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Xp21.2 region (includes NR0B1) Gain
ISCA-46302-Gain 2

Fetal anomalies
Gene: ROBO1

ROBO1 (roundabout guidance receptor 1)
EnsemblGeneIds (GRCh38): ENSG00000169855
EnsemblGeneIds (GRCh37): ENSG00000169855
OMIM: 602430, Gene2Phenotype
ROBO1 is in 6 panels

4 reviews

Achchuthan Shanmugasundram (Genomics England Curator)

Green List (high evidence)

The mode of inheritance of this gene has been updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Created: 25 Feb 2025, 11:15 a.m. | Last Modified: 25 Feb 2025, 11:15 a.m.

Panel Version: 5.78

This gene and phenotype were reviewed during meetings between November 2024 & January 2025. The meetings included representatives of the Central & South and North Thames R21 testing GLHs and from the R21 Clinical Oversight Group. Clinical review and curation was performed by Stephanie Allen, Natalie Bibb, and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Sunayna Best, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Esther Kinning, Sahar Mansour, Soo-Mi Park, and Elizabeth Wall (R21 Clinical Oversight Group).
Created: 20 Feb 2025, 9:40 p.m. | Last Modified: 20 Feb 2025, 9:40 p.m.

Panel Version: 5.16

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Created: 20 Feb 2025, 9:40 p.m.
Last Modified: 20 Feb 2025, 9:40 p.m.
Panel version: 5.78

Sarah Graham (West Midlands Regional Genetics Laboratory, Birmingham Women's and Children’s NHS Foundation Trust)

Green List (high evidence)

Originally included on this panel due to reports of heterozygous loss-of-function variants in 3 patients with congenital heart disease +/- facial features (PMID: 28592524), however there is no definitive association between ROBO1 variants and heart defects. Heterozygous loss-of-function variants have more recently been reported in association with pituitary abnormalities in multiple families (OMIM 620303; PMID: 30530901, 28402530, 38444307, 38717911) - amber on pituitary hormone deficiency panel.Biallelic variants are associated with neurooculorenal syndrome (OMIM 620305) - phenotype ranges from prenatal lethality with kidney and brain abnormalities to developmental delay and dysmorphism without kidney abnormalities (PMID: 35227688, 29194579, 30692597, 29194579, 34193621, 28286008).
Created: 20 Feb 2025, 9:35 p.m. | Last Modified: 20 Feb 2025, 9:35 p.m.

Panel Version: 5.15

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neurooculorenal syndrome, MIM#620305

Publications

Created: 20 Feb 2025, 9:35 p.m.
Last Modified: 20 Feb 2025, 9:35 p.m.
Panel version: 5.15

Arina Puzriakova (Genomics England Curator)

Comment on mode of inheritance: Should be updated from 'monoallelic' to 'both mono- and biallelic' at the next GMS panel update.

Biallelic variants in the ROBO1 gene are associated with neurooculorenal syndrome (OMIM:620305). Clinical manifestations are generally highly variable and involve several organ systems. However, some cases do present in utero with renal agenesis and structural brain abnormalities (PMID: 29194579; 35227688) indicating that the phenotype is relevant to this panel.
Created: 20 Mar 2024, 12:25 p.m. | Last Modified: 20 Mar 2024, 12:25 p.m.

Panel Version: 3.142

Created: 20 Mar 2024, 12:25 p.m.
Last Modified: 20 Mar 2024, 12:25 p.m.
Panel version: 3.142

Rebecca Foulger (Genomics England curator)

Green List (high evidence)

Comment on list classification: Updated rating from Amber to Green based on 3 probands reported in PMID:28592524 with ROBO loss of function variants and ventral septal heart defects.
Created: 24 Apr 2019, 12:38 p.m.

Evidence for inclusion on the PAGE Additional gene list comes from a single study in Kruszka et al. (2017, PMID:28592524) but 3 families of different ethnicities; each proband had a ventricular septal defect, and one proband had tetralogy of Fallot. Plus proband 1 had craniofacial findings, consistent with the mouse model. VSD can be detected prenatally (e.g. see PMID:24456562) so is relevant for the panel.
Created: 24 Apr 2019, 12:36 p.m.

ROBO1 was added to the Fetal anomalies panel as Amber based on a 'probable' rating in the PAGE original Additional gene list. In the PAGE paper (Lord et al., 2019, PMID:30712880), ROBO1 is listed as an Additional gene (Supplementary Table 2) based on association with a prenatal phenotype reported in the literature. At the time of curation (April 2019), ROBO1 is not currently associated with a disorder in DD-Gene2Phenotype or in OMIM.
Created: 24 Apr 2019, 12:06 p.m.

Additional evidence from PAGE study: Potentially clinically useful variant identified in this gene from fetal exome sequencing in Lord et al., 2019 (PMID:30712880).
Created: 18 Apr 2019, 3:01 p.m.

Rating in original PAGE list (Additional gene list) for 'tetralogy of Fallot and septal defects': probable. Mode of inheritance: monoallelic. Mode of pathogenicity: loss of function.
Created: 11 Dec 2018, 9:05 a.m.

Created: 11 Dec 2018, 9:05 a.m.

Panel version: 0.318

Details

Mode of Inheritance

BIALLELIC, autosomal or pseudoautosomal

Sources

NHS GMS
Expert Review Green
PAGE Additional Gene List

Phenotypes

Neurooculorenal syndrome, OMIM:620305

OMIM

602430

Clinvar variants

Variants in ROBO1

Penetrance

None

Publications

Panels with this gene

History Filter Activity

25 Feb 2025, Gel status: 3

Removed Tag, Removed Tag

Achchuthan Shanmugasundram (Genomics England Curator)

Tag Q1_25_ NHS_review was removed from gene: ROBO1. Tag Q1_24_MOI was removed from gene: ROBO1.

25 Feb 2025, Gel status: 3

Set mode of inheritance

Achchuthan Shanmugasundram (Genomics England Curator)

Mode of inheritance for gene ROBO1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BIALLELIC, autosomal or pseudoautosomal

21 Feb 2025, Gel status: 3

Added Tag

Achchuthan Shanmugasundram (Genomics England Curator)

Tag Q1_25_ NHS_review tag was added to gene: ROBO1.

20 Feb 2025, Gel status: 3

Set Phenotypes

Achchuthan Shanmugasundram (Genomics England Curator)

Phenotypes for gene: ROBO1 were changed from Neurooculorenal syndrome, OMIM:620305; Tetralogy of Fallot and septal defects to Neurooculorenal syndrome, OMIM:620305

20 Feb 2025, Gel status: 3

Added New Source, Set Phenotypes, Set publications

Achchuthan Shanmugasundram (Genomics England Curator)

Source NHS GMS was added to ROBO1. Added phenotypes Neurooculorenal syndrome, OMIM:620305 for gene: ROBO1 Publications for gene: ROBO1 were updated from 28592524; 28485101; 30712880; 29194579; 35227688 to 35227688; 28592524; 28286008; 28485101; 30712880; 29194579

20 Mar 2024, Gel status: 3