ROBO1 (roundabout, axon guidance receptor, homolog 1 (Drosophila))
2008-12-01 Joern Groene , Oliver Doebler AffiliationDNA/RNA
Description
30 Exons, 30 coding exons, 992672bp of genomic DNA.
Transcription
Two mRNA transcript variants. Transcript variant 1 contains of 6629b coded by 30 exons. Transcript variant 2 utilizes an alternate exon that contains a different 5UTR and translation start site than that of variant 1. The N-terminus differs from isoform a encoded by variant 1. Transcript variant 2 contains of 6456b coded by 28 exons.
Pseudogene
None known.
Proteins
Description
ROBO1 is a single-pass type 1 membrane protein and interacts with SLIT1 and SLIT2. ROBO1 belongs to the immunglobulin super family of ROBO proteins. It contains of 3 fibronectin type-III domains and 5 immunoglobuline-like C2-type domains. There are 3 protein isoforms existing of ROBO1 produced by alternative splicing.
Expression
ROBO1 expression is seen in a number different tissues and organs.
Localisation
ROBO1 proteins are located in the cellular membrane as a transmembrane protein.
Function
Receptor for SLIT1 and SLIT2 which are thought to act as molecular guidance cue in cellular migration, including axonal navigation at the ventral midline of the neural tube and projection of axons to different regions during neuronal development. In axon growth cones, the silencing of the attractive effect of NTN1 by SLIT2 may require the formation of a ROBO1-DCC complex. Robo1 plays also a role in cell-adhesion. ROBO1 may be required for lung development. It is indicated that ROBO/SLIT is involved in angiogenic mechanisms whereas endothelial cells expressing ROBO1 receptors are attracted by SLIT2 which is secreted by human tumor cells.
Homology
There are 3 paralogs of human ROBO1 : ROBO2, ROBO3 and ROBO4. Orthologs have been identified in mouse, rat, cow, dog, chimpanzee.
Implicated in
Entity name
Lung cancer
Oncogenesis
A deletion of chromosome 3 allele and dysfunction or lack of ROBO1 receptors might be an early somatic genetic change in lung tumor development (Xian et al., 2001; Dallol et al., 2002b; Tsujiuchi et al., 2004; Xian et al., 2004).
Entity name
Breast cancer
Oncogenesis
Breast cancer tumors and tumor cell lines show a suppressed expression of ROBO1 gene (Dallol et al., 2002a; Dallol et al., 2002b).
Entity name
Prostate cancer
Oncogenesis
Human prostate tumors and tumor cell lines show an overexpression of ROBO1 gene (Bonner et al., 2003).
Entity name
Angiogenesis of malignant tumors
Oncogenesis
ROBO1 gene is highly expressed in tumor vessel endothelium. Blocking of ROBO1 receptors causes loss of microvessel density in tumors e.g. malignant melanoma, colorectal cancer (Wang et al., 2003; Suchting et al., 2005; Groene et al., 2006; Legg et al., 2008).
Entity name
Colorectal cancer
Oncogenesis
ROBO1 gene is overexpressed in human colorectal cancer tumor probes and colorectal cancer cell lines (Groene et al., 2006).
Entity name
Cervical cancer
Oncogenesis
Cervical Cancer exhibits highly complex genomic alterations. These include hemizygous deletions at 4p15.3, 10q24, 5q35, 3p12.3, and 11q24, the chromosomal sites of SLIT-ROBO pathway genes (Narayan et al., 2006).
Entity name
Hepatocellular carcinoma
Oncogenesis
ROBO1, a member of the immunoglobulin superfamily, is highly expressed in hepatocellular carcinoma, whereas it showes only a limited distribution in normal liver tissue. Strikingly, the ectodomain of ROBO1 was detected not only in the culture medium of liver cancer cell lines (PLC/PRF/5, HepG2, etc.) but also in sera from hepatocellular carcinoma patients (Ito et al., 2006).
Entity name
Oncogenesis
ROBO1 gene alterations were detected in subpopulations with childhood T-acute lymphoblastic leukaemia (Haltrich et al., 2007).
Entity name
Nasopharyngeal carcinoma
Oncogenesis
In an inducible Epstein-Barr virus (EBV) nasopharyngeal cell line was a increased expression of ROBO1 detected that may be cause a role in this tumor carcinogenesis (Lee et al., 2008).
Entity name
Dyslexia
Disease
Dyslexia may be caused by partial haplo-insufficiency for ROBO1 in rare families. A slight disturbance in neuronal axon crossing across the midline between brain hemispheres, dendrite guidance, or another function of ROBO1 may manifest as a specific reading disability in humans (Hannula-Jouppi et al., 2005; Fisher and Francks, 2006; McGrath et al., 2006; Shastry, 2007; Paracchini et al., 2007).
Entity name
Autism
Disease
Gene expression analysis show a reduced expression for ROBO1 in the autistic patient group and may play a role in pathogenesis of autism (Anitha et al., 2008).
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 18270976 | 2008 | Genetic analyses of roundabout (ROBO) axon guidance receptors in autism. | Anitha A et al |
| 12807961 | 2003 | Gene expression signatures identify novel regulatory pathways during murine lung development: implications for lung tumorigenesis. | Bonner AE et al |
| 12384551 | 2002 | SLIT2, a human homologue of the Drosophila Slit2 gene, has tumor suppressor activity and is frequently inactivated in lung and breast cancers. | Dallol A et al |
| 12082532 | 2002 | Tumour specific promoter region methylation of the human homologue of the Drosophila Roundabout gene DUTT1 (ROBO1) in human cancers. | Dallol A et al |
| 16675285 | 2006 | Genes, cognition and dyslexia: learning to read the genome. | Fisher SE et al |
| 16685377 | 2006 | Robo1/Robo4: differential expression of angiogenic markers in colorectal cancer. | Gröne J et al |
| 17175380 | 2007 | Multipoint interphase FISH in childhood T-acute lymphoblastic leukemia detects subpopulations that carry different chromosome 3 aberrations. | Haltrich I et al |
| 16254601 | 2005 | The axon guidance receptor gene ROBO1 is a candidate gene for developmental dyslexia. | Hannula-Jouppi K et al |
| 16740745 | 2006 | Identification of ROBO1 as a novel hepatocellular carcinoma antigen and a potential therapeutic and diagnostic target. | Ito H et al |
| 12471613 | 2003 | Quantification of expression of netrins, slits and their receptors in human prostate tumors. | Latil A et al |
| 18656687 | 2008 | Amplicons on chromosome 3 contain oncogenes induced by recurrent exposure to 12-O-tetradecanoylphorbol-13-acetate and sodium n-butyrate and Epstein-Barr virus reactivation in a nasopharyngeal carcinoma cell line. | Lee CH et al |
| 18264786 | 2008 | Slits and Roundabouts in cancer, tumour angiogenesis and endothelial cell migration. | Legg JA et al |
| 16781891 | 2006 | Breakthroughs in the search for dyslexia candidate genes. | McGrath LM et al |
| 17704564 | 2007 | Production of Slit2 LRR domains in mammalian cells for structural studies and the structure of human Slit2 domain 3. | Morlot C et al |
| 16700909 | 2006 | Promoter hypermethylation-mediated inactivation of multiple Slit-Robo pathway genes in cervical cancer progression. | Narayan G et al |
| 17444811 | 2007 | The genetic lexicon of dyslexia. | Paracchini S et al |
| 17094062 | 2006 | [Genetics of dyslexia]. | Schulte-Körne G et al |
| 17111266 | 2007 | Developmental dyslexia: an update. | Shastry BS et al |
| 15486058 | 2005 | Soluble Robo4 receptor inhibits in vivo angiogenesis and endothelial cell migration. | Suchting S et al |
| 15264215 | 2004 | Alterations of the Dutt1/Robo1 gene in lung adenocarcinomas induced by N-nitrosobis(2-hydroxypropyl)amine in rats. | Tsujiuchi T et al |
| 12892710 | 2003 | Induction of tumor angiogenesis by Slit-Robo signaling and inhibition of cancer growth by blocking Robo activity. | Wang B et al |
| 18201275 | 2008 | Targeting Slit-Roundabout signaling inhibits tumor angiogenesis in chemical-induced squamous cell carcinogenesis. | Wang LJ et al |
| 15374951 | 2004 | Targeted disruption of the 3p12 gene, Dutt1/Robo1, predisposes mice to lung adenocarcinomas and lymphomas with methylation of the gene promoter. | Xian J et al |
| 11734623 | 2001 | Inadequate lung development and bronchial hyperplasia in mice with a targeted deletion in the Dutt1/Robo1 gene. | Xian J et al |
Other Information
Locus ID:
NCBI: 6091
MIM: 602430
HGNC: 10249
Ensembl: ENSG00000169855
Variants:
dbSNP: 6091
ClinVar: 6091
TCGA: ENSG00000169855
COSMIC: ROBO1
RNA/Proteins
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 38414132 | 2024 | Stromal Cell-SLIT3/Cardiomyocyte-ROBO1 Axis Regulates Pressure Overload-Induced Cardiac Hypertrophy. | 0 |
| 38414132 | 2024 | Stromal Cell-SLIT3/Cardiomyocyte-ROBO1 Axis Regulates Pressure Overload-Induced Cardiac Hypertrophy. | 0 |
| 36459288 | 2023 | MicroRNA-588 regulates the invasive, migratory and vasculogenic mimicry-forming abilities of hypoxic glioma cells by targeting ROBO1. | 1 |
| 38019913 | 2023 | ROBO1 deficiency impairs HSPC homeostasis and erythropoiesis via CDC42 and predicts poor prognosis in MDS. | 0 |
| 36459288 | 2023 | MicroRNA-588 regulates the invasive, migratory and vasculogenic mimicry-forming abilities of hypoxic glioma cells by targeting ROBO1. | 1 |
| 38019913 | 2023 | ROBO1 deficiency impairs HSPC homeostasis and erythropoiesis via CDC42 and predicts poor prognosis in MDS. | 0 |
| 34490644 | 2022 | Ductular reaction promotes intrahepatic angiogenesis through Slit2-Roundabout 1 signaling. | 14 |
| 35227688 | 2022 | Biallelic pathogenic variants in roundabout guidance receptor 1 associate with syndromic congenital anomalies of the kidney and urinary tract. | 6 |
| 35236289 | 2022 | miR-152-3p impedes the malignant phenotypes of hepatocellular carcinoma by repressing roundabout guidance receptor 1. | 4 |
| 35348658 | 2022 | Novel dominant and recessive variants in human ROBO1 cause distinct neurodevelopmental defects through different mechanisms. | 3 |
| 35534675 | 2022 | Identification of non-synonymous variations in ROBO1 and GATA5 genes in a family with bicuspid aortic valve disease. | 3 |
| 35584116 | 2022 | An ancient founder mutation located between ROBO1 and ROBO2 is responsible for increased microtia risk in Amerindigenous populations. | 3 |
| 36029493 | 2022 | MiR-218 Targeted Regulation of Robol Expression Regulates Proliferation, Invasion and Migration of Glioma Cells. | 0 |
| 36042257 | 2022 | NMR analysis suggests the terminal domains of Robo1 remain extended but are rigidified in the presence of heparan sulfate. | 1 |
| 36277474 | 2022 | Tumor-Derived Exosomal miR-29b Reduces Angiogenesis in Pancreatic Cancer by Silencing ROBO1 and SRGAP2. | 7 |
Citation
Joern Groene ; Oliver Doebler
ROBO1 (roundabout, axon guidance receptor, homolog 1 (Drosophila))
Atlas Genet Cytogenet Oncol Haematol. 2008-12-01
Online version: http://atlasgeneticsoncology.org/gene/42140/robo1-(roundabout-axon-guidance-receptor-homolog-1-(drosophila))
