PRDX1

Chr 1

peroxiredoxin 1

Also known as: MSP23, NKEF-A, NKEFA, PAG, PAGA, PAGB, PRX1, PRXI

NCBI Gene: 5052 ENSG00000117450 UniProt: Q06830

This gene encodes a thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, protecting cells against oxidative stress. Mutations cause methylmalonic aciduria and homocystinuria, cblC type, through digenic inheritance, which involves defects in vitamin B12 metabolism. The gene shows very low constraint against loss-of-function variants (pLI near zero) and follows autosomal recessive inheritance.

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the peroxiredoxin family of antioxidant enzymes, which reduce hydrogen peroxide and alkyl hydroperoxides. The encoded protein may play an antioxidant protective role in cells, and may contribute to the antiviral activity of CD8(+) T-cells. This protein may have a proliferative effect and play a role in cancer development or progression. Four transcript variants encoding the same protein have been identified for this gene. [provided by RefSeq, Jan 2011]

ResearchGenerating clinical summary…

DNmechanismLOEUF 1.91

Clinical Summary— PRDX1

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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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ClinVar Variants

3 unique Pathogenic / Likely Pathogenic· 38 VUS of 88 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 →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.91LOEUF

pLI 0.000

Z-score -1.08

OE 1.40 (0.88–1.91)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.20Z-score

OE missense 0.95 (0.81–1.11)

103 obs / 108.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.40 (0.88–1.91)

0≤0.351.4

Missense OE?0.95 (0.81–1.11)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 12 / 8.6Missense obs/exp: 103 / 108.9Syn Z: -0.13

This gene — mechanism propensity

0.6259th %ile

GOF

0.5955th %ile

LOF

0.3842th %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.

ClinVar Variant Classifications

88 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

Likely Pathogenic1

VUS38

Likely Benign23

Benign12

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	0	1	0	2
Likely Pathogenic	1	0	0	0	1
VUS	4	28	5	1	38
Likely Benign	0	0	9	14	23
Benign	0	0	11	1	12
Total	6	28	26	16	76

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

View in ClinVar →

7 pathogenic / likely-pathogenic (of 21) ClinVar copy-number / structural variants overlap PRDX1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →