AGO4

Chr 1

argonaute RISC component 4

The protein is an Argonaute family member that binds microRNAs and represses translation of complementary mRNAs, playing a critical role in RNA-mediated gene silencing. Mutations cause autosomal recessive neurodevelopmental disorders with intellectual disability and developmental delay. This gene is highly constrained against loss-of-function variants, indicating that complete loss of protein function is likely incompatible with normal development.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 0.22
Clinical SummaryAGO4
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.
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.22LOEUF
pLI 1.000
Z-score 5.77
OE 0.10 (0.050.22)
Highly constrained

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

Missense Constraint
3.79Z-score
OE missense 0.52 (0.470.58)
257 obs / 494.4 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.10 (0.050.22)
00.351.4
Missense OE0.52 (0.470.58)
00.61.4
Synonymous OE0.84
01.21.6
LoF obs/exp: 5 / 48.2Missense obs/exp: 257 / 494.4Syn Z: 1.64

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

AGO4 · 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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