CCNE1

Chr 19

cyclin E1

Also known as: CCNE, pCCNE1

NCBI Gene: 898 ENSG00000105173 UniProt: P24864

Cyclin E1 is essential for cell cycle control at the G1/S transition, where it forms a complex with and regulates CDK2 kinase activity. Mutations cause autosomal dominant developmental delays, intellectual disability, and growth abnormalities. This gene is highly constrained against loss-of-function variants (pLI 0.97, LOEUF 0.32), indicating that haploinsufficiency is likely not tolerated in the general population.

Summary from RefSeq, UniProt

P/LP submissions

P/LP missense

0.32

LOEUF· LoF intol.

LOF

Mechanism· predicted

Clinical Summary— CCNE1

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.97). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

13 unique Pathogenic / Likely Pathogenic· 39 VUS of 76 total submissions

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Clinical Trials

5 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint

0.32LOEUF

pLI 0.972

Z-score 4.00

OE 0.12 (0.06–0.32)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint

1.53Z-score

OE missense 0.72 (0.63–0.82)

168 obs / 233.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios

LoF OE0.12 (0.06–0.32)

0≤0.351.4

Missense OE0.72 (0.63–0.82)

0≤0.61.4

Synonymous OE1.04

0≤1.21.6

LoF obs/exp: 3 / 24.3Missense obs/exp: 168 / 233.8Syn Z: -0.31

0.3793th %ile

GOF

0.3590th %ile

LOF

0.67top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.32

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

76 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10

Likely Pathogenic3

VUS39

Likely Benign5

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Total
Pathogenic	0	10	10
Likely Pathogenic	0	3	3
VUS	35	4	39
Likely Benign	5	0	5
Benign	0	0	0
Total	40	17	57

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

View in ClinVar →

Protein Context — Lollipop Plot

CCNE1 · 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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Recurrent Ovarian High Grade Serous AdenocarcinomaRecurrent Platinum-Resistant Ovarian Carcinoma

Testing the Addition of Abemaciclib to Olaparib for Women With Recurrent Ovarian Cancer

RECRUITING

NCT04633239Phase PHASE1National Cancer Institute (NCI)Started 2021-07-02

AbemaciclibBiopsy ProcedureBiospecimen Collection

Ovarian CancerPlatinum-resistant Ovarian CancerPrimary Peritoneal Carcinoma

A Study of ZN-c3 and Niraparib in Subjects With Platinum-Resistant Ovarian Cancer

ACTIVE NOT RECRUITING

NCT05198804Phase PHASE1, PHASE2K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, IncStarted 2022-01-27

ZN-c3Niraparib

Metastatic Colorectal AdenocarcinomaRefractory Colorectal AdenocarcinomaStage III Colorectal Cancer AJCC v8

Testing the Effectiveness of the Anti-cancer Drug Pidnarulex (CX-5461) in Combination With Another Anti-cancer Drug Cemiplimab (REGN2810), in Treating Refractory Microsatellite Stable Colorectal Cancer

NOT YET RECRUITING

NCT07147231Phase PHASE1, PHASE2National Cancer Institute (NCI)Started 2026-03-31

Biopsy ProcedureBiospecimen CollectionCemiplimab

Advanced Fallopian Tube CarcinomaAdvanced Malignant Solid NeoplasmAdvanced Ovarian Carcinoma

Testing the Addition of an Anti-cancer Drug, Elimusertib (BAY 1895344) ATR Inhibitor, to the Chemotherapy Treatment (Gemcitabine) for Advanced Pancreatic and Ovarian Cancer, and Advanced Solid Tumors

ACTIVE NOT RECRUITING

NCT04616534Phase PHASE1National Cancer Institute (NCI)Started 2021-06-01

Biopsy ProcedureBiospecimen CollectionDiagnostic Imaging Testing

Solid Tumors

Study of INCB123667 in Subjects With Advanced Solid Tumors

RECRUITING

NCT05238922Phase PHASE1Incyte CorporationStarted 2022-07-05

INCB0123667PalbociclibBevacizumab

Clinical Literature

Open Research Assistant →

Landmark / reviewRecent case evidence

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