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Intellectual disability
Gene: ROBO1

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

3 reviews

Arina Puzriakova (Genomics England Curator)

Green List (high evidence)

The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Created: 11 Oct 2023, 9:34 a.m. | Last Modified: 11 Oct 2023, 9:34 a.m.

Panel Version: 5.286

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Created: 11 Oct 2023, 9:34 a.m.
Last Modified: 11 Oct 2023, 9:34 a.m.
Panel version: 5.286

Achchuthan Shanmugasundram (Genomics England Curator)

Green List (high evidence)

Comment on gene classification: This gene should be rated green as this gene has been associated with intellectual disability from six unrelated cases. However, the MOI should be set as "BIALLELIC, autosomal or pseudoautosomal" as five of these cases were reported with biallelic variants and only one case was reported with monoallelic variant.

PMID:28286008 reported a boy with compound heterozygous variants that was presented with developmental delay in 13 months and had severe intellectual disability and hyperactivity at nine years of age. He was nonverbal and wheelchair dependent because of spastic diplegia and ataxia.

PMID:30692597 reported a five year old boy identified with a homozygous ROBO1 variant who had combined pituitary hormone deficiency, psychomotor developmental delay, severe intellectual disability, sensorineural hearing loss, strabismus and characteristic facial features.

PMID:35227688 reported eight patients including the boy reported in PMID:30692597. Of the other seven patients, three were presented with intellectual disability. Of these three patients, two harboured compound heterozygous and one harboured homozygous variants.

PMID:35348658 reported a patient identified with monoallelic de novo variant (p.D422G) who presented with early-onset epileptic encephalopathy and had severe developmental delay.

This gene has not yet been associated with any phenotypes in OMIM or Gene2Phenotype.
Created: 22 Feb 2023, 4:34 p.m. | Last Modified: 22 Feb 2023, 4:43 p.m.

Panel Version: 4.72

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
intellectual disability, MONDO:0001071

Publications

Created: 22 Feb 2023, 4:34 p.m.
Last Modified: 22 Feb 2023, 4:43 p.m.
Panel version: 4.69

Konstantinos Varvagiannis (Other)

I don't know

DD/ID has been reported in some individuals with biallelic (e.g. 4 subjects in the study by Münch et al, 1 additional case reported by Calloni et al) or monoallelic ROBO1 variants (e.g. P2 in the study by Huang et al, with a diagnosis of EOEE due to a neomorphic variant).

Consider amber rating pending further review.

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Huang et al (2022 - PMID: 35348658) Monoallelic & Biallelic
Novel dominant and recessive variants in human ROBO1 cause distinct neurodevelopmental defects through different mechanisms.

Münch et al (2022 - PMID: 35227688) Biallelic
Biallelic pathogenic variants in roundabout guidance receptor 1 associate with syndromic congenital anomalies of the kidney and urinary tract

Woodring et al (2021 - PMID: 34193621) - Probably not relevant (VUS)
Uncertain, Not Unimportant: Callosal Dysgenesis and Variants of Uncertain Significance in ROBO1

Liu et al (2020 - PMID: 31448886) Monoallelic
A Novel Missense Mutation in Human Receptor Roundabout-1 (ROBO1) Gene Associated with Pituitary Stalk Interruption Syndrome.

Dateki et al (2019 - PMID: 30692597) Biallelic - This individual has been incl. in the study by Munch et al
A homozygous splice site ROBO1 mutation in a patient with a novel syndrome with combined pituitary hormone deficiency

Rasmussen et al (2018 - PMID: 29194579) Biallelic
Targeted gene sequencing and whole-exome sequencing in autopsied fetuses with prenatally diagnosed kidney anomalies

Kruszka et al (2017 - PMID: 28592524) Monoallelic
Loss of function in ROBO1 is associated with tetralogy of Fallot and septal defects

Bashamboo et al (2017 - PMID: 28402530) Monoallelic
Mutations in the Human ROBO1 Gene in Pituitary Stalk Interruption Syndrome

Calloni et al (2017 - PMID: 28286008) Biallelic
Compound Heterozygous Variants in ROBO1 Cause a Neurodevelopmental Disorder With Absence of Transverse Pontine Fibers and Thinning of the Anterior Commissure and Corpus Callosum
Sources: Literature
Created: 11 May 2022, 6:07 a.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
ROBO1-related NDD

Publications

Created: 11 May 2022, 6:07 a.m.

Panel version: 3.1568

Details

Mode of Inheritance

BIALLELIC, autosomal or pseudoautosomal

Sources

Expert Review Green
NHS GMS

Phenotypes

Intellectual disability, MONDO:0001071
Neurooculorenal syndrome, OMIM:620305

Tags

watchlist_moi

OMIM

602430

Clinvar variants

Variants in ROBO1

Penetrance

unknown

Publications

Panels with this gene

History Filter Activity

20 Mar 2024, Gel status: 3

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag watchlist_moi tag was added to gene: ROBO1.

16 Oct 2023, Gel status: 3

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: ROBO1 were changed from ROBO1-related NDD; intellectual disability, MONDO:0001071 to Intellectual disability, MONDO:0001071; Neurooculorenal syndrome, OMIM:620305

11 Oct 2023, Gel status: 3

Removed Tag

Arina Puzriakova (Genomics England Curator)

Tag Q1_23_promote_green was removed from gene: ROBO1.

11 Oct 2023, Gel status: 3

Added New Source, Added New Source, Status Update

Arina Puzriakova (Genomics England Curator)

Source NHS GMS was added to ROBO1. Source Expert Review Green was added to ROBO1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)

22 Feb 2023, Gel status: 2