The HED-causing mutations in the TNF domain which affect the function of EDA have been previously analyzed: most mutations (His252Leu, Gly291Trp, Gly291Arg, Gly299Ser, Tyr320Cys, and Ala349Asp) are likely to affect the overall structure of EDA, and some mutations (Tyr343Cys, Ser374Arg, Thr378Pro, and Thr378Met) alter the receptor binding site [27]. Here, EDA is linked to hypohidrotic ectodermal dysplasia.