AGO3

Chr 1

argonaute RISC catalytic component 3

Also known as: EIF2C3

NCBI Gene: 192669ENSG00000126070UniProt: Q9H9G7

This gene encodes a member of the Argonaute family of proteins which play a role in RNA interference. The encoded protein is highly basic, contains a PAZ domain and a PIWI domain, and may play a role in short-interfering-RNA-mediated gene silencing. This gene is located on chromosome 1 in a tandem cluster of closely related family members including argonaute 4 and eukaryotic translation initiation factor 2C, 1. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

83
ClinVar variants
10
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— AGO3
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
10 Pathogenic / Likely Pathogenic· 51 VUS of 83 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.19LOEUF
pLI 1.000
Z-score 5.84
OE 0.08 (0.04–0.19)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
5.26Z-score
OE missense 0.34 (0.30–0.39)
170 obs / 501.4 exp
Constrained

Extremely missense-constrained (top ~0.01%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.08 (0.04–0.19)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.34 (0.30–0.39)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.85
0≤1.21.6
LoF obs/exp: 4 / 47.4Missense obs/exp: 170 / 501.4Syn Z: 1.55

ClinVar Variant Classifications

83 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7
Likely Pathogenic3
VUS51
Likely Benign15
Benign7
7
Pathogenic
3
Likely Pathogenic
51
VUS
15
Likely Benign
7
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
7
0
7
Likely Pathogenic
0
0
3
0
3
VUS
0
44
7
0
51
Likely Benign
0
0
1
14
15
Benign
0
1
0
6
7
Total045182083

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

AGO3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Burden re-analysis of neurodevelopmental disorder cohorts for prioritization of candidate genes.
Smal N et al.·Eur J Hum Genet
2024Cohort
Novel de Novo Nonsense Variants in AGO3 and KHSRP: Insights into Global Developmental Delay and Autism Spectrum Disorders through Whole Genome Analysis.
Ćuk M et al.·Am J Case Rep
2024Case report
Argonaute, Vault, and Ribosomal Proteins Targeted by Autoantibodies in Systemic Lupus Erythematosus.
Moadab F et al.·J Rheumatol
2023
Involvement of argonaute proteins in gene silencing and activation by RNAs complementary to a non-coding transcript at the progesterone receptor promoter.
Chu Y et al.·Nucleic Acids Res
2010
An alternative miRISC targets a cancer-associated coding sequence mutation in FOXL2.
Shin E et al.·EMBO J
2020
Argonaute-2 autoantibodies: a promising biomarker for predicting mortality in HBV-related acute-on-chronic liver failure patients with cirrhosis.
Wang Y et al.·Front Cell Infect Microbiol
2024Cohort
Argonaute-2 expression is regulated by epidermal growth factor receptor and mitogen-activated protein kinase signaling and correlates with a transformed phenotype in breast cancer cells.
Adams BD et al.·Endocrinology
2009
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools