These mutations are found in all of the major components of the pathway including MSH2, MSH6, MLH3, MLH1, and PMS2 (PMS2 is the human homolog of yeast PMS1) with the majority of the mutations identified in MSH2 and MLH1. Many of the identified missense mutations do not show a clear link to cancer predisposition, and for roughly half of the kindreds displaying the Amsterdam criteria for HNPCC, mutation in a MMR gene has not been identified [24],[25]. This evidence concerns the gene PMS1 and hereditary nonpolyposis colon cancer.