TLX1 is highly expressed in zeugopod region and is used to maintain normal development of ulna and radius.[22] BTRC plays a role in ubiquitination factor of proteins which is involved in various signaling transduction pathways such as Wnt/â-catenin, Sonic hedgehog and NF-êB.[23] For example, the duplication of BTRC in SHFM3 may result to lower levels of â-catenin in the AER and also leads to ectrodactyly. This evidence concerns the gene FBXW4 and split hand-foot malformation.