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

ENSG00000169855 ∙ NCBI:6091 ∙ OMIM:602430 ∙ HGNC:10249 ∙ Uniprot:Q9Y6N7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

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

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pituitary hormone deficiency, combined or isolated, 8; Neurooculorenal syndrome	AD/AR	Cardiovascular; Endocrine; Renal	The 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 sequelae	Cardiovascular; Craniofacial; Endocrine; Genitourinary; Neurologic; Ophthalmologic; Renal	28286008; 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	25	79
missense		1	134	14	8	157
nonsense	2	11	2			15
start loss						0
frameshift	2	3	1			6
inframe indel			5			5
splice donor/acceptor (+/-2bp)	2	3	2			7
splice region			8	14	7	29
non coding			1	20	10	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)
3-78598940-C-T			Likely benign (Oct 15, 2021)
3-78600102-A-T			Likely benign (Jun 24, 2021)
3-78600119-T-A		Inborn genetic diseases	Uncertain significance (Dec 12, 2023)
3-78600118-A-ATTC			Uncertain significance (Nov 20, 2021)
3-78600143-T-A		Inborn genetic diseases	Uncertain significance (Jul 31, 2023)
3-78600181-T-C			Uncertain significance (Oct 22, 2023)
3-78600208-G-T		Inborn genetic diseases	Uncertain significance (Jan 23, 2023)
3-78600219-G-A			Uncertain significance (Jul 26, 2022)
3-78600227-T-C		ROBO1-related disorder	Likely benign (Jul 17, 2019)
3-78600231-G-C		Bilateral renal agenesis • Neurooculorenal syndrome	Likely pathogenic (Jan 09, 2021)
3-78600235-T-C		Inborn genetic diseases	Uncertain significance (Oct 27, 2022)
3-78600251-G-A		ROBO1-related disorder	Likely benign (Nov 16, 2023)
3-78600254-A-C		ROBO1-related disorder	Conflicting classifications of pathogenicity (Jan 18, 2024)
3-78600262-GATT-G		Heart, malformation of	Uncertain significance (Jan 09, 2021)
3-78600303-A-G			Uncertain significance (Jul 13, 2022)
3-78600306-T-G			Uncertain significance (Jan 13, 2022)
3-78606715-GC-G			Likely benign (Aug 02, 2023)
3-78606727-G-A		ROBO1-related disorder	Benign/Likely benign (Jan 08, 2024)
3-78606729-G-C			Uncertain significance (Dec 12, 2023)
3-78606756-G-A			Uncertain significance (Jun 25, 2022)
3-78606758-T-A		ROBO1-related disorder	Likely benign (Aug 01, 2022)
3-78606773-T-G		ROBO1-related disorder	Benign (Jan 16, 2024)
3-78606783-T-C			Uncertain significance (Mar 28, 2022)
3-78606794-T-G		Inborn genetic diseases	Uncertain significance (Dec 21, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ROBO1	protein_coding	protein_coding	ENST00000464233	30	1170576

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.27e-16	1.00	124765	0	69	124834	0.000276

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.07	825	916	0.900	0.0000510	10698
Missense in Polyphen		468	521.74	0.897		6120
Synonymous	-2.45	395	338	1.17	0.0000197	3300
Loss of Function	4.72	41	89.1	0.460	0.00000545	965

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000560	0.000555
Ashkenazi Jewish	0.000236	0.000199
East Asian	0.000176	0.000167
Finnish	0.000331	0.000325
European (Non-Finnish)	0.000314	0.000309
Middle Eastern	0.000176	0.000167
South Asian	0.000234	0.000229
Other	0.000334	0.000330

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
• gene_indispensability_pred: E
• gene_indispensability_score: 0.676

Gene Damage Prediction

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

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