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

Summary

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 establishment of endothelial barrier. Located in extracellular exosome. Implicated in aortic valve disease 3. Biomarker of pre-eclampsia and thyroid gland carcinoma. [provided by Alliance of Genome Resources, Dec 2024]
Expression: Broad expression in fat (RPKM 35.9), spleen (RPKM 32.4) and 17 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 11q24.2

Exon count:: 18

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	11	NC_000011.10 (124883691..124897865, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	11	NC_060935.1 (124912311..124926485, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (124753587..124767761, complement)

Chromosome 11 - NC_000011.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The Role of SLIT3-ROBO4 Signaling in Endoplasmic Reticulum Stress-Induced Delayed Corneal Epithelial and Nerve Regeneration.
Title: The Role of SLIT3-ROBO4 Signaling in Endoplasmic Reticulum Stress-Induced Delayed Corneal Epithelial and Nerve Regeneration.
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.
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.
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.
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.
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.
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.
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.
Regulatory mechanisms of Robo4 and their effects on angiogenesis.
Title: Regulatory mechanisms of Robo4 and their effects on angiogenesis.
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.

Submit: New GeneRIF Correction See all GeneRIFs (47)

Phenotypes

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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

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D11S4610 (e-PCR)
- UniSTS:48677

ROBO4_9796 (e-PCR)
- UniSTS:468653

WI-20325 (e-PCR)
- UniSTS:73134

D11S4610 (e-PCR)
- UniSTS:27867

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 more info	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

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Preferred Names: roundabout homolog 4

Names: roundabout homolog 4, magic roundabout; roundabout, axon guidance receptor, homolog 4

NCBI Reference Sequences (RefSeq)

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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)

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
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_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000011.10 Reference GRCh38.p14 Primary Assembly

Range

124883691..124897865 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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