Human Gene Module / Chromosome 1 / AGO3

AGO3argonaute RISC catalytic component 3

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
7 / 9
Rare Variants / Common Variants
9 / 0
Aliases
AGO3, EIF2C3
Associated Syndromes
-
Chromosome Band
1p34.3
Associated Disorders
-
Relevance to Autism

De novo missense variants in the AGO3 gene have been identified in two probands with ASD (De Rubeis et al., 2014; Yuen et al., 2017) and one proband with an unspecified developmental disorder (Deciphering Developmental Disorders Study 2017). An integrated meta-analysis of de novo mutation data from a combined dataset of 10,927 individuals with neurodevelopmental disorders identified AGO3 as a gene with an excess of missense variants with CADD scores > 30 (false discovery rata < 5%, count >1) (Coe et al., 2018).

Molecular Function

Required for RNA-mediated gene silencing (RNAi). Binds to short RNAs such as microRNAs (miRNAs) and represses the translation of mRNAs which are complementary to them.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to AGO3 (9 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Synaptic, transcriptional and chromatin genes disrupted in autism De Rubeis S , et al. (2014) Yes -
2 Support Prevalence and architecture of de novo mutations in developmental disorders et al. (2017) No -
3 Support Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder C Yuen RK et al. (2017) Yes -
4 Recent Recommendation Neurodevelopmental disease genes implicated by de novo mutation and copy number variation morbidity Coe BP , et al. (2018) No -
5 Support Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders Wang T et al. (2020) Yes -
6 Support - Zhou X et al. (2022) Yes -
7 Support - Cirnigliaro M et al. (2023) Yes -
8 Support - Omri Bar et al. (2024) Yes ID
9 Support - Noor Smal et al. () Yes -
Rare Variants   (9)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.980C>T p.Pro327Leu missense_variant De novo - - 28135719 et al. (2017)
c.25G>C p.Ala9Pro missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.904G>A p.Gly302Ser missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.841C>T p.Arg281Cys missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.994G>A p.Gly332Arg missense_variant De novo - - 25363760 De Rubeis S , et al. (2014)
c.2285G>A p.Arg762His missense_variant De novo - Simplex 38965372 Noor Smal et al. ()
c.1711A>C p.Lys571Gln missense_variant De novo - Multiplex 38256266 Omri Bar et al. (2024)
c.1115C>A p.Ser372Tyr missense_variant De novo - Multiplex 28263302 C Yuen RK et al. (2017)
c.1878C>A p.Tyr626Ter stop_gained Familial Maternal Multiplex 37506195 Cirnigliaro M et al. (2023)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

De novo missense variants in the AGO3 gene have been identified in two probands with ASD (De Rubeis et al., 2014; Yuen et al., 2017) and one proband with an unspecified developmental disorder (Deciphering Developmental Disorders Study 2017). An integrated meta-analysis of de novo mutation data from a combined dataset of 10,927 individuals with neurodevelopmental disorders identified AGO3 as a gene with an excess of missense variants with CADD scores > 30 (false discovery rata < 5%, count >1) (Coe et al., 2018).

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

De novo missense variants in the AGO3 gene have been identified in two probands with ASD (De Rubeis et al., 2014; Yuen et al., 2017) and one proband with an unspecified developmental disorder (Deciphering Developmental Disorders Study 2017). An integrated meta-analysis of de novo mutation data from a combined dataset of 10,927 individuals with neurodevelopmental disorders identified AGO3 as a gene with an excess of missense variants with CADD scores > 30 (false discovery rata < 5%, count >1) (Coe et al., 2018).

10/1/2020
3
icon
3

Decreased from 3 to 3

Description

De novo missense variants in the AGO3 gene have been identified in two probands with ASD (De Rubeis et al., 2014; Yuen et al., 2017) and one proband with an unspecified developmental disorder (Deciphering Developmental Disorders Study 2017). An integrated meta-analysis of de novo mutation data from a combined dataset of 10,927 individuals with neurodevelopmental disorders identified AGO3 as a gene with an excess of missense variants with CADD scores > 30 (false discovery rata < 5%, count >1) (Coe et al., 2018).

Reports Added
[Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders2020]
10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

De novo missense variants in the AGO3 gene have been identified in two probands with ASD (De Rubeis et al., 2014; Yuen et al., 2017) and one proband with an unspecified developmental disorder (Deciphering Developmental Disorders Study 2017). An integrated meta-analysis of de novo mutation data from a combined dataset of 10,927 individuals with neurodevelopmental disorders identified AGO3 as a gene with an excess of missense variants with CADD scores > 30 (false discovery rata < 5%, count >1) (Coe et al., 2018).

Reports Added
[New Scoring Scheme]
1/1/2019
icon
4

Increased from to 4

Description

De novo missense variants in the AGO3 gene have been identified in two probands with ASD (De Rubeis et al., 2014; Yuen et al., 2017) and one proband with an unspecified developmental disorder (Deciphering Developmental Disorders Study 2017). An integrated meta-analysis of de novo mutation data from a combined dataset of 10,927 individuals with neurodevelopmental disorders identified AGO3 as a gene with an excess of missense variants with CADD scores > 30 (false discovery rata < 5%, count >1) (Coe et al., 2018).

Krishnan Probability Score

Score 0.44788956555564

Ranking 11906/25841 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 0.99999884361456

Ranking 313/18225 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 0.94041268482771

Ranking 14558/18665 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
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