U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

ROBO4 roundabout guidance receptor 4 [ Homo sapiens (human) ]

Gene ID: 54538, updated on 5-Mar-2024

Summary

Go to the top of the page Help
Official Symbol
ROBO4provided by HGNC
Official Full Name
roundabout guidance receptor 4provided by HGNC
Primary source
HGNC:HGNC:17985
See related
Ensembl:ENSG00000154133 MIM:607528; AllianceGenome:HGNC:17985
Gene type
protein coding
RefSeq status
VALIDATED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
MRB; AOVD3; ECSM4
Summary
Predicted to enable cell-cell adhesion mediator activity. Involved in angiogenesis and establishment of endothelial barrier. Located in extracellular exosome. Implicated in aortic valve disease 3. [provided by Alliance of Genome Resources, Apr 2022]
Expression
Broad expression in fat (RPKM 35.9), spleen (RPKM 32.4) and 17 other tissues See more
Orthologs
mouse all
NEW
Try the new Gene table
Try the new Transcript table

Genomic context

Go to the top of the page Help
Location:
11q24.2
Exon count:
18
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (124883691..124897865, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (124912311..124926485, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (124753587..124767761, complement)

Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene MSANTD2 antisense RNA 1 Neighboring gene E3 ubiquitin-protein ligase RNF181-like Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:124712489-124713052 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:124713053-124713614 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:124732803-124733304 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:124735644-124736320 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:124738370-124738900 Neighboring gene Sharpr-MPRA regulatory region 2144 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4035 Neighboring gene roundabout guidance receptor 3 Neighboring gene Sharpr-MPRA regulatory region 10426 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:124756054-124756568 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:124756569-124757082 Neighboring gene uncharacterized LOC107984406 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:124767654-124768276 Neighboring gene hepatic and glial cell adhesion molecule Neighboring gene hepatocellular carcinoma, down-regulated 1 Neighboring gene H3K27ac hESC enhancer GRCh37_chr11:124823758-124824301 Neighboring gene CCDC15 divergent transcript

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help
  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

Go to the top of the pageHelp

Related articles in PubMed

  1. Downregulation of ROBO4 in Pancreatic Cancer Serves as a Biomarker of Poor Prognosis and Indicates Increased Cell Motility and Proliferation Through Activation of MMP-9. Yamanaka M, et al. Ann Surg Oncol, 2022 Oct. PMID 35726111
  2. PRC2 Components Maintain DNA Hypermethylation of the Upstream Promoter and Regulate Robo4 Expression in Endothelial Cells. Izawa K, et al. Biol Pharm Bull, 2020. PMID 32238717
  3. Regulatory mechanisms of Robo4 and their effects on angiogenesis. Dai C, et al. Biosci Rep, 2019 Jul 31. PMID 31160487, Free PMC Article
  4. Robo 4 - the double-edged sword in prostate cancer: impact on cancer cell aggressiveness and tumor vasculature. Pircher A, et al. Int J Med Sci, 2019. PMID 30662335, Free PMC Article
  5. Validation of RT-qPCR reference genes and determination of Robo4 expression levels in human retinal endothelial cells under hypoxia and/or hyperglycemia. Xie J, et al. Gene, 2016 Jul 1. PMID 27041242

See all (64) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. The role of TET2-mediated ROBO4 hypomethylation in the development of diabetic retinopathy.
    Title: The role of TET2-mediated ROBO4 hypomethylation in the development of diabetic retinopathy.
  2. Downregulation of ROBO4 in Pancreatic Cancer Serves as a Biomarker of Poor Prognosis and Indicates Increased Cell Motility and Proliferation Through Activation of MMP-9.
    Title: Downregulation of ROBO4 in Pancreatic Cancer Serves as a Biomarker of Poor Prognosis and Indicates Increased Cell Motility and Proliferation Through Activation of MMP-9.
  3. Rare deleterious variants of NOTCH1, GATA4, SMAD6, and ROBO4 are enriched in BAV with early onset complications but not in BAV with heritable thoracic aortic disease.
    Title: Rare deleterious variants of NOTCH1, GATA4, SMAD6, and ROBO4 are enriched in BAV with early onset complications but not in BAV with heritable thoracic aortic disease.
  4. miR-140-5p regulates vascular smooth muscle cell viability, migration and apoptosis by targeting ROBO4 gene expression in atherosclerosis.
    Title: miR-140-5p regulates vascular smooth muscle cell viability, migration and apoptosis by targeting ROBO4 gene expression in atherosclerosis.
  5. Structural insights and evaluation of the potential impact of missense variants on the interactions of SLIT2 with ROBO1/4 in cancer progression.
    Title: Structural insights and evaluation of the potential impact of missense variants on the interactions of SLIT2 with ROBO1/4 in cancer progression.
  6. Nuclear Localization of Robo is Associated with Better Survival in Bladder Cancer.
    Title: Nuclear Localization of Robo is Associated with Better Survival in Bladder Cancer.
  7. PRC2 Components Maintain DNA Hypermethylation of the Upstream Promoter and Regulate Robo4 Expression in Endothelial Cells.
    Title: PRC2 Components Maintain DNA Hypermethylation of the Upstream Promoter and Regulate Robo4 Expression in Endothelial Cells.
  8. Regulatory mechanisms of Robo4 and their effects on angiogenesis.
    Title: Regulatory mechanisms of Robo4 and their effects on angiogenesis.
  9. VEGF and Robo4 were co-expressed in FVMs from proliferative diabetic retinopathy (PDR) patients. In the early stages, VEGF was upregulated and contributed to retinopahy development, whereas, in the late stage, VEGF and Robo4 worked together to aggravate disease progression. However, miR-15a could downregulate VEGF and Robo4 to ameliorate Diabetic retinopathy development.
    Title: Upregulated VEGF and Robo4 correlate with the reduction of miR-15a in the development of diabetic retinopathy.
  10. In human brain endothelial cells that were damaged by hypoxia plus IL-1beta, treatment with recombinant ANXA2 (rA2) rescued the expression of junctional proteins and decreased trans-endothelial permeability. The protective effects were mediated in part by interactions with F-actin and VE-cadherin, and the ability of rA2 to modulate signaling via Robo4 -paxillin- ARF6.
    Title: Annexin A2 is a Robo4 ligand that modulates ARF6 activation-associated cerebral trans-endothelial permeability.
Submit: New GeneRIF Correction See all GeneRIFs (46)

Phenotypes

Go to the top of the page Help

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Aortic valve disease 3
MedGen: C5193127 OMIM: 618496 GeneReviews: Not available
Compare labs

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

Go to the top of the page Help

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env Interaction of SLIT2 with Robo4 significantly inhibits HIV-1 gp120-induced phosphorylation of c-Src in human lymphatic endothelial cells PubMed
env HIV-1 gp120 induces phosphorylation of fibronectin and enhances a physical association between fibronectin and Robo4 in human lymphatic endothelial cells PubMed
env The fibronectin domains of Robo4 are critical for HIV-1 gp120-induced hyperpermeability of human lymphatic endothelial cell monolayers PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

Go to the top of the page

Interactions

Go to the top of the page Help
Products Interactant Other Gene Complex Source Pubs Description

General gene information

Go to the top of the page Help

Markers

Homology

Clone Names

  • FLJ20798, MGC133352, MGC133353

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables cell-cell adhesion mediator activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables signaling receptor activity TAS
Traceable Author Statement
more info
 PubMed 
Process Evidence Code Pubs
involved_in angiogenesis IEA
Inferred from Electronic Annotation
more info
  
involved_in axon guidance IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in dendrite self-avoidance IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in establishment of endothelial barrier IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in homophilic cell adhesion via plasma membrane adhesion molecules IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in regulation of cell migration NAS
Non-traceable Author Statement
more info
 PubMed 
Component Evidence Code Pubs
is_active_in axon IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in extracellular exosome HDA PubMed 
located_in membrane TAS
Traceable Author Statement
more info
 PubMed 
is_active_in plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
  

General protein information

Go to the top of the page Help
Preferred Names
roundabout homolog 4
Names
roundabout homolog 4, magic roundabout
roundabout, axon guidance receptor, homolog 4

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

NEW Try the new Transcript table

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001301088.2 → NP_001288017.1  roundabout homolog 4 isoform 2

    See identical proteins and their annotated locations for NP_001288017.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (2) uses an alternate splice junction at the 5' end of the second exon and starts translation at a downstream AUG compared to variant 1. The resulting isoform (2) is shorter at the N-terminus compared to isoform 1.
    Source sequence(s)
    AF361473, AK302628, AP003501, DC424813
    Consensus CDS
    CCDS73409.1
    UniProtKB/TrEMBL
    B4DYV8
    Related
    ENSP00000437129.1, ENST00000533054.5
    Conserved Domains (3) summary
    smart00410
    Location:1 → 75
    IG_like; Immunoglobulin like
    pfam00041
    Location:205 → 287
    fn3; Fibronectin type III domain
    cl11960
    Location:1 → 80
    Ig; Immunoglobulin domain

  2. NM_019055.6 → NP_061928.4  roundabout homolog 4 isoform 1 precursor

    See identical proteins and their annotated locations for NP_061928.4

    Status: VALIDATED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
    Source sequence(s)
    AF361473, AP003501, DC424813
    Consensus CDS
    CCDS8455.1
    UniProtKB/Swiss-Prot
    A8K154, Q14DU7, Q8TEG1, Q8WZ75, Q96JV6, Q9H718, Q9NWJ8
    Related
    ENSP00000304945.3, ENST00000306534.8
    Conserved Domains (4) summary
    cd05724
    Location:141 → 225
    Ig2_Robo; Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors
    pfam07679
    Location:139 → 220
    I-set; Immunoglobulin I-set domain
    pfam00041
    Location:350 → 432
    fn3; Fibronectin type III domain
    cl11960
    Location:31 → 133
    Ig; Immunoglobulin domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000011.10 Reference GRCh38.p14 Primary Assembly

    Range
    124883691..124897865 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_006718861.3 → XP_006718924.1  roundabout homolog 4 isoform X1

    Conserved Domains (4) summary
    cd05724
    Location:141 → 225
    Ig2_Robo; Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors
    pfam07679
    Location:139 → 220
    I-set; Immunoglobulin I-set domain
    pfam00041
    Location:350 → 432
    fn3; Fibronectin type III domain
    cl11960
    Location:31 → 133
    Ig; Immunoglobulin domain

  2. XM_011542875.2 → XP_011541177.1  roundabout homolog 4 isoform X2

    Conserved Domains (1) summary
    PHA03247
    Location:125 → 434
    PHA03247; large tegument protein UL36; Provisional

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060935.1 Alternate T2T-CHM13v2.0

    Range
    124912311..124926485 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054369168.1 → XP_054225143.1  roundabout homolog 4 isoform X1

  2. XM_054369169.1 → XP_054225144.1  roundabout homolog 4 isoform X2

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q8WZ75.1 GenPept UniProtKB/Swiss-Prot:Q8WZ75

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

Chemical Information
Molecular Biology Databases
Research Materials
Tools
Miscellaneous