Human Gene Module / Chromosome 3 / ROBO2

ROBO2roundabout guidance receptor 2

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
7 / 11
Rare Variants / Common Variants
10 / 2
Aliases
ROBO2, SAX3
Associated Syndromes
-
Chromosome Band
3p12.3
Associated Disorders
DD/NDD
Relevance to Autism

A novel recurrent deletion involving the ROBO2 gene was identified in two unrelated ASD cases (Prasad et al., 2012).

Molecular Function

The protein encoded by this gene belongs to the ROBO family, part of the immunoglobulin superfamily of proteins that are highly conserved from fly to human. The encoded protein is a transmembrane receptor for the slit homolog 2 protein and functions in axon guidance and cell migration.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to ROBO2 (11 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Decreased expression of axon-guidance receptors in the anterior cingulate cortex in autism Suda S , et al. (2011) Yes -
2 Primary A discovery resource of rare copy number variations in individuals with autism spectrum disorder Prasad A , et al. (2013) Yes -
3 Positive Association Common variation near ROBO2 is associated with expressive vocabulary in infancy St Pourcain B , et al. (2014) No -
4 Support Large-scale discovery of novel genetic causes of developmental disorders Deciphering Developmental Disorders Study (2014) No -
5 Recent Recommendation Systems genetics identifies a convergent gene network for cognition and neurodevelopmental disease Johnson MR , et al. (2015) No -
6 Support Mutations in Human Accelerated Regions Disrupt Cognition and Social Behavior Doan RN , et al. (2016) Yes -
7 Support The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies Redin C , et al. (2016) No Multiple congenital anomalies
8 Positive Association A genome-wide investigation into parent-of-origin effects in autism spectrum disorder identifies previously associated genes including SHANK3 Connolly S , et al. (2016) Yes -
9 Support - Zhou X et al. (2022) Yes -
10 Support - Cirnigliaro M et al. (2023) Yes -
11 Support - Yasser Al-Sarraj et al. (2024) Yes -
Rare Variants   (10)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - translocation De novo - - 27841880 Redin C , et al. (2016)
c.109+428168T>C - intergenic_variant - - Unknown 27667684 Doan RN , et al. (2016)
c.110-110851T>A - intergenic_variant - - Unknown 27667684 Doan RN , et al. (2016)
- - copy_number_loss Unknown Unknown Multiplex 23275889 Prasad A , et al. (2013)
c.3040G>A p.Ala1014Thr missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.429A>C p.Glu143Asp synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
- - copy_number_loss Familial Maternal Multiplex 23275889 Prasad A , et al. (2013)
c.3214A>T p.Lys1072Ter stop_gained Familial Maternal Extended multiplex 37506195 Cirnigliaro M et al. (2023)
c.3259C>T p.Pro1087Ser missense_variant Familial Both parents Unknown 38572415 Yasser Al-Sarraj et al. (2024)
c.2518C>T p.Arg840Cys missense_variant De novo - Unknown 25533962 Deciphering Developmental Disorders Study (2014)
Common Variants   (2)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.437-96606C>T;c.389-96606C>T;c.-1530-96606C>T;.458-96606C>T - intron_variant - - - 27876814 Connolly S , et al. (2016)
- G/A downstream_gene_variant - - - 25226531 St Pourcain B , et al. (2014)
SFARI Gene score
2

Strong Candidate

A novel recurrent deletion involving the ROBO2 gene was identified in two unrelated ASD cases (Prasad et al., 2012). Significantly reduced expression of ROBO2 was observed in the anterior cingulate cortex and primary motor cortex of autistic brains compared to control brains in PMID 21859478. A SNP located ~19 kb 3' of the ROBO2 gene (rs7642482) reached genome-wide significance for association with expressive vocabulary during early phase language acquisition (PMID 25226531).

Score Delta: Score remained at 2

criteria met
See SFARI Gene'scoring criteria
2

Strong Candidate

See all Category 2 Genes

We considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.

10/1/2019
3
icon
2

Decreased from 3 to 2

New Scoring Scheme
Description

A novel recurrent deletion involving the ROBO2 gene was identified in two unrelated ASD cases (Prasad et al., 2012). Significantly reduced expression of ROBO2 was observed in the anterior cingulate cortex and primary motor cortex of autistic brains compared to control brains in PMID 21859478. A SNP located ~19 kb 3' of the ROBO2 gene (rs7642482) reached genome-wide significance for association with expressive vocabulary during early phase language acquisition (PMID 25226531).

Reports Added
[New Scoring Scheme]
10/1/2016
3
icon
3

Decreased from 3 to 3

Description

A novel recurrent deletion involving the ROBO2 gene was identified in two unrelated ASD cases (Prasad et al., 2012). Significantly reduced expression of ROBO2 was observed in the anterior cingulate cortex and primary motor cortex of autistic brains compared to control brains in PMID 21859478. A SNP located ~19 kb 3' of the ROBO2 gene (rs7642482) reached genome-wide significance for association with expressive vocabulary during early phase language acquisition (PMID 25226531).

Reports Added
[Mutations in Human Accelerated Regions Disrupt Cognition and Social Behavior.2016] [A genome-wide investigation into parent-of-origin effects in autism spectrum disorder identifies previously associated genes including SHANK3.2016] [The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies.2016]
1/1/2016
3
icon
3

Decreased from 3 to 3

Description

A novel recurrent deletion involving the ROBO2 gene was identified in two unrelated ASD cases (Prasad et al., 2012). Significantly reduced expression of ROBO2 was observed in the anterior cingulate cortex and primary motor cortex of autistic brains compared to control brains in PMID 21859478. A SNP located ~19 kb 3' of the ROBO2 gene (rs7642482) reached genome-wide significance for association with expressive vocabulary during early phase language acquisition (PMID 25226531).

Reports Added
[Decreased expression of axon-guidance receptors in the anterior cingulate cortex in autism.2011] [A discovery resource of rare copy number variations in individuals with autism spectrum disorder.2013] [Common variation near ROBO2 is associated with expressive vocabulary in infancy.2014] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [Systems genetics identifies a convergent gene network for cognition and neurodevelopmental disease.2015]
7/1/2015
icon
3

Increased from to 3

Description

A novel recurrent deletion involving the ROBO2 gene was identified in two unrelated ASD cases (Prasad et al., 2012). Significantly reduced expression of ROBO2 was observed in the anterior cingulate cortex and primary motor cortex of autistic brains compared to control brains in PMID 21859478. A SNP located ~19 kb 3' of the ROBO2 gene (rs7642482) reached genome-wide significance for association with expressive vocabulary during early phase language acquisition (PMID 25226531).

Krishnan Probability Score

Score 0.56607941906261

Ranking 1224/25841 scored genes


[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning approach on a human brain-specific gene network. The method was first presented in Nat Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed in column G of supplementary table 3 (see: http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at asd.princeton.edu.
Original Source
ExAC Score

Score 0.99999613022592

Ranking 381/18225 scored genes


[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of- function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of- function mutations in autism in such a gene would be more likely to confer risk. For a full list of pLI scores see: ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle aned_exac_nonTCGA_z_pli_rec_null_data.txt
Original Source
Sanders TADA Score

Score 0.94373783419948

Ranking 15803/18665 scored genes


[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013), and is a statistic that integrates evidence from both de novo and transmitted mutations. It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233 (2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper (the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Original Source
Zhang D Score

Score 0.14523785342124

Ranking 5279/20870 scored genes


[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures), or D score, was developed to combine evidence from de novo loss-of- function mutation with evidence from cell-type- specific gene expression in the mouse brain (specifically translational profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with positive D scores are more likely to be associated with autism risk, with higher-confidence genes having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204- 215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in supplementary table 2 from that paper.
Original Source
Interactome
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
PPP1R1B protein phosphatase 1, regulatory (inhibitor) subunit 1B Human Protein Binding 84152 Q9UD71
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