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ROBO3

Synonyms
HGPPS, HGPPS1, HGPS, RBIG1, RIG1
External resources
Summary
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.

Variant counts

The variants found in rare patients tested by 3billion are classified and counted according to ACMG guidelines. The variants with over 5% variant frequency in population genome databases ( gnomAD, dbSNP, etc) are excluded.

Pathogenic
660
Likely pathogenic
0
VUS
6,013
Likely benign
6,199
Benign
612

Patient phenotypes

Proportions of phenotypes among 627 patients carrying pathogenic or likely pathogenic variants on ROBO3 gene are displayed below.

Phenotype class
Patients in 3billion (%)
Abnormality of the nervous system
40.2%
Abnormality of the musculoskeletal system
26.5%
Abnormality of the eye
23.3%
Abnormality of head or neck
18.8%
Abnormality of limbs
13.7%
Abnormality of the integument
12%
Growth abnormality
11.8%
Abnormality of the digestive system
10.4%
Abnormality of the immune system
9.9%
Abnormality of the genitourinary system
9.7%
Abnormality of the cardiovascular system
9.6%
Abnormality of the ear
9.3%
Abnormality of the endocrine system
7.3%
Abnormality of blood and blood-forming tissues
7%
Neoplasm
4.3%
Abnormality of the respiratory system
3%
Constitutional symptom
2.7%
Abnormal cellular phenotype
2.4%
Abnormality of prenatal development or birth
1.1%
Abnormality of the voice
0.8%
Abnormality of the breast
0.6%
Abnormality of metabolism homeostasis
0%
Abnormality of the thoracic cavity
0%

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