ROBO2

roundabout guidance receptor 2, the group of Fibronectin type III domain containing|I-set domain containing|Ig-like cell adhesion molecule family

Basic information

Region (hg38): 3:75906695-77649964

Links

ENSG00000185008 ∙ NCBI:6092 ∙ OMIM:602431 ∙ HGNC:10250 ∙ Uniprot:Q9HCK4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• vesicoureteral reflux 2 (Strong), mode of inheritance: AD
• familial vesicoureteral reflux (Supportive), mode of inheritance: AD
• vesicoureteral reflux 2 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Vesicoureteral reflux 2	AD	Renal	Monitoring and intervention related to vesicoureteral reflux may be beneficial in terms of helping to preserve renal function	Renal	17357069

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ROBO2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ROBO2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			9	51	9	69
missense			146	20	9	175
nonsense						0
start loss						0
frameshift			1			1
inframe indel			1			1
splice donor/acceptor (+/-2bp)			3			3
splice region			2	6	8	16
non coding			42	16	89	147
Total	0	0	202	87	107

Variants in ROBO2

This is a list of pathogenic ClinVar variants found in the ROBO2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-75937491-G-T		ROBO2-related disorder	Likely benign (Nov 27, 2019)
3-75937512-C-A		Vesicoureteral reflux 2 • ROBO2-related disorder	Benign (Feb 15, 2016)
3-75937534-C-G		ROBO2-related disorder	Uncertain significance (Nov 29, 2023)
3-75937535-A-G		ROBO2-related disorder	Benign (Nov 18, 2020)
3-75937544-G-A		ROBO2-related disorder	Benign (Nov 18, 2020)
3-75937547-A-G		ROBO2-related disorder	Likely benign (Feb 27, 2019)
3-75937566-G-A		Vesicoureteral reflux 2 • ROBO2-related disorder	Benign (May 19, 2016)
3-75937568-G-A			Likely benign (Dec 01, 2022)
3-75937568-G-C		ROBO2-related disorder	Benign (Nov 18, 2020)
3-75937590-G-T		Vesicoureteral reflux 2	Conflicting classifications of pathogenicity (Aug 01, 2023)
3-77039944-C-G			Benign (Nov 12, 2018)
3-77040215-C-G		Vesicoureteral reflux 2	Uncertain significance (Jan 13, 2018)
3-77040224-A-G		Vesicoureteral reflux 2	Uncertain significance (Jan 13, 2018)
3-77040244-T-C		Vesicoureteral reflux 2	Benign (Nov 12, 2018)
3-77040304-C-T		Vesicoureteral reflux 2	Uncertain significance (Jan 13, 2018)
3-77040327-G-A		Vesicoureteral reflux 2	Benign (Jan 13, 2018)
3-77040382-G-C		Vesicoureteral reflux 2	Benign (Jun 20, 2021)
3-77040548-T-G		Vesicoureteral reflux 2	Benign (Nov 12, 2018)
3-77040620-C-T		Vesicoureteral reflux 2	Uncertain significance (Jan 13, 2018)
3-77040676-C-G		Vesicoureteral reflux 2	Uncertain significance (Jan 13, 2018)
3-77040793-T-A		Inborn genetic diseases	Uncertain significance (Jan 26, 2024)
3-77040820-G-A			Uncertain significance (Apr 17, 2023)
3-77040837-C-T			Likely benign (Jul 24, 2022)
3-77040961-C-T			Benign (Jun 20, 2021)
3-77097797-A-T			Benign (Jun 20, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ROBO2	protein_coding	protein_coding	ENST00000487694	25	1743270

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	2.79e-8	124784	0	10	124794	0.0000401

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.65	660	791	0.835	0.0000446	9063
Missense in Polyphen		50	93.59	0.53425		934
Synonymous	-1.42	317	286	1.11	0.0000165	2781
Loss of Function	7.36	6	74.5	0.0805	0.00000424	784

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000936	0.0000936
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000620	0.0000530
Middle Eastern	0.00	0.00
South Asian	0.0000660	0.0000654
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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 development.
• Disease: DISEASE: Vesicoureteral reflux 2 (VUR2) [MIM:610878]: A disease belonging to the group of congenital anomalies of the kidney and urinary tract. It is characterized by the reflux of urine from the bladder into the ureters and sometimes into the kidneys, and is a risk factor for urinary tract infections. Primary disease results from a developmental defect of the ureterovesical junction. In combination with intrarenal reflux, the resulting inflammatory reaction may result in renal injury or scarring, also called reflux nephropathy. Extensive renal scarring impairs renal function and may predispose patients to hypertension, proteinuria, renal insufficiency and end-stage renal disease. {ECO:0000269|PubMed:17357069}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=A chromosomal aberration involving ROBO2 is a cause of multiple congenital abnormalities, including severe bilateral VUR with ureterovesical junction defects. Translocation t(Y;3)(p11;p12) with PCDH11Y. This translocation disrupts ROBO2 and produces dominant-negative ROBO2 proteins that abrogate SLIT- ROBO signaling in vitro.
• Pathway: Axon guidance - Homo sapiens (human);Developmental Biology;ROBO receptors bind AKAP5;Regulation of expression of SLITs and ROBOs;Signaling by ROBO receptors;Axon guidance;Regulation of cortical dendrite branching (Consensus)

Recessive Scores

• pRec: 0.126

Intolerance Scores

• loftool: 0.324
• rvis_EVS: -1.5
• rvis_percentile_EVS: 3.6

Haploinsufficiency Scores

• pHI: 0.339
• hipred: Y
• hipred_score: 0.596
• ghis: 0.583

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.520

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Robo2
• Phenotype: muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype; renal/urinary system phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); reproductive system phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: robo2
• Affected structure: retinal ganglion cell
• Phenotype tag: abnormal
• Phenotype quality: increased occurrence

Gene ontology

• Biological process: metanephros development;ureteric bud development;outflow tract septum morphogenesis;aortic valve morphogenesis;pulmonary valve morphogenesis;endocardial cushion formation;homophilic cell adhesion via plasma membrane adhesion molecules;axon guidance;central nervous system development;brain development;axon midline choice point recognition;spinal cord development;olfactory bulb interneuron development;retinal ganglion cell axon guidance;cellular response to hormone stimulus;Roundabout signaling pathway;positive regulation of Notch signaling pathway involved in heart induction;aorta development;positive regulation of axonogenesis;negative regulation of negative chemotaxis;negative regulation of synapse assembly;ventricular septum morphogenesis;apoptotic process involved in luteolysis
• Cellular component: plasma membrane;cell surface;integral component of membrane;axolemma;extracellular exosome
• Molecular function: protein binding;axon guidance receptor activity;identical protein binding