The ROBO1 gene encodes a member of the Neural Cell Adhesion Molecule (NCAM) family, a subset of the Immunoglobulin superfamily (IgSF). The ROBO1 protein functions as an integral membrane receptor for SLIT1 and SLIT2, and is involved in axon guidance and cell migration. It is particularly involved in axonal navigation at the ventral midline of the neural tube, thus ensuring appropriate nervous system development. The protein is also engaged in the biological processes of chemorepulsion involved in postnatal olfactory bulb interneuron migration, cell migration involved in sprouting angiogenesis, inhibition of mammary gland epithelial cell proliferation and inhibition of the chemokine-mediated signaling pathway.
Researchers have noted the presence of a splice variant, designated DUTT1, that differs in function from ROBO1. While ROBO1 plays a role in neuronal development, DUTT1 is believed to be involved in tumor suppression. Haploinsufficiency of the ROBO1 gene has been suggested to predispose humans to developmental dyslexia. Studies have also identified an age-varying association between a ROBO1 SNP and obesity.
The ROBO1 gene is located on the short arm of chromosome 3. It spans a length of 1170.7 kb of DNA and its coding sequence is spread across 35 exons. The gene encodes a 180.9 kDa protein product composed of 1651 amino acids. Several additional isoforms of the ROBO1 protein exist due to alternatively spliced transcript variants. The gene is widely expressed in the human body, particularly in the nervous system, lung and heart.
The translocation t(3;8)(p12;q11) affecting intron 1 of the gene is tentatively associated with dyslexia while the SNP rs1455832 has an age-dependent association with increased BMI (Body Mass Index).
Monies et al. (2017) illustrated the genomic landscape of Saudi Arabia based on the findings of 1000 diagnostic panels and exomes. One patient, a 7-year-old male, presented with Intellectual disability, epilepsy, autism, ADHD and mitral regurgitation. Whole exome sequencing helped identify a heterozygous mutation (c.2990A>T, p.D997V) in exon 21 of the patient’s ROBO1 gene. This gene mutation was considered a candidate for pathogenicity as it was a novel variant predicted to be deleterious; and the ROBO1 gene has been suggested to be associated with autism. Also, the gene has a %HI score of 3 in DECIPHER. The authors noted that further studies are required to confirm this association.