 Phenotypes caused by deficiency of MSX1 protein might depend on the localization of mutations and their effect on the protein structure and function.Two substitution mutations, Arg196Pro and Met61Lys cause only familial non-syndromic tooth agenesis.Frameshift mutations, Ser202Stop mutation, resulting in a protein that lacks the C-terminal end of the homeodomain, impairs not only teeth but also nail formation, while Ser105Stop mutation, causing complete absence of the MSX1 homeodomain, is responsible for the most severe phenotype, which includes orofacial clefts with accompanied tooth agenesis.