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ROBO2 Gene(Protein Coding)

Roundabout Guidance Receptor 2

GCID:
GC03P075955
GIFtS:
49
Genes Participants
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Aliases for ROBO2 Gene

Aliases for ROBO2 Gene

  • Roundabout Guidance Receptor 2 2 3 5
  • Roundabout, Axon Guidance Receptor, Homolog 2 (Drosophila) 2
  • Roundabout (Axon Guidance Receptor, Drosophila) Homolog 2 2
  • Roundabout, Axon Guidance Receptor, Homolog 2 3
  • Roundabout Homolog 2 3
  • KIAA1568 4
  • SAX3 3

External Ids for ROBO2 Gene

Previous GeneCards Identifiers for ROBO2 Gene

  • GC03P075389
  • GC03P077181
  • GC03P076895
  • GC03P077010
  • GC03P077009
  • GC03P077172
  • GC03P077608
  • GC03P076069

Summaries for ROBO2 Gene

Entrez Gene Summary for ROBO2 Gene

  • The protein encoded by this gene belongs to the ROBO family, part of the immunoglobulin superfamily of proteins that are highly conserved from fly to human. The encoded protein is a transmembrane receptor for the slit homolog 2 protein and functions in axon guidance and cell migration. Mutations in this gene are associated with vesicoureteral reflux, characterized by the backward flow of urine from the bladder into the ureters or the kidney. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

GeneCards Summary for ROBO2 Gene

ROBO2 (Roundabout Guidance Receptor 2) is a Protein Coding gene. Diseases associated with ROBO2 include Vesicoureteral Reflux 2 and Familial Vesicoureteral Reflux. Among its related pathways are Developmental Biology and Development Slit-Robo signaling. Gene Ontology (GO) annotations related to this gene include identical protein binding and axon guidance receptor activity. An important paralog of this gene is ROBO1.

UniProtKB/Swiss-Prot for ROBO2 Gene

  • Receptor for SLIT2, and probably SLIT1, 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.

Gene Wiki entry for ROBO2 Gene

Additional gene information for ROBO2 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for ROBO2 Gene

Genomics for ROBO2 Gene

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  1. Regulatory Element

GeneHancer (GH) Regulatory Elements for ROBO2 Gene

Promoters and enhancers for ROBO2 Gene
GeneHancer (GH) Identifier GH Type GH
Score		 GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites		 Gene Targets
GH03J075906 Enhancer 0.4 ENCODE 650.7 -0.1 -67 0.9 CTCF L3MBTL2 POLR2A ROBO2 ZNF717
GH03J076684 Enhancer 0.2 FANTOM5 4.5 +777.7 777688 0.2 ROBO2 LOC102724949 GC03P076507
GH03J076556 Enhancer 0.2 FANTOM5 2.4 +649.7 649696 0.4 ROBO2 GC03P076507 LOC102724949
GH03J076042 Enhancer 0.7 ENCODE dbSUPER 0.1 +137.3 137262 2.2 CTCF NANOG HLF POU5F1 ZNF24 ETS1 HNRNPA3P6 GC03P076036 GC03M076048 ROBO2
GH03J076037 Enhancer 0.6 ENCODE dbSUPER 0.1 +132.1 132056 2.5 NANOG POU5F1 ETS1 LINC00960 GC03P076036 GC03M076048 ROBO2
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around ROBO2 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the ROBO2 gene promoter:
  • Lmo2
  • Tal-1beta
  • E47
  • Pax-4a
  • AREB6
  • STAT2
  • STAT4
  • STAT3
  • STAT1beta
  • STAT1alpha

Genomic Locations for ROBO2 Gene

Genomic Locations for ROBO2 Gene
chr3:75,906,675-77,649,964
(GRCh38/hg38)
Size:
1,743,290 bases
Orientation:
Plus strand
chr3:75,955,845-77,699,115
(GRCh37/hg19)
Size:
1,743,271 bases
Orientation:
Plus strand

Genomic View for ROBO2 Gene

Genes around ROBO2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
ROBO2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for ROBO2 Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for ROBO2 Gene

Proteins for ROBO2 Gene

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  • Protein details for ROBO2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9HCK4-ROBO2_HUMAN
    Recommended name:
    Roundabout homolog 2
    Protein Accession:
    Q9HCK4
    Secondary Accessions:
    • O43608
    • Q19AB4
    • Q19AB5

    Protein attributes for ROBO2 Gene

    Size:
    1378 amino acids
    Molecular mass:
    151200 Da
    Quaternary structure:
    • Interacts with SLIT2.
    SequenceCaution:
    • Sequence=AAC39576.1; Type=Frameshift; Positions=601; Evidence={ECO:0000305}; Sequence=BAB13394.1; Type=Erroneous initiation; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for ROBO2 Gene

    Alternative splice isoforms for ROBO2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for ROBO2 Gene

Protein Expression for ROBO2 Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Post-translational modifications for ROBO2 Gene

  • Glycosylation at posLast=845845, posLast=789789, Asn782, Asn752, posLast=426426, and posLast=123123
  • Modification sites at PhosphoSitePlus

Other Protein References for ROBO2 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for ROBO2 Gene

Domains & Families for ROBO2 Gene

Gene Families for ROBO2 Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Plasma proteins
  • Predicted intracellular proteins
  • Predicted membrane proteins

Protein Domains for ROBO2 Gene

Blocks:
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for ROBO2 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q9HCK4

UniProtKB/Swiss-Prot:

ROBO2_HUMAN :
  • Belongs to the immunoglobulin superfamily. ROBO family.
Family:
  • Belongs to the immunoglobulin superfamily. ROBO family.
genes like me logo Genes that share domains with ROBO2: view

Function for ROBO2 Gene

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  2. CRISPR
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Molecular function for ROBO2 Gene

UniProtKB/Swiss-Prot Function:
Receptor for SLIT2, and probably SLIT1, 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.

Phenotypes From GWAS Catalog for ROBO2 Gene

Gene Ontology (GO) - Molecular Function for ROBO2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IEA,IPI 12504588
GO:0008046 axon guidance receptor activity NAS 9458045
GO:0042802 identical protein binding IDA 12504588
genes like me logo Genes that share ontologies with ROBO2: view
genes like me logo Genes that share phenotypes with ROBO2: view

Human Phenotype Ontology for ROBO2 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for ROBO2 Gene

MGI Knock Outs for ROBO2:

Animal Model Products

Clone Products

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for ROBO2 Gene

Localization for ROBO2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for ROBO2 Gene

Membrane; Single-pass type I membrane protein.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for ROBO2 gene
Compartment Confidence
plasma membrane 5
extracellular 5
cytoskeleton 2
nucleus 2
peroxisome 1
endoplasmic reticulum 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Microtubule organizing center (2)
  • Nucleus (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for ROBO2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005886 plasma membrane TAS --
GO:0009986 cell surface IDA 12504588
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
GO:0030673 axolemma ISS,IEA --
genes like me logo Genes that share ontologies with ROBO2: view

Pathways & Interactions for ROBO2 Gene

genes like me logo Genes that share pathways with ROBO2: view

Pathways by source for ROBO2 Gene

1 KEGG pathway for ROBO2 Gene
1 GeneGo (Thomson Reuters) pathway for ROBO2 Gene

Gene Ontology (GO) - Biological Process for ROBO2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001656 metanephros development ISS --
GO:0001657 ureteric bud development IMP 17357069
GO:0001822 kidney development IEA --
GO:0006935 chemotaxis IEA --
GO:0007155 cell adhesion IEA --
genes like me logo Genes that share ontologies with ROBO2: view

No data available for SIGNOR curated interactions for ROBO2 Gene

Drugs & Compounds for ROBO2 Gene

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  1. Drug
No Compound Related Data Available

Transcripts for ROBO2 Gene

Products:

  1. CRISPR
  2. miRNA
  3. Inhibitory RNA
  4. Clone

mRNA/cDNA for ROBO2 Gene

(31) REFSEQ mRNAs :
(12) Additional mRNA sequences :
(90) Selected AceView cDNA sequences:
(13) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for ROBO2 Gene

Roundabout, axon guidance receptor, homolog 2 (Drosophila):
Representative Sequences:

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for ROBO2 Gene

No ASD Table

Relevant External Links for ROBO2 Gene

GeneLoc Exon Structure for
ROBO2
ECgene alternative splicing isoforms for
ROBO2

Expression for ROBO2 Gene

Products:

  1. Primer
  2. Gene Expression Assay

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for ROBO2 Gene

mRNA expression in normal human tissues for ROBO2 Gene
mRNA expression by GTEx for ROBO2 GenemRNA expression by BioGPS for ROBO2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for ROBO2 Gene

This gene is overexpressed in Brain - Anterior cingulate cortex (BA24) (x5.7), Brain - Putamen (basal ganglia) (x5.1), Brain - Caudate (basal ganglia) (x5.0), and Brain - Frontal Cortex (BA9) (x4.1).

Protein differential expression in normal tissues from HIPED for ROBO2 Gene

This gene is overexpressed in Fetal Brain (24.9), Heart (18.0), and Breast (18.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for ROBO2 Gene



Protein tissue co-expression partners for ROBO2 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of ROBO2 Gene:

ROBO2

SOURCE GeneReport for Unigene cluster for ROBO2 Gene:

Hs.13305

Evidence on tissue expression from TISSUES for ROBO2 Gene

  • Nervous system(4.8)
  • Kidney(2.1)

Phenotype-based relationships between genes and organs from Gene ORGANizer for ROBO2 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • immune
  • reproductive
  • skeleton
  • urinary
Regions:
Abdomen:
  • kidney
Pelvis:
  • placenta
  • ureter
  • urethra
  • urinary bladder
  • uterus
Limb:
  • ankle
  • digit
  • elbow
  • finger
  • foot
  • hand
  • hip
  • knee
  • lower limb
  • shoulder
  • toe
  • upper limb
  • wrist
General:
  • blood
  • white blood cell
genes like me logo Genes that share expression patterns with ROBO2: view

No data available for mRNA Expression by UniProt/SwissProt for ROBO2 Gene

Orthologs for ROBO2 Gene

This gene was present in the common ancestor of animals.

Orthologs for ROBO2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
 Mammalia ROBO2 34 33
  • 98.52 (n)
 OneToOne
platypus
(Ornithorhynchus anatinus)
 Mammalia -- 34
  • 94 (a)
 ManyToMany
dog
(Canis familiaris)
 Mammalia LOC487691 33
  • 91.07 (n)
ROBO2 34
  • 88 (a)
 OneToOne
cow
(Bos Taurus)
 Mammalia LOC534842 33
  • 90.01 (n)
ROBO2 34
  • 90 (a)
 OneToOne
mouse
(Mus musculus)
 Mammalia Robo2 16 34 33
  • 88.18 (n)
rat
(Rattus norvegicus)
 Mammalia Robo2 33
  • 84.32 (n)
oppossum
(Monodelphis domestica)
 Mammalia ROBO2 34
  • 84 (a)
 OneToOne
chicken
(Gallus gallus)
 Aves ROBO2 34 33
  • 82.81 (n)
 OneToOne
lizard
(Anolis carolinensis)
 Reptilia ROBO2 34
  • 82 (a)
 OneToOne
tropical clawed frog
(Silurana tropicalis)
 Amphibia robo2 33
  • 78.09 (n)
zebrafish
(Danio rerio)
 Actinopterygii robo2 34 34 33 33
  • 70.49 (n)
 OneToMany
fruit fly
(Drosophila melanogaster)
 Insecta robo 34 33
  • 48.23 (n)
 ManyToMany
robo3 34
  • 27 (a)
 ManyToMany
lea 34
  • 25 (a)
 ManyToMany
African malaria mosquito
(Anopheles gambiae)
 Insecta AgaP_AGAP010969 33
  • 44.66 (n)
worm
(Caenorhabditis elegans)
 Secernentea sax-3 34
  • 32 (a)
 OneToMany
sea squirt
(Ciona savignyi)
 Ascidiacea -- 34
  • 20 (a)
 OneToMany
Species where no ortholog for ROBO2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for ROBO2 Gene

ENSEMBL:
Gene Tree for ROBO2 (if available)
TreeFam:
Gene Tree for ROBO2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for ROBO2: view image

Paralogs for ROBO2 Gene

Paralogs for ROBO2 Gene

(11) SIMAP similar genes for ROBO2 Gene using alignment to 9 proteins:

  • ROBO2_HUMAN
  • F8W703_HUMAN
  • F8WBR3_HUMAN
  • H7C4J7_HUMAN
  • H7C4U9_HUMAN
  • H7C4V8_HUMAN
  • H7C4W9_HUMAN
  • H9XFA4_HUMAN
  • R4GMM8_HUMAN

Pseudogenes.org Pseudogenes for ROBO2 Gene

genes like me logo Genes that share paralogs with ROBO2: view

Variants for ROBO2 Gene

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Sequence variations from dbSNP and Humsavar for ROBO2 Gene

SNP ID Clin Chr 03 pos Variation AA Info Type
rs1031377 benign, Vesicoureteral reflux 77,647,271(+) C/T 3_prime_UTR_variant
rs1036593490 uncertain-significance, Vesicoureteral reflux 77,574,534(+) A/C coding_sequence_variant, synonymous_variant
rs10865561 benign, Vesicoureteral reflux 77,649,978(+) C/T downstream_transcript_variant
rs11127602 benign, Vesicoureteral reflux 77,647,169(+) G/A 3_prime_UTR_variant
rs113680429 likely-benign, Vesicoureteral reflux 77,481,096(+) C/T intron_variant

Structural Variations from Database of Genomic Variants (DGV) for ROBO2 Gene

Variant ID Type Subtype PubMed ID
dgv8392n54 CNV gain 21841781
esv1000557 CNV deletion 20482838
esv1093026 CNV insertion 17803354
esv1136393 CNV insertion 17803354
esv1228509 CNV deletion 17803354
esv1519897 CNV insertion 17803354
esv1623331 CNV insertion 17803354
esv1701230 CNV insertion 17803354
esv2662491 CNV deletion 23128226
esv2675710 CNV deletion 23128226
esv2678855 CNV deletion 23128226
esv2725535 CNV deletion 23290073
esv2725536 CNV deletion 23290073
esv2725537 CNV deletion 23290073
esv2725538 CNV deletion 23290073
esv2725539 CNV deletion 23290073
esv2759158 CNV gain 17122850
esv29384 CNV gain+loss 19812545
esv3329708 CNV duplication 20981092
esv3562106 CNV deletion 23714750
esv3562107 CNV deletion 23714750
esv3562108 CNV deletion 23714750
esv3596655 CNV loss 21293372
esv3596656 CNV gain 21293372
esv3596657 CNV loss 21293372
esv3596658 CNV loss 21293372
esv3596659 CNV loss 21293372
esv989139 CNV deletion 20482838
nsv1012185 CNV loss 25217958
nsv1013631 CNV gain 25217958
nsv1072702 CNV deletion 25765185
nsv1117947 CNV deletion 24896259
nsv1118702 CNV duplication 24896259
nsv1145817 CNV duplication 26484159
nsv3886 CNV deletion 18451855
nsv509832 OTHER sequence alteration 20534489
nsv509833 OTHER sequence alteration 20534489
nsv512806 CNV insertion 21212237
nsv525804 CNV loss 19592680
nsv590732 CNV loss 21841781
nsv819347 CNV gain 19587683
nsv822146 CNV loss 20364138
nsv834739 CNV gain 17160897
nsv834740 CNV gain+loss 17160897
nsv954896 CNV duplication 24416366
nsv956271 CNV deletion 24416366
nsv967241 CNV deletion 23825009
nsv979849 CNV duplication 23825009

Variation tolerance for ROBO2 Gene

Residual Variation Intolerance Score: 5.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.82; 58.45% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for ROBO2 Gene

Human Gene Mutation Database (HGMD)
ROBO2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
ROBO2

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for ROBO2 Gene

Disorders for ROBO2 Gene

MalaCards: The human disease database

(5) MalaCards diseases for ROBO2 Gene - From: HGMD, OMIM, ClinVar, GTR, Orphanet, Swiss-Prot, DISEASES, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search ROBO2 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

ROBO2_HUMAN
  • Vesicoureteral reflux 2 (VUR2) [MIM:610878]: A disease belonging to the group of congenital anomalies of the kidney and urinary tract. It is characterized by the reflux of urine from the bladder into the ureters and sometimes into the kidneys, and is a risk factor for urinary tract infections. Primary disease results from a developmental defect of the ureterovesical junction. In combination with intrarenal reflux, the resulting inflammatory reaction may result in renal injury or scarring, also called reflux nephropathy. Extensive renal scarring impairs renal function and may predispose patients to hypertension, proteinuria, renal insufficiency and end-stage renal disease. {ECO:0000269 PubMed:17357069}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Note=A chromosomal aberration involving ROBO2 is a cause of multiple congenital abnormalities, including severe bilateral VUR with ureterovesical junction defects. Translocation t(Y;3)(p11;p12) with PCDH11Y. This translocation disrupts ROBO2 and produces dominant-negative ROBO2 proteins that abrogate SLIT-ROBO signaling in vitro.

Additional Disease Information for ROBO2

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with ROBO2: view

No data available for Genatlas for ROBO2 Gene

Publications for ROBO2 Gene

  1. Roundabout controls axon crossing of the CNS midline and defines a novel subfamily of evolutionarily conserved guidance receptors. (PMID: 9458045) Kidd T … Tear G (Cell 1998) 2 3 4 58
  2. Human variation in alcohol response is influenced by variation in neuronal signaling genes. (PMID: 20201926) Joslyn G … White RL (Alcoholism, clinical and experimental research 2010) 3 44 58
  3. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PMID: 20379614) Rose JE … Uhl GR (Molecular medicine (Cambridge, Mass.) 2010) 3 44 58
  4. Whole-genome linkage and association scan in primary, nonsyndromic vesicoureteric reflux. (PMID: 19959718) Cordell HJ … UK VUR Study Group (Journal of the American Society of Nephrology : JASN 2010) 3 44 58
  5. In search of genes associated with risk for psychopathic tendencies in children: a two-stage genome-wide association study of pooled DNA. (PMID: 20345837) Viding E … Plomin R (Journal of child psychology and psychiatry, and allied disciplines 2010) 3 44 58

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