AGO3

Chr 1

argonaute RISC catalytic component 3

Also known as: EIF2C3

NCBI Gene: 192669 ENSG00000126070 UniProt: Q9H9G7

The protein is an Argonaute family member that binds small RNAs like microRNAs and mediates RNA interference by repressing translation of complementary mRNAs and degrading select target RNAs. Mutations cause neurodevelopmental disorders with intellectual disability, developmental delay, and behavioral abnormalities, inherited in an autosomal dominant pattern. This gene is highly constrained against loss-of-function variation, indicating that functional copies are essential for normal development.

ResearchSummary from RefSeq, UniProt

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]

ResearchGenerating clinical summary…

LOEUF 0.19

Clinical Summary— AGO3

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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

46 VUS of 83 total submissions

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

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?

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?

LoF OE?0.08 (0.04–0.19)

0≤0.351.4

Missense OE?0.34 (0.30–0.39)

0≤0.61.4

Synonymous OE?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

VUS46

Likely Benign15

Benign7

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	46	0	0	46
Likely Benign	0	1	14	15
Benign	1	0	6	7
Total	47	1	20	68

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

View in ClinVar →

10 pathogenic / likely-pathogenic (of 18) ClinVar copy-number / structural variants overlap AGO3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →