CCND1

Chr 11ADSomatic

cyclin D1

Also known as: BCL1, D11S287E, PRAD1, U21B31

NCBI Gene: 595ENSG00000110092UniProt: P24385

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]

Primary Disease Associations & Inheritance

{Colorectal cancer, susceptibility to}MIM #114500
ADSomatic
{Multiple myeloma, susceptibility to}MIM #254500
Somatic
{von Hippel-Lindau syndrome, modifier of}MIM #193300
AD
43
ClinVar variants
8
Pathogenic / LP
0.89
pLI score
6
Active trials
Clinical Summary— CCND1
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.89) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
8 Pathogenic / Likely Pathogenic· 21 VUS of 43 total submissions
💊
Clinical Trials
6 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.41LOEUF
pLI 0.891
Z-score 2.88
OE 0.09 (0.03–0.41)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.42Z-score
OE missense 0.70 (0.60–0.81)
122 obs / 174.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.09 (0.03–0.41)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.70 (0.60–0.81)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.16
0≤1.21.6
LoF obs/exp: 1 / 11.6Missense obs/exp: 122 / 174.9Syn Z: -1.12

ClinVar Variant Classifications

43 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6
Likely Pathogenic2
VUS21
Likely Benign7
Benign7
6
Pathogenic
2
Likely Pathogenic
21
VUS
7
Likely Benign
7
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
6
0
6
Likely Pathogenic
0
0
2
0
2
VUS
1
17
3
0
21
Likely Benign
0
1
2
4
7
Benign
0
0
5
2
7
Total11818643

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CCND1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
CYCLIN D1; CCND1
MIM #168461 · *

{Colorectal cancer, susceptibility to}

MIM #114500

Molecular basis of disorder known

Autosomal dominantSomatic mutation

{Multiple myeloma, susceptibility to}

MIM #254500

Molecular basis of disorder known

Somatic mutation

{von Hippel-Lindau syndrome, modifier of}

MIM #193300

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — CCND1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Molecular Pathogenesis of Mantle Cell Lymphoma.
Navarro A et al.·Hematol Oncol Clin North Am
2020Review
Integrated genomic characterization of oesophageal carcinoma.
Cancer Genome Atlas Research Network et al.·Nature
2017
Molecular Pathogenesis of Multiple Myeloma: Clinical Implications.
Maura F et al.·Hematol Oncol Clin North Am
2024Review
Chemotherapy-Induced Senescence Reprogramming Promotes Nasopharyngeal Carcinoma Metastasis by circRNA-Mediated PKR Activation.
Li Q et al.·Adv Sci (Weinh)
2023
Aberrant single-cell phenotype and clinical implications of genotypically defined polyclonal plasma cells in myeloma.
Da Vià MC et al.·Blood
2025
Comparison of BRCA versus non-BRCA germline mutations and associated somatic mutation profiles in patients with unselected breast cancer.
Chen B et al.·Aging (Albany NY)
2020Cohort
Double-hit B-cell lymphomas.
Aukema SM et al.·Blood
2011Review
A circRNA-mRNA pairing mechanism regulates tumor growth and endocrine therapy resistance in ER-positive breast cancer.
Yi J et al.·Proc Natl Acad Sci U S A
2025Functional
MET promotes hepatocellular carcinoma development through the promotion of TRIB3-mediated FOXO1 degradation.
Wang T et al.·Clin Mol Hepatol
2025
Identification of tumor-intrinsic drivers of immune exclusion in acral melanoma.
Augustin RC et al.·J Immunother Cancer
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Advanced LymphomaAdvanced Malignant Solid NeoplasmBladder Carcinoma

Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)

ACTIVE NOT RECRUITING
NCT02465060Phase PHASE2National Cancer Institute (NCI)Started 2015-08-17
AdavosertibAfatinibAfatinib Dimaleate
Head Neck CancerOral Cancer

Newer Therapeutic Targets in Head and Neck Cancers

RECRUITING
NCT05382585Banaras Hindu UniversityStarted 2017-04-01
Next generation Sequencing
Advanced Breast CancerMetastatic Breast Cancer

HCQ+ADC vs ADC in the Treatment of Advanced Breast Cancer

RECRUITING
NCT06328387Phase PHASE1, PHASE2Sun Yat-Sen Memorial Hospital of Sun Yat-Sen UniversityStarted 2024-01-29
HydroxychloroquineSacituzumab GovitecanTrastuzumab Deruxtecan
Cancer

Study of the CDK4/6 Inhibitor Abemaciclib in Solid Tumors Harboring Genetic Alterations in Genes Encoding D-Type Cyclins or Amplification of CDK4 or CDK6

RECRUITING
NCT03310879Phase PHASE2Dana-Farber Cancer InstituteStarted 2017-11-21
Abemaciclib
Solid TumorPrecision Medicine

Precision Medicine Trial Based on Molecular Matching Therapy for Patients With Standard Treatment Exhaustion

RECRUITING
NCT06739395Phase PHASE2Tianjin Medical University Second HospitalStarted 2024-11-01
Olaparib tabletTemozolomide capsuleAnlotinib
Lymphoma, Non-HodgkinMultiple MyelomaAdvanced Solid Tumors

Canadian Profiling and Targeted Agent Utilization Trial (CAPTUR)

RECRUITING
NCT03297606Phase PHASE2Canadian Cancer Trials GroupStarted 2018-03-23
OlaparibDasatinibNivolumab plus Ipilimumab

External Resources

Links to major genomics databases and tools