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GeneBe

ROBO1

roundabout guidance receptor 1, the group of Ig-like cell adhesion molecule family|Fibronectin type III domain containing|I-set domain containing

Basic information

Region (hg38): 3:78597238-79767998

Links

ENSG00000169855NCBI:6091OMIM:602430HGNC:10249Uniprot:Q9Y6N7AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • pituitary stalk interruption syndrome (Supportive), mode of inheritance: AD
  • neurooculorenal syndrome (Strong), mode of inheritance: AR
  • pituitary hormone deficiency, combined or isolated, 8 (Strong), mode of inheritance: AD
  • neurooculorenal syndrome (Definitive), mode of inheritance: AR
  • pituitary hormone deficiency, combined or isolated, 8 (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Pituitary hormone deficiency, combined or isolated, 8; Neurooculorenal syndromeAD/ARCardiovascular; Endocrine; RenalThe conditions can involve centrally-mediated deficiency of multiple hormones, and diagnosis may allow medical management of endocrine deficiencies; Neurooculorenal syndrome may involve a spectrum of cardiovascular and renal tract anomalies, and awareness may allow diagnosis and interventions to help manage sequelaeCardiovascular; Craniofacial; Endocrine; Genitourinary; Neurologic; Ophthalmologic; Renal28286008; 28402530; 28592524; 30692597; 31448886; 33270637; 34193621; 35227688; 35348658

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ROBO1 gene.

  • not provided (261 variants)
  • Inborn genetic diseases (49 variants)
  • Congenital anomaly of kidney and urinary tract (13 variants)
  • ROBO1-related condition (9 variants)
  • Neurooculorenal syndrome (6 variants)
  • Heart, malformation of (4 variants)
  • Pituitary stalk interruption syndrome (4 variants)
  • Intellectual disability (3 variants)
  • Pituitary hormone deficiency, combined or isolated, 8 (3 variants)
  • Tetralogy of Fallot (2 variants)
  • Bilateral renal agenesis (2 variants)
  • Neurodevelopmental delay (2 variants)
  • Nystagmus, congenital, autosomal recessive (2 variants)
  • not specified (1 variants)
  • Increased nuchal translucency (1 variants)
  • 6 conditions (1 variants)
  • ROBO1-related disorder (1 variants)
  • Congenital nystagmus (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ROBO1 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
54
clinvar
25
clinvar
79
missense
1
clinvar
134
clinvar
14
clinvar
8
clinvar
157
nonsense
2
clinvar
11
clinvar
2
clinvar
15
start loss
0
frameshift
2
clinvar
3
clinvar
1
clinvar
6
inframe indel
5
clinvar
5
splice donor/acceptor (+/-2bp)
2
clinvar
3
clinvar
2
clinvar
7
splice region
8
14
7
29
non coding
1
clinvar
20
clinvar
10
clinvar
31
Total 6 18 145 88 43

Highest pathogenic variant AF is 0.00000658

Variants in ROBO1

This is a list of pathogenic ClinVar variants found in the ROBO1 region.

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

Position Type Phenotype Significance ClinVar
3-78598919-T-A Uncertain significance (Dec 03, 2023)2808190
3-78598940-C-T Likely benign (Oct 15, 2021)1641801
3-78600102-A-T Likely benign (Jun 24, 2021)1543198
3-78600118-A-ATTC Uncertain significance (Nov 20, 2021)1383848
3-78600143-T-A Inborn genetic diseases Uncertain significance (Jul 31, 2023)2373263
3-78600181-T-C Uncertain significance (Oct 22, 2023)2964233
3-78600208-G-T Inborn genetic diseases Uncertain significance (Jan 23, 2023)2477466
3-78600219-G-A Uncertain significance (Jul 26, 2022)1467019
3-78600227-T-C ROBO1-related condition Likely benign (Jul 17, 2019)3049416
3-78600231-G-C Bilateral renal agenesis • Neurooculorenal syndrome Likely pathogenic (Jan 09, 2021)996101
3-78600251-G-A ROBO1-related condition Likely benign (Nov 16, 2023)736441
3-78600254-A-C ROBO1-related condition Conflicting classifications of pathogenicity (Jan 18, 2024)2061944
3-78600262-GATT-G Heart, malformation of Uncertain significance (Jan 09, 2021)995985
3-78600303-A-G Uncertain significance (Jul 13, 2022)1878687
3-78600306-T-G Uncertain significance (Jan 13, 2022)1697092
3-78606715-GC-G Likely benign (Aug 02, 2023)2880187
3-78606727-G-A ROBO1-related condition Benign/Likely benign (Jan 08, 2024)713549
3-78606729-G-C Uncertain significance (Dec 12, 2023)2767018
3-78606756-G-A Uncertain significance (Jun 25, 2022)2202553
3-78606758-T-A ROBO1-related condition Likely benign (Aug 01, 2022)2653979
3-78606773-T-G ROBO1-related condition Benign (Jan 16, 2024)1529664
3-78606783-T-C Uncertain significance (Mar 28, 2022)1931765
3-78606794-T-G Inborn genetic diseases Uncertain significance (Dec 21, 2023)2067862
3-78606800-G-A Likely benign (Aug 02, 2023)3003053
3-78606809-C-T Likely benign (Jun 05, 2021)1564117

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
ROBO1protein_codingprotein_codingENST00000464233 301170576
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
7.27e-161.001247650691248340.000276
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense1.078259160.9000.000051010698
Missense in Polyphen468521.740.8976120
Synonymous-2.453953381.170.00001973300
Loss of Function4.724189.10.4600.00000545965

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0005600.000555
Ashkenazi Jewish0.0002360.000199
East Asian0.0001760.000167
Finnish0.0003310.000325
European (Non-Finnish)0.0003140.000309
Middle Eastern0.0001760.000167
South Asian0.0002340.000229
Other0.0003340.000330

dbNSFP

Source: dbNSFP

Function
FUNCTION: Receptor for SLIT1 and SLIT2 that mediates cellular responses to molecular guidance cues in cellular migration, including axonal navigation at the ventral midline of the neural tube and projection of axons to different regions during neuronal development (PubMed:10102268, PubMed:24560577). Interaction with the intracellular domain of FLRT3 mediates axon attraction towards cells expressing NTN1 (PubMed:24560577). In axon growth cones, the silencing of the attractive effect of NTN1 by SLIT2 may require the formation of a ROBO1-DCC complex (By similarity). Plays a role in the regulation of cell migration via its interaction with MYO9B; inhibits MYO9B-mediated stimulation of RHOA GTPase activity, and thereby leads to increased levels of active, GTP- bound RHOA (PubMed:26529257). May be required for lung development (By similarity). {ECO:0000250|UniProtKB:O89026, ECO:0000269|PubMed:10102268, ECO:0000269|PubMed:24560577, ECO:0000269|PubMed:26529257, ECO:0000305}.;
Pathway
Axon guidance - Homo sapiens (human);Angiogenesis overview;Developmental Biology;SLIT2:ROBO1 increases RHOA activity;Activation of RAC1;Regulation of commissural axon pathfinding by SLIT and ROBO;Inactivation of CDC42 and RAC1;Posttranslational regulation of adherens junction stability and dissassembly;Netrin-1 signaling;Regulation of expression of SLITs and ROBOs;Signaling by ROBO receptors;Axon guidance;Regulation of cortical dendrite branching;Role of ABL in ROBO-SLIT signaling (Consensus)

Recessive Scores

pRec
0.124

Intolerance Scores

loftool
0.687
rvis_EVS
-1.96
rvis_percentile_EVS
1.85

Haploinsufficiency Scores

pHI
0.947
hipred
Y
hipred_score
0.666
ghis
0.559

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
gene_indispensability_pred
E
gene_indispensability_score
0.676

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Robo1
Phenotype
skeleton phenotype; renal/urinary system 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; 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); normal phenotype; reproductive system phenotype; 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); neoplasm; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype; craniofacial phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; endocrine/exocrine gland phenotype;

Zebrafish Information Network

Gene name
robo1
Affected structure
endocardium
Phenotype tag
abnormal
Phenotype quality
mislocalised

Gene ontology

Biological process
cell migration involved in sprouting angiogenesis;outflow tract septum morphogenesis;aortic valve morphogenesis;pulmonary valve morphogenesis;endocardial cushion formation;activation of cysteine-type endopeptidase activity involved in apoptotic process;cell adhesion;homophilic cell adhesion via plasma membrane adhesion molecules;nervous system development;axon guidance;positive regulation of gene expression;negative regulation of gene expression;axon midline choice point recognition;chemorepulsion involved in postnatal olfactory bulb interneuron migration;negative regulation of cell migration;negative regulation of mammary gland epithelial cell proliferation;positive regulation of Rho protein signal transduction;Roundabout signaling pathway;positive regulation of Notch signaling pathway involved in heart induction;aorta development;positive regulation of MAP kinase activity;positive regulation of axonogenesis;negative regulation of negative chemotaxis;ventricular septum morphogenesis;negative regulation of chemokine-mediated signaling pathway;positive regulation of vascular endothelial growth factor signaling pathway
Cellular component
cytoplasm;plasma membrane;integral component of plasma membrane;cell surface;axon;endoplasmic reticulum-Golgi intermediate compartment membrane
Molecular function
protein binding;axon guidance receptor activity;LRR domain binding;identical protein binding