Human Gene Module / Chromosome 5 / RICTOR

RICTORRPTOR independent companion of MTOR complex 2

SFARI Gene Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
3 / 4
Rare Variants / Common Variants
12 / 0
Aliases
-
Associated Syndromes
-
Chromosome Band
5p13.1
Associated Disorders
-
Relevance to Autism

Carapito et al., 2024 reported eight unrelated patients carrying de novo or heterozygous variants inherited from an affected parent in the RICTOR gene presenting with developmental delay/intellectual disability and associated features including abnormal behavior (including two individuals with autism spectrum disorder), seizures, growth failure, feeding difficulties, hypertonia, brain anomalies, dysmorphic features, and other congenital malformations; fibroblasts from a patient with a de novo RICTOR missense variant (p.His72Tyr) and a clinical presentation of ASD, developmental delay, intellectual disability, and seizures displayed hyperactivation of the mTORC2 pathway, indicating a gain-of-function effect. De novo missense variants in RICTOR have also been identified in ASD probands from the Simons Simplex Collection, the SPARK cohort, and a Chinese ASD cohort (Iossifov et al., 2014; Zhou et al., 2022; Wang et al., 2023).

Molecular Function

RICTOR is a component of the mTORC2 signalling complex that regulates cell growth and survival in response to hormonal signals.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to RICTOR (4 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
2 Support - Zhou X et al. (2022) Yes -
3 Support - Wang J et al. (2023) Yes -
4 Primary - Raphael Carapito et al. () No ASD, ADHD, epilepsy/seizures
Rare Variants   (12)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss Familial Maternal Simplex 39738822 Raphael Carapito et al. ()
c.1859A>G p.Gln620Arg missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.4657G>T p.Asp1553Tyr missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.4253A>G p.Tyr1418Cys missense_variant De novo - Simplex 37393044 Wang J et al. (2023)
c.214C>T p.His72Tyr missense_variant De novo - Simplex 39738822 Raphael Carapito et al. ()
c.4138T>A p.Phe1380Ile missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.689C>T p.Thr230Ile missense_variant De novo - Simplex 39738822 Raphael Carapito et al. ()
c.1851+3G>C p.? splice_region_variant De novo - Simplex 39738822 Raphael Carapito et al. ()
c.2101dup p.Thr701AsnfsTer4 frameshift_variant De novo - Simplex 39738822 Raphael Carapito et al. ()
c.1378G>C p.Asp460His missense_variant Familial Maternal Multiplex 39738822 Raphael Carapito et al. ()
c.4450C>T p.Arg1484Ter stop_gained Familial Paternal Extended multiplex 39738822 Raphael Carapito et al. ()
c.4607_4611delAACTG p.Leu1537CysfsTer4 frameshift_variant De novo - Simplex 39738822 Raphael Carapito et al. ()
Common Variants  

No common variants reported.

SFARI Gene score
3

Suggestive Evidence

criteria met
See SFARI Gene'scoring criteria
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.

4/1/2025
3

Initial score established: 3

Krishnan Probability Score

Score 0.56898494165373

Ranking 1074/25841 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 0.99999999986929

Ranking 75/18225 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 0.85821787408146

Ranking 3775/18665 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 0.35759225547788

Ranking 1920/20870 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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