CCNE1

Chr 19

cyclin E1

Also known as: CCNE, pCCNE1

NCBI Gene: 898 ENSG00000105173 UniProt: P24864 OMIM: 123837

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.

OMIM ResearchSummary from RefSeq, 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 through 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 CDK2, whose activity is required for cell cycle G1/S transition. This protein accumulates at the G1-S phase boundary and is degraded as cells progress through S phase. Overexpression of this gene has been observed in many tumors, which results in chromosome instability, and thus may contribute to tumorigenesis. This protein was found to associate with, and be involved in, the phosphorylation of NPAT protein (nuclear protein mapped to the ATM locus), which participates in cell-cycle regulated histone gene expression and plays a critical role in promoting cell-cycle progression in the absence of pRB. [provided by RefSeq, Apr 2016]

OMIM ResearchGenerating clinical summary…

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

227

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.32

LOEUF· LoF intol.

LOF

Mechanism· predicted

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 OE?0.12 (0.06–0.32)

0≤0.351.4

Missense OE?0.72 (0.63–0.82)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

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

Background carrier burden — how many people carry a rare variant somewhere in CCNE1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 180

458 rare PASS variants

Rare truncating (LoF)

1 in 4,300

35 rare PASS variants

Rare synonymous (reference)

1 in 430

189 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CCNE1. 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 140	1 in 5,100
South Asian	~43k	1 in 150	1 in 5,000
Remaining (unassigned)	~30k	1 in 180	≈ 1 in 30,000
European (Finnish)	~27k	1 in 470	none seen
Admixed American	~22k	1 in 160	≈ 1 in 22,000
African / African American	~21k	1 in 110	1 in 2,500
East Asian	~20k	1 in 220	none seen
Ashkenazi Jewish	~13k	1 in 1,200	none seen
Middle Eastern	~2,884	1 in 410	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): 10 of 11 coding exons well covered in gnomAD exomes; exon 7 marginal. Genomes: all 11.? see exons ↓