Human Gene Module / Chromosome 1 / AGO1

AGO1argonaute 1, RISC catalytic component

Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
3 / 7
Rare Variants / Common Variants
7 / 0
AGO1, EIF2C,  EIF2C1,  GERP95,  Q99,  hAgo1
Associated Syndromes
Genetic Category
Rare Single Gene Mutation
Chromosome Band
Associated Disorders
Relevance to Autism

De novo missense variants that were predicted in silico to be damaging were observed in the AGO1 gene in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014) and an ASD proband from a cohort of 262 Japanese trios (Takata et al., 2018). TADA-Denovo analysis using a combined dataset of previously published cohorts from the Simons Simplex Collection and the Autism Sequencing Consortium, as well as the Japanese ASD cohort from Takata et al., 2018, identified AGO1 as a gene significantly enriched in damaging de novo mutations in ASD cases (pBH < 0.05).

Molecular Function

This gene encodes a member of the argonaute family of proteins, which associate with small RNAs and have important roles in RNA interference (RNAi) and RNA silencing. This protein binds to microRNAs (miRNAs) or small interfering RNAs (siRNAs) and represses translation of mRNAs that are complementary to them. It is also involved in transcriptional gene silencing (TGS) of promoter regions that are complementary to bound short antigene RNAs (agRNAs), as well as in the degradation of miRNA-bound mRNA targets.

Reports related to AGO1 (7 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study. Rauch A , et al. (2012) No Absent speech,motor delay
2 Support De novo mutations in moderate or severe intellectual disability. Hamdan FF , et al. (2014) No Speech delay
3 Primary The contribution of de novo coding mutations to autism spectrum disorder. Iossifov I , et al. (2014) Yes -
4 Support High diagnostic yield of syndromic intellectual disability by targeted next-generation sequencing. Martnez F , et al. (2016) No Speech delay, motor delay
5 Recent Recommendation Integrative Analyses of De Novo Mutations Provide Deeper Biological Insights into Autism Spectrum Disorder. Takata A , et al. (2018) Yes -
6 Recent recommendation Further evidence of a causal association between AGO1, a critical regulator of microRNA formation, and intellectual disability/autism spectrum diso... Sakaguchi A , et al. (2018) No Epilepsy/seizures
7 Support Whole genome sequencing and variant discovery in the ASPIRE autism spectrum disorder cohort. Callaghan DB , et al. (2019) Yes -
Rare Variants   (7)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.569T>C p.Leu190Pro missense_variant De novo - - 23020937 Rauch A , et al. (2012)
c.595G>A p.Gly199Ser missense_variant De novo - - 25356899 Hamdan FF , et al. (2014)
c.583G>A p.Glu195Lys missense_variant De novo - - 27620904 Martnez F , et al. (2016)
C>T p.Pro800Leu missense_variant Unknown - Simplex 31038196 Callaghan DB , et al. (2019)
c.596G>T p.Gly199Val missense_variant De novo - Simplex 29346770 Takata A , et al. (2018)
c.1064C>T p.Thr355Ile missense_variant De novo - Simplex 25363768 Iossifov I , et al. (2014)
c.595G>A p.Gly199Ser missense_variant De novo - Simplex 30213762 Sakaguchi A , et al. (2018)
Common Variants  

No common variants reported.

SFARI Gene score

Suggestive Evidence



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.


Initial score established: 4.4



Krishnan Probability Score

Score 0.49238830169244

Ranking 4561/25841 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: A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at
ExAC Score

Score 0.99999946347142

Ranking 268/18225 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 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: aned_exac_nonTCGA_z_pli_rec_null_data.txt
Sanders TADA Score

Score 0.64014937032946

Ranking 855/18665 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
CNVs associated with AGO1(1 CNVs)
1p34.3 10 Deletion-Duplication 18  /  39
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