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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): 3:75906694-77649964

Links

ENSG00000185008NCBI:6092OMIM:602431HGNC:10250Uniprot:Q9HCK4AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

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

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Vesicoureteral reflux 2ADRenalMonitoring and intervention related to vesicoureteral reflux may be beneficial in terms of helping to preserve renal functionRenal17357069

ClinVar

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

  • Vesicoureteral reflux 2 (174 variants)
  • not provided (165 variants)
  • Inborn genetic diseases (48 variants)
  • Congenital anomaly of kidney and urinary tract (18 variants)
  • Vesicoureteral reflux (7 variants)
  • ROBO2-related condition (3 variants)
  • not specified (1 variants)

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
8
clinvar
39
clinvar
6
clinvar
53
missense
111
clinvar
18
clinvar
10
clinvar
139
nonsense
0
start loss
0
frameshift
1
clinvar
1
inframe indel
1
clinvar
1
splice donor/acceptor (+/-2bp)
3
clinvar
3
splice region
?
2
6
8
non coding
?
42
clinvar
12
clinvar
88
clinvar
142
Total 0 0 166 69 104

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
3-75937512-C-A Vesicoureteral reflux 2 Benign (Feb 15, 2016)518348
3-75937566-G-A Vesicoureteral reflux 2 Benign (May 19, 2016)518349
3-75937568-G-A Likely benign (Dec 01, 2022)2653976
3-75937590-G-T Vesicoureteral reflux 2 Conflicting classifications of pathogenicity (Aug 01, 2023)224347
3-77039944-C-G Benign (Nov 12, 2018)1251594
3-77040215-C-G Vesicoureteral reflux 2 Uncertain significance (Jan 13, 2018)346665
3-77040224-A-G Vesicoureteral reflux 2 Uncertain significance (Jan 13, 2018)346666
3-77040244-T-C Vesicoureteral reflux 2 Benign (Nov 12, 2018)346667
3-77040304-C-T Vesicoureteral reflux 2 Uncertain significance (Jan 13, 2018)346668
3-77040327-G-A Vesicoureteral reflux 2 Benign (Jan 13, 2018)346669
3-77040382-G-C Vesicoureteral reflux 2 Benign (Jun 20, 2021)346670
3-77040548-T-G Vesicoureteral reflux 2 Benign (Nov 12, 2018)346671
3-77040620-C-T Vesicoureteral reflux 2 Uncertain significance (Jan 13, 2018)346672
3-77040676-C-G Vesicoureteral reflux 2 Uncertain significance (Jan 13, 2018)346673
3-77040793-T-A Uncertain significance (Jan 26, 2024)2712373
3-77040837-C-T Likely benign (Jul 24, 2022)1966076
3-77040961-C-T Benign (Jun 20, 2021)1247361
3-77097797-A-T Benign (Jun 20, 2021)1245198
3-77097856-G-A Benign (Nov 12, 2018)1245909
3-77097888-C-A Benign (Nov 12, 2018)1253088
3-77097961-G-A Benign (Nov 12, 2018)1282281
3-77098000-G-A Benign (Oct 26, 2022)1896931
3-77098000-G-T Vesicoureteral reflux 2 Benign (Sep 28, 2022)346674
3-77098044-C-T Inborn genetic diseases Uncertain significance (Feb 10, 2022)2276747
3-77098046-C-A Vesicoureteral reflux 2 Benign (Oct 26, 2022)346675

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
ROBO2protein_codingprotein_codingENST00000487694 251743270
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
1.002.79e-81247840101247940.0000401
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense1.656607910.8350.00004469063
Missense in Polyphen5093.590.53425934
Synonymous-1.423172861.110.00001652781
Loss of Function7.36674.50.08050.00000424784

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.00009360.0000936
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.000.00
European (Non-Finnish)0.00006200.0000530
Middle Eastern0.000.00
South Asian0.00006600.0000654
Other0.000.00

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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