Human Gene Module / Chromosome 1 / RGS7

RGS7regulator of G-protein signaling 7

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
4 / 6
Rare Variants / Common Variants
6 / 0
Aliases
RGS7, RP11-80B9.3
Associated Syndromes
-
Chromosome Band
1q43
Associated Disorders
-
Relevance to Autism

Rare variants in the RGS7 gene have been identified with autism (Pinto et al., 2010; Najmabadi et al., 2011).

Molecular Function

Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits thereby driving them into their inactive GDP-bound form. Activity on G(o)-alpha is specifically enhanced by the RGS6/GNG5 dimer. May play a role in synaptic vesicle exocytosis as well as an important role in the rapid regulation of neuronal excitability and the cellular responses to short-lived stimulations.

External Links
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Human
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Reports related to RGS7 (6 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Highly Cited Interaction between RGS7 and polycystin Kim E , et al. (1999) No -
2 Recent Recommendation Gbeta5 recruits R7 RGS proteins to GIRK channels to regulate the timing of neuronal inhibitory signaling Xie K , et al. (2010) No -
3 Primary Functional impact of global rare copy number variation in autism spectrum disorders Pinto D , et al. (2010) Yes -
4 Support Deep sequencing reveals 50 novel genes for recessive cognitive disorders Najmabadi H , et al. (2011) Yes -
5 Support A discovery resource of rare copy number variations in individuals with autism spectrum disorder Prasad A , et al. (2013) Yes -
6 Support Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder Girirajan S , et al. (2013) Yes -
Rare Variants   (6)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_gain - - - 20531469 Pinto D , et al. (2010)
- - copy_number_loss - - - 20531469 Pinto D , et al. (2010)
- - copy_number_loss Unknown - Unknown 23275889 Prasad A , et al. (2013)
- - copy_number_loss Familial Paternal Unknown 23275889 Prasad A , et al. (2013)
- - copy_number_gain Familial Maternal Simplex 23375656 Girirajan S , et al. (2013)
- p.Asn304fs frameshift_variant Familial Both parents Multiplex 21937992 Najmabadi H , et al. (2011)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

Rare variants in the RGS7 gene have been identified with autism in two studies. In the first (PMID 20531469), the RGS7 gene occurs in large CNVS. In the second (PMID 21937992), one pedigree is found with a homozygous nonsense mutation in the RGS7 gene. This pedigree's LOD score is approximately 2.4.

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

Rare variants in the RGS7 gene have been identified with autism in two studies. In the first (PMID 20531469), the RGS7 gene occurs in large CNVS. In the second (PMID 21937992), one pedigree is found with a homozygous nonsense mutation in the RGS7 gene. This pedigree's LOD score is approximately 2.4.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Rare variants in the RGS7 gene have been identified with autism in two studies. In the first (PMID 20531469), the RGS7 gene occurs in large CNVS. In the second (PMID 21937992), one pedigree is found with a homozygous nonsense mutation in the RGS7 gene. This pedigree's LOD score is approximately 2.4.

Reports Added
[New Scoring Scheme]
7/1/2014
No data
icon
4

Increased from No data to 4

Description

Rare variants in the RGS7 gene have been identified with autism in two studies. In the first (PMID 20531469), the RGS7 gene occurs in large CNVS. In the second (PMID 21937992), one pedigree is found with a homozygous nonsense mutation in the RGS7 gene. This pedigree's LOD score is approximately 2.4.

4/1/2014
No data
icon
4

Increased from No data to 4

Description

Rare variants in the RGS7 gene have been identified with autism in two studies. In the first (PMID 20531469), the RGS7 gene occurs in large CNVS. In the second (PMID 21937992), one pedigree is found with a homozygous nonsense mutation in the RGS7 gene. This pedigree's LOD score is approximately 2.4.

Krishnan Probability Score

Score 0.62185373064369

Ranking 80/25841 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 0.78174587289319

Ranking 4042/18225 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 0.89028537869644

Ranking 5536/18665 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
Larsen Cumulative Evidence Score

Score 14

Ranking 139/461 scored genes


[Show Scoring Methodology]
Larsen and colleagues generated gene scores based on the sum of evidence for all available ASD-associated variants in a gene, with assessments based on mode of inheritance, effect size, and variant frequency in the general population. The approach was first presented in Mol Autism 7:44 (2016), and scores for 461 genes can be found in column I in supplementary table 4 from that paper.
Original Source
Zhang D Score

Score 0.24263362185936

Ranking 3578/20870 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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