CYP2J2

Chr 1

cytochrome P450 family 2 subfamily J member 2

ENSG00000134716 UniProt: P51589 OMIM: 601258

This gene encodes a cytochrome P450 monooxygenase that catalyzes the epoxidation of arachidonic acid and other polyunsaturated fatty acids in cardiac tissue, producing epoxyeicosatrienoic acids that have cardiovascular effects. The gene shows low constraint against loss-of-function variants (LOEUF 1.39), and no established Mendelian diseases have been definitively linked to CYP2J2 mutations in the pediatric population. While variants in this gene have been studied in relation to cardiovascular phenotypes, clear disease associations with defined inheritance patterns remain to be established.

OMIM ResearchSummary from RefSeq, UniProt

A cytochrome P450 monooxygenase involved in the metabolism of polyunsaturated fatty acids (PUFA) in the cardiovascular system (PubMed:19965576, PubMed:8631948). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:19965576, PubMed:8631948). Catalyzes the epoxidation of double bonds of PUFA (PubMed:19965576, PubMed:8631948). Converts arachidonic acid to four regioisomeric epoxyeicosatrienoic acids (EpETrE), likely playing a major role in the epoxidation of endogenous cardiac arachidonic acid pools (PubMed:8631948). In endothelial cells, participates in eicosanoids metabolism by converting hydroperoxide species into hydroxy epoxy metabolites. In combination with 15-lipoxygenase metabolizes arachidonic acid and converts hydroperoxyicosatetraenoates (HpETEs) into hydroxy epoxy eicosatrienoates (HEETs), which are precursors of vasodilatory trihydroxyicosatrienoic acids (THETAs). This hydroperoxide isomerase activity is NADPH- and O2-independent (PubMed:19737933). Catalyzes the monooxygenation of a various xenobiotics, such as danazol, amiodarone, terfenadine, astemizole, thioridazine, tamoxifen, cyclosporin A and nabumetone (PubMed:19923256). Catalyzes hydroxylation of the anthelmintics albendazole and fenbendazole (PubMed:23959307). Catalyzes the sulfoxidation of fenbedazole (PubMed:19923256)

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.39

Clinical Summary— CYP2J2

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.39LOEUF

pLI 0.000

Z-score 0.08

OE 0.98 (0.70–1.39)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.14Z-score

OE missense 0.98 (0.88–1.08)

270 obs / 276.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.98 (0.70–1.39)

0≤0.351.4

Missense OE?0.98 (0.88–1.08)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 23 / 23.4Missense obs/exp: 270 / 276.4Syn Z: 0.55

This gene — mechanism propensity

0.6840th %ile

GOF

0.5465th %ile

LOF

0.3549th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction 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.