A computational study has been done on the functional activity and relationship of the human skin genes such as POMC, TYRP1, MC1R, FLG, IFNG and DSG1.These specific genes is a protein-coding gene that has the close related evolutionary relationship. Phylogenetic analysis was performed and mutation analysis using Biobase Human Gene Mutation Database, (HGMD) has been done to obtain protein changes of the mutation and the observable phenotype when each of the gene undergoes mutation. Further analysis on protein modelling of each gene is performed with the aid of RaptorX modelling server and validation of the protein using the SAVES server. As a conclusion, the functional activity and the relationship between the human skin genes can identified using computational method. © 2018, All India Institute of Medical Sciences. All rights reserved.