ROBO4 (roundabout guidance receptor 4)

Gene

• Entrez ID: 54538
• Gene name: Roundabout guidance receptor 4
• Gene symbol: ROBO4
• Synonyms (NCBI Gene): AOVD3, ECSM4, MRB
• Chromosome: 11
• Chromosome location: 11q24.2

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs764038221	C>A,T	Pathogenic, likely-pathogenic	Splice donor variant
rs1565322176	GC>AG	Likely-pathogenic	Coding sequence variant, missense variant, intron variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT017942	hsa-miR-335-5p	Microarray	18185580
MIRT723779	hsa-miR-6074	HITS-CLIP	19536157
MIRT723778	hsa-miR-4778-5p	HITS-CLIP	19536157
MIRT723777	hsa-miR-6801-3p	HITS-CLIP	19536157
MIRT723776	hsa-miR-6810-3p	HITS-CLIP	19536157
MIRT723774	hsa-miR-6752-3p	HITS-CLIP	19536157
MIRT723775	hsa-miR-3667-3p	HITS-CLIP	19536157
MIRT723773	hsa-miR-18a-3p	HITS-CLIP	19536157
MIRT723772	hsa-miR-938	HITS-CLIP	19536157
MIRT723771	hsa-miR-6886-3p	HITS-CLIP	19536157
MIRT723770	hsa-miR-337-3p	HITS-CLIP	19536157
MIRT723769	hsa-miR-202-5p	HITS-CLIP	19536157
MIRT569896	hsa-miR-6805-5p	PAR-CLIP	20371350
MIRT569897	hsa-miR-6761-5p	PAR-CLIP	20371350
MIRT569895	hsa-miR-3928-5p	PAR-CLIP	20371350
MIRT569894	hsa-miR-6806-3p	PAR-CLIP	20371350
MIRT569893	hsa-miR-4448	PAR-CLIP	20371350
MIRT569892	hsa-miR-4283	PAR-CLIP	20371350
MIRT569891	hsa-miR-6846-5p	PAR-CLIP	20371350
MIRT569890	hsa-miR-6848-5p	PAR-CLIP	20371350
MIRT569895	hsa-miR-3928-5p	PAR-CLIP	26701625
MIRT569892	hsa-miR-4283	PAR-CLIP	26701625
MIRT569893	hsa-miR-4448	PAR-CLIP	26701625
MIRT569897	hsa-miR-6761-5p	PAR-CLIP	26701625
MIRT569896	hsa-miR-6805-5p	PAR-CLIP	26701625
MIRT569894	hsa-miR-6806-3p	PAR-CLIP	26701625
MIRT569891	hsa-miR-6846-5p	PAR-CLIP	26701625
MIRT569890	hsa-miR-6848-5p	PAR-CLIP	26701625
MIRT723779	hsa-miR-6074	HITS-CLIP	19536157
MIRT723778	hsa-miR-4778-5p	HITS-CLIP	19536157
MIRT723777	hsa-miR-6801-3p	HITS-CLIP	19536157
MIRT723776	hsa-miR-6810-3p	HITS-CLIP	19536157
MIRT723774	hsa-miR-6752-3p	HITS-CLIP	19536157
MIRT723775	hsa-miR-3667-3p	HITS-CLIP	19536157
MIRT723773	hsa-miR-18a-3p	HITS-CLIP	19536157
MIRT723772	hsa-miR-938	HITS-CLIP	19536157
MIRT723771	hsa-miR-6886-3p	HITS-CLIP	19536157
MIRT723770	hsa-miR-337-3p	HITS-CLIP	19536157
MIRT723769	hsa-miR-202-5p	HITS-CLIP	19536157
MIRT569896	hsa-miR-6805-5p	PAR-CLIP	20371350
MIRT569897	hsa-miR-6761-5p	PAR-CLIP	20371350
MIRT569895	hsa-miR-3928-5p	PAR-CLIP	20371350
MIRT569894	hsa-miR-6806-3p	PAR-CLIP	20371350
MIRT569893	hsa-miR-4448	PAR-CLIP	20371350
MIRT569892	hsa-miR-4283	PAR-CLIP	20371350
MIRT569891	hsa-miR-6846-5p	PAR-CLIP	20371350
MIRT569890	hsa-miR-6848-5p	PAR-CLIP	20371350
MIRT1314621	hsa-miR-140-3p	CLIP-seq
MIRT1314622	hsa-miR-329	CLIP-seq
MIRT1314623	hsa-miR-362-3p	CLIP-seq
MIRT1314624	hsa-miR-3667-5p	CLIP-seq
MIRT1314625	hsa-miR-4690-3p	CLIP-seq
MIRT1314626	hsa-miR-584	CLIP-seq
MIRT2093560	hsa-miR-3929	CLIP-seq
MIRT2093561	hsa-miR-4419b	CLIP-seq
MIRT2093562	hsa-miR-4478	CLIP-seq
MIRT2318100	hsa-miR-541	CLIP-seq
MIRT2318101	hsa-miR-654-5p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001525	Process	Angiogenesis	IEA
GO:0005515	Function	Protein binding	IPI	32296183
GO:0005886	Component	Plasma membrane	IBA
GO:0007156	Process	Homophilic cell adhesion via plasma membrane adhesion molecules	IBA
GO:0007411	Process	Axon guidance	IBA
GO:0009897	Component	External side of plasma membrane	IEA
GO:0016020	Component	Membrane	IEA
GO:0016020	Component	Membrane	TAS	14527427
GO:0030154	Process	Cell differentiation	IEA
GO:0030334	Process	Regulation of cell migration	NAS	15894287
GO:0030424	Component	Axon	IBA
GO:0038023	Function	Signaling receptor activity	IEA
GO:0038023	Function	Signaling receptor activity	TAS	14527427
GO:0043534	Process	Blood vessel endothelial cell migration	IEA
GO:0043537	Process	Negative regulation of blood vessel endothelial cell migration	IEA
GO:0061028	Process	Establishment of endothelial barrier	IMP	30455415
GO:0070062	Component	Extracellular exosome	HDA	23533145
GO:0070593	Process	Dendrite self-avoidance	IBA
GO:0098632	Function	Cell-cell adhesion mediator activity	IBA

Other IDs

• MIM: 607528
• HGNC: 17985
• e!Ensembl: ENSG00000154133

Protein

• UniProt ID: Q8WZ75
• Protein name: Roundabout homolog 4 (Magic roundabout)
• Protein 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 e
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF13927	Ig_3	31 → 118		Domain
  PF07679	I-set	137 → 224	Immunoglobulin I-set domain	Domain
  PF00041	fn3	348 → 432	Fibronectin type III domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Specifically expressed in endothelial cells. Expressed in endothelial and intimal cells of the ascending aorta (PubMed:30455415). {ECO:0000269|PubMed:11944987, ECO:0000269|PubMed:30455415}.
• Sequence:

  MGSGGDSLLGGRGSLPLLLLLIMGGMAQDSPPQILVHPQDQLFQGPGPARMSCQASGQPP
  PTIRWLLNGQPLSMVPPDPHHLLPDGTLLLLQPPARGHAHDGQALSTDLGVYTCEASNRL
  GTAVSRGARLSVAVLREDFQIQPRDMVAVVGEQFTLECGPPWGHPEPTVSWWKDGKPLAL
  QPGRHTVSGGSLLMARAEKSDEGTYMCVATNSAGHRESRAARVSIQEPQDYTEPVELLAV
  RIQLENVTLLNPDPAEGPKPRPAVWLSWKVSGPAAPAQSYTALFRTQTAPGGQGAPWAEE
  LLAGWQSAELGGLHWGQDYEFKVRPSSGRARGPDSNVLLLRLPEKVPSAPPQEVTLKPGN
  GTVFVSWVPPPAENHNGIIRGYQVWSLGNTSLPPANWTVVGEQTQLEIATHMPGSYCVQV
  AAVTGAGAGEPSRPVCLLLEQAMERATQEPSEHGPWTLEQLRATLKRPEVIATCGVALWL
  LLLGTAVCIHRRRRARVHLGPGLYRYTSEDAILKHRMDHSDSQWLADTWRSTSGSRDLSS
  SSSLSSRLGADARDPLDCRRSLLSWDSRSPGVPLLPDTSTFYGSLIAELPSSTPARPSPQ
  VPAVRRLPPQLAQLSSPCSSSDSLCSRRGLSSPRLSLAPAEAWKAKKKQELQHANSSPLL
  RGSHSLELRACELGNRGSKNLSQSPGAVPQALVAWRALGPKLLSSSNELVTRHLPPAPLF
  PHETPPTQSQQTQPPVAPQAPSSILLPAAPIPILSPCSPPSPQASSLSGPSPASSRLSSS
  SLSSLGEDQDSVLTPEEVALCLELSEGEETPRNSVSPMPRAPSPPTTYGYISVPTASEFT
  DMGRTGGGVGPKGGVLLCPPRPCLTPTPSEGSLANGWGSASEDNAASARASLVSSSDGSF
  LADAHFARALAVAVDSFGFGLEPREADCVFIDASSPPSPRDEIFLTPNLSLPLWEWRPDW
  LEDMEVSHTQRLGRGMPPWPPDSQISSQRSQLHCRMPKAGASPVDYS

• Sequence length: 1007

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Aortic valve disease 3	Likely pathogenic	rs2135378156, rs2497396246, rs764038221	RCV001808294 RCV003147905 RCV000787048	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Ascending tubular aorta aneurysm	Likely pathogenic	rs1565322176, rs764038221, rs138111911, rs755569942, rs1565326476, rs755747435, rs779392207, rs138370967	RCV000754500 RCV000754502 RCV000754499 RCV000754503 RCV000754495 RCV000754498 RCV000754497 RCV000754493	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Bicuspid aortic valve	Likely pathogenic	rs1565322176, rs764038221, rs138111911, rs755569942, rs1565326476, rs755747435, rs779392207, rs138370967	RCV000754500 RCV000754502 RCV000754499 RCV000754503 RCV000754495 RCV000754498 RCV000754497 RCV000754493	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
ROBO4-related disorder	Likely pathogenic	rs138370967	RCV004756008	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Thoracic aortic aneurysm	Likely pathogenic	rs2135366023, rs776228672	RCV001751797 RCV001751798	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
AORTIC ANEURYSM, THORACIC	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AORTIC VALVE DISEASE 1	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTISTIC DISORDER	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BICUSPID AORTIC VALVE DISEASE	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital diaphragmatic hernia	risk factor	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Familial thoracic aortic aneurysm and aortic dissection	Benign; Conflicting classifications of pathogenicity; Likely benign; Uncertain significance	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
TETRALOGY OF FALLOT	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
VENOUS THROMBOEMBOLISM	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
ANOPHTHALMIA AND PULMONARY HYPOPLASIA	Syndromic microphthalmia	BEFREE	24448236		★☆☆☆☆ Found in Text Mining only
Aortic Aneurysm, Thoracic	Aortic Aneurysm	CTD_human_DG	30455415		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Aortic Aneurysm, Thoracoabdominal	Aortic Aneurysm	CTD_human_DG	30455415		★☆☆☆☆ Found in Text Mining only
Aortic Valve Disease 1	Aortic valve calcification	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Aortic Valve Stenosis	Aortic Valve Sclerosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Atherosclerosis	Atherosclerosis	Pubtator	33495827	Associate	★☆☆☆☆ Found in Text Mining only
Autistic Disorder	Autism	BEFREE	18270976		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Autistic Disorder	Autism	CTD_human_DG	18270976		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Bicuspid aortic valve	Bicuspid aortic valve	BEFREE	30455415		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Bicuspid aortic valve	Bicuspid aortic valve	CTD_human_DG	30455415		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Bicuspid aortic valve	Bicuspid aortic valve	HPO_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Bicuspid Aortic Valve Disease	Bicuspid aortic valve	Pubtator	32748548, 33631418, 36855159	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Bladder Neoplasm	Bladder Neoplasm	BEFREE	30019121, 31802889		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	21803008	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	19114000	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma of bladder	Bladder carcinoma	BEFREE	30019121, 31802889		★☆☆☆☆ Found in Text Mining only
Carcinoma Pancreatic Ductal	Pancreatic ductal carcinoma	Pubtator	31956659	Associate	★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	16685377		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal Neoplasms	LHGDN	16685377		★☆☆☆☆ Found in Text Mining only
Congenital diaphragmatic hernia	Congenital diaphragmatic hernia	CLINVAR_DG			★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Diabetes	Diabetes	BEFREE	28116460		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus	Diabetes Mellitus	BEFREE	28116460		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Non-Insulin-Dependent	Diabetes Mellitus	BEFREE	28116460		★☆☆☆☆ Found in Text Mining only
Diabetic Retinopathy	Diabetic Retinopathy	BEFREE	27041242, 28341181, 30980286, 31094072, 31773667		★☆☆☆☆ Found in Text Mining only
Endometriosis	Endometriosis	BEFREE	30251099		★☆☆☆☆ Found in Text Mining only
Gilles de la Tourette syndrome	Tourette Syndrome	BEFREE	17671968		★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	BEFREE	25470344, 25833462, 25859844		★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	Pubtator	25833462	Inhibit	★☆☆☆☆ Found in Text Mining only
Heart Defects Congenital	Congenital heart defect	Pubtator	36855159	Associate	★☆☆☆☆ Found in Text Mining only
Hyperglycemia	Hyperglycemia	BEFREE	27041242, 28341181, 30980286		★☆☆☆☆ Found in Text Mining only
Hypertensive disease	Hypertension	LHGDN	17496152		★☆☆☆☆ Found in Text Mining only
Hypoglycemia	Hypoglycemia	BEFREE	29590401		★☆☆☆☆ Found in Text Mining only
Immunologic Deficiency Syndromes	Immunologic Deficiency Syndromes	BEFREE	24376772		★☆☆☆☆ Found in Text Mining only
leukemia	Leukemia	BEFREE	25794001		★☆☆☆☆ Found in Text Mining only
Leukemia	Leukemia	Pubtator	25794001	Associate	★☆☆☆☆ Found in Text Mining only
Leukemia Myeloid Acute	Myeloid leukemia	Pubtator	25794001	Associate	★☆☆☆☆ Found in Text Mining only
Leukemia, Myelocytic, Acute	Leukemia	BEFREE	25794001		★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	19114000		★☆☆☆☆ Found in Text Mining only
Lung Neoplasms	Lung neoplasms	Pubtator	39595659	Associate	★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of prostate	Prostate cancer	BEFREE	30662335		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of urinary bladder	Urinary bladder cancer	BEFREE	30019121, 31802889		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	25348086, 30662335		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	16685377, 23664449, 24376772, 25348086, 30662335, 31160487		★☆☆☆☆ Found in Text Mining only
Non-Small Cell Lung Carcinoma	Lung carcinoma	BEFREE	15949592, 23664449		★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	BEFREE	27611116		★☆☆☆☆ Found in Text Mining only
Ovarian Neoplasms	Ovarian neoplasm	Pubtator	22132142	Inhibit	★☆☆☆☆ Found in Text Mining only
PIGMENTARY DISORDER, RETICULATE, WITH SYSTEMIC MANIFESTATIONS	Pigmentary Disorder, Reticulate, With Systemic Manifestations	BEFREE	30980286		★☆☆☆☆ Found in Text Mining only
Proliferative diabetic retinopathy	Proliferative Diabetic Retinopathy	BEFREE	19495426, 30980286		★☆☆☆☆ Found in Text Mining only
Prostate carcinoma	Prostate cancer	BEFREE	30662335		★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Prostatic neoplasm	Pubtator	30662335	Associate	★☆☆☆☆ Found in Text Mining only
Pulmonary Fibrosis	Pulmonary Fibrosis	LHGDN	17496152		★☆☆☆☆ Found in Text Mining only
Systemic Scleroderma	Scleroderma	BEFREE	30021803		★☆☆☆☆ Found in Text Mining only
Tetralogy of Fallot	Tetralogy of fallot	Pubtator	36855159	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroid Neoplasms	Thyroid cancer	Pubtator	32626543	Associate	★☆☆☆☆ Found in Text Mining only
Urinary Bladder Neoplasms	Urinary bladder neoplasms	Pubtator	30019121	Associate	★☆☆☆☆ Found in Text Mining only