ROBO3

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

Basic information

Region (hg38): 11:124865432-124881471

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.

Inborn_genetic_diseases (211 variants)
Gaze_palsy,_familial_horizontal,_with_progressive_scoliosis_1 (129 variants)
not_provided (89 variants)
ROBO3-related_disorder (33 variants)
not_specified (5 variants)
Tuberous_sclerosis_syndrome (3 variants)
Conjugate_gaze_palsy (1 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. These statistics are base on transcript: NM_000022370.4. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			12 clinvar	38 clinvar	7 clinvar	57
missense		18 clinvar	236 clinvar	22 clinvar	6 clinvar	282
nonsense	4 clinvar	2 clinvar				6
start loss						0
frameshift	9 clinvar	4 clinvar			2 clinvar	15
splice donor/acceptor (+/-2bp)	3 clinvar	1 clinvar				4
Total	16	25	248	60	15

Highest pathogenic variant AF is 0.00009164

Loading clinvar variants...

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