ROBO2 (roundabout guidance receptor 2)

Gene

• Entrez ID: 6092
• Gene name: Roundabout guidance receptor 2
• Gene symbol: ROBO2
• Synonyms: SAX3
• Chromosome: 3
• Chromosome location: 3p12.3
• Summary: 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 ax

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs267607014	T>C	Pathogenic	Coding sequence variant, missense variant
rs267607015	G>A,C	Pathogenic	Coding sequence variant, missense variant
rs754279676	G>A	Likely-pathogenic	5 prime UTR variant, coding sequence variant, missense variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT005809	hsa-miR-145-5p	In situ hybridization, Luciferase reporter assay, qRT-PCR, western blot	21276775
MIRT005809	hsa-miR-145-5p	Reporter assay	21276775
MIRT038206	hsa-miR-342-5p	CLASH	23622248
MIRT541770	hsa-miR-8084	PAR-CLIP	21572407
MIRT541769	hsa-miR-4731-3p	PAR-CLIP	21572407
MIRT541768	hsa-miR-4801	PAR-CLIP	21572407
MIRT541767	hsa-miR-6844	PAR-CLIP	21572407
MIRT541766	hsa-miR-514a-3p	PAR-CLIP	21572407
MIRT541765	hsa-miR-514b-3p	PAR-CLIP	21572407
MIRT541770	hsa-miR-8084	PAR-CLIP	21572407
MIRT541769	hsa-miR-4731-3p	PAR-CLIP	21572407
MIRT541768	hsa-miR-4801	PAR-CLIP	21572407
MIRT541767	hsa-miR-6844	PAR-CLIP	21572407
MIRT541766	hsa-miR-514a-3p	PAR-CLIP	21572407
MIRT541765	hsa-miR-514b-3p	PAR-CLIP	21572407
MIRT1314590	hsa-miR-1305	CLIP-seq
MIRT1314591	hsa-miR-205	CLIP-seq
MIRT1314592	hsa-miR-2278	CLIP-seq
MIRT1314593	hsa-miR-23a	CLIP-seq
MIRT1314594	hsa-miR-23b	CLIP-seq
MIRT1314595	hsa-miR-23c	CLIP-seq
MIRT1314596	hsa-miR-297	CLIP-seq
MIRT1314597	hsa-miR-3149	CLIP-seq
MIRT1314598	hsa-miR-338-5p	CLIP-seq
MIRT1314599	hsa-miR-33a	CLIP-seq
MIRT1314600	hsa-miR-33b	CLIP-seq
MIRT1314601	hsa-miR-380	CLIP-seq
MIRT1314602	hsa-miR-4279	CLIP-seq
MIRT1314603	hsa-miR-4682	CLIP-seq
MIRT1314604	hsa-miR-4711-3p	CLIP-seq
MIRT1314605	hsa-miR-4720-5p	CLIP-seq
MIRT1314606	hsa-miR-4799-3p	CLIP-seq
MIRT1314607	hsa-miR-511	CLIP-seq
MIRT1314608	hsa-miR-513a-3p	CLIP-seq
MIRT1314609	hsa-miR-567	CLIP-seq
MIRT1314610	hsa-miR-582-5p	CLIP-seq
MIRT1314611	hsa-miR-587	CLIP-seq
MIRT1314612	hsa-miR-646	CLIP-seq
MIRT1314613	hsa-miR-654-3p	CLIP-seq
MIRT1314614	hsa-miR-155	CLIP-seq
MIRT1314615	hsa-miR-208a	CLIP-seq
MIRT1314616	hsa-miR-208b	CLIP-seq
MIRT1314617	hsa-miR-4432	CLIP-seq
MIRT1314618	hsa-miR-448	CLIP-seq
MIRT1314619	hsa-miR-499-5p	CLIP-seq
MIRT1314620	hsa-miR-622	CLIP-seq
MIRT2093556	hsa-miR-1911	CLIP-seq
MIRT2093557	hsa-miR-4474-3p	CLIP-seq
MIRT2093558	hsa-miR-4762-3p	CLIP-seq
MIRT2093559	hsa-miR-580	CLIP-seq
MIRT1314618	hsa-miR-448	CLIP-seq
MIRT2318092	hsa-miR-1267	CLIP-seq
MIRT2318093	hsa-miR-141	CLIP-seq
MIRT2318094	hsa-miR-200a	CLIP-seq
MIRT1314597	hsa-miR-3149	CLIP-seq
MIRT2318095	hsa-miR-345	CLIP-seq
MIRT2318096	hsa-miR-3913-3p	CLIP-seq
MIRT2318097	hsa-miR-4652-3p	CLIP-seq
MIRT2318098	hsa-miR-489	CLIP-seq
MIRT2318099	hsa-miR-514	CLIP-seq
MIRT2393856	hsa-miR-3688-3p	CLIP-seq
MIRT1314602	hsa-miR-4279	CLIP-seq
MIRT1314608	hsa-miR-513a-3p	CLIP-seq
MIRT2093556	hsa-miR-1911	CLIP-seq
MIRT2458501	hsa-miR-4539	CLIP-seq
MIRT2458502	hsa-miR-4724-5p	CLIP-seq
MIRT2093556	hsa-miR-1911	CLIP-seq
MIRT2458501	hsa-miR-4539	CLIP-seq
MIRT2458502	hsa-miR-4724-5p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001656	Process	Metanephros development	ISS
GO:0001657	Process	Ureteric bud development	IMP	17357069
GO:0003148	Process	Outflow tract septum morphogenesis	ISS
GO:0003180	Process	Aortic valve morphogenesis	ISS
GO:0003184	Process	Pulmonary valve morphogenesis	ISS
GO:0003272	Process	Endocardial cushion formation	ISS
GO:0005515	Function	Protein binding	IPI	12504588, 15207848, 32296183
GO:0005886	Component	Plasma membrane	TAS
GO:0007156	Process	Homophilic cell adhesion via plasma membrane adhesion molecules	IDA	12504588
GO:0007411	Process	Axon guidance	ISS
GO:0007411	Process	Axon guidance	TAS
GO:0007417	Process	Central nervous system development	NAS	9458045
GO:0007420	Process	Brain development	IEP	10197527
GO:0008046	Function	Axon guidance receptor activity	ISS
GO:0008046	Function	Axon guidance receptor activity	NAS	9458045
GO:0009986	Component	Cell surface	IDA	12504588
GO:0016021	Component	Integral component of membrane	IEA
GO:0016199	Process	Axon midline choice point recognition	ISS
GO:0021891	Process	Olfactory bulb interneuron development	ISS
GO:0030673	Component	Axolemma	ISS
GO:0031290	Process	Retinal ganglion cell axon guidance	ISS
GO:0032870	Process	Cellular response to hormone stimulus	IEP	18566128
GO:0035481	Process	Positive regulation of Notch signaling pathway involved in heart induction	ISS
GO:0035904	Process	Aorta development	ISS
GO:0042802	Function	Identical protein binding	IDA	12504588
GO:0050772	Process	Positive regulation of axonogenesis	IDA	12504588
GO:0050925	Process	Negative regulation of negative chemotaxis	IDA	11748139
GO:0051964	Process	Negative regulation of synapse assembly	ISS
GO:0060412	Process	Ventricular septum morphogenesis	ISS
GO:0061364	Process	Apoptotic process involved in luteolysis	IEP	18566128
GO:0070062	Component	Extracellular exosome	HDA	19056867

Other IDs

• MIM: 602431
• HGNC: 10250
• e!Ensembl: ENSG00000185008

Protein

• UniProt ID: Q9HCK4
• Protein name: Roundabout homolog 2
• Protein 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
• PDB: 1UEM, 1UJT, 2EDJ, 5NOI, 6I9S, 6IAA
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF13927	Ig_3	30 → 114		Domain
  PF07679	I-set	133 → 221	Immunoglobulin I-set domain	Domain
  PF07679	I-set	225 → 310	Immunoglobulin I-set domain	Domain
  PF07679	I-set	314 → 408	Immunoglobulin I-set domain	Domain
  PF07679	I-set	418 → 505	Immunoglobulin I-set domain	Domain
  PF00041	fn3	523 → 607	Fibronectin type III domain	Domain
  PF00041	fn3	640 → 724	Fibronectin type III domain	Domain
  PF00041	fn3	738 → 826	Fibronectin type III domain	Domain

• Sequence:

  MSLLMFTQLLLCGFLYVRVDGSRLRQEDFPPRIVEHPSDVIVSKGEPTTLNCKAEGRPTP
  TIEWYKDGERVETDKDDPRSHRMLLPSGSLFFLRIVHGRRSKPDEGSYVCVARNYLGEAV
  SRNASLEVALLRDDFRQNPTDVVVAAGEPAILECQPPRGHPEPTIYWKKDKVRIDDKEER
  ISIRGGKLMISNTRKSDAGMYTCVGTNMVGERDSDPAELTVFERPTFLRRPINQVVLEEE
  AVEFRCQVQGDPQPTVRWKKDDADLPRGRYDIKDDYTLRIKKTMSTDEGTYMCIAENRVG
  KMEASATLTVRAPPQFVVRPRDQIVAQGRTVTFPCETKGNPQPAVFWQKEGSQNLLFPNQ
  PQQPNSRCSVSPTGDLTITNIQRSDAGYYICQALTVAGSILAKAQLEVTDVLTDRPPPII
  LQGPANQTLAVDGTALLKCKATGDPLPVISWLKEGFTFPGRDPRATIQEQGTLQIKNLRI
  SDTGTYTCVATSSSGETSWSAVLDVTESGATISKNYDLSDLPGPPSKPQVTDVTKNSVTL
  SWQPGTPGTLPASAYIIEAFSQSVSNSWQTVANHVKTTLYTVRGLRPNTIYLFMVRAINP
  QGLSDPSPMSDPVRTQDISPPAQGVDHRQVQKELGDVLVRLHNPVVLTPTTVQVTWTVDR
  QPQFIQGYRVMYRQTSGLQATSSWQNLDAKVPTERSAVLVNLKKGVTYEIKVRPYFNEFQ
  GMDSESKTVRTTEEAPSAPPQSVTVLTVGSYNSTSISVSWDPPPPDHQNGIIQEYKIWCL
  GNETRFHINKTVDAAIRSVIIGGLFPGIQYRVEVAASTSAGVGVKSEPQPIIIGRRNEVV
  ITENNNSITEQITDVVKQPAFIAGIGGACWVILMGFSIWLYWRRKKRKGLSNYAVTFQRG
  DGGLMSNGSRPGLLNAGDPSYPWLADSWPATSLPVNNSNSGPNEIGNFGRGDVLPPVPGQ
  GDKTATMLSDGAIYSSIDFTTKTSYNSSSQITQATPYATTQILHSNSIHELAVDLPDPQW
  KSSIQQKTDLMGFGYSLPDQNKGNNGGKGGKKKKNKNSSKPQKNNGSTWANVPLPPPPVQ
  PLPGTELEHYAVEQQENGYDSDSWCPPLPVQTYLHQGLEDELEEDDDRVPTPPVRGVASS
  PAISFGQQSTATLTPSPREEMQPMLQAHLDELTRAYQFDIAKQTWHIQSNNQPPQPPVPP
  LGYVSGALISDLETDVADDDADDEEEALEIPRPLRALDQTPGSSMDNLDSSVTGKAFTSS
  QRPRPTSPFSTDSNTSAALSQSQRPRPTKKHKGGRMDQQPALPHRREGMTDEEALVPYSK
  PSFPSPGGHSSSGTASSKGSTGPRKTEVLRAGHQRNASDLLDIGYMGSNSQGQFTGEL

• Sequence length: 1378

Pathways

KEGG:

Axon guidance

Reactome:

Signaling by ROBO receptors
Regulation of commissural axon pathfinding by SLIT and ROBO

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Autism	Autistic Disorder	rs121964908, rs121912597, rs2710102, rs7794745, rs142990298, rs62643608, rs181327458, rs797046134, rs869312704, rs1555013332, rs876657679, rs1057518999, rs1057518658, rs771827120, rs1555187899, rs773080572, rs753871454, rs1684130791, rs1684180699, rs1553510219, rs1684182454, rs1559060428, rs1553510677, rs1576352885, rs1574152522, rs1574152672, rs1696658542, rs1751123722, rs1750373491, rs1751075634	18270976
Prostate cancer	Malignant neoplasm of prostate, Prostate carcinoma	rs121909139, rs121909140, rs121909141, rs121909142, rs121909143, rs606231169, rs606231170, rs137852584, rs137852578, rs137852580, rs137852581, rs137852582	29662167, 27515689
Vesicoureteral reflux	Vesico-Ureteral Reflux, Vesicoureteral Reflux 2, Familial vesicoureteral reflux	rs587777684, rs148731211	17357069

Unknown
Disease name	Disease term	dbSNP ID	References
Cholangiocarcinoma	Cholangiocarcinoma, Extrahepatic Cholangiocarcinoma	rs1800795, rs1800872, rs2227983, rs4444903, rs1143634	22561520
Intrahepatic cholangiocarcinoma	Intrahepatic Cholangiocarcinoma		22561520
Mental depression	Major Depressive Disorder	rs587778876, rs587778877	29942085
Prostatic neoplasms	Prostatic Neoplasms		29662167
Renal hypoplasia	Congenital hypoplasia of kidney	rs561111097