Manganese is an essential element for organisms that can also be toxic. It has been stated that more than 5 mM Mn inhibits the growth of wild-type S. cerevisiae BY4741 strain. In the cases when this amount is exceeded, the stress upon manganese toxicity arises and it leads to a range of responses to normalize the manganese level. However, the genes accountable for that case are unknown. Manganese toxicity is a restrictor factor in the production of agricultural products. Identification and characterization of the genes that play a role in manganese homeostasis are rather essential. In this study, we have used Sanger Centre's Saccharomyces Genome Resequencing Project (SGRP) strains, which are collected from different regions of the world. After screened the whole collection, we have identified four manganese resistant strains; S. cerevisiae BY474, S. paradoxus Y6.5, S. cerevisiae 378604X and S. paradoxus Q74.4. Manganese-related genes were selected via the Saccharomyces genome database (SGD). Expression levels of these genes under manganese stress in most resistant strain Q74.4 analyzed by RT-Q-PCR. As a result, GCR-1 dependent translation factor GDT1 and high-affinity phosphate transporter PHO84 were found to be upregulated in Q74.4 that endure high levels of manganese toxicity. These genes are probably accountable for manganese tolerance in Q74.4 strain. The results arising from that study, will take the lead to the development of biotechnological exercises for manganese bioremediation. Meanwhile, it might help molecular mechanisms to be able to develop resistance to stressful conditions that manganese generates and shed light to further studies.