ROBO3

roundabout guidance receptor 3, the group of Fibronectin type III domain containing|I-set domain containing

Basic information

Region (hg38): 11:124865431-124881471

Previous symbols: [ "HGPPS" ]

Links

ENSG00000154134 ∙ NCBI:64221 ∙ OMIM:608630 ∙ HGNC:13433 ∙ Uniprot:Q96MS0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• gaze palsy, familial horizontal, with progressive scoliosis 1 (Definitive), mode of inheritance: AR
• gaze palsy, familial horizontal, with progressive scoliosis 1 (Strong), mode of inheritance: AR
• gaze palsy, familial horizontal, with progressive scoliosis 1 (Strong), mode of inheritance: AR
• gaze palsy, familial horizontal, with progressive scoliosis 1 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Gaze palsy, familial horizontal, with progressive scoliosis 1	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Musculoskeletal; Neurologic	15105459; 16525029; 18829051; 19633821; 21592015; 21850172

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ROBO3 gene.

• Gaze palsy, familial horizontal, with progressive scoliosis 1 (140 variants)
• Inborn genetic diseases (78 variants)
• not provided (75 variants)
• ROBO3-related condition (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ROBO3 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			10	21	10	41
missense		16	108	7	8	139
nonsense	1	1				2
start loss						0
frameshift	3	2	2		2	9
inframe indel			2		1	3
splice donor/acceptor (+/-2bp)	1	1				2
splice region			2	5	2	9
non coding			15	3	6	24
Total	5	20	137	31	27

Highest pathogenic variant AF is 0.0000132

Variants in ROBO3

This is a list of pathogenic ClinVar variants found in the ROBO3 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-124865458-G-C		Gaze palsy, familial horizontal, with progressive scoliosis 1	Benign (Jan 13, 2018)
11-124865518-G-T		Gaze palsy, familial horizontal, with progressive scoliosis 1	Uncertain significance (Jan 13, 2018)
11-124865591-T-C		Gaze palsy, familial horizontal, with progressive scoliosis 1	Likely pathogenic (Jan 09, 2021)
11-124865596-A-C		Inborn genetic diseases	Uncertain significance (Jan 03, 2022)
11-124865611-A-C		Inborn genetic diseases	Uncertain significance (Aug 04, 2023)
11-124865620-T-C		Gaze palsy, familial horizontal, with progressive scoliosis 1 • Inborn genetic diseases	Uncertain significance (Nov 03, 2022)
11-124865623-G-A		Gaze palsy, familial horizontal, with progressive scoliosis 1	Likely benign (Jul 28, 2021)
11-124865653-T-C		Inborn genetic diseases	Uncertain significance (Jun 28, 2022)
11-124865668-T-C		ROBO3-related disorder	Likely benign (Dec 29, 2023)
11-124865737-G-A			Uncertain significance (Nov 03, 2021)
11-124865749-C-T		Gaze palsy, familial horizontal, with progressive scoliosis 1	Likely benign (Jan 13, 2018)
11-124868810-G-A		Inborn genetic diseases	Uncertain significance (Feb 21, 2024)
11-124868817-C-T		Inborn genetic diseases	Uncertain significance (Mar 03, 2022)
11-124868837-A-C		Gaze palsy, familial horizontal, with progressive scoliosis 1	Likely pathogenic (Jan 09, 2021)
11-124868866-C-T		ROBO3-related disorder	Likely benign (Jan 31, 2023)
11-124868867-TCCCGAGGCGAGCCCGCCA-T		ROBO3-related disorder	Uncertain significance (Sep 19, 2023)
11-124868912-C-T		Gaze palsy, familial horizontal, with progressive scoliosis 1	Likely pathogenic (Jan 09, 2021)
11-124868925-T-C		Gaze palsy, familial horizontal, with progressive scoliosis 1	Likely pathogenic (Jan 09, 2021)
11-124868976-G-C		Gaze palsy, familial horizontal, with progressive scoliosis 1	Likely pathogenic (Jan 09, 2021)
11-124868995-G-A		ROBO3-related disorder	Benign (Feb 24, 2020)
11-124869057-G-T		Gaze palsy, familial horizontal, with progressive scoliosis 1	Likely pathogenic (Jan 09, 2021)
11-124869090-G-A		ROBO3-related disorder	Uncertain significance (Oct 04, 2022)
11-124869107-A-C		Inborn genetic diseases	Uncertain significance (Jan 23, 2023)
11-124869109-C-T		Gaze palsy, familial horizontal, with progressive scoliosis 1	Uncertain significance (Jan 12, 2018)
11-124869436-A-C		Gaze palsy, familial horizontal, with progressive scoliosis 1	Benign (Nov 07, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ROBO3	protein_coding	protein_coding	ENST00000397801	28	16085

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.00e-15	1.00	124605	0	56	124661	0.000225

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.608	743	791	0.939	0.0000430	8665
Missense in Polyphen		266	318.84	0.83428		3563
Synonymous	1.35	286	317	0.903	0.0000173	2948
Loss of Function	3.48	35	65.4	0.535	0.00000310	703

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000774	0.000720
Ashkenazi Jewish	0.0000994	0.0000994
East Asian	0.000337	0.000334
Finnish	0.00	0.00
European (Non-Finnish)	0.000182	0.000177
Middle Eastern	0.000337	0.000334
South Asian	0.000461	0.000458
Other	0.000171	0.000165

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Thought to be involved during neural development in axonal navigation at the ventral midline of the neural tube. In spinal chord development plays a role in guiding commissural axons probably by preventing premature sensitivity to Slit proteins thus inhibiting Slit signaling through ROBO1 (By similarity). Required for hindbrain axon midline crossing. {ECO:0000250, ECO:0000269|PubMed:15105459}.
• Disease: DISEASE: Gaze palsy, familial horizontal, with progressive scoliosis, 1 (HGPPS1) [MIM:607313]: An autosomal recessive neurologic disorder characterized by eye movement abnormalities apparent from birth, childhood-onset progressive scoliosis, distinctive brainstem malformation and defective crossing of some brainstem neuronal pathways. {ECO:0000269|PubMed:15105459}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Axon guidance - Homo sapiens (human);Developmental Biology;Regulation of commissural axon pathfinding by SLIT and ROBO;ROBO receptors bind AKAP5;Regulation of expression of SLITs and ROBOs;Signaling by ROBO receptors;Axon guidance (Consensus)

Recessive Scores

• pRec: 0.132

Intolerance Scores

• loftool: 0.572
• rvis_EVS: 0.65
• rvis_percentile_EVS: 84.18

Haploinsufficiency Scores

• pHI: 0.462
• hipred: N
• hipred_score: 0.475
• ghis: 0.419

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.189

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Robo3
• Phenotype: embryo phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); 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); hearing/vestibular/ear phenotype; cellular phenotype; homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: robo3
• Affected structure: Mauthner neuron
• Phenotype tag: abnormal
• Phenotype quality: mislocalised

Gene ontology

• Biological process: homophilic cell adhesion via plasma membrane adhesion molecules;axon guidance;axon midline choice point recognition;Roundabout signaling pathway;chemoattraction of axon;dendrite self-avoidance;commissural neuron axon guidance
• Cellular component: plasma membrane;integral component of membrane;axon
• Molecular function: protein binding;cell-cell adhesion mediator activity