ROBO3 (Roundabout Guidance Receptor 3) is a Protein Coding gene. Diseases associated with ROBO3 include gaze palsy, horizontal, with progressive scoliosis and scoliosis. Among its related pathways are Developmental Biology and Development Slit-Robo signaling. An important paralog of this gene is IGDCC3. This gene is a member of the Roundabout (ROBO) gene family that controls neurite outgrowth, growth cone guidance, and axon fasciculation. ROBO proteins are a subfamily of the immunoglobulin transmembrane receptor superfamily. SLIT proteins 1-3, a family of secreted chemorepellants, are ligands for ROBO proteins and SLIT/ROBO interactions regulate myogenesis, leukocyte migration, kidney morphogenesis, angiogenesis, and vasculogenesis in addition to neurogenesis. This gene, ROBO3, has a putative extracellular domain with five immunoglobulin (Ig)-like loops and three fibronectin (Fn) type III motifs, a transmembrane segment, and a cytoplasmic tail with three conserved signaling motifs: CC0, CC2, and CC3 (CC for conserved cytoplasmic). Unlike other ROBO family members, ROBO3 lacks motif CC1. The ROBO3 gene regulates axonal navigation at the ventral midline of the neural tube. In mouse, loss of Robo3 results in a complete failure of commissural axons to cross the midline throughout the spinal cord and the hindbrain. Mutations ROBO3 result in horizontal gaze palsy with progressive scoliosis (HGPPS); an autosomal recessive disorder characterized by congenital absence of horizontal gaze, progressive scoliosis, and failure of the corticospinal and somatosensory axon tracts to cross the midline in the medulla. Alternative transcript variants have been described but have not been experimentally validated.
Familial horizontal gaze palsy with progressive scoliosis (HGPPS) [MIM:607313]: Patients show a medulla where motor and sensory projections appear uncrossed. Note=The disease is caused by mutations affecting the gene represented in this entry. Roundabout homolog 3 is a protein that in humans is encoded by the ROBO3 gene. 0ROBO3, members of the ROBO family are a group of highly conserved transmembrane glycoproteins that make up a small subgroup of the immunoglobulin (Ig) superfamily. They are characterized structurally by five C2-type Ig-like repeats, three fibronectin type III domains, a transmembrane region, and an intracellular domain with three (ROBO3) or four (ROBO1, 2) CC (conserved cytoplasmic) motifs. ROBO4, a fourth putative family member, has been identified, but lacks one of the three fibronectin-like domains and two of the five Ig-like domains. ROBOs are best known for their roles as receptors for the Slit family of repellent axon guidance cues.