CYP2E1

Chr 10

cytochrome P450 family 2 subfamily E member 1

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

NCBI Gene: 1571 ENSG00000130649 UniProt: P05181 OMIM: 124040

This gene encodes cytochrome P450 2E1, a monooxygenase that metabolizes fatty acids by hydroxylation at the omega-1 position and also metabolizes various endogenous substrates like ethanol and exogenous compounds including drugs and xenobiotics. The gene is not highly constrained against loss-of-function variants, and while CYP2E1 variants can affect drug metabolism and potentially influence susceptibility to certain toxins, clear Mendelian disease associations with this gene have not been well-established in pediatric populations.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

Active trials

360

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.17

LOEUF

Multiple*

Mechanism· predicted

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

Background carrier burden — how many people carry a rare variant somewhere in CYP2E1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 100

634 rare PASS variants

Rare truncating (LoF)

1 in 1,300

86 rare PASS variants

Rare synonymous (reference)

1 in 130

245 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CYP2E1. 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 120	1 in 1,300
South Asian	~43k	1 in 89	1 in 2,100
Remaining (unassigned)	~30k	1 in 73	1 in 700
European (Finnish)	~27k	1 in 220	1 in 2,900
Admixed American	~22k	1 in 94	1 in 1,700
African / African American	~21k	1 in 67	1 in 3,200
East Asian	~20k	1 in 95	1 in 570
Ashkenazi Jewish	~13k	1 in 930	none seen
Middle Eastern	~2,884	1 in 93	≈ 1 in 2,900

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 9 coding exons well covered in gnomAD exomes and genomes.? see exons ↓