AGO4

Chr 1

argonaute RISC component 4

Also known as: EIF2C4

NCBI Gene: 192670 ENSG00000134698 UniProt: Q9HCK5 OMIM: 607356

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.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the Argonaute family of proteins which contain PAZ and PIWI domains and play an integral role in RNA interference and short-interfering-RNA-mediated gene silencing. This gene is located on chromosome 1 in a cluster of related family members. [provided by RefSeq, Mar 2017]

OMIM ResearchGenerating clinical summary…

LOEUF 0.22

Clinical Summary— AGO4

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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

79 VUS of 102 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.22LOEUF

pLI 1.000

Z-score 5.77

OE 0.10 (0.05–0.22)

Highly constrained

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

Missense Constraint?

3.79Z-score

OE missense 0.52 (0.47–0.58)

257 obs / 494.4 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.10 (0.05–0.22)

0≤0.351.4

Missense OE?0.52 (0.47–0.58)

0≤0.61.4

Synonymous OE?0.84

0≤1.21.6

LoF obs/exp: 5 / 48.2Missense obs/exp: 257 / 494.4Syn Z: 1.64

ClinVar Variant Classifications

102 submitted variants in ClinVar

ClinVar

Classification Summary

VUS79

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	1	78	79
Likely Benign	0	0	0
Benign	0	0	0
Total	1	78	79

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 AGO4 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →