AGO4

protein-coding

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

Gene summary

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]

Previous symbols:

EIF2C4

MANE transcript

NM_017629.4

Inheritance

—

ClinVar variants

U:94

Top phenotype

AGO4-related disorder

gnomAD constraint

pLI —, LoF o/e 0.1

Max pathogenic AF

—

Genomic locus

chr1:35,808,016-35,857,890

External References & Databases

Ensembl (ENSG00000134698)

Transcript & Mutation Effects

hg38 • Region Span ~49.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to AGO4 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 77

not providedTotal: 3

AGO4-related disorderTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_017629.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			6 clinvar			6
missense			81 clinvar			81
nonsense			2 clinvar			2
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	94	0	0	94

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_017629.4	RefSeq	NP_060099.2	18	MANE Select
ENST00000373210.4	Ensembl	ENSP00000362306.3	18	MANE Select
ENST00000965193.1	Ensembl	ENSP00000635252.1	17	Standard
ENST00000965193.2	Ensembl	ENSP00000635252.1	17	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Competing endogenous RNAs (ceRNAs) regulate PTEN translation
Signal Transduction
Gene expression (Transcription)
Generic Transcription Pathway
Oncogene Induced Senescence

Biological Process

mRNA catabolic process
synaptonemal complex assembly
male meiotic nuclear division
Wnt signaling pathway, calcium modulating pathway
male gonad development

Molecular Function

double-stranded RNA binding
single-stranded RNA binding
protein binding
miRNA binding

Cellular Component

P-body
nucleoplasm
cytoplasm
cytosol
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000373210
Coding exons: 18
Length: 49719
Individuals with no LoFs: 125728
Homozygous LoFs: 0
Heterozygous LoFs: 18
Defined: 125746
p: 0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.79	257	494	0.520	0.0000270	5631
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00018	0.00018	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00017	0.00016	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000079	0.000079	rare
South Asian	0.000033	0.000033	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.140

Intolerance Scores

RVIS EVS: -0.89
RVIS percentile EVS: 10.3

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N

Gene Damage Prediction

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