AGO4argonaute RISC catalytic component 4
Autism Reports / Total Reports
3 / 5Rare Variants / Common Variants
5 / 0Aliases
AGO4, EIF2C4Associated Syndromes
-Chromosome Band
1p34.3Associated Disorders
-Relevance to Autism
De novo missense variants in the AGO4 gene have been identified in two ASD probands (De Rubeis et al., 2014). An integrated meta-analysis of de novo mutation data from a combined dataset of 10,927 individuals with neurodevelopmental disorders identified AGO4 as a gene with an excess of missense variants (false discovery rata < 5%, count >1); AGO4 was similarly identified as a gene with an excess of de novo missense variants (false discovery rata < 5%, count >1) following analysis of 5,624 cases with a primary diagnosis of ASD (Coe et al., 2018).
Molecular Function
This gene encodes a member of the Argonaute family of proteins which contain PAZ and PIWI domains and play an integral role in RNA interference and short-interfering-RNA-mediated gene silencing.
External Links
SFARI Genomic Platforms
Reports related to AGO4 (5 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 | Recent Recommendation | Neurodevelopmental disease genes implicated by de novo mutation and copy number variation morbidity | Coe BP , et al. (2018) | No | - |
3 | Support | Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks | Ruzzo EK , et al. (2019) | Yes | - |
4 | Support | - | Zhou X et al. (2022) | Yes | - |
5 | Support | - | et al. () | No | - |
Rare Variants (5)
Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
---|---|---|---|---|---|---|---|---|
c.760+1G>A | - | splice_site_variant | De novo | - | Simplex | 37788244 | et al. () | |
c.733C>T | p.Arg245Cys | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
c.167G>T | p.Arg56Leu | missense_variant | De novo | - | - | 25363760 | De Rubeis S , et al. (2014) | |
c.1797G>T | p.Lys599Asn | missense_variant | De novo | - | - | 25363760 | De Rubeis S , et al. (2014) | |
c.808C>T | p.Arg270Ter | stop_gained | Familial | Paternal | Multiplex | 31398340 | Ruzzo EK , et al. (2019) |
Common Variants
No common variants reported.
SFARI Gene score
Strong Candidate
![](https://gene.sfari.org//wp-content/themes/sfari-gene/img/color-band/2.png)
![](https://gene.sfari.org//wp-content/themes/sfari-gene/img/color-band/s-null.png)
De novo missense variants in the AGO4 gene have been identified in two ASD probands (De Rubeis et al., 2014). An integrated meta-analysis of de novo mutation data from a combined dataset of 10,927 individuals with neurodevelopmental disorders identified AGO4 as a gene with an excess of missense variants (false discovery rata < 5%, count >1); AGO4 was similarly identified as a gene with an excess of de novo missense variants (false discovery rata < 5%, count >1) following analysis of 5,624 cases with a primary diagnosis of ASD (Coe et al., 2018).
Score Delta: Score remained at 2
criteria met
See SFARI Gene'scoring criteriaWe 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.
10/1/2019
![icon](https://gene.sfari.org//wp-content/themes/sfari-gene/img/score-down.png)
Decreased from 3 to 2
New Scoring Scheme
Description
De novo missense variants in the AGO4 gene have been identified in two ASD probands (De Rubeis et al., 2014). An integrated meta-analysis of de novo mutation data from a combined dataset of 10,927 individuals with neurodevelopmental disorders identified AGO4 as a gene with an excess of missense variants (false discovery rata < 5%, count >1); AGO4 was similarly identified as a gene with an excess of de novo missense variants (false discovery rata < 5%, count >1) following analysis of 5,624 cases with a primary diagnosis of ASD (Coe et al., 2018).
Reports Added
[New Scoring Scheme]7/1/2019
![icon](https://gene.sfari.org//wp-content/themes/sfari-gene/img/score-same.png)
Decreased from 3 to 3
Description
De novo missense variants in the AGO4 gene have been identified in two ASD probands (De Rubeis et al., 2014). An integrated meta-analysis of de novo mutation data from a combined dataset of 10,927 individuals with neurodevelopmental disorders identified AGO4 as a gene with an excess of missense variants (false discovery rata < 5%, count >1); AGO4 was similarly identified as a gene with an excess of de novo missense variants (false discovery rata < 5%, count >1) following analysis of 5,624 cases with a primary diagnosis of ASD (Coe et al., 2018).
1/1/2019
![icon](https://gene.sfari.org//wp-content/themes/sfari-gene/img/score-up.png)
Increased from to 3
Description
De novo missense variants in the AGO4 gene have been identified in two ASD probands (De Rubeis et al., 2014). An integrated meta-analysis of de novo mutation data from a combined dataset of 10,927 individuals with neurodevelopmental disorders identified AGO4 as a gene with an excess of missense variants (false discovery rata < 5%, count >1); AGO4 was similarly identified as a gene with an excess of de novo missense variants (false discovery rata < 5%, count >1) following analysis of 5,624 cases with a primary diagnosis of ASD (Coe et al., 2018).
Krishnan Probability Score
Score 0.4709626659492
Ranking 8880/25841 scored genes
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ExAC Score
Score 0.99004381211104
Ranking 1801/18225 scored genes
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Iossifov Probability Score
Score 0.801
Ranking 238/239 scored genes
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Sanders TADA Score
Score 0.93833279372734
Ranking 13827/18665 scored genes
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