AGO1

argonaute RISC component 1, the group of Argonaute RISC component family

Basic information

Region (hg38): 1:35869808-35930532

Previous symbols: [ "EIF2C1" ]

Links

ENSG00000092847 ∙ NCBI:26523 ∙ OMIM:606228 ∙ HGNC:3262 ∙ Uniprot:Q9UL18 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodevelopmental disorder with language delay and behavioral abnormalities, with or without seizures (Strong), mode of inheritance: AD
• neurodevelopmental disorder with language delay and behavioral abnormalities, with or without seizures (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with language delay and behavioral abnormalities, with or without seizures	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Neurologic	23020937; 25356899; 27620904; 30213762; 34930816

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the AGO1 gene.

• Intellectual disability (1 variants)
• AGO1-associated disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AGO1 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				13	7	20
missense		6	40			46
nonsense			1			1
start loss						0
frameshift			3			3
inframe indel		1				1
splice donor/acceptor (+/-2bp)	1		2			3
splice region			1		2	3
non coding			2			2
Total	1	7	48	13	7

Variants in AGO1

This is a list of pathogenic ClinVar variants found in the AGO1 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-35883445-A-T		not specified	Uncertain significance (Aug 01, 2024)
1-35883453-G-A		not specified	Benign (May 04, 2022)
1-35888430-C-G			Likely benign (Jul 01, 2024)
1-35888434-C-T		AGO1-related disorder	Likely benign (May 24, 2018)
1-35888443-G-GC		AGO1-related disorder	Uncertain significance (Apr 09, 2024)
1-35888474-C-G			Uncertain significance (May 24, 2016)
1-35888478-G-A		AGO1-related disorder	Uncertain significance (Sep 02, 2023)
1-35888509-C-G			Uncertain significance (Feb 07, 2024)
1-35888566-C-T		AGO1-related disorder	Benign (Dec 31, 2019)
1-35888584-G-A		AGO1-related disorder	Benign (Dec 31, 2019)
1-35888584-G-C		AGO1-related disorder	Benign (Dec 31, 2019)
1-35893108-G-C		Inborn genetic diseases	Uncertain significance (Apr 22, 2024)
1-35893182-G-T			Uncertain significance (Mar 06, 2024)
1-35893198-C-G			Benign (Jul 13, 2018)
1-35893208-G-A		Inborn genetic diseases	Uncertain significance (Feb 23, 2023)
1-35893214-A-T		Inborn genetic diseases	Uncertain significance (Mar 31, 2024)
1-35893231-G-A		AGO1-related disorder	Likely benign (Aug 21, 2019)
1-35893262-C-T		AGO1-related disorder	Uncertain significance (Mar 24, 2023)
1-35893673-G-A			Uncertain significance (Mar 18, 2023)
1-35893682-C-T			Uncertain significance (Dec 19, 2022)
1-35893694-CCTT-C		Inborn genetic diseases • See cases • Neurodevelopmental abnormality • Seizure;Self-injurious behavior;Tremor;Intellectual disability, severe;Severe global developmental delay • Neurodevelopmental disorder with language delay and behavioral abnormalities, with or without seizures	Conflicting classifications of pathogenicity (Mar 06, 2024)
1-35893699-T-C		Neurodevelopmental disorder with language delay and behavioral abnormalities, with or without seizures	Uncertain significance (Jun 07, 2024)
1-35893727-C-T		Neurodevelopmental disorder with language delay and behavioral abnormalities, with or without seizures	Conflicting classifications of pathogenicity (Aug 09, 2024)
1-35893730-T-C		Neurodevelopmental abnormality • Neurodevelopmental disorder with language delay and behavioral abnormalities, with or without seizures	Likely pathogenic (Dec 08, 2021)
1-35893730-T-G		Intellectual disability • Neurodevelopmental disorder with language delay and behavioral abnormalities, with or without seizures	Pathogenic/Likely pathogenic (Mar 22, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AGO1	protein_coding	protein_coding	ENST00000373204	19	59803

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	5.52e-9	125745	0	3	125748	0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	5.68	171	543	0.315	0.0000337	5599
Missense in Polyphen		73	285.11	0.25605		2867
Synonymous	-0.0111	200	200	1.00	0.0000117	1688
Loss of Function	6.71	0	52.4	0.00	0.00000317	517

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000266	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for RNA-mediated gene silencing (RNAi). Binds to short RNAs such as microRNAs (miRNAs) or short interfering RNAs (siRNAs), 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 transcriptional gene silencing (TGS) of promoter regions which are complementary to bound short antigene RNAs (agRNAs). {ECO:0000269|PubMed:16289642, ECO:0000269|PubMed:16936728, 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;Transcriptional regulation by small RNAs;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: 0.161

Intolerance Scores

• rvis_EVS: -0.8
• rvis_percentile_EVS: 12.24

Haploinsufficiency Scores

• pHI: 0.0853
• hipred: Y
• hipred_score: 0.785
• ghis: 0.576

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: Ago1
• Phenotype: integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; normal phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: nuclear-transcribed mRNA catabolic process;Wnt signaling pathway, calcium modulating pathway;RNA secondary structure unwinding;miRNA metabolic process;positive regulation of gene expression;negative regulation of gene expression;negative regulation of angiogenesis;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;regulation of megakaryocyte differentiation;positive regulation of transcription by RNA polymerase II;regulation of gene silencing by miRNA;RNA phosphodiester bond hydrolysis, endonucleolytic;mRNA cleavage involved in gene silencing by siRNA;positive regulation of NIK/NF-kappaB signaling
• Cellular component: P-body;nucleus;nucleoplasm;cytoplasm;cytosol;polysome;RISC complex;micro-ribonucleoprotein complex;RISC-loading complex;ribonucleoprotein complex
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;RNA polymerase II complex binding;core promoter binding;RNA binding;double-stranded RNA binding;single-stranded RNA binding;endoribonuclease activity;protein binding;miRNA binding