FBXW4 and split hand-foot malformation: The best known gene is TP63, mutations that are associated with both syndromal and non-syndromal SHFM.[15,16] Expectedly, the search for TP63 binding sites revealed locations within 300 Kilobyte of genes with several other SHFM loci, which suggests that these sites might consist of the regulatory elements which contributes to SHFM.[15,16] FBXW4 is a member of the F-box-WD40 gene family, whose members encode subunits of ubiquitin ligases that present phosphorylated protein which targets ubiquitin-containing enzymes for degradation.