Human Gene Module / Chromosome 18 / RIT2

RIT2Ras-like without CAAX 2

Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
3 / 3
Rare Variants / Common Variants
0 / 4
Aliases
RIT2, RIBA,  RIN,  ROC2
Associated Syndromes
-
Genetic Category
Genetic Association
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).

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
3

Suggestive Evidence

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: Decreased from 4 to 3

3

Suggestive Evidence

See all Category 3 Genes

The literature is replete with relatively small studies of candidate genes, using either common or rare variant approaches, which do not reach the criteria set out for categories 1 and 2. Genes that had two such lines of supporting evidence were placed in category 3, and those with one line of evidence were placed in category 4. Some additional lines of "accessory evidence" (indicated as "acc" in the score cards) could also boost a gene from category 4 to 3.

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.
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
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).
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.
Submit New Gene

Report an Error

SFARI Gene Update

We are pleased to announce some changes to the ongoing curation of the data in SFARI Gene. In the context of a continued effort to develop the human gene module and its manually curated list of autism risk genes, we are modifying other aspects of the site to focus on the information that is of greatest interest to the research community. The version of SFARI Gene that has been developed until now will be frozen and will remain available as “SFARI Gene Archive”. Please see the announcement for more details.
Close