| Modification Notes |
SHFM3 (split-hand/foot malformation type 3), also known as FBXW4 (F-box and WD-40 domain-containing protein 4) or Dactylin, is a 412 amino acid protein that is primarily involved in signaling pathways that are essential for normal limb development. Specifically, SHFM3 promotes ubiquination and degradation of certain phosphorylated proteins. Defects in the gene encoding SHFM3 are the cause of split-hand/foot malformation type 3, an autosomal dominant disorder that is characterized by hypoplasia/aplasia of the central digits, causing variable fusion with the remaining digits. The disease is not a result of a point mutation, but rather a genomic rearrangement resulting in a tandem duplication that contains a disrupted copy of the gene encoding SHFM3, as well as extra copies of two other genes that are linked to limb development. SHFM3 is typically expressed in kidney, brain, lung and liver, with highest expression in fetal brain. |