic associations with CCND1 status
Drug-specific guidance:
- No formal dosing adjustments based on CCND1 genotype for CDK4/6 inhibitors currently in clinical guidelines
- CCND1 status is sometimes assessed as a predictive biomarker for patient stratification in clinical trials, but routine testing is not standard practice
- CDK4/6 inhibitors (palbociclib, ribociclib, abemaciclib) are approved based on clinical benefit across HR+ breast cancer populations regardless of CCND1 status
Expression profiles
Tissue Expression (Bgee — Human)
| Rank | Tissue/Anatomical Structure | Expression Score | Quality |
|---|---|---|---|
| 1 | Endometrium epithelium | 99.09 | Gold |
| 2 | Stromal cell of endometrium | 98.30 | Gold |
| 3 | Upper arm skin | 97.20 | Gold |
| 4 | Esophagus squamous epithelium | 97.00 | Gold |
| 5 | Upper leg skin | 96.62 | Gold |
| 6 | Mucosa of paranasal sinus | 96.57 | Gold |
| 7 | Sural nerve | 96.44 | Gold |
| 8 | Epithelium of esophagus | 96.30 | Gold |
| 9 | Squamous epithelium | 96.19 | Gold |
| 10 | Gingival epithelium | 96.07 | Gold |
| 11 | Nipple | 96.05 | Gold |
| 12 | Lower esophagus mucosa | 95.92 | Gold |
| 13 | Tibia | 95.86 | Gold |
| 14 | Esophagus mucosa | 95.42 | Gold |
| 15 | Gingiva | 95.38 | Gold |
| 16 | Hair follicle | 95.36 | Gold |
| 17 | Skin of abdomen | 95.32 | Gold |
| 18 | Palpebral conjunctiva | 95.04 | Gold |
| 19 | Zone of skin | 94.77 | Gold |
| 20 | Right coronary artery | 94.72 | Gold |
| 21 | Oral cavity | 94.50 | Gold |
| 22 | Skin of leg | 94.45 | Gold |
| 23 | Cervix squamous epithelium | 94.37 | Silver |
| 24 | Penis | 94.28 | Gold |
| 25 | Caput epididymis | 94.01 | Gold |
| 26 | Skin of hip | 93.86 | Gold |
| 27 | Apex of heart | 93.80 | Gold |
| 28 | Prostate gland | 93.65 | Gold |
| 29 | Mammalian vulva | 93.57 | Gold |
| 30 | Ascending aorta | 93.56 | Gold |
Expression breadth: Ubiquitous (280/295 conditions present across tissues and cell types; 270 gold quality calls)
Average expression score: 84.04 (scale 0–100)
Pattern: CCND1 shows highest expression in rapidly dividing epithelial tissues (endometrium, skin, esophageal and oral epithelium, hair follicles, nail bed tissues). Strong presence in tissues with high cell turnover rates, consistent with its role as a cell cycle regulator (G1/S phase progression).
Single-Cell Expression (SCXA Datasets)
19 datasets contain CCND1 expression across diverse human tissues and conditions:
- E-MTAB-10287 — Endometrial tissue (full depth + superficial; 340,047 cells)
- E-CURD-53 — SARS-CoV-1/2 infected cell lines (187,349 cells)
- E-CURD-79 — Thymic development T cell repertoire (152,320 cells)
- E-MTAB-8894 — Fetal lateral ganglionic eminence (neural development; 150,129 cells)
- E-MTAB-8495 — Biliary tree (160,459 cells)
- E-MTAB-6308 — Lung tumor endothelial heterogeneity (113,132 cells)
- E-CURD-120 — Ankylosing spondylitis lymphocytes; peripheral blood & synovial fluid (62,428 cells)
- E-MTAB-9435 — IDHwt glioblastoma patient tumors (62,867 cells)
- E-MTAB-9689 — RPE1-MYCN-ER cells; MYCN activation timecourse (10,476 cells)
- E-CURD-53 — Pancreatic tissue (2,544 cells)
- E-GEOD-125970 — Human intestine; differential nutrient absorption (23,809 cells)
- E-MTAB-10485 — Brain development neural progenitors (18,649 cells)
- E-HCAD-38 — Proximal epididymis cell types and CFTR function (17,692 cells)
- E-GEOD-124858 — Bone marrow stromal cell subpopulations (247 cells)
- E-MTAB-6524 — Induced pluripotent stem cells (iPSCs; 10,926 cells)
- E-MTAB-8530 — Disseminated tumor cells from lung adenocarcinoma (9,812 cells)
- E-ENAD-20 — Patient-derived xenograft; BRAF/MEK inhibitor response (674 cells)
- E-GEOD-75140 — Cerebral organoid neocortex development (734 cells)
- E-GEOD-109979 — H9 cell definitive endoderm differentiation (329 cells)
Notable populations: CCND1 is highly expressed in proliferating stem/progenitor cells and differentiating epithelial cell populations, reflecting its cell cycle-regulatory function.
Disease associations
Mendelian/Monogenic Diseases
| Disease | Disease ID | Type | Inheritance | Evidence |
|---|---|---|---|---|
| Von Hippel-Lindau disease | Orphanet: 892, MONDO: 0008667 | Monogenic | Autosomal dominant | Supportive |
| Romano-Ward syndrome (Long QT syndrome) | Orphanet: 101016, MONDO: 0019171 | Monogenic | Autosomal dominant | Supportive |
Phenotype Associations (Top 30 HPO Terms)
| HPO ID | Phenotype | Context |
|---|---|---|
| HP:0000006 | Autosomal dominant inheritance | Inheritance pattern |
| HP:0000014 | Abnormality of the bladder | Von Hippel-Lindau |
| HP:0000098 | Tall stature | General |
| HP:0000100 | Nephrotic syndrome | Kidney involvement |
| HP:0000112 | Nephropathy | Kidney involvement |
| HP:0000360 | Tinnitus | Von Hippel-Lindau |
| HP:0000407 | Sensorineural hearing impairment | Von Hippel-Lindau |
| HP:0000478 | Abnormality of the eye | Von Hippel-Lindau (very frequent) |
| HP:0000541 | Retinal detachment | Von Hippel-Lindau |
| HP:0000572 | Visual loss | Von Hippel-Lindau |
| HP:0000739 | Anxiety | Von Hippel-Lindau |
| HP:0000822 | Hypertension | Von Hippel-Lindau (frequent) |
| HP:0000938 | Osteopenia | General |
| HP:0000975 | Hyperhidrosis | Von Hippel-Lindau |
| HP:0000980 | Pallor | Von Hippel-Lindau |
| HP:0001085 | Papilledema | Von Hippel-Lindau |
| HP:0001095 | Hypertensive retinopathy | Von Hippel-Lindau |
| HP:0001279 | Syncope | Long QT syndrome (frequent) |
| HP:0001297 | Stroke | Von Hippel-Lindau |
| HP:0001442 | Somatic mosaicism | General |
| HP:0001638 | Cardiomyopathy | Von Hippel-Lindau |
| HP:0001645 | Sudden cardiac death | Long QT syndrome |
| HP:0001658 | Myocardial infarction | Von Hippel-Lindau |
| HP:0001688 | Sinus bradycardia | Long QT syndrome (frequent) |
| HP:0001737 | Pancreatic cysts | Von Hippel-Lindau |
| HP:0001744 | Splenomegaly | General |
| HP:0001824 | Weight loss | General |
| HP:0001901 | Polycythemia | Von Hippel-Lindau |
| HP:0001903 | Anemia | General |
| HP:0001919 | Acute kidney injury | Kidney involvement |
Complex Disease / GWAS Associations (Top 30)
| Trait | Gene Region | P-value | Study ID |
|---|---|---|---|
| Breast cancer | LINC01488 - PNCRNA-D | 4.0e-95 | GCST004988_532 |
| Breast cancer | LINC01488 - PNCRNA-D | 6.0e-47 | GCST004988_540 |
| Cutaneous malignant melanoma | LINC01488 - PNCRNA-D | 9.0e-21 | GCST010304_63 |
| Nevus count or cutaneous melanoma | LINC01488 - PNCRNA-D | 4.0e-18 | GCST010303_55 |
| Craniofacial microsomia | FGF3 - ANO1 | 4.0e-17 | GCST004412_6 |
| Breast cancer | LINC01488 | 2.0e-15 | GCST002346_17 |
| Breast cancer | LINC01488 - PNCRNA-D | 3.0e-15 | GCST000678_13 |
| Hip circumference adjusted for BMI | CCND1 | 7.0e-15 | GCST90020028_464 |
| Height | LINC02952 - LINC02747 | 1.0e-11 | GCST002702_41 |
| Birth weight | LINC01488 - PNCRNA-D | 9.0e-12 | GCST008362_29 |
| Cutaneous malignant melanoma | LINC01488 - PNCRNA-D | 2.0e-12 | GCST003061_6 |
| Melanoma | LINC01488 - PNCRNA-D | 2.0e-12 | GCST004142_21 |
| Type 2 diabetes | LINC01488 - PNCRNA-D | 5.0e-12 | GCST009379_270 |
| Blond vs brown/black hair color | LINC01488 - PNCRNA-D | 4.0e-13 | GCST006988_77 |
| Body fat distribution (arm fat ratio) | LTO1 | 5.0e-12 | GCST007293_89 |
| Multiple myeloma (IgH translocation) | CCND1 | 2.0e-11 | GCST001906_21 |
| Multiple myeloma (IgH translocation) | CCND1 | 8.0e-11 | GCST001906_1 |
| Immunoglobulin light chain (AL) amyloidosis | CCND1 | 8.0e-11 | GCST004028_5 |
| Total body bone mineral density | LINC01488 | 1.0e-08 | GCST005348_241 |
| Waist-hip index | LINC01488 - PNCRNA-D | 3.0e-08 | GCST012228_550 |
| Waist-to-hip ratio adjusted for BMI | LINC01488 - PNCRNA-D | 5.0e-08 | GCST012230_219 |
| Waist-to-hip ratio adjusted for BMI | CCND1 | 3.0e-08 | GCST90020025_1306 |
| Hip circumference | LINC02952 - LINC02747 | 8.0e-06 | GCST004066_105 |
| Breast size | MYEOV | 5.0e-06 | GCST001585_32 |
| Breast cancer (early onset) | LINC01488 - PNCRNA-D | 1.0e-08 | GCST002346_12 |
| Hip circumference | LINC02952 - LINC02747 | 4.0e-08 | GCST004066_6 |
| Adult body size | LINC01488 - PNCRNA-D | 8.0e-10 | GCST010988_516 |
| White blood cell count | CCND1 | 9.0e-10 | GCST90002407_104 |
| Hip index | CCND1 | 1.0e-09 | GCST90020026_51 |
| Breast size | MYEOV | 1.0e-09 | GCST003985_8 |