Manganese Genetics: How Genes Affect Absorption and Levels

Last reviewed: May 12, 2026 Last updated: May 12, 2026

Written by: Jay Hastings , CEO of PlexusDx

Jay Hastings is the CEO of PlexusDx, a precision health company focused on genetic testing, blood biomarker insights, and personalized wellness recommendations. He has more than 20 years of experience across healthcare innovation, genomics, laboratory operations, healthcare investing, and strategic finance. His work has included scaling healthcare startups, leading CLIA lab integrations, and helping expand consumer access to precision health tools.

Medically reviewed by: Jayden Lee, PharmD, EMBA

Jayden Lee, PharmD, EMBA, is the PlexusDx Medical Science Liaison with a PharmD and MBA specializing in pharmacogenomics and clinical product development, with a proven ability to bridge the gap between genomic research and practical patient outcomes. Dr. Lee has more than 10 years of professional experience in clinical pharmacy, academia, and research.

This article is part of the PlexusDx Education Hub — your resource for evidence-based guidance on trace minerals and genetics. Browse all Nutrition & Minerals education

Manganese is a trace mineral most people never think about, yet the body depends on it for building bone, metabolizing carbohydrates, and defending cells against oxidative stress. Both too little and too much can cause problems, and how efficiently you absorb and clear manganese is shaped in part by your genes. Understanding that inherited layer can make sense of otherwise puzzling mineral levels.

Why Manganese Matters in the Body

Manganese is a required cofactor for several enzymes. It activates glutamine synthetase in the brain, arginase in the urea cycle, and pyruvate carboxylase in energy metabolism. It is also the metal at the core of manganese superoxide dismutase, the mitochondrial enzyme that neutralizes reactive oxygen species. Because these roles touch so many systems, the body keeps manganese within a narrow range rather than simply storing surplus.

Most adults get enough manganese from whole grains, nuts, legumes, leafy greens, and tea. True dietary deficiency is rare. The more common concern is dysregulation — the body absorbing or retaining too much, or failing to excrete it through bile as it should.

How the Body Absorbs and Regulates Manganese

Manganese is taken up in the small intestine, carried in the blood, and cleared mainly through bile into the stool. A small set of transporter proteins moves manganese across cell membranes in each of these steps. When one of these transporters works differently because of a genetic variant, the whole balance can shift — sometimes toward accumulation, sometimes toward lower circulating levels. This is why two people eating similar diets can land at different manganese concentrations.

SLC39A8 (ZIP8) and the rs13107325 Variant

SLC39A8 encodes ZIP8, a transporter that carries manganese, zinc, and iron into cells. The common missense variant rs13107325 (A391T) reduces ZIP8 activity and is one of the most consistently replicated signals in human genetics — it has been linked in large studies to lower blood manganese, altered protein glycosylation, blood pressure, and body-mass measures. Carriers often show reduced manganese uptake, which in turn can affect enzymes that depend on the mineral. It is a clear example of a single named variant with wide biological reach.

SLC30A10 and SLC39A14: The Manganese Exporters

SLC30A10 is a dedicated manganese efflux transporter that helps the liver dump excess manganese into bile. Rare loss-of-function mutations cause an inherited manganese-overload syndrome with neurological features, because the body can no longer clear the mineral efficiently. SLC39A14 plays a complementary role in delivering circulating manganese to the liver for excretion. Together these two genes illustrate that "regulation" is as much about getting rid of manganese as taking it in.

Manganese, MnSOD, and Oxidative Balance

One of manganese's most important jobs is supplying the active site of manganese superoxide dismutase, encoded by SOD2. The well-studied SOD2 variant rs4880 (Val16Ala) changes how efficiently the enzyme is imported into mitochondria, influencing antioxidant capacity. When manganese availability and SOD2 function are considered together, you get a fuller picture of how well a person's cells buffer oxidative stress — a genuinely gene-times-nutrient interaction.

Working With a Provider on Manganese Balance

Because both deficiency and overload carry risks, manganese is not a mineral to supplement casually. Whole-food sources are generally safe; high-dose supplements and certain occupational or water exposures are where problems arise. If a blood test flags an unusual level, a clinician can look at diet, liver function, and exposure history in context. Genetic variants add background — they do not replace testing or clinical judgment.

Frequently Asked Questions About Manganese and Genetics

Can genetics cause high or low manganese levels?

Yes. Variants in transporter genes such as SLC39A8, SLC30A10, and SLC39A14 change how efficiently the body absorbs and excretes manganese. These inherited differences help explain why people on similar diets can have different blood levels, though diet, liver function, and exposure still play major roles.

Should I take a manganese supplement?

Most people meet their needs through whole grains, nuts, legumes, and leafy greens, so routine supplementation is rarely necessary. Because excess manganese can be harmful, especially with certain genetic or liver conditions, discuss any supplement with a qualified provider rather than self-dosing based on general advice.

What does a genetic test tell me about manganese?

A pathway-level genetic test offers educational context about how your biology handles minerals and oxidative stress, including genes like SOD2 that depend on manganese. It does not diagnose a deficiency or overload and does not replace a blood test interpreted by your healthcare provider.

Want to understand how your biology handles minerals at the pathway level? The Precision Peptide Genetic Test analyzes 14 pathways, 49 peptides, 150+ genetic insights — offering educational, pathway-level context about the biology discussed here, not a diagnosis or a treatment plan. Your results are a starting point for a conversation with your provider, not the end of one.

The Precision Peptide Genetic Test analyzes how your genes influence peptide-related biological pathways. It does not recommend, prescribe, or determine which peptides you should use, and it does not diagnose, treat, cure, manage, or prevent any condition. Consult a qualified healthcare provider before beginning any peptide protocol or making changes to your care.

This article is part of the PlexusDx Education Hub. Browse all Nutrition & Minerals education

Medical and Editorial Standards

Medical review process: This article was reviewed for medical accuracy, scientific clarity, evidence alignment, and appropriate discussion of genetics, medications, supplements, biomarkers, and health-related claims.

Sources and evidence: PlexusDx educational content is developed using peer-reviewed research, clinical literature, reputable medical references, and, where applicable, public health or regulatory guidance. References are included at the end of the article when scientific, medical, or health-related claims are discussed.

Commercial transparency: PlexusDx offers genetic testing, blood biomarker testing, personalized supplement recommendations, and related precision wellness services. Product mentions are intended to help readers understand available options and should not be interpreted as medical advice.

Important disclaimer: PlexusDx educational content is for informational purposes only and should not be used as a substitute for professional medical advice, diagnosis, or treatment. Always consult a qualified healthcare provider before making decisions about medications, supplements, genetic testing, lab testing, or health-related care.