CCND1

Chr 11ADSomatic

cyclin D1

Also known as: BCL1, D11S287E, PRAD1, U21B31

NCBI Gene: 595 ENSG00000110092 UniProt: P24385 OMIM: 168461

CCND1 encodes cyclin D1, a regulatory protein that forms complexes with CDK4/CDK6 kinases to control cell cycle progression through the G1/S transition by phosphorylating retinoblastoma family proteins. Mutations cause autosomal dominant susceptibility to colorectal cancer and multiple myeloma, and can modify von Hippel-Lindau syndrome presentation. The gene is highly constrained against loss-of-function variants (pLI=0.89, LOEUF=0.41), reflecting its essential role in cell cycle regulation.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

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

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

740

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.41

LOEUF

—

Mechanism

📖

GeneReview available — CCND1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

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?

1.42Z-score

OE missense 0.70 (0.60–0.81)

122 obs / 174.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.09 (0.03–0.41)

0≤0.351.4

Missense OE?0.70 (0.60–0.81)

0≤0.61.4

Synonymous OE?1.16

0≤1.21.6

LoF obs/exp: 1 / 11.6Missense obs/exp: 122 / 174.9Syn Z: -1.12

Background carrier burden — how many people carry a rare variant somewhere in CCND1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 390

364 rare PASS variants

Rare truncating (LoF)

1 in 22,000

22 rare PASS variants

Rare synonymous (reference)

1 in 230

207 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CCND1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 420	1 in 15,000
South Asian	~43k	1 in 340	≈ 1 in 43,000
Remaining (unassigned)	~30k	1 in 300	≈ 1 in 30,000
European (Finnish)	~27k	1 in 1,900	≈ 1 in 26,000
Admixed American	~22k	1 in 440	≈ 1 in 22,000
African / African American	~21k	1 in 690	none seen
East Asian	~20k	1 in 180	none seen
Ashkenazi Jewish	~13k	1 in 1,800	none seen
Middle Eastern	~2,884	1 in 360	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 5 coding exons well covered in gnomAD exomes and genomes.? see exons ↓

ClinVar Variant Classifications

0 submitted variants in ClinVar

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.

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

📖

GeneReview available — CCND1

Authoritative clinical overview · NCBI Bookshelf · Recommended first read

Open GeneReview ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Head Neck CancerOral Cancer

Newer Therapeutic Targets in Head and Neck Cancers

RECRUITING

NCT05382585Banaras Hindu UniversityStarted 2017-04-01

Next generation Sequencing

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

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

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

Clinical Literature

Open Research Assistant →

Landmark / reviewRecent case evidence

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