CYP2W1

Chr 7

cytochrome P450 family 2 subfamily W member 1

NCBI Gene: 54905 ENSG00000073067 UniProt: Q8TAV3 OMIM: 615967

The protein is a cytochrome P450 monooxygenase that hydroxylates all-trans-retinoic acid to regulate retinoid clearance and metabolizes various lysophospholipids involved in cellular signaling. Mutations cause autosomal recessive retinitis pigmentosa, a progressive inherited retinal dystrophy that typically begins in childhood with night blindness and peripheral vision loss. The gene shows moderate tolerance to loss-of-function variants (LOEUF 1.099), suggesting some mutational flexibility.

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. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.10

Clinical Summary— CYP2W1

⚡

Population Constraint (gnomAD)

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

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?

1.10LOEUF

pLI 0.000

Z-score 1.24

OE 0.69 (0.45–1.10)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.17Z-score

OE missense 0.97 (0.89–1.07)

306 obs / 314.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.69 (0.45–1.10)

0≤0.351.4

Missense OE?0.97 (0.89–1.07)

0≤0.61.4

Synonymous OE?1.13

0≤1.21.6

LoF obs/exp: 13 / 18.8Missense obs/exp: 306 / 314.6Syn Z: -1.31

This gene — mechanism propensity

0.7326th %ile

GOF

0.73top 25%

LOF

0.2582th %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.