ROBO1 (roundabout, axon guidance receptor, homolog 1 (Drosophila))

2008-12-01 Joern Groene , Oliver Doebler Affiliation

Identity

HGNC

ROBO1

LOCATION

3p12.3

LOCUSID

6091

ALIAS

DUTT1,SAX3

FUSION GENES

Show Gene Fusions

DNA/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

T-acute lymphoblastic leukaemia

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

Gene ID	Transcript ID	Uniprot
ENSG00000169855	ENST00000436010	A0A0A0MSX4
ENSG00000169855	ENST00000464233	Q9Y6N7
ENSG00000169855	ENST00000467549	Q9Y6N7
ENSG00000169855	ENST00000472273	H7C545
ENSG00000169855	ENST00000492990	F8WEV8
ENSG00000169855	ENST00000495273	Q9Y6N7
ENSG00000169855	ENST00000495961	H7C4Y7
ENSG00000169855	ENST00000618833	A0A087WTM1
ENSG00000169855	ENST00000618846	A0A087WZ85

Expression (GTEx)

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

Pathway	Source	External ID
Axon guidance	KEGG	ko04360
Axon guidance	KEGG	hsa04360
Developmental Biology	REACTOME	R-HSA-1266738
Axon guidance	REACTOME	R-HSA-422475
Netrin-1 signaling	REACTOME	R-HSA-373752
Signaling by Robo receptor	REACTOME	R-HSA-376176
Regulation of Commissural axon pathfinding by Slit and Robo	REACTOME	R-HSA-428542
Inactivation of Cdc42 and Rac	REACTOME	R-HSA-428543
Activation of Rac	REACTOME	R-HSA-428540
Role of Abl in Robo-Slit signaling	REACTOME	R-HSA-428890

Protein levels (Protein atlas)

Not detected

Low

Medium

High

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