← Back to Knowledge Base

Primary topic: oxidative stress defense pathway

Oxidative Stress Defense Pathway: Why Recovery Can Become the Bottleneck

Oxidative stress is often treated as vague wellness language, but redox defense is a real system that can become a limiting factor under load.

What this pathway does

This pathway manages oxidative load using enzymes and antioxidant systems that buffer stress at the cellular level. It influences recovery, resilience, and inflammatory spillover.

Why it matters

When the pathway is pressured, people often experience lower recovery tolerance, more fatigue under workload, or a sense that stress accumulates faster than expected.

What creates pressure on this pathway

  • higher oxidative workload
  • less efficient antioxidant enzymes
  • recovery mismatch between demand and buffering capacity

Validation markers to consider

  • GSH/GSSG ratio
  • inflammatory context such as hs-CRP
  • recovery and workload tracking

Genes and SNPs connected to this pathway

This is about how well your body handles wear and tear from bad sleep, alcohol, illness, pollution, stress, or hard workouts.

Study rows support the SNP/gene claim. The pathway connection comes from the curated gene-to-pathway map.

What may run higher

Bad sleep, alcohol, illness, or hard workouts may wear you down faster.

What may work more slowly

You may recover more slowly after stress.

What to check next

Check recovery pattern, hs-CRP, GGT, ALT, AST, fasting glucose, HbA1c, ApoB, uric acid, and oxidized LDL if available.

14mapped genes
17mapped SNPs
29SNP/gene claims
21report eligible
CAT2 SNPs - 6 claimsShow SNPsOpen gene page
rs10011793 claims - 6 study rows

expression - TT

CAT gene expression

Moderate

rs1001179 TT is associated with increased CAT gene expression.

CAT rs1001179 is scored as a tendency toward higher CAT expression for T-containing genotypes, strongest for TT.

Likely effectHigher gene expression signal
Signal sizeModerate signal
Evidence supportModerate support
Report useIncluded in pathway scoring
Show study evidence
PubMed 11182520functional assay - directForsberg et al. studied the CAT promoter polymorphism rs1001179, also described as -262C/T. In reporter experiments, the T variant showed higher transcriptional activity in HepG2 and K562 cells, and red blood cell catalase levels were higher in donors carrying the T allele than in CC donors. This supports a higher CAT expression tendency for T-containing genotypes.PubMed 27225276expression eqtl - directA study of healthy peripheral blood cells reported significant differences in CAT mRNA levels by CAT promoter genotypes including C-262T rs1001179. This supports treating rs1001179 as an expression-related variant, while keeping the certainty moderate because expression can vary by tissue and study design.

expression - CT

CAT gene expression

Moderate

rs1001179 CT is associated with increased CAT gene expression.

CAT rs1001179 is scored as a tendency toward higher CAT expression for T-containing genotypes, strongest for TT.

Likely effectHigher gene expression signal
Signal sizeSmall signal
Evidence supportModerate support
Report useIncluded in pathway scoring
Show study evidence
PubMed 11182520functional assay - directForsberg et al. studied the CAT promoter polymorphism rs1001179, also described as -262C/T. In reporter experiments, the T variant showed higher transcriptional activity in HepG2 and K562 cells, and red blood cell catalase levels were higher in donors carrying the T allele than in CC donors. This supports a higher CAT expression tendency for T-containing genotypes.PubMed 27225276expression eqtl - directA study of healthy peripheral blood cells reported significant differences in CAT mRNA levels by CAT promoter genotypes including C-262T rs1001179. This supports treating rs1001179 as an expression-related variant, while keeping the certainty moderate because expression can vary by tissue and study design.

expression - CC

CAT gene expression

Not used for pathway scoring

rs1001179 CC has no scored directional claim for CAT gene expression.

CAT rs1001179 is scored as a tendency toward higher CAT expression for T-containing genotypes, strongest for TT.

Likely effectNo clear expression signal
Signal sizeMinimal signal
Evidence supportVery limited support
Report useEvidence only, not scored
Show study evidence
PubMed 11182520functional assay - directForsberg et al. studied the CAT promoter polymorphism rs1001179, also described as -262C/T. In reporter experiments, the T variant showed higher transcriptional activity in HepG2 and K562 cells, and red blood cell catalase levels were higher in donors carrying the T allele than in CC donors. This supports a higher CAT expression tendency for T-containing genotypes.PubMed 27225276expression eqtl - directA study of healthy peripheral blood cells reported significant differences in CAT mRNA levels by CAT promoter genotypes including C-262T rs1001179. This supports treating rs1001179 as an expression-related variant, while keeping the certainty moderate because expression can vary by tissue and study design.
rs7692173 claims - 6 study rows

enzyme activity - TT

CAT enzyme activity

Moderate

rs769217 TT is associated with reduced CAT enzyme activity.

CAT rs769217 is scored as a modest lower catalase enzyme-activity tendency for T-containing genotypes.

Likely effectLower enzyme activity signal
Signal sizeSmall signal
Evidence supportModerate support
Report useIncluded in pathway scoring
Show study evidence
Evidence 1functional assay - directIn a Danish prospective cohort analysis, CAT rs769217 was associated with erythrocyte catalase enzyme activity. Activity decreased for each T allele overall, with the clearest signal among controls; the case-only signal was weaker. This supports a conservative lower-activity tendency for T-containing genotypes.PubMed 28968965functional assay - directThe PubMed abstract for the same study states that functional polymorphisms in CAT, SOD1, and GSR were evaluated with measured antioxidant enzyme activities, and that several polymorphisms were strongly associated with enzyme activity but not with breast cancer risk by themselves. This supports using rs769217 for enzyme-activity tendency only, not disease prediction.

enzyme activity - CT

CAT enzyme activity

Not used for pathway scoring

rs769217 CT is associated with reduced CAT enzyme activity.

CAT rs769217 is scored as a modest lower catalase enzyme-activity tendency for T-containing genotypes.

Likely effectLower enzyme activity signal
Signal sizeSmall signal
Evidence supportModerate support
Report useEvidence only, not scored
Show study evidence
Evidence 1functional assay - directIn a Danish prospective cohort analysis, CAT rs769217 was associated with erythrocyte catalase enzyme activity. Activity decreased for each T allele overall, with the clearest signal among controls; the case-only signal was weaker. This supports a conservative lower-activity tendency for T-containing genotypes.PubMed 28968965functional assay - directThe PubMed abstract for the same study states that functional polymorphisms in CAT, SOD1, and GSR were evaluated with measured antioxidant enzyme activities, and that several polymorphisms were strongly associated with enzyme activity but not with breast cancer risk by themselves. This supports using rs769217 for enzyme-activity tendency only, not disease prediction.

enzyme activity - CC

CAT enzyme activity

Not used for pathway scoring

rs769217 CC has no scored directional claim for CAT enzyme activity.

CAT rs769217 is scored as a modest lower catalase enzyme-activity tendency for T-containing genotypes.

Likely effectNo clear enzyme signal
Signal sizeMinimal signal
Evidence supportVery limited support
Report useEvidence only, not scored
Show study evidence
Evidence 1functional assay - directIn a Danish prospective cohort analysis, CAT rs769217 was associated with erythrocyte catalase enzyme activity. Activity decreased for each T allele overall, with the clearest signal among controls; the case-only signal was weaker. This supports a conservative lower-activity tendency for T-containing genotypes.PubMed 28968965functional assay - directThe PubMed abstract for the same study states that functional polymorphisms in CAT, SOD1, and GSR were evaluated with measured antioxidant enzyme activities, and that several polymorphisms were strongly associated with enzyme activity but not with breast cancer risk by themselves. This supports using rs769217 for enzyme-activity tendency only, not disease prediction.
G6PD2 SNPs - 4 claimsShow SNPsOpen gene page
rs10508283 claims - 9 study rows

enzyme activity - TT

G6PD enzyme activity

Strong

rs1050828 TT is associated with reduced G6PD enzyme activity.

G6PD rs1050828 is scored as a lower G6PD enzyme-activity tendency for T-containing genotypes, strongest for TT and intermediate for CT.

Likely effectLower enzyme activity signal
Signal sizeLarge signal
Evidence supportModerate support
Report useIncluded in pathway scoring
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP places rs1050828 in G6PD. In the G6PD transcript annotation, C corresponds to the usual Val form at this position and T corresponds to the Met form of the c.202G>A variant.PMC4236593functional assay - directA Kenyan fine-mapping study of erythrocyte G6PD activity found that c.202G>A, rs1050828, accounted for most observed activity variation. The authors reported a strong association with lower enzyme activity, supporting a stronger negative score for two-copy variant status than for one-copy status.PubMed 36145477review - close proxyA systematic review and meta-analysis reported low G6PD activity for the A- haplotype that includes c.202G>A and c.376A>G, with lower median activity in hemi- or homozygous carriers than in heterozygotes. This supports a stronger negative score for TT than CT while keeping clinical interpretation cautious.

enzyme activity - CT

G6PD enzyme activity

Moderate

rs1050828 CT is associated with reduced G6PD enzyme activity.

G6PD rs1050828 is scored as a lower G6PD enzyme-activity tendency for T-containing genotypes, strongest for TT and intermediate for CT.

Likely effectLower enzyme activity signal
Signal sizeSmall signal
Evidence supportModerate support
Report useIncluded in pathway scoring
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP places rs1050828 in G6PD. In the G6PD transcript annotation, C corresponds to the usual Val form at this position and T corresponds to the Met form of the c.202G>A variant.PMC4236593functional assay - directA Kenyan fine-mapping study of erythrocyte G6PD activity found that c.202G>A, rs1050828, accounted for most observed activity variation. The authors reported a strong association with lower enzyme activity, supporting a stronger negative score for two-copy variant status than for one-copy status.PubMed 36145477review - close proxyA systematic review and meta-analysis reported low G6PD activity for the A- haplotype that includes c.202G>A and c.376A>G, with lower median activity in hemi- or homozygous carriers than in heterozygotes. This supports a stronger negative score for TT than CT while keeping clinical interpretation cautious.

enzyme activity - CC

G6PD enzyme activity

Not used for pathway scoring

rs1050828 CC has no scored directional claim for G6PD enzyme activity.

G6PD rs1050828 is scored as a lower G6PD enzyme-activity tendency for T-containing genotypes, strongest for TT and intermediate for CT.

Likely effectNo clear enzyme signal
Signal sizeMinimal signal
Evidence supportVery limited support
Report useEvidence only, not scored
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP places rs1050828 in G6PD. In the G6PD transcript annotation, C corresponds to the usual Val form at this position and T corresponds to the Met form of the c.202G>A variant.PMC4236593functional assay - directA Kenyan fine-mapping study of erythrocyte G6PD activity found that c.202G>A, rs1050828, accounted for most observed activity variation. The authors reported a strong association with lower enzyme activity, supporting a stronger negative score for two-copy variant status than for one-copy status.PubMed 36145477review - close proxyA systematic review and meta-analysis reported low G6PD activity for the A- haplotype that includes c.202G>A and c.376A>G, with lower median activity in hemi- or homozygous carriers than in heterozygotes. This supports a stronger negative score for TT than CT while keeping clinical interpretation cautious.
rs50308681 claims - 2 study rows

enzyme activity - A

G6PD enzyme activity and NADPH redox reserve

Strong

rs5030868 A, the plus-strand allele corresponding to G6PD Mediterranean c.563C>T / p.Ser188Phe, is associated with lower G6PD enzyme activity and reduced NADPH-linked redox reserve.

G6PD rs5030868 A is staged as a strong lower-function G6PD Mediterranean signal relevant to oxidative-stress reserve.

Likely effectLower enzyme activity signal
Signal sizeLarge signal
Evidence supportStrong support
Report useIncluded in pathway scoring
Show study evidence
ClinVar Variation ID 100057clinical curation - directClinVar maps rs5030868 to the G6PD Mediterranean c.563C>T / p.Ser188Phe variant and records pathogenic or likely pathogenic classifications for G6PD deficiency-related phenotypes.PMCID PMC1683892clinical curation - directThe checked G6PD Mediterranean molecular study describes the Mediterranean phenotype as severe enzyme deficiency and identifies the same c.563C>T change causing the Ser188Phe substitution.
GCLC1 SNPs - 3 claimsShow SNPsOpen gene page
rs178839013 claims - 3 study rows

expression - AA

GCLC gene expression

Moderate

rs17883901 AA is associated with reduced GCLC gene expression.

GCLC rs17883901 is scored as a lower GCLC expression tendency for A-containing genotypes, strongest for AA.

Likely effectLower gene expression signal
Signal sizeModerate signal
Evidence supportModerate support
Report useIncluded in pathway scoring
Show study evidence
PubMed 12598062functional assay - directKoide et al. studied a promoter polymorphism in GCLC and reported lower promoter activity, about 50% to 60% of the comparison allele, in response to H2O2 in human endothelial cells. Because GCLC encodes the catalytic subunit of glutamate-cysteine ligase, this supports a lower expression tendency for the lower-promoter-activity genotype pattern.

expression - AG

GCLC gene expression

Moderate

rs17883901 AG is associated with reduced GCLC gene expression.

GCLC rs17883901 is scored as a lower GCLC expression tendency for A-containing genotypes, strongest for AA.

Likely effectLower gene expression signal
Signal sizeSmall signal
Evidence supportModerate support
Report useIncluded in pathway scoring
Show study evidence
PubMed 12598062functional assay - directKoide et al. studied a promoter polymorphism in GCLC and reported lower promoter activity, about 50% to 60% of the comparison allele, in response to H2O2 in human endothelial cells. Because GCLC encodes the catalytic subunit of glutamate-cysteine ligase, this supports a lower expression tendency for the lower-promoter-activity genotype pattern.

expression - GG

GCLC gene expression

Not used for pathway scoring

rs17883901 GG has no scored directional claim for GCLC gene expression.

GCLC rs17883901 is scored as a lower GCLC expression tendency for A-containing genotypes, strongest for AA.

Likely effectNo clear expression signal
Signal sizeMinimal signal
Evidence supportVery limited support
Report useEvidence only, not scored
Show study evidence
PubMed 12598062functional assay - directKoide et al. studied a promoter polymorphism in GCLC and reported lower promoter activity, about 50% to 60% of the comparison allele, in response to H2O2 in human endothelial cells. Because GCLC encodes the catalytic subunit of glutamate-cysteine ligase, this supports a lower expression tendency for the lower-promoter-activity genotype pattern.
NAT22 SNPs - 2 claimsShow SNPsOpen gene page
rs14957411 claims - 2 study rows

enzyme activity - G

NAT2 acetylator status tendency

Strong

rs1495741 G near NAT2 tags higher NAT2 acetylator activity tendency in populations of European background.

NAT2 rs1495741 G is staged as a rapid-acetylator tag allele for NAT2 activity tendency.

Likely effectHigher enzyme activity signal
Signal sizeSmall signal
Evidence supportStrong support
Report useIncluded in pathway scoring
Show study evidence
PMCID PMC3003749biomarker association - directThe checked source reports that rs1495741 predicts the 7-SNP inferred NAT2 phenotype with high sensitivity/specificity in European-background populations and that rs1495741 genotypes were strongly related to NAT2 catalytic activity in cryopreserved human hepatocytes.PMCID PMC4079945gwas - close proxyThe checked GWAS source identifies rs1495741 as an NAT2 acetylator-status tag SNP and states that the fast-acetylator genotype was associated with lower skin fluorescence and glyoxal-derived AGE measures.
rs18012801 claims - 2 study rows

enzyme activity - C

arylamine acetylation activity tendency

Strong

rs1801280 C / NAT2 Ile114Thr is associated with lower arylamine acetylation activity tendency.

NAT2 rs1801280 C is staged as a lower NAT2 acetylation activity allele and NAT2*5 slow-acetylator marker.

Likely effectLower enzyme activity signal
Signal sizeModerate signal
Evidence supportStrong support
Report useIncluded in pathway scoring
Show study evidence
PMCID PMC2507886functional assay - directThe checked NAT2 structure-function source identifies T341C / rs1801280 / I114T and reports that I114T causes slow acetylator phenotype in recombinant bacterial and yeast systems with reduced active enzyme.PMCID PMC3285565functional assay - directThe checked human hepatocyte source includes rs1801280 in NAT2 genotyping panels and reports 341T>C activities differed significantly across homozygous common, heterozygote, and homozygous variant samples, consistent with lower SMZ N-acetyltransferase activity.
NQO11 SNPs - 3 claimsShow SNPsOpen gene page
rs18005663 claims - 9 study rows

enzyme activity - AA

NQO1 enzyme activity

Strong

rs1800566 AA is associated with reduced NQO1 enzyme activity.

NQO1 rs1800566 is scored as a lower NQO1 enzyme-activity tendency for A-containing genotypes, strongest for AA and intermediate for AG.

Likely effectLower enzyme activity signal
Signal sizeModerate signal
Evidence supportStrong support
Report useIncluded in pathway scoring
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP identifies rs1800566 in NQO1 and annotates the common A allele as the coding p.Pro187Ser change in transcript NM_000903.3. This record scores the common A/G genotype set for NQO1 enzyme-activity tendency.PMC2727266functional assay - directA HuGE review describes the NQO1 609C>T / Pro187Ser polymorphism as causing loss of enzyme activity through protein instability, with homozygous variant activity almost undetectable and heterozygous activity intermediate between variant homozygotes and wild type. This supports strong lower-activity scoring for AA and moderate lower-activity scoring for AG.PubMed 30518535review - directPey et al. reviewed NQO1 biochemistry and reported that the p.Pro187Ser variant has much lower activity than wild type, mainly because reduced FAD affinity lowers protein stability. This supports interpreting A-containing genotypes as a lower NQO1 enzyme-activity tendency.

enzyme activity - AG

NQO1 enzyme activity

Strong

rs1800566 AG is associated with reduced NQO1 enzyme activity.

NQO1 rs1800566 is scored as a lower NQO1 enzyme-activity tendency for A-containing genotypes, strongest for AA and intermediate for AG.

Likely effectLower enzyme activity signal
Signal sizeSmall signal
Evidence supportStrong support
Report useIncluded in pathway scoring
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP identifies rs1800566 in NQO1 and annotates the common A allele as the coding p.Pro187Ser change in transcript NM_000903.3. This record scores the common A/G genotype set for NQO1 enzyme-activity tendency.PMC2727266functional assay - directA HuGE review describes the NQO1 609C>T / Pro187Ser polymorphism as causing loss of enzyme activity through protein instability, with homozygous variant activity almost undetectable and heterozygous activity intermediate between variant homozygotes and wild type. This supports strong lower-activity scoring for AA and moderate lower-activity scoring for AG.PubMed 30518535review - directPey et al. reviewed NQO1 biochemistry and reported that the p.Pro187Ser variant has much lower activity than wild type, mainly because reduced FAD affinity lowers protein stability. This supports interpreting A-containing genotypes as a lower NQO1 enzyme-activity tendency.

enzyme activity - GG

NQO1 enzyme activity

Not used for pathway scoring

rs1800566 GG has no scored directional claim for NQO1 enzyme activity.

NQO1 rs1800566 is scored as a lower NQO1 enzyme-activity tendency for A-containing genotypes, strongest for AA and intermediate for AG.

Likely effectNo clear enzyme signal
Signal sizeMinimal signal
Evidence supportVery limited support
Report useEvidence only, not scored
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP identifies rs1800566 in NQO1 and annotates the common A allele as the coding p.Pro187Ser change in transcript NM_000903.3. This record scores the common A/G genotype set for NQO1 enzyme-activity tendency.PMC2727266functional assay - directA HuGE review describes the NQO1 609C>T / Pro187Ser polymorphism as causing loss of enzyme activity through protein instability, with homozygous variant activity almost undetectable and heterozygous activity intermediate between variant homozygotes and wild type. This supports strong lower-activity scoring for AA and moderate lower-activity scoring for AG.PubMed 30518535review - directPey et al. reviewed NQO1 biochemistry and reported that the p.Pro187Ser variant has much lower activity than wild type, mainly because reduced FAD affinity lowers protein stability. This supports interpreting A-containing genotypes as a lower NQO1 enzyme-activity tendency.
CYBA1 SNPs - 1 claimsShow SNPsOpen gene page
rs46731 claims - 2 study rows

enzyme activity - T

NADPH oxidase superoxide burst tendency

Strong

rs4673 T / CYBA C242T is associated with lower NADPH oxidase respiratory-burst superoxide production tendency, strongest in TT carriers.

CYBA rs4673 T is staged as a lower p22phox/NADPH oxidase superoxide burst allele in TT context.

Likely effectLower enzyme activity signal
Signal sizeSmall signal
Evidence supportStrong support
Report useIncluded in pathway scoring
Show study evidence
PMID 15078863functional assay - directThe checked PubMed abstract reports significantly lower superoxide production from stimulated neutrophils in CYBA C242T TT carriers compared with CC/CT carriers.PMCID PMC2871250biomarker association - close proxyThe checked exercise/oxidative-stress source reports lower baseline urinary 8-iso-PGF2alpha in C242T TT homozygotes and summarizes prior reduced NADPH oxidase activity evidence for the T allele.
GPX41 SNPs - 1 claimsShow SNPsOpen gene page
rs7130411 claims - 1 study rows

enzyme activity - C

low-selenium GPX4 redox activity

Moderate

rs713041 C is associated with lower GPX4 redox activity under low selenium conditions.

GPX4 rs713041 is staged as a selenium-context redox functional claim rather than a broad antioxidant-capacity claim.

Likely effectLower enzyme activity signal
Signal sizeSmall signal
Evidence supportModerate support
Report useIncluded in pathway scoring
Show study evidence
PMCID PMC3793862functional assay - directThe checked functional study compared GPX4 rs713041 T/C 3-UTR constructs in Caco-2 cells and found the C variant had worse oxidative-stress and GPx activity readouts under low selenium conditions.
GSTA11 SNPs - 1 claimsShow SNPsOpen gene page
rs39573571 claims - 2 study rows

expression - T

GSTA1 expression and glutathione conjugation capacity tendency

Moderate

rs3957357 T in the GSTA1 promoter is associated with lower GSTA1 promoter activity and lower glutathione-conjugation capacity tendency, strongest in GSTA1*B promoter-haplotype context.

GSTA1 rs3957357 T is staged as a promoter-expression marker relevant to alpha-class glutathione transferase capacity.

Likely effectLower gene expression signal
Signal sizeSmall signal
Evidence supportStrong support
Report useIncluded in pathway scoring
Show study evidence
PMCID PMC7930039functional assay - close proxyThe checked promoter-diversity study identifies rs3957357 as the GSTA1 promoter -69 SNP, reports luciferase reporter assays for GSTA1 promoter haplotypes, and supports lower promoter activity for GSTA1*B haplotype contexts containing the T allele.PMCID PMC5147914biomarker association - close proxyThe checked exact-SNP study genotyped rs3957357C>T and states that the TT genotype is known to downregulate GSTA1 mRNA expression; it is used only as expression-direction support, not as a disease-risk scoring row.
NFE2L21 SNPs - 1 claimsShow SNPsOpen gene page
rs67219611 claims - 2 study rows

expression - T

NRF2 promoter activity tendency

Strong

rs6721961 T / NFE2L2 promoter variant is associated with lower NRF2 promoter activity tendency.

NFE2L2 rs6721961 T is staged as a lower NRF2 promoter/transcriptional response allele.

Likely effectLower gene expression signal
Signal sizeModerate signal
Evidence supportStrong support
Report useIncluded in pathway scoring
Show study evidence
PMCID PMC3599320functional assay - directThe checked source identifies rs6721961 as -617C/A and reports that the -617A variant promoter construct reduced NFE2L2 luciferase activity by about 42% versus wild type.PMCID PMC4484894functional assay - directThe checked source states that rs6721961 T had less than half the luciferase activity of the G allele and reduced NFE2L2 gene expression in reporter/EMSA context.
NOS31 SNPs - 3 claimsShow SNPsOpen gene page
rs17999833 claims - 9 study rows

enzyme activity - TT

NOS3 enzyme activity

Moderate

rs1799983 TT is associated with reduced NOS3 enzyme activity.

NOS3 rs1799983 is scored as a cautious tendency toward lower endothelial nitric oxide synthase activity for T-containing genotypes, strongest for TT.

Likely effectLower enzyme activity signal
Signal sizeSmall signal
Evidence supportModerate support
Report useIncluded in pathway scoring
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP identifies rs1799983 in NOS3 and annotates the common G and T alleles with the endothelial nitric oxide synthase Glu298Asp protein difference. This record scores the common G/T genotype set for a simplified NOS3 functional tendency.PubMed 17449720functional assay - directJoshi et al. studied human endothelial cells by NOS3 Glu298Asp genotype and found that Asp-variant genotypes had lower nitric oxide metabolite production before and after shear exposure, with altered NOS3 caveolar localization and impaired shear response. This supports a lower NOS3 activity tendency for T-containing genotypes.PubMed 37451608review - directA 2023 systematic review and meta-analysis notes that published studies have reported lower circulating nitric oxide with the NOS3 Glu298Asp polymorphism, while clinical association results vary by ancestry and endpoint. This supports keeping the effect as a cautious enzyme-activity tendency rather than a disease prediction.

enzyme activity - GT

NOS3 enzyme activity

Not used for pathway scoring

rs1799983 GT is associated with reduced NOS3 enzyme activity.

NOS3 rs1799983 is scored as a cautious tendency toward lower endothelial nitric oxide synthase activity for T-containing genotypes, strongest for TT.

Likely effectLower enzyme activity signal
Signal sizeSmall signal
Evidence supportModerate support
Report useEvidence only, not scored
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP identifies rs1799983 in NOS3 and annotates the common G and T alleles with the endothelial nitric oxide synthase Glu298Asp protein difference. This record scores the common G/T genotype set for a simplified NOS3 functional tendency.PubMed 17449720functional assay - directJoshi et al. studied human endothelial cells by NOS3 Glu298Asp genotype and found that Asp-variant genotypes had lower nitric oxide metabolite production before and after shear exposure, with altered NOS3 caveolar localization and impaired shear response. This supports a lower NOS3 activity tendency for T-containing genotypes.PubMed 37451608review - directA 2023 systematic review and meta-analysis notes that published studies have reported lower circulating nitric oxide with the NOS3 Glu298Asp polymorphism, while clinical association results vary by ancestry and endpoint. This supports keeping the effect as a cautious enzyme-activity tendency rather than a disease prediction.

enzyme activity - GG

NOS3 enzyme activity

Not used for pathway scoring

rs1799983 GG has no scored directional claim for NOS3 enzyme activity.

NOS3 rs1799983 is scored as a cautious tendency toward lower endothelial nitric oxide synthase activity for T-containing genotypes, strongest for TT.

Likely effectNo clear enzyme signal
Signal sizeMinimal signal
Evidence supportVery limited support
Report useEvidence only, not scored
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP identifies rs1799983 in NOS3 and annotates the common G and T alleles with the endothelial nitric oxide synthase Glu298Asp protein difference. This record scores the common G/T genotype set for a simplified NOS3 functional tendency.PubMed 17449720functional assay - directJoshi et al. studied human endothelial cells by NOS3 Glu298Asp genotype and found that Asp-variant genotypes had lower nitric oxide metabolite production before and after shear exposure, with altered NOS3 caveolar localization and impaired shear response. This supports a lower NOS3 activity tendency for T-containing genotypes.PubMed 37451608review - directA 2023 systematic review and meta-analysis notes that published studies have reported lower circulating nitric oxide with the NOS3 Glu298Asp polymorphism, while clinical association results vary by ancestry and endpoint. This supports keeping the effect as a cautious enzyme-activity tendency rather than a disease prediction.
PON11 SNPs - 1 claimsShow SNPsOpen gene page
rs6621 claims - 2 study rows

enzyme activity - C

paraoxon/chlorpyrifos-oxon hydrolysis tendency

Strong

rs662 C / PON1 192R is associated with higher paraoxon and chlorpyrifos-oxon hydrolysis tendency.

PON1 rs662 C is staged only as a substrate-specific higher organophosphate-oxon hydrolysis allele.

Likely effectHigher enzyme activity signal
Signal sizeSmall signal
Evidence supportStrong support
Report useIncluded in pathway scoring
Show study evidence
PMCID PMC7924808functional assay - directThe checked PON1-status protocol source states that PON1 Q192R affects catalytic efficiency for paraoxon and chlorpyrifos-oxon hydrolysis while not affecting some other substrates.PMCID PMC3588879biomarker association - close proxyThe checked PON1 activity genetics source identifies rs662 / PON1 Q192R as a well-established functional PON1 mutation while emphasizing that AREase is less affected by Q192R than toxic-substrate hydrolysis.
SLC23A11 SNPs - 1 claimsShow SNPsOpen gene page
rs339723131 claims - 2 study rows

biomarker tendency - A

circulating vitamin C tendency

Moderate

rs33972313 A / Met allele is associated with lower circulating vitamin C tendency.

SLC23A1 rs33972313 A is staged as a vitamin C biomarker close proxy for antioxidant support.

Likely effectLower biomarker tendency
Signal sizeSmall signal
Evidence supportStrong support
Report useIncluded in pathway scoring
Show study evidence
PMCID PMC3605792biomarker association - close proxyThe checked SLC23A1 source reports that rs33972313 rare allele carriage is associated with lower circulating L-ascorbic acid across five studies, supporting vitamin C biomarker direction.PMCID PMC4266888biomarker association - close proxyThe second checked source uses rs33972313 as an SLC23A1 vitamin-C-associated variant and is used only for vitamin C biomarker support, not cardiometabolic outcomes.
SOD31 SNPs - 1 claimsShow SNPsOpen gene page
rs17998951 claims - 2 study rows

biomarker tendency - G

extracellular SOD3 distribution tendency

Strong

rs1799895 G / SOD3 Arg213Gly is associated with lower matrix binding and higher circulating or airway-fluid extracellular SOD3 tendency.

SOD3 rs1799895 G is staged as a redistribution allele that increases soluble/extracellular-fluid SOD3 while reducing tissue-matrix binding.

Likely effectHigher biomarker tendency
Signal sizeSmall signal
Evidence supportStrong support
Report useIncluded in pathway scoring
Show study evidence
PMCID PMC5874528functional assay - directThe checked source reports that the SOD3 R213G SNP decreases matrix binding affinity and that R213G mice had lower lung SOD3 protein expression but increased serum SOD3 protein and serum SOD activity.PMID 28878123biomarker association - directThe checked JCI Insight abstract reports that rs1799895/R213G changes lung distribution of extracellular SOD and can result in high EC-SOD in airway-lining fluid.
TTPA1 SNPs - 1 claimsShow SNPsOpen gene page
rs359168401 claims - 2 study rows

transport activity - AA or compound-heterozygous TTPA deficiency context

Alpha-tocopherol transfer tendency

Strong

rs35916840 A / TTPA c.661C>T p.Arg221Trp is associated with lower alpha-tocopherol transfer activity tendency in recessive or compound-heterozygous vitamin E deficiency contexts.

TTPA rs35916840 A is staged as a recessive alpha-tocopherol transfer protein allele affecting plasma vitamin E handling and antioxidant-status context.

Likely effectLower transport signal
Signal sizeModerate signal
Evidence supportStrong support
Report useIncluded in pathway scoring
Show study evidence
ClinVar RCV000522097clinical curation - directClinVar maps rs35916840 to TTPA c.661C>T / p.Arg221Trp and classifies it as pathogenic for ataxia with vitamin E deficiency in the checked RCV record.GeneReviews Ataxia With Vitamin E Deficiencyclinical curation - directGeneReviews supports TTPA pathogenic variants as impairing alpha-tocopherol transfer protein function and producing low plasma vitamin E in ataxia with vitamin E deficiency.

Where DNA analysis helps

DNA helps identify whether oxidative-stress defense deserves attention before broad antioxidant strategies are used without evidence.

Example interpretation

Your oxidative-stress defense pathway may have lower reserve than expected, which can make recovery become the real bottleneck.

Suggested validation: GSH/GSSG ratio.

What to do next

  • validate redox markers before assuming supplementation is the answer
  • connect lab data to sleep, training, and workload context
  • compare redox genes as a system rather than individually

Related pages

SOD2

SOD2 oxidative stress gene

GPX1

GPX1 antioxidant gene

Low energy

low energy metabolism causes

GSH/GSSG ratio

GSH GSSG ratio explained

Oxidative stress panel

oxidative stress panel and redox load

Can DNA predict metabolism?

can DNA predict metabolism

Best DNA test for metabolism

best DNA test for metabolism

Get the full report

Use your DNA file to see which pathways may be worth validating first.