RAC1Rac family small GTPase 1
Autism Reports / Total Reports
3 / 10Rare Variants / Common Variants
17 / 0Aliases
RAC1, MIG5, Rac-1, TC-25, p21-Rac1Associated Syndromes
-Chromosome Band
7p22.1Associated Disorders
ASDRelevance to Autism
Viral expression of a dominant-negative form of Rac1 following bilateral injection into the prelimbic regions of wild-type mice resulted in ASD-like social deficits and reduced NMDAR-ESPC in PFC pyramidal neurons; conversely, viral expression of constitutively active Rac1 in SHANK3-deficient mice rescued ASD-like social deficits and NMDAR hypofunction (Duffney et al., 2015). De novo ASD-associated missense variants in the TRIO gene were experimentally shown to affect Rac1 activiation in two studies (Sadybekov et al., 2017; Katrancha et al., 2017). De novo missense variants in the RAC1 gene were identified in seven individuals presenting with intellectual disability and brain malformations; two of these individuals presented with stereotypic movements, and one was diagnosed with autism (Reijnders et al., 2017). Ma et al., 2022 recently demonstrated that bidirectional dysregulation of Rac1 activity in the medial prefrontal cortex (mPFC) dictated shared social deficits in mice.
Molecular Function
The protein encoded by this gene is a GTPase which belongs to the RAS superfamily of small GTP-binding proteins. Members of this superfamily appear to regulate a diverse array of cellular events, including the control of cell growth, cytoskeletal reorganization, and the activation of protein kinases.
External Links
SFARI Genomic Platforms
Reports related to RAC1 (10 Reports)
# | Type | Title | Author, Year | Autism Report | Associated Disorders |
---|---|---|---|---|---|
1 | Primary | Autism-like Deficits in Shank3-Deficient Mice Are Rescued by Targeting Actin Regulators | Duffney LJ , et al. (2015) | No | - |
2 | Recent Recommendation | RAC1 Missense Mutations in Developmental Disorders with Diverse Phenotypes | Reijnders MRF , et al. (2017) | No | ASD, stereotypic movements |
3 | Support | An autism spectrum disorder-related de novo mutation hotspot discovered in the GEF1 domain of Trio | Sadybekov A , et al. (2017) | No | - |
4 | Support | Neurodevelopmental disease-associated de novo mutations and rare sequence variants affect TRIO GDP/GTP exchange factor activity | Katrancha SM , et al. (2017) | No | - |
5 | Support | An Intellectual Disability-Related Missense Mutation in Rac1 Prevents LTP Induction | Tian C , et al. (2018) | No | - |
6 | Support | - | Banka S et al. (2022) | No | Autistic features, stereotypy, ADHD |
7 | Support | - | Zhou X et al. (2022) | Yes | - |
8 | Recent Recommendation | - | Ma B et al. (2022) | Yes | - |
9 | Support | - | Spataro N et al. (2023) | Yes | Learning disability |
10 | Support | - | Priolo M et al. (2023) | No | - |
Rare Variants (17)
Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
---|---|---|---|---|---|---|---|---|
c.181C>G | p.Gln61Glu | missense_variant | De novo | - | - | 35139179 | Banka S et al. (2022) | |
c.190T>G | p.Tyr64Asp | missense_variant | De novo | - | - | 35139179 | Banka S et al. (2022) | |
c.190T>G | p.Tyr64Asp | missense_variant | Unknown | - | - | 35139179 | Banka S et al. (2022) | |
c.191A>G | p.Tyr64Cys | missense_variant | De novo | - | - | 35139179 | Banka S et al. (2022) | |
c.202C>A | p.Arg68Ser | missense_variant | Unknown | - | - | 35139179 | Banka S et al. (2022) | |
c.218C>T | p.Pro73Leu | missense_variant | De novo | - | - | 36980980 | Spataro N et al. (2023) | |
c.53G>A | p.Cys18Tyr | missense_variant | De novo | - | - | 28886345 | Reijnders MRF , et al. (2017) | |
c.116A>G | p.Asn39Ser | missense_variant | De novo | - | - | 28886345 | Reijnders MRF , et al. (2017) | |
c.151G>A | p.Val51Met | missense_variant | De novo | - | - | 28886345 | Reijnders MRF , et al. (2017) | |
c.151G>C | p.Val51Leu | missense_variant | De novo | - | - | 28886345 | Reijnders MRF , et al. (2017) | |
c.190T>G | p.Tyr64Asp | missense_variant | De novo | - | - | 28886345 | Reijnders MRF , et al. (2017) | |
c.218C>T | p.Pro73Leu | missense_variant | De novo | - | - | 28886345 | Reijnders MRF , et al. (2017) | |
c.126C>T | p.Ala42%3D | synonymous_variant | De novo | - | Simplex | 35982159 | Zhou X et al. (2022) | |
c.184G>A | p.Glu62Lys | missense_variant | De novo | - | Simplex | 37059841 | Priolo M et al. (2023) | |
c.470G>A | p.Cys157Tyr | missense_variant | De novo | - | - | 28886345 | Reijnders MRF , et al. (2017) | |
c.475G>A | p.Ala159Thr | missense_variant | De novo | - | Simplex | 37059841 | Priolo M et al. (2023) | |
c.202C>G | p.Arg68Gly | missense_variant | Unknown | Not maternal | - | 35139179 | Banka S et al. (2022) |
Common Variants
No common variants reported.
SFARI Gene score
Syndromic
Viral expression of a dominant-negative form of Rac1 following bilateral injection into the prelimbic regions of wild-type mice resulted in ASD-like social deficits and reduced NMDAR-ESPC in PFC pyramidal neurons; conversely, viral expression of constitutively active Rac1 in SHANK3-deficient mice rescued ASD-like social deficits and NMDAR hypofunction (Duffney et al., 2015). De novo ASD-associated missense variants in the TRIO gene were experimentally shown to affect Rac1 activiation in two studies (Sadybekov et al., 2017; Katrancha et al., 2017). De novo missense variants in the RAC1 gene were identified in seven individuals presenting with intellectual disability and brain malformations; two of these individuals presented with stereotypic movements, and one was diagnosed with autism (Reijnders et al., 2017).
Score Delta: Score remained at S
criteria met
See SFARI Gene'scoring criteriaThe syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."
10/1/2019
Score remained at S
New Scoring Scheme
Description
Viral expression of a dominant-negative form of Rac1 following bilateral injection into the prelimbic regions of wild-type mice resulted in ASD-like social deficits and reduced NMDAR-ESPC in PFC pyramidal neurons; conversely, viral expression of constitutively active Rac1 in SHANK3-deficient mice rescued ASD-like social deficits and NMDAR hypofunction (Duffney et al., 2015). De novo ASD-associated missense variants in the TRIO gene were experimentally shown to affect Rac1 activiation in two studies (Sadybekov et al., 2017; Katrancha et al., 2017). De novo missense variants in the RAC1 gene were identified in seven individuals presenting with intellectual disability and brain malformations; two of these individuals presented with stereotypic movements, and one was diagnosed with autism (Reijnders et al., 2017).
Reports Added
[New Scoring Scheme]7/1/2019
Decreased from 5 to S
Description
Viral expression of a dominant-negative form of Rac1 following bilateral injection into the prelimbic regions of wild-type mice resulted in ASD-like social deficits and reduced NMDAR-ESPC in PFC pyramidal neurons; conversely, viral expression of constitutively active Rac1 in SHANK3-deficient mice rescued ASD-like social deficits and NMDAR hypofunction (Duffney et al., 2015). De novo ASD-associated missense variants in the TRIO gene were experimentally shown to affect Rac1 activiation in two studies (Sadybekov et al., 2017; Katrancha et al., 2017). De novo missense variants in the RAC1 gene were identified in seven individuals presenting with intellectual disability and brain malformations; two of these individuals presented with stereotypic movements, and one was diagnosed with autism (Reijnders et al., 2017).
7/1/2018
Decreased from 5 to 5
Description
Viral expression of a dominant-negative form of Rac1 following bilateral injection into the prelimbic regions of wild-type mice resulted in ASD-like social deficits and reduced NMDAR-ESPC in PFC pyramidal neurons; conversely, viral expression of constitutively active Rac1 in SHANK3-deficient mice rescued ASD-like social deficits and NMDAR hypofunction (Duffney et al., 2015). De novo ASD-associated missense variants in the TRIO gene were experimentally shown to affect Rac1 activiation in two studies (Sadybekov et al., 2017; Katrancha et al., 2017). De novo missense variants in the RAC1 gene were identified in seven individuals presenting with intellectual disability and brain malformations; two of these individuals presented with stereotypic movements, and one was diagnosed with autism (Reijnders et al., 2017).
10/1/2017
Increased from to 5
Description
Viral expression of a dominant-negative form of Rac1 following bilateral injection into the prelimbic regions of wild-type mice resulted in ASD-like social deficits and reduced NMDAR-ESPC in PFC pyramidal neurons; conversely, viral expression of constitutively active Rac1 in SHANK3-deficient mice rescued ASD-like social deficits and NMDAR hypofunction (Duffney et al., 2015). De novo ASD-associated missense variants in the TRIO gene were experimentally shown to affect Rac1 activiation in two studies (Sadybekov et al., 2017; Katrancha et al., 2017). De novo missense variants in the RAC1 gene were identified in seven individuals presenting with intellectual disability and brain malformations; two of these individuals presented with stereotypic movements, and one was diagnosed with autism (Reijnders et al., 2017).
Krishnan Probability Score
Score 0.56887306472334
Ranking 1087/25841 scored genes
[Show Scoring Methodology]
ExAC Score
Score 0.57239505272813
Ranking 5126/18225 scored genes
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Sanders TADA Score
Score 0.87693811435697
Ranking 4666/18665 scored genes
[Show Scoring Methodology]
Zhang D Score
Score 0.11739909768326
Ranking 5773/20870 scored genes
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