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Genetics Home Reference: your guide to understanding genetic conditions
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ROBO3

Reviewed March 2009

What is the official name of the ROBO3 gene?

The official name of this gene is “roundabout guidance receptor 3.”

ROBO3 is the gene's official symbol. The ROBO3 gene is also known by other names, listed below.

What is the normal function of the ROBO3 gene?

The ROBO3 gene provides instructions for making a protein that is critical for the normal development of the nervous system. The protein is active in the developing spinal cord and in the brainstem, a region that connects the upper parts of the brain with the spinal cord. In the brainstem, the ROBO3 protein helps direct nerve cells (neurons) to their proper positions in a process called neuronal migration. The protein also helps guide the growth of axons, which are specialized extensions of neurons that transmit nerve impulses throughout the nervous system. Some axons are very long, connecting neurons in the brain with those in the spinal cord and elsewhere in the body.

For the brain and body to communicate effectively, certain bundles of axons must cross from one side of the body to the other in the brainstem. These include axons of motor neurons, which transmit information about voluntary muscle movement, and axons of sensory neurons, which transmit information about sensory input (such as touch, pain, and temperature). The ROBO3 protein plays a critical role in ensuring that this crossing over occurs during brain development.

Does the ROBO3 gene share characteristics with other genes?

The ROBO3 gene belongs to a family of genes called fibronectin type III domain containing (fibronectin type III domain containing). It also belongs to a family of genes called immunoglobulin superfamily, immunoglobulin-like domain containing (immunoglobulin superfamily, immunoglobulin-like domain containing). It also belongs to a family of genes called immunoglobulin superfamily, I-set domain containing (immunoglobulin superfamily, I-set domain containing).

A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.

How are changes in the ROBO3 gene related to health conditions?

horizontal gaze palsy with progressive scoliosis - caused by mutations in the ROBO3 gene

At least 19 different mutations in the ROBO3 gene have been identified in people with horizontal gaze palsy with progressive scoliosis (HGPPS). These mutations change the structure of the ROBO3 protein in different ways; however, all of the mutations appear to result in a nonfunctional protein. A lack of functional ROBO3 protein disrupts normal brainstem development.

In people with HGPPS, the axons of motor and sensory neurons do not cross over in the brainstem, but stay on the same side of the body. Researchers believe that this miswiring is the underlying cause of the eye movement abnormalities associated with the disorder. The cause of progressive scoliosis in HGPPS is unclear. Researchers are working to determine why the effects of ROBO3 mutations appear to be limited to horizontal eye movement and scoliosis.

Where is the ROBO3 gene located?

Cytogenetic Location: 11q24.2

Molecular Location on chromosome 11: base pairs 124,865,005 to 124,881,473

The ROBO3 gene is located on the long (q) arm of chromosome 11 at position 24.2.

The ROBO3 gene is located on the long (q) arm of chromosome 11 at position 24.2.

More precisely, the ROBO3 gene is located from base pair 124,865,005 to base pair 124,881,473 on chromosome 11.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about ROBO3?

You and your healthcare professional may find the following resources about ROBO3 helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the ROBO3 gene or gene products?

  • FLJ21044
  • HGPS
  • RBIG1
  • retinoblastoma inhibiting gene 1
  • RIG1
  • ROBO3_HUMAN
  • roundabout, axon guidance receptor, homolog 3
  • roundabout, axon guidance receptor, homolog 3 (Drosophila)
  • Roundabout homolog 3
  • Roundabout-like protein 3

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding ROBO3?

axons ; brainstem ; crossing over ; gene ; motor ; nervous system ; neuronal migration ; palsy ; protein ; receptor ; scoliosis ; voluntary muscle

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.

References

  • Abu-Amero KK, al Dhalaan H, al Zayed Z, Hellani A, Bosley TM. Five new consanguineous families with horizontal gaze palsy and progressive scoliosis and novel ROBO3 mutations. J Neurol Sci. 2009 Jan 15;276(1-2):22-6. doi: 10.1016/j.jns.2008.08.026. Epub 2008 Oct 1. (http://www.ncbi.nlm.nih.gov/pubmed/18829051?dopt=Abstract)
  • Amoiridis G, Tzagournissakis M, Christodoulou P, Karampekios S, Latsoudis H, Panou T, Simos P, Plaitakis A. Patients with horizontal gaze palsy and progressive scoliosis due to ROBO3 E319K mutation have both uncrossed and crossed central nervous system pathways and perform normally on neuropsychological testing. J Neurol Neurosurg Psychiatry. 2006 Sep;77(9):1047-53. Epub 2006 Jun 13. (http://www.ncbi.nlm.nih.gov/pubmed/16772357?dopt=Abstract)
  • Chan WM, Traboulsi EI, Arthur B, Friedman N, Andrews C, Engle EC. Horizontal gaze palsy with progressive scoliosis can result from compound heterozygous mutations in ROBO3. J Med Genet. 2006 Mar;43(3):e11. (http://www.ncbi.nlm.nih.gov/pubmed/16525029?dopt=Abstract)
  • Jen JC, Chan WM, Bosley TM, Wan J, Carr JR, Rüb U, Shattuck D, Salamon G, Kudo LC, Ou J, Lin DD, Salih MA, Kansu T, Al Dhalaan H, Al Zayed Z, MacDonald DB, Stigsby B, Plaitakis A, Dretakis EK, Gottlob I, Pieh C, Traboulsi EI, Wang Q, Wang L, Andrews C, Yamada K, Demer JL, Karim S, Alger JR, Geschwind DH, Deller T, Sicotte NL, Nelson SF, Baloh RW, Engle EC. Mutations in a human ROBO gene disrupt hindbrain axon pathway crossing and morphogenesis. Science. 2004 Jun 4;304(5676):1509-13. Epub 2004 Apr 22. (http://www.ncbi.nlm.nih.gov/pubmed/15105459?dopt=Abstract)
  • Jen JC. Effects of failure of development of crossing brainstem pathways on ocular motor control. Prog Brain Res. 2008;171:137-41. doi: 10.1016/S0079-6123(08)00618-3. (http://www.ncbi.nlm.nih.gov/pubmed/18718292?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/64221)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: March 2009
Published: August 24, 2015