The TRESK (KCNK18) gene plays a crucial role in the formation of the protein TWIK related spinal cord potassium channel which is involved in transmission of signals between the nerve cells. Mutation in the TRESK gene will inhibit the function of TRESK protein thereby causing Migraines disorder. In the present study, we have employed the different genomic algorithms for the prioritization of missense mutations available in the SNP database. A total of 26 SNPs were retrieved for our analysis. The result indicates that 2 nsSNPs such as C110R and A156P were predicted to be highly significant mutation in the TRESK gene. Subsequently the structural and functional effect of these mutations was examined using molecular dynamics simulation study. We sincerely hope that the results could of immense importance in the understanding genetic basis of the migraines disorder. Copyright © 2013 American Scientific Publishers.