AGO1

Chr 1

argonaute RISC component 1

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

NCBI Gene: 26523 ENSG00000092847 UniProt: Q9UL18

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.

ResearchSummary from RefSeq, OMIM, UniProt

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]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtNeurodevelopmental disorder with language delay and behavioral abnormalities, with or without seizures

Clinical highlights

Gene-disease validity (ClinGen)

complex neurodevelopmental disorder · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.06

LOEUF· LoF intol.

LOF

Mechanism· predicted

Some data sources returned errors (1)

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