Human Gene Module / Chromosome 18 / RIT2

RIT2Ras-like without CAAX 2

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
3 / 3
Rare Variants / Common Variants
0 / 4
Aliases
RIT2, RIBA,  RIN,  ROC2
Associated Syndromes
-
Chromosome Band
18q12.3
Associated Disorders
SCZ, BPD
Relevance to Autism

A SNP downstream of the RIT2 gene (rs16976358) associated with ASD in a case-control analysis of 156 Japanese ASD cases and 620 Japanese controls (P-value 4.54E-06; OR 2.246, 95% CI 1.578-3.197) (Liu et al., 2015). Assocation of this SNP with ASD was replicated in a case-control analysis of 470 Iranian ASD cases and 470 Iranian controls (P-value 1.40; OR 1.40, 95% CI 1.08-1.81) (Emamalizadeh et al., 2016).

Molecular Function

This gene belongs to the RAS superfamily of small GTPases and demonstrates neuron-specific tissue expression. RIT2 has been identified as a susceptibility gene for Parkinson's disease in multiple association studies (Pankratz et al., 2012; Emamalizadeh et al., 2014; Nie et al., 2014; Wang et al., 2014; Liu et al., 2015; Zhang et al., 2015).

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to RIT2 (3 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Genome-wide Association Study of Autism Spectrum Disorder in the East Asian Populations Liu X , et al. (2015) Yes -
2 Positive Association RIT2 Polymorphisms: Is There a Differential Association? Emamalizadeh B , et al. (2016) Yes SCZ, BPD
3 Positive Association Ras-like without CAAX 2 (RIT2): a susceptibility gene for autism spectrum disorder Hamedani SY , et al. (2017) Yes -
Rare Variants  

No rare variants reported.

Common Variants   (4)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
- - intergenic_variant - - - 26314684 Liu X , et al. (2015)
- - intergenic_variant - - - 28190241 Hamedani SY , et al. (2017)
- - intergenic_variant - - - 26941103 Emamalizadeh B , et al. (2016)
c.103+17147A>G - intron_variant - - - 28190241 Hamedani SY , et al. (2017)
SFARI Gene score
2

Strong Candidate

A SNP downstream of the RIT2 gene (rs16976358) associated with ASD in a case-control analysis of 156 Japanese ASD cases and 620 Japanese controls (P-value 4.54E-06; OR 2.246, 95% CI 1.578-3.197) (Liu et al., 2015). Assocation of this SNP with ASD was replicated in a case-control analysis of 470 Iranian ASD cases and 470 Iranian controls (P-value 1.40; OR 1.40, 95% CI 1.08-1.81) (Emamalizadeh et al., 2016).

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.

4/1/2022
3
icon
2

Decreased from 3 to 2

Description

A SNP downstream of the RIT2 gene (rs16976358) associated with ASD in a case-control analysis of 156 Japanese ASD cases and 620 Japanese controls (P-value 4.54E-06; OR 2.246, 95% CI 1.578-3.197) (Liu et al., 2015). Assocation of this SNP with ASD was replicated in a case-control analysis of 470 Iranian ASD cases and 470 Iranian controls (P-value 1.40; OR 1.40, 95% CI 1.08-1.81) (Emamalizadeh et al., 2016).

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

A SNP downstream of the RIT2 gene (rs16976358) associated with ASD in a case-control analysis of 156 Japanese ASD cases and 620 Japanese controls (P-value 4.54E-06; OR 2.246, 95% CI 1.578-3.197) (Liu et al., 2015). Assocation of this SNP with ASD was replicated in a case-control analysis of 470 Iranian ASD cases and 470 Iranian controls (P-value 1.40; OR 1.40, 95% CI 1.08-1.81) (Emamalizadeh et al., 2016).

Reports Added
[New Scoring Scheme]
4/1/2016
icon
4

Increased from to 4

Description

A SNP downstream of the RIT2 gene (rs16976358) associated with ASD in a case-control analysis of 156 Japanese ASD cases and 620 Japanese controls (P-value 4.54E-06; OR 2.246, 95% CI 1.578-3.197) (Liu et al., 2015). Assocation of this SNP with ASD was replicated in a case-control analysis of 470 Iranian ASD cases and 470 Iranian controls (P-value 1.40; OR 1.40, 95% CI 1.08-1.81) (Emamalizadeh et al., 2016).

Krishnan Probability Score

Score 0.59634637053045

Ranking 437/25841 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 0.0600485284509

Ranking 8374/18225 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 0.92965747732342

Ranking 11224/18665 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 0.2427014375366

Ranking 3576/20870 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
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