PRDX6

Chr 1

peroxiredoxin 6

Also known as: 1-Cys, AOP2, HEL-S-128m, LPCAT-5, NSGPx, PRX, aiPLA2, p29

NCBI Gene: 9588 ENSG00000117592 UniProt: P30041 OMIM: 602316

This gene encodes a bifunctional antioxidant enzyme that reduces hydrogen peroxide and organic hydroperoxides to protect cells from oxidative damage, and also functions as a phospholipase to regulate phospholipid turnover. Mutations cause autosomal recessive neurodevelopmental disorder with microcephaly, epilepsy, and brain atrophy. The gene is not highly constrained against loss-of-function variants, consistent with the recessive inheritance pattern observed in affected patients.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a member of the thiol-specific antioxidant protein family. This protein is a bifunctional enzyme with two distinct active sites. It is involved in redox regulation of the cell; it can reduce H(2)O(2) and short chain organic, fatty acid, and phospholipid hydroperoxides. It may play a role in the regulation of phospholipid turnover as well as in protection against oxidative injury. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.59

Clinical Summary— PRDX6

⚡

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?

1.59LOEUF

pLI 0.000

Z-score 0.34

OE 0.87 (0.49–1.59)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.46Z-score

OE missense 0.63 (0.52–0.76)

78 obs / 123.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.87 (0.49–1.59)

0≤0.351.4

Missense OE?0.63 (0.52–0.76)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 7 / 8.0Missense obs/exp: 78 / 123.9Syn Z: 0.13

This gene — mechanism propensity

0.6455th %ile

GOF

0.6248th %ile

LOF

0.3067th %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.