CYP2E1

Chr 10

cytochrome P450 family 2 subfamily E member 1

Also known as: CPE1, CYP2E, P450-J, P450C2E

NCBI Gene: 1571ENSG00000130649UniProt: P05181OMIM: 124040

This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and is induced by ethanol, the diabetic state, and starvation. The enzyme metabolizes both endogenous substrates, such as ethanol, acetone, and acetal, as well as exogenous substrates including benzene, carbon tetrachloride, ethylene glycol, and nitrosamines which are premutagens found in cigarette smoke. Due to its many substrates, this enzyme may be involved in such varied processes as gluconeogenesis, hepatic cirrhosis, diabetes, and cancer. [provided by RefSeq, Jul 2008]

OMIMResearchGenerating clinical summary…
MultiplemechanismLOEUF 1.17
Clinical Summary— CYP2E1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
47 VUS of 73 total submissions
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Clinical Trials
1 active or recruiting trial — 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
Tolerant — LoF & missense variants common in population
LoF Constraint?
1.17LOEUF
pLI 0.000
Z-score 1.00
OE 0.76 (0.51–1.17)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
0.88Z-score
OE missense 0.86 (0.77–0.95)
254 obs / 296.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.76 (0.51–1.17)
0≤0.351.4
Missense OE?0.86 (0.77–0.95)
0≤0.61.4
Synonymous OE?1.01
0≤1.21.6
LoF obs/exp: 15 / 19.8Missense obs/exp: 254 / 296.5Syn Z: -0.12

This gene — mechanism propensity

DN
0.79top 25%
GOF
0.6737th %ile
LOF
0.2484th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

73 submitted variants in ClinVar

ClinVar

Classification Summary

VUS47
Likely Benign10
Benign8
47
VUS
10
Likely Benign
8
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
0
0
0
0
0
VUS
0
47
0
0
47
Likely Benign
0
9
0
1
10
Benign
0
1
2
5
8
Total0572665

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

View in ClinVar →

98 pathogenic / likely-pathogenic (of 180) ClinVar copy-number / structural variants overlap CYP2E1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

CYP2E1 · 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