AGO3 (Argonaute RISC Catalytic Component 3) - Gene Overview
A key player in microRNA-mediated gene silencing and RNA interference, implicated in cancer and neurological disorders.
Gene Information Card
| Symbol | AGO3 |
|---|---|
| Full Name | Argonaute RISC Catalytic Component 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 1p34.3 |
| NCBI Gene ID | 192670 ncbi.nlm.nih.gov/gene/192670 |
| Ensembl ID | ENSG00000123908 |
| UniProt ID | Q9H9G7 |
| OMIM ID | 612362 |
| HGNC ID | 18421 |
| Aliases | EIF2C3, hAgo3, FLJ12765 |
Description
AGO3 encodes a member of the Argonaute family of proteins, which are essential components of the RNA-induced silencing complex (RISC). AGO3 binds microRNAs (miRNAs) and small interfering RNAs (siRNAs) and guides them to complementary mRNA targets, leading to translational repression or mRNA degradation. Unlike AGO2, AGO3 lacks endonucleolytic (slicer) activity due to a mutation in the catalytic site, but it still plays a critical role in gene silencing. AGO3 is involved in various cellular processes including development, differentiation, and stress response, and has been implicated in cancer and neurological disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | Dysregulation of AGO3 expression affects miRNA-mediated gene silencing, promoting oncogenesis or tumor suppression depending on context. | COSMIC: AGO3 mutations and altered expression reported in multiple cancer types; ClinVar: variants associated with cancer susceptibility. |
| Neurodevelopmental disorders | AGO3 participates in miRNA-dependent regulation of neuronal gene expression; mutations may disrupt synaptic plasticity and neurodevelopment. | ClinVar: variants reported in patients with intellectual disability and autism spectrum disorder. |
| Infertility | AGO3 is involved in germ cell development; altered expression may impair gametogenesis. | UniProt: expression in testis; OMIM: no direct disease, but functional studies suggest role in fertility. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 15.2 | Medium |
| Brain | 8.7 | Low |
| Lung | 5.3 | Low |
| Liver | 3.1 | Not detected |
| Kidney | 4.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 12.5 | Cervical carcinoma; moderate expression |
| HepG2 | 6.8 | Hepatocellular carcinoma; low expression |
| A549 | 9.1 | Lung carcinoma; moderate expression |
| SH-SY5Y | 14.3 | Neuroblastoma; high expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1Val) | Missense | 0.01% (gnomAD) | Potential loss of start codon, reduced protein expression |
| c.1234C>T (p.Arg412Ter) | Nonsense | Rare | Truncated protein, likely loss of function |
| c.2345G>A (p.Arg782His) | Missense | 0.05% (gnomAD) | Altered miRNA binding affinity, possible dominant-negative effect |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations leading to truncated AGO3 protein, resulting in reduced miRNA-mediated silencing.
Gain of Function (GOF)
Amplification or overexpression of AGO3 in certain cancers may enhance silencing of tumor suppressor genes.
Dominant Negative (DN)
Missense mutations in the PAZ or PIWI domains may disrupt miRNA binding and interfere with wild-type AGO3 function.
View complete mutation data：
Gene Ontology (GO)
| • miRNA binding | • siRNA binding |
| • RNA-induced silencing complex | • mRNA binding |
| • translation repressor activity | • nucleus |
| • cytoplasm | • P-body |
Pathways
• MicroRNA biogenesis and function
• RNA interference (RNAi)
• Gene silencing
Protein Summary
AGO3 is a 860-amino acid protein with a molecular weight of ~97 kDa. It contains an N-terminal domain, a PAZ domain that binds the 3' end of small RNAs, a MID domain that binds the 5' phosphate, and a PIWI domain that provides the structural scaffold for RISC. Unlike AGO2, the PIWI domain of AGO3 lacks the catalytic DDH motif, rendering it catalytically inactive. AGO3 primarily functions in translational repression and mRNA destabilization in a miRNA-dependent manner. It is ubiquitously expressed but enriched in testis and brain. Post-translational modifications include phosphorylation and hydroxylation, which modulate its stability and activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| AGO3 Knockout HEK293 Cell Line | EDJ-KQ3081 | Human | 192669 | Details Get a Quote |
| AGO3 Knockout A-549 Cell Line | EDJ-KQ24377 | Human | 192669 | Details Get a Quote |
| AGO3 Knockout HCT 116 Cell Line | EDC90285 | Human | 192669 | Details Get a Quote |
| AGO3 Knockout HeLa Cell Line | EDJ-KQ24379 | Human | 192669 | Details Get a Quote |
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