AGO4

argonaute RISC component 4, the group of Argonaute RISC component family

Basic information

Region (hg38): 1:35808016-35857890

Previous symbols: [ "EIF2C4" ]

Links

ENSG00000134698 ∙ NCBI:192670 ∙ OMIM:607356 ∙ HGNC:18424 ∙ Uniprot:Q9HCK5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the AGO4 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AGO4 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense			43			43
nonsense			1			1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	44	0	0

Variants in AGO4

This is a list of pathogenic ClinVar variants found in the AGO4 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-35816908-C-G		not specified	Uncertain significance (Jan 24, 2023)
1-35816911-C-T		not specified	Uncertain significance (May 16, 2025)
1-35816944-A-G		not specified	Uncertain significance (Sep 27, 2024)
1-35817029-G-A		not specified	Uncertain significance (Oct 20, 2024)
1-35822879-T-C		not specified	Uncertain significance (Nov 30, 2021)
1-35822885-G-A		not specified	Uncertain significance (Sep 27, 2024)
1-35822917-C-T			Uncertain significance (May 14, 2020)
1-35822927-A-G		not specified	Uncertain significance (Mar 29, 2022)
1-35822939-G-A		not specified	Uncertain significance (Dec 28, 2024)
1-35822956-C-T		not specified	Uncertain significance (May 01, 2024)
1-35822969-T-C		not specified	Uncertain significance (Dec 04, 2024)
1-35822974-C-G		not specified	Uncertain significance (Mar 01, 2023)
1-35822975-G-A		not specified	Uncertain significance (Dec 07, 2024)
1-35825320-T-C		not specified	Uncertain significance (Dec 12, 2024)
1-35825425-A-G		not specified	Uncertain significance (Aug 08, 2023)
1-35825443-A-T		not specified	Uncertain significance (May 30, 2025)
1-35825463-G-T		not specified	Uncertain significance (May 20, 2025)
1-35825488-C-A		AGO4-related disorder	Uncertain significance (Nov 15, 2022)
1-35825488-C-G		not specified	Uncertain significance (Feb 21, 2024)
1-35825716-G-C		not specified	Uncertain significance (Apr 12, 2025)
1-35825730-C-A		not specified	Uncertain significance (Mar 14, 2023)
1-35825958-A-G		not specified	Uncertain significance (Jun 10, 2025)
1-35826001-A-G		not specified	Uncertain significance (Aug 10, 2024)
1-35826748-G-T		not specified	Uncertain significance (Nov 08, 2024)
1-35826816-C-T		AGO4-related disorder • not specified	Uncertain significance (May 09, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AGO4	protein_coding	protein_coding	ENST00000373210	18	49719

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000100	125728	0	18	125746	0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.79	257	494	0.520	0.0000270	5631
Missense in Polyphen		56	174.99	0.32003		1980
Synonymous	1.64	137	164	0.837	0.00000794	1689
Loss of Function	5.77	5	48.2	0.104	0.00000280	515

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000214	0.000214
Ashkenazi Jewish	0.00	0.00
East Asian	0.000166	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.0000794	0.0000791
Middle Eastern	0.000166	0.000163
South Asian	0.0000327	0.0000327
Other	0.000166	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for RNA-mediated gene silencing (RNAi). Binds to short RNAs such as microRNAs (miRNAs) and represses the translation of mRNAs which are complementary to them. Lacks endonuclease activity and does not appear to cleave target mRNAs. Also required for RNA-directed transcription and replication of the human hapatitis delta virus (HDV). {ECO:0000255|HAMAP- Rule:MF_03033, ECO:0000269|PubMed:15337849, ECO:0000269|PubMed:18552826, ECO:0000269|PubMed:18771919}.
• Pathway: Competing endogenous RNAs (ceRNAs) regulate PTEN translation;Signal Transduction;Gene expression (Transcription);Generic Transcription Pathway;Oncogene Induced Senescence;Oxidative Stress Induced Senescence;Cellular Senescence;Cellular responses to stress;RNA Polymerase II Transcription;Pre-NOTCH Transcription and Translation;Pre-NOTCH Expression and Processing;Signaling by NOTCH;TP53 Regulates Metabolic Genes;Cellular responses to external stimuli;Regulation of PTEN mRNA translation;PTEN Regulation;PIP3 activates AKT signaling;Signaling by Nuclear Receptors;Transcriptional Regulation by TP53;Regulation of RUNX1 Expression and Activity;Estrogen-dependent gene expression;ESR-mediated signaling;Intracellular signaling by second messengers;MicroRNA (miRNA) biogenesis;Transcriptional regulation by RUNX1;Small interfering RNA (siRNA) biogenesis;Post-transcriptional silencing by small RNAs;Gene Silencing by RNA (Consensus)

Recessive Scores

• pRec: 0.140

Intolerance Scores

• rvis_EVS: -0.89
• rvis_percentile_EVS: 10.3

Haploinsufficiency Scores

• pHI: 0.0848
• hipred: Y
• hipred_score: 0.756
• ghis: 0.572

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Ago4
• Phenotype: cellular phenotype; endocrine/exocrine gland phenotype; reproductive system phenotype

Gene ontology

• Biological process: mRNA catabolic process;synaptonemal complex assembly;male meiotic nuclear division;Wnt signaling pathway, calcium modulating pathway;male gonad development;RNA secondary structure unwinding;miRNA metabolic process;positive regulation of gene expression;negative regulation of gene expression;regulation of cell morphogenesis;pre-miRNA processing;posttranscriptional gene silencing by RNA;production of miRNAs involved in gene silencing by miRNA;miRNA mediated inhibition of translation;mRNA cleavage involved in gene silencing by miRNA;miRNA loading onto RISC involved in gene silencing by miRNA;negative regulation of apoptotic process;regulation of megakaryocyte differentiation;mRNA cleavage involved in gene silencing by siRNA
• Cellular component: P-body;nucleoplasm;cytoplasm;cytosol;membrane;RISC complex;nuclear body;micro-ribonucleoprotein complex;RISC-loading complex
• Molecular function: double-stranded RNA binding;single-stranded RNA binding;protein binding;miRNA binding