TMPRSS6 V736A — mild iron-deficiency tendency
One copy of the TMPRSS6 V736A variant detected.
You have one copy of a TMPRSS6 version that tends to nudge iron levels slightly lower.
One copy of V736A is associated with mildly lower average serum iron, transferrin saturation, and haemoglobin. The effect is small and well within the normal range for most carriers, but heterozygotes are modestly more prone to dietary iron deficiency under stress (menstruation, pregnancy, vegetarian diets).
One copy of this DNA change tends to pull your iron and haemoglobin levels slightly lower than average. For most carriers, this stays well within normal — but you may be a little more prone to running low on iron during heavy periods, pregnancy, or on a low-iron diet.
What this means
TMPRSS6 codes for matriptase-2, a hepatocyte protease that suppresses the iron-regulator hepcidin. Loss-of-function mutations cause iron- refractory iron deficiency anaemia. The common V736A variant (rs855791) is the dominant common-variant predictor of iron status in the general population: A-allele carriers have slightly elevated hepcidin, slightly reduced iron absorption, slightly lower serum iron, transferrin saturation, and haemoglobin. The effect is small per allele but is consistently among the top hits in GWAS of iron biomarkers, and is genuinely the mirror image of the HFE iron- *overload* story.
TMPRSS6 makes an enzyme in the liver that tells the body to soak more iron out of food. A common DNA change makes that signal a little weaker, so people who carry it tend to have slightly lower iron and haemoglobin levels. The effect on any one person is small — most carriers test in the normal range — but it is the strongest common DNA change linked to iron status, and it's a nice mirror to the HFE genes that pull in the other direction (storing too much iron). Practically, this matters most for people who lose iron regularly (heavy periods, pregnancy) or whose diets are low in iron-rich foods.
Caveats
- Effect per allele is small; most carriers test within the normal range.
- Iron status depends much more strongly on diet, blood loss, and pregnancy than on this variant.
- A simple iron panel (ferritin, transferrin saturation, haemoglobin) gives the real clinical picture.
- This is unrelated to hereditary haemochromatosis (the HFE story) — it pulls iron in the opposite direction.
Populations
- Studied across European, East Asian, and South Asian populations; effect direction consistent
References
- Benyamin et al. — Common variants in TMPRSS6 are associated with iron status and erythrocyte volume (Nature Genetics, 2009)
- Chambers et al. — Genome-wide association study identifies variants in TMPRSS6 associated with hemoglobin levels (Nature Genetics, 2009)
- Bell et al. — A genome-wide meta-analysis yields 46 new loci associating with biomarkers of iron homeostasis (Communications Biology, 2021)