Nature Publishing Group Acta Medica Okayama 2041-1723 7 2016 A heavy metal P-type ATPase OsHMA4 prevents copper accumulation in rice grain 12138 EN Xin-Yuan Huang Institute of Biological and Environmental Sciences, University of Aberdeen Fenglin Deng Institute of Plant Science and Resources, Okayama University Naoki Yamaji Institute of Plant Science and Resources, Okayama University Shannon R.M. Pinson USDA-ARS Dale Bumpers National Rice Research Center Miho Fujii-Kashino Institute of Plant Science and Resources, Okayama University John Danku Institute of Biological and Environmental Sciences, University of Aberdeen Alex Douglas Mary Lou Guerinot Department of Biological Sciences, Dartmouth College David E. Salt Institute of Biological and Environmental Sciences, University of Aberdeen Jian Feng Ma Institute of Plant Science and Resources, Okayama University Rice is a major source of calories and mineral nutrients for over half the world's human population. However, little is known in rice about the genetic basis of variation in accumulation of copper (Cu), an essential but potentially toxic nutrient. Here we identify OsHMA4 as the likely causal gene of a quantitative trait locus controlling Cu accumulation in rice grain. We provide evidence that OsHMA4 functions to sequester Cu into root vacuoles, limiting Cu accumulation in the grain. The difference in grain Cu accumulation is most likely attributed to a single amino acid substitution that leads to different OsHMA4 transport activity. The allele associated with low grain Cu was found in 67 of the 1,367 rice accessions investigated. Identification of natural allelic variation in OsHMA4 may facilitate the development of rice varieties with grain Cu concentrations tuned to both the concentration of Cu in the soil and dietary needs. No potential conflict of interest relevant to this article was reported.