ROBO4 Gene (Protein Coding)

Roundabout Guidance Receptor 4

GC11M124883
GIFtS:
41
See more...

Aliases for ROBO4 Gene

Aliases for ROBO4 Gene

  • Roundabout Guidance Receptor 4 2 3 5
  • Roundabout Homolog 4 3 4
  • Magic Roundabout 2 4
  • ECSM4 2 3
  • MRB 2 3
  • Roundabout, Axon Guidance Receptor, Homolog 4 (Drosophila) 2
  • Roundabout, Axon Guidance Receptor, Homolog 4 3
  • Roundabout Homolog 4, Magic Roundabout 3
  • Roundabout Homolog 4 (Drosophila) 2
  • FLJ20798 2
  • AOVD3 3
  • ROBO4 5

External Ids for ROBO4 Gene

Previous GeneCards Identifiers for ROBO4 Gene

  • GC11M126754
  • GC11M126266
  • GC11M124787
  • GC11M124291
  • GC11M124258
  • GC11M120696
  • GC11M124753

Summaries for ROBO4 Gene

CIViC Summary for ROBO4 Gene

GeneCards Summary for ROBO4 Gene

ROBO4 (Roundabout Guidance Receptor 4) is a Protein Coding gene. Diseases associated with ROBO4 include Aortic Valve Disease 3 and Diaphragmatic Hernia, Congenital. Among its related pathways are Development Slit-Robo signaling. An important paralog of this gene is SDK1.

UniProtKB/Swiss-Prot Summary for ROBO4 Gene

  • Receptor for Slit proteins, at least for SLIT2, and seems to be involved in angiogenesis and vascular patterning. May mediate the inhibition of primary endothelial cell migration by Slit proteins (By similarity). Involved in the maintenance of endothelial barrier organization and function (PubMed:30455415).

Gene Wiki entry for ROBO4 Gene

Additional gene information for ROBO4 Gene

No data available for Entrez Gene Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for ROBO4 Gene

Genomics for ROBO4 Gene

GeneHancer (GH) Regulatory Elements Pubs

Download GeneHancer 2017 data
Promoters and enhancers for ROBO4 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around ROBO4 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for ROBO4

Top Transcription factor binding sites by QIAGEN in the ROBO4 gene promoter:
  • AML1a
  • AP-4
  • C/EBPalpha
  • ER-alpha
  • HNF-1
  • HNF-1A
  • Nkx6-1
  • NRSF form 1
  • NRSF form 2
  • RORalpha1

Genomic Locations for ROBO4 Gene

Genomic Locations for ROBO4 Gene
chr11:124,883,691-124,898,500
(GRCh38/hg38)
Size:
14,810 bases
Orientation:
Minus strand
chr11:124,753,587-124,768,396
(GRCh37/hg19)
Size:
14,810 bases
Orientation:
Minus strand

Genomic View for ROBO4 Gene

Genes around ROBO4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
ROBO4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for ROBO4 Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for ROBO4 Gene

Proteins for ROBO4 Gene

Products:

  1. Antibody
  2. Protein
  3. Assay

  • Protein details for ROBO4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8WZ75-ROBO4_HUMAN
    Recommended name:
    Roundabout homolog 4
    Protein Accession:
    Q8WZ75
    Secondary Accessions:
    • A8K154
    • Q14DU7
    • Q8TEG1
    • Q96JV6
    • Q9H718
    • Q9NWJ8

    Protein attributes for ROBO4 Gene

    Size:
    1007 amino acids
    Molecular mass:
    107457 Da
    Quaternary structure:
    • Interacts with SLIT2 and ENAH.
    SequenceCaution:
    • Sequence=AAH64643.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=BAA91382.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=BAB15082.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=BAB55411.1; Type=Frameshift; Evidence={ECO:0000305};

    Alternative splice isoforms for ROBO4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for ROBO4 Gene

Protein Expression for ROBO4 Gene

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

Post-translational modifications for ROBO4 Gene

  • Glycosylation at Asn246, Asn360, Asn389, Asn396, and Asn680
  • Modification sites at PhosphoSitePlus
  • Glycosylation from GlyConnect
    • ROBO4_HUMAN (2004)

Other Protein References for ROBO4 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

  • Abcam antibodies for ROBO4
  • Santa Cruz Biotechnology (SCBT) Antibodies for ROBO4

No data available for DME Specific Peptides for ROBO4 Gene

Domains & Families for ROBO4 Gene

Gene Families for ROBO4 Gene

HGNC:
Human Protein Atlas (HPA):
  • Plasma proteins
  • Predicted membrane proteins

Protein Domains for ROBO4 Gene

InterPro:
Blocks:
  • Immunoglobulin C-2 type
  • Immunoglobulin I-set
ProtoNet:

Suggested Antigen Peptide Sequences for ROBO4 Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ54518, highly similar to Roundabout homolog 4 (B4DYV8_HUMAN)
  • Magic roundabout (ROBO4_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q8WZ75

UniProtKB/Swiss-Prot:

ROBO4_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 ROBO4: view

Function for ROBO4 Gene

Products:

  1. Animal Model
  2. CRISPR
  3. miRNA
  4. Inhibitory RNA
  5. Clone
  6. Cell Line

Molecular function for ROBO4 Gene

UniProtKB/Swiss-Prot Function:
Receptor for Slit proteins, at least for SLIT2, and seems to be involved in angiogenesis and vascular patterning. May mediate the inhibition of primary endothelial cell migration by Slit proteins (By similarity). Involved in the maintenance of endothelial barrier organization and function (PubMed:30455415).

Phenotypes From GWAS Catalog for ROBO4 Gene

Gene Ontology (GO) - Molecular Function for ROBO4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IEA --
GO:0038023 signaling receptor activity TAS 14527427
GO:0098632 cell-cell adhesion mediator activity IBA 21873635
genes like me logo Genes that share ontologies with ROBO4: view
genes like me logo Genes that share phenotypes with ROBO4: view

Human Phenotype Ontology for ROBO4 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for ROBO4 Gene

MGI Knock Outs for ROBO4:

Animal Model Products

  • Taconic Biosciences Mouse Models for ROBO4

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for ROBO4

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for ROBO4 Gene

Localization for ROBO4 Gene

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 ROBO4 gene
Compartment Confidence
extracellular 5
plasma membrane 4
cytoskeleton 2
nucleus 2
mitochondrion 1
endoplasmic reticulum 1
endosome 1
cytosol 1
lysosome 1
golgi apparatus 1
peroxisome 0

Subcellular locations from the

Human Protein Atlas (HPA)
  • Plasma membrane (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for ROBO4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005886 plasma membrane IBA 21873635
GO:0016021 integral component of membrane TAS 14527427
GO:0030424 axon IBA 21873635
GO:0070062 extracellular exosome HDA 23533145
genes like me logo Genes that share ontologies with ROBO4: view

No data available for Subcellular locations from UniProtKB/Swiss-Prot for ROBO4 Gene

Pathways & Interactions for ROBO4 Gene

PathCards logo

SuperPathways for ROBO4 Gene

SuperPathway Contained pathways
1 Development Slit-Robo signaling
Development Slit-Robo signaling
.44
genes like me logo Genes that share pathways with ROBO4: view

Pathways by source for ROBO4 Gene

1 GeneGo (Thomson Reuters) pathway for ROBO4 Gene
  • Development Slit-Robo signaling

SIGNOR curated interactions for ROBO4 Gene

Is activated by:

Gene Ontology (GO) - Biological Process for ROBO4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001525 angiogenesis IGI 15849270
GO:0007156 homophilic cell adhesion via plasma membrane adhesion molecules IBA 21873635
GO:0007275 multicellular organism development IEA --
GO:0007411 axon guidance IBA 21873635
GO:0030154 cell differentiation IEA --
genes like me logo Genes that share ontologies with ROBO4: view

Drugs & Compounds for ROBO4 Gene

Products:

  1. Drug
No Compound Related Data Available

Transcripts for ROBO4 Gene

Products:

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

mRNA/cDNA for ROBO4 Gene

2 REFSEQ mRNAs :
16 NCBI additional mRNA sequence :
10 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for ROBO4

Alternative Splicing Database (ASD) splice patterns (SP) for ROBO4 Gene

No ASD Table

Relevant External Links for ROBO4 Gene

GeneLoc Exon Structure for
ROBO4

Expression for ROBO4 Gene

Products:

  1. Primer
  2. Gene Expression Assay

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for ROBO4 Gene

mRNA expression in normal human tissues for ROBO4 Gene
mRNA expression by GTEx for ROBO4 GenemRNA expression by BioGPS for ROBO4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for ROBO4 Gene

This gene is overexpressed in Spleen (x5.5) and Adipose - Visceral (Omentum) (x4.2).

Protein differential expression in normal tissues from HIPED for ROBO4 Gene

This gene is overexpressed in Urine (32.9), Bone marrow mesenchymal stem cell (16.1), Serum (10.7), and Plasma (6.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for ROBO4 Gene



Protein tissue co-expression partners for ROBO4 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for ROBO4

SOURCE GeneReport for Unigene cluster for ROBO4 Gene:

Hs.524121

mRNA Expression by UniProt/SwissProt for ROBO4 Gene:

Q8WZ75-ROBO4_HUMAN
Tissue specificity: Specifically expressed in endothelial cells. Expressed in endothelial and intimal cells of the ascending aorta (PubMed:30455415).

Evidence on tissue expression from TISSUES for ROBO4 Gene

  • Nervous system(4.9)
  • Intestine(4.3)
  • Liver(4.3)
  • Bone marrow(4.3)
  • Heart(2.8)
  • Lung(2.4)
  • Spleen(2.4)
  • Muscle(2.3)
  • Kidney(2.2)
genes like me logo Genes that share expression patterns with ROBO4: view

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for ROBO4 Gene

Orthologs for ROBO4 Gene

This gene was present in the common ancestor of chordates.

Orthologs for ROBO4 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
 Mammalia ROBO4 30 31
  • 99.26 (n)
 OneToOne
Dog
(Canis familiaris)
 Mammalia ROBO4 30 31
  • 86.16 (n)
 OneToOne
Cow
(Bos Taurus)
 Mammalia ROBO4 30 31
  • 84.95 (n)
 OneToOne
Mouse
(Mus musculus)
 Mammalia Robo4 30 17 31
  • 81.61 (n)
 OneToOne
Rat
(Rattus norvegicus)
 Mammalia LOC100911068 30
  • 81.06 (n)
Oppossum
(Monodelphis domestica)
 Mammalia ROBO4 31
  • 66 (a)
 OneToOne
Platypus
(Ornithorhynchus anatinus)
 Mammalia -- 31
  • 50 (a)
 OneToMany
-- 31
  • 49 (a)
 OneToMany
Chicken
(Gallus gallus)
 Aves ROBO4 31
  • 37 (a)
 OneToOne
Lizard
(Anolis carolinensis)
 Reptilia ROBO4 31
  • 36 (a)
 OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
 Amphibia LOC100493397 30
  • 47.56 (n)
Zebrafish
(Danio rerio)
 Actinopterygii robo4 31
  • 28 (a)
 OneToOne
Species where no ortholog for ROBO4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • 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)
  • Fruit Fly (Drosophila melanogaster)
  • 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 Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • 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)
  • Worm (Caenorhabditis elegans)

Evolution for ROBO4 Gene

ENSEMBL:
Gene Tree for ROBO4 (if available)
TreeFam:
Gene Tree for ROBO4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for ROBO4: view image

Paralogs for ROBO4 Gene

Paralogs for ROBO4 Gene

(1) SIMAP similar genes for ROBO4 Gene using alignment to 2 proteins:

  • ROBO4_HUMAN
  • B4DYV8_HUMAN
genes like me logo Genes that share paralogs with ROBO4: view

Variants for ROBO4 Gene

Products:

  1. SNP Genotyping and Copy Number Assay

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for ROBO4 Gene

SNP ID Clinical significance and condition Chr 11 pos Variation AA Info Type
713013 Likely Benign: not provided 124,891,430(-) C/T MISSENSE_VARIANT
717253 Benign: not provided 124,885,135(-) G/A SYNONYMOUS_VARIANT
732298 Benign: not provided 124,893,906(-) G/A SYNONYMOUS_VARIANT
753185 Likely Benign: not provided 124,897,182(-) C/T SYNONYMOUS_VARIANT,INTRON_VARIANT
768494 Benign: not provided 124,894,280(-) T/C SYNONYMOUS_VARIANT

Additional dbSNP identifiers (rs#s) for ROBO4 Gene

Structural Variations from Database of Genomic Variants (DGV) for ROBO4 Gene

Variant ID Type Subtype PubMed ID
nsv1054824 CNV gain 25217958
nsv520150 CNV loss 19592680
nsv531 CNV insertion 18451855
nsv952753 CNV deletion 24416366

Variation tolerance for ROBO4 Gene

Residual Variation Intolerance Score: 98.4% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 10.73; 91.55% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for ROBO4 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
ROBO4

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for ROBO4 Gene

Disorders for ROBO4 Gene

MalaCards: The human disease database

(9) MalaCards diseases for ROBO4 Gene - From: UniProtKB/Swiss-Prot, OMIM, ClinVar, DISEASES, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search ROBO4 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

ROBO4_HUMAN
  • Aortic valve disease 3 (AOVD3) [MIM:618496]: A common defect in the aortic valve in which two rather than three leaflets are present. It is often associated with aortic valve calcification, stenosis and insufficiency. In extreme cases, the blood flow may be so restricted that the left ventricle fails to grow, resulting in hypoplastic left heart syndrome. AOVD3 features are bicuspid aortic valve, aortic valve stenosis, and ascending aortic aneurysm. Some patients have atrial septal defects. AOVD3 inheritance is autosomal dominant with incomplete penetrance. {ECO:0000269 PubMed:30455415}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.

Additional Disease Information for ROBO4

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with ROBO4: view

No data available for Genatlas for ROBO4 Gene

Publications for ROBO4 Gene

  1. ROBO4 variants predispose individuals to bicuspid aortic valve and thoracic aortic aneurysm. (PMID: 30455415) Gould RA … Dietz HC (Nature genetics 2019) 3 4
  2. Genetic analyses of roundabout (ROBO) axon guidance receptors in autism. (PMID: 18270976) Anitha A … Mori N (American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 2008) 3 41
  3. Association study between Gilles de la Tourette Syndrome and two genes in the Robo-Slit pathway located in the chromosome 11q24 linked/associated region. (PMID: 17671968) Miranda DM … Barr CL (American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 2008) 3 41
  4. Robo1/Robo4: differential expression of angiogenic markers in colorectal cancer. (PMID: 16685377) Gröne J … Bhargava S (Oncology reports 2006) 3 23
  5. Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry. (PMID: 16335952) Liu T … Smith RD (Journal of proteome research 2005) 3 4

ExternalLinks

View latest publications for ROBO4 gene in Mastermind

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