AGO1

Chr 1AD

argonaute RISC component 1

Also known as: EIF2C, EIF2C1, GERP95, NEDLBAS, Q99, hAgo1

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. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. A recent study showed this gene to be an authentic stop codon readthrough target, and that its mRNA could give rise to an additional C-terminally extended isoform by use of an alternative in-frame translation termination codon. [provided by RefSeq, Nov 2015]

OMIMResearchGenerating clinical summary…
LOFmechanismADLOEUF 0.061 OMIM phenotype
Clinical SummaryAGO1
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Gene-Disease Validity (ClinGen)
complex neurodevelopmental disorder · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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.
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ClinVar Variants
16 unique Pathogenic / Likely Pathogenic· 123 VUS of 190 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint?
0.06LOEUF
pLI 1.000
Z-score 6.71
OE 0.00 (0.000.06)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?
5.68Z-score
OE missense 0.31 (0.280.36)
171 obs / 543.3 exp
Constrained

Extremely missense-constrained (top ~0.01%)

Observed / Expected Ratios?
LoF OE?0.00 (0.000.06)
00.351.4
Missense OE?0.31 (0.280.36)
00.61.4
Synonymous OE?1.00
01.21.6
LoF obs/exp: 0 / 52.4Missense obs/exp: 171 / 543.3Syn Z: -0.01
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongAGO1-related developmental disorderOTHERAD

This gene — mechanism propensity

DN
0.2499th %ile
GOF
0.2796th %ile
LOF
0.76top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.06

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

190 submitted variants in ClinVar

Classification Summary

Pathogenic1
Likely Pathogenic15
VUS123
Likely Benign21
Benign7
Conflicting4
1
Pathogenic
15
Likely Pathogenic
123
VUS
21
Likely Benign
7
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
0
0
1
Likely Pathogenic
1
14
0
0
15
VUS
14
104
3
2
123
Likely Benign
0
1
0
20
21
Benign
0
0
2
5
7
Conflicting
4
Total16119527171

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

View in ClinVar →

9 pathogenic / likely-pathogenic (of 16) ClinVar copy-number / structural variants overlap AGO1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

AGO1 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →