AGO1

Chr 1AD

argonaute RISC component 1

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

The protein binds to microRNAs and small interfering RNAs to repress translation of complementary mRNAs and mediate transcriptional gene silencing, functioning as a key component of the RNA interference pathway. Mutations cause autosomal dominant neurodevelopmental disorder with language delay and behavioral abnormalities, with or without seizures. This gene is highly constrained against loss-of-function variants, indicating that such variants are likely pathogenic when they occur.

OMIMResearchSummary from RefSeq, OMIM, UniProt
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.

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 OE0.00 (0.000.06)
00.351.4
Missense OE0.31 (0.280.36)
00.61.4
Synonymous OE1.00
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
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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

AGO1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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