What you carry at this position in your DNA and what research says about it.
Mitochondrial Antioxidant Defense: 5/10 evidence, 62 publications.
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Sample genotype (not yours): A/A
Lower Mitochondrial Antioxidant Activity
This genotype is associated with reduced transport of the protective SOD2 enzyme into the mitochondria, leading to lower antioxidant activity. It is linked to a higher risk of oxidative stress-related conditions like diabetic kidney disease and heart complications.
What this genotype means: Reduced mitochondrial antioxidant capacity; Increased risk of diabetic kidney complications; Higher susceptibility to heart complications under iron overload.
Sample genotype (not yours): A/G
Intermediate Mitochondrial Antioxidant Activity
This genotype results in a balanced mix of both the lower-activity and higher-activity forms of the SOD2 enzyme. It generally provides a typical level of antioxidant defense and average risk for oxidative stress-related conditions.
What this genotype means: Moderate mitochondrial antioxidant capacity; Typical baseline risk for oxidative stress-related diseases; Slightly increased risk of liver sensitivity to certain medications.
Sample genotype (not yours): G/G
Higher Mitochondrial Antioxidant Activity
This genotype is associated with highly efficient transport of the SOD2 enzyme into the mitochondria, resulting in optimal antioxidant activity. It is linked to a lower risk of diabetic kidney disease and cardiovascular complications.
What this genotype means: Optimal mitochondrial antioxidant capacity; Lower risk of diabetic kidney complications; Increased risk of liver sensitivity to certain medications.
Gene function and biological role
Gene Function: Superoxide dismutase 2 is a critical antioxidant enzyme that operates exclusively inside the mitochondria, the energy-producing powerhouses of cells. It acts as the first line of defense against cellular damage by converting toxic superoxide free radicals into less harmful molecules [1]. Without adequate levels of this enzyme, reactive oxygen species can accumulate, leading to mitochondrial dysfunction and cellular aging [2]. Variations in the gene encoding this enzyme can significantly alter how well cells handle oxidative stress [3].
Variant Impact: The rs4880 variant is a missense mutation that alters the 16th amino acid of the superoxide dismutase 2 protein from valine to alanine. This specific change occurs within the mitochondrial targeting sequence, which is responsible for directing the newly synthesized protein from the cytoplasm into the mitochondrial matrix [1]. The alanine-encoding version of the protein maintains a stable structural shape that allows for highly efficient transport into the mitochondria [4]. In contrast, the valine-encoding version forms a less stable structure, slowing down transport and reducing the amount of active enzyme inside the mitochondria [3]. This structural difference directly influences how effectively cells can neutralize free radicals under metabolic stress [2].
Read on the Mitochondrial Antioxidant page
Key Insight: The structural difference in this variant changes how the enzyme folds, altering its transport speed into the cell's powerhouses by up to forty percent.
Location: SOD2. Chromosome 6 · 6q25.3 · 159.7 Mb
Estimated prevalence by population
Global 28.6%; European 24.7%; African 33.1%; East Asian 73.4%; South Asian 23.8%; Americas 21.5%; Ashkenazi 23.1%; Finnish 28.4%; Middle Eastern 28.5%; Amish 26.0%.
Estimated AA genotype frequency.
Global 48.8%; European 50.0%; African 48.9%; East Asian 24.6%; South Asian 50.0%; Americas 49.7%; Ashkenazi 49.9%; Finnish 49.8%; Middle Eastern 49.8%; Amish 50.0%.
Estimated AG genotype frequency.
Global 22.7%; European 25.3%; African 18.0%; East Asian 2.1%; South Asian 26.2%; Americas 28.8%; Ashkenazi 27.0%; Finnish 21.8%; Middle Eastern 21.7%; Amish 24.0%.
Estimated GG genotype frequency.
Showing effects for A/A genotype
Nutrition & Metabolism
Blood Chemistry & Metabolites
Antioxidant Activity. Evidence: 5/10. Source: PMID 16538174. Reduced Activity.
Organ Systems
Kidney Function & Disease
Diabetic Kidney Disease. Evidence: 4/10. Source: PMID 17192491. Increased Risk.
Cardiovascular & Metabolic
Heart Disease
Heart Disease. Evidence: 3/10. Source: PMID 15591282. Increased Risk.
Pharmacogenomics
Adverse Drug Reactions
Drug-Induced Liver Injury. Evidence: 5/10. Source: PMID 17400324. Lower Risk.
Showing effects for A/G genotype
Antioxidant Activity. Evidence: 5/10. Source: PMID 16538174. Typical Activity.
Diabetic Kidney Disease. Evidence: 4/10. Source: PMID 17192491. Typical Risk.
Heart Disease. Evidence: 3/10. Source: PMID 15591282. Typical Risk.
Drug-Induced Liver Injury. Evidence: 5/10. Source: PMID 17400324. Increased Risk.
Showing effects for G/G genotype
Antioxidant Activity. Evidence: 5/10. Source: PMID 16538174. Optimal Activity.
Diabetic Kidney Disease. Evidence: 4/10. Source: PMID 17192491. Lower Risk.
Heart Disease. Evidence: 3/10. Source: PMID 15591282. Lower Risk.
What this genotype means for the people who carry it
Sample genotype: AA (Homozygous)
Mitochondrial protection is compromised with this genotype because the valine-encoding protein is imported into the mitochondrial matrix less efficiently [1]. This slower transport results in up to a forty percent reduction in active enzyme levels compared to the alanine-encoding version [2]. Consequently, cells are more vulnerable to oxidative damage from accumulated superoxide free radicals [3]. Over time, this elevated oxidative stress is associated with an increased risk of diabetic kidney complications and chronic kidney disease [4]. There is also a higher susceptibility to heart disease, particularly in individuals with iron overload or hereditary hemochromatosis [5]. Interestingly, this lower baseline enzyme activity may offer a protective effect against certain drug-induced liver toxicities, as some medications require mitochondrial processing to become toxic [6].
Reduced mitochondrial antioxidant capacity; Increased risk of diabetic kidney complications; Higher susceptibility to heart complications under iron overload.
Sample genotype: AG (Heterozygous)
Antioxidant defense operates at an intermediate capacity with this heterozygous genotype because both the valine and alanine versions of the protein are produced [1]. Slower transport of the valine-encoding protein is partially offset by the highly efficient transport of the alanine-encoding protein [2]. This balance maintains a typical level of active enzyme inside the mitochondria to neutralize free radicals [3]. Risks for chronic kidney disease and diabetic complications are generally near the population average [4]. However, exposure to certain medications, such as cyclophosphamide or common pain relievers, may still carry a slightly elevated risk of liver toxicity compared to the valine-only genotype [5]. Maintaining a diet rich in natural antioxidants can help support cellular defense mechanisms [6].
Moderate mitochondrial antioxidant capacity; Typical baseline risk for oxidative stress-related diseases; Slightly increased risk of liver sensitivity to certain medications.
Sample genotype: GG (Homozygous)
Mitochondrial defense is highly efficient with this genotype because the alanine-encoding protein is rapidly and successfully imported into the mitochondrial matrix [1]. This optimal transport leads to significantly higher levels of active enzyme to neutralize harmful superoxide free radicals [2]. As a result, cells are better shielded from the chronic oxidative damage that contributes to cellular aging [3]. This robust defense is associated with a lower risk of developing diabetic nephropathy and chronic kidney disease [4]. It also provides a protective effect against certain cardiovascular complications and heart disease [5]. However, because the enzyme is highly active, it can sometimes produce an excess of hydrogen peroxide, which may increase the risk of liver sensitivity when taking certain medications like NSAIDs or chemotherapy drugs [6].
Optimal mitochondrial antioxidant capacity; Lower risk of diabetic kidney complications; Increased risk of liver sensitivity to certain medications.
Variants with shared genetic architecture
rs5746136 · SOD2 Gene · Chr 6 · Antioxidant Defense
rs35979828 · NFE2 Gene · Chr 12 · Blood Cell Production
rs1001179 · CAT Gene · Chr 11 · Antioxidant Enzyme Activity
A functional polymorphism in the manganese superoxide dismutase gene and diabetic nephropathy.
Content updated August 2026.
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