AGO2

Summary

AGO2 (argonaute RISC catalytic component 2, HGNC:3263) is a protein-coding gene on chromosome 8q24.3, encoding Protein argonaute-2 (Q9UKV8). Required for RNA-mediated gene silencing (RNAi) by the RNA-induced silencing complex (RISC).

This gene encodes a member of the Argonaute family of proteins which play a role in RNA interference. The encoded protein is highly basic, and contains a PAZ domain and a PIWI domain. It may interact with dicer1 and play a role in short-interfering-RNA-mediated gene silencing. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 27161 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Lessel-Kreienkamp syndrome (Definitive, ClinGen)
• GWAS associations: 11
• Clinical variants (ClinVar): 234 total — 4 pathogenic, 13 likely-pathogenic
• Regional missense constraint (gnomAD): 2 of 6 regions constrained (≈11% of expected missense variation)
• GTEx eGene: eQTL in 15 tissues, sQTL in 2 (q < 0.05)
• Phenotypes (HPO): 36
• ChEMBL bioactivity: 4 clinical-phase molecules tested; no curated mechanism-of-action drug
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.10 (highly constrained)
• MANE Select transcript: NM_012154
• Interaction hub: 6,276 STRING partners (top 1% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3263
Approved symbol	AGO2
Name	argonaute RISC catalytic component 2
Location	8q24.3
Locus type	gene with protein product
Status	Approved
Aliases	hAGO2, Q10, LINC00980
Ensembl gene	ENSG00000123908
Ensembl biotype	protein_coding
OMIM	606229
Entrez	27161

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 5 protein_coding, 4 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined, 3 retained_intron

MANE Select: ENST00000220592

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 2: 3, TSL 3: 3, TSL 5: 1

ENST00000220592, ENST00000517293, ENST00000518019, ENST00000519347, ENST00000519980, ENST00000520412, ENST00000520628, ENST00000521325, ENST00000523609, ENST00000524328, ENST00000978227, ENST00000978228, ENST00001041070, ENST00001041071, ENST00001135053

RefSeq mRNA: 2 — MANE Select: NM_012154 NM_001164623, NM_012154

CCDS: CCDS55279, CCDS6380

Canonical transcript exons

ENST00000220592 — 19 exons

Exon	Start	End
ENSE00002115766	140635485	140635633
ENSE00002573500	140520156	140532152
ENSE00003465478	140572812	140572932
ENSE00003468648	140555896	140556018
ENSE00003476350	140532416	140532615
ENSE00003498594	140559395	140559529
ENSE00003499669	140556167	140556286
ENSE00003528791	140541164	140541358
ENSE00003544094	140562453	140562634
ENSE00003548954	140549114	140549298
ENSE00003569278	140557089	140557236
ENSE00003594655	140544213	140544303
ENSE00003598658	140551303	140551436
ENSE00003601006	140585119	140585311
ENSE00003641526	140539320	140539454
ENSE00003644665	140535468	140535569
ENSE00003660001	140558485	140558572
ENSE00003661900	140560374	140560510
ENSE00003679723	140547468	140547627

Expression profiles

Bgee: expression breadth ubiquitous, 279 present calls, max score 95.46.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.4114 / max 236.6233, expressed in 1799 samples.

Highest expression (Bgee): colonic epithelium, cartilage tissue, cauda epididymis, superficial temporal artery, trabecular bone tissue.

Genetic regulation across tissues (GTEx eQTL / sQTL)

AGO2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 15 tissues and its splicing (sQTL) in 2 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

17 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	eqtl	6.9e-53	-0.74	8:140642366:G:T
Cells Cultured fibroblasts	eqtl	1.8e-43	-0.26	8:140528747:T:C
Artery Tibial	eqtl	5.4e-07	-0.11	8:140529749:T:G
Testis	sqtl	8.8e-06	+0.69	8:140642366:G:T
Brain Frontal Cortex BA9	eqtl	2.7e-04	-0.20	8:140541308:G:A
Esophagus Muscularis	eqtl	3.4e-04	-0.11	8:140537613:T:C
Brain Caudate basal ganglia	eqtl	3.0e-03	-0.14	8:140663257:G:GA
Brain Cortex	eqtl	8.6e-03	-0.17	8:140536524:A:G
Nerve Tibial	eqtl	8.6e-03	-0.26	8:140533185:C:T
Thyroid	eqtl	1.2e-02	-0.12	8:140519902:T:C
Pancreas	eqtl	1.4e-02	-0.15	8:140539247:CT:C
Brain Putamen basal ganglia	eqtl	2.0e-02	-0.17	8:140534649:A:G
Brain Hippocampus	eqtl	2.3e-02	-0.13	8:140594585:C:G
Colon Transverse	sqtl	2.5e-02	-1.35	8:141611166:A:G
Heart Atrial Appendage	eqtl	2.9e-02	-0.11	8:140536503:T:C
Cells EBV-transformed lymphocytes	eqtl	4.4e-02	-0.18	8:140535094:C:T
Muscle Skeletal	eqtl	4.5e-02	+0.32	8:141142897:G:A

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
95335	20.9811	1796
95326	0.4303	211

Top tissues by expression

showing 100 of 296 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
colonic epithelium	UBERON:0000397	95.46	gold quality
cartilage tissue	UBERON:0002418	94.78	gold quality
cauda epididymis	UBERON:0004360	94.45	gold quality
superficial temporal artery	UBERON:0001614	93.40	gold quality
trabecular bone tissue	UBERON:0002483	93.38	gold quality
corpus epididymis	UBERON:0004359	92.91	gold quality
mucosa of paranasal sinus	UBERON:0005030	92.73	gold quality
lower lobe of lung	UBERON:0008949	92.68	gold quality
tendon	UBERON:0000043	92.43	gold quality
calcaneal tendon	UBERON:0003701	92.31	gold quality
caput epididymis	UBERON:0004358	91.89	gold quality
corpus callosum	UBERON:0002336	91.69	gold quality
parietal pleura	UBERON:0002400	91.55	gold quality
blood	UBERON:0000178	91.41	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	91.30	gold quality
adrenal tissue	UBERON:0018303	91.26	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	91.10	gold quality
tendon of biceps brachii	UBERON:0008188	90.96	gold quality
visceral pleura	UBERON:0002401	90.74	gold quality
pleura	UBERON:0000977	90.71	gold quality
seminal vesicle	UBERON:0000998	90.08	gold quality
medial globus pallidus	UBERON:0002477	89.47	gold quality
oocyte	CL:0000023	89.46	gold quality
adult organism	UBERON:0007023	89.39	gold quality
biceps brachii	UBERON:0001507	89.34	gold quality
secondary oocyte	CL:0000655	89.06	gold quality
sural nerve	UBERON:0015488	89.03	gold quality
globus pallidus	UBERON:0001875	88.98	gold quality
synovial joint	UBERON:0002217	88.98	gold quality
tibia	UBERON:0000979	88.86	gold quality
epithelium of nasopharynx	UBERON:0001951	88.81	gold quality
nasopharynx	UBERON:0001728	88.79	gold quality
tibialis anterior	UBERON:0001385	88.59	silver quality
gingival epithelium	UBERON:0001949	88.38	gold quality
germinal epithelium of ovary	UBERON:0001304	88.18	gold quality
subthalamic nucleus	UBERON:0001906	88.17	gold quality
mucosa of sigmoid colon	UBERON:0004993	88.07	gold quality
gingiva	UBERON:0001828	87.84	gold quality
saphenous vein	UBERON:0007318	87.77	gold quality
jejunum	UBERON:0002115	87.76	gold quality
gastrocnemius	UBERON:0001388	87.57	gold quality
oral cavity	UBERON:0000167	87.52	gold quality
inferior vagus X ganglion	UBERON:0005363	87.47	gold quality
hindlimb stylopod muscle	UBERON:0004252	87.35	gold quality
mammary duct	UBERON:0001765	87.27	gold quality
muscle of leg	UBERON:0001383	87.26	gold quality
bone marrow	UBERON:0002371	87.21	gold quality
cardia of stomach	UBERON:0001162	86.93	gold quality
Brodmann (1909) area 23	UBERON:0013554	86.90	gold quality
upper leg skin	UBERON:0004262	86.70	gold quality
body of tongue	UBERON:0011876	86.68	gold quality
epithelium of mammary gland	UBERON:0003244	86.66	gold quality
skin of hip	UBERON:0001554	86.62	gold quality
ventral tegmental area	UBERON:0002691	86.50	gold quality
jejunal mucosa	UBERON:0000399	86.41	gold quality
lateral nuclear group of thalamus	UBERON:0002736	86.15	gold quality
vena cava	UBERON:0004087	85.98	silver quality
parietal lobe	UBERON:0001872	85.81	gold quality
postcentral gyrus	UBERON:0002581	85.81	gold quality
colonic mucosa	UBERON:0000317	85.68	gold quality
tongue	UBERON:0001723	85.61	gold quality
heart right ventricle	UBERON:0002080	85.32	gold quality
nipple	UBERON:0002030	85.30	gold quality
stromal cell of endometrium	CL:0002255	85.28	gold quality
superior vestibular nucleus	UBERON:0007227	85.22	gold quality
placenta	UBERON:0001987	85.21	gold quality
mammalian vulva	UBERON:0000997	85.16	gold quality
pylorus	UBERON:0001166	85.02	gold quality
endometrium epithelium	UBERON:0004811	85.00	gold quality
urethra	UBERON:0000057	84.80	gold quality
lateral globus pallidus	UBERON:0002476	84.80	gold quality
entorhinal cortex	UBERON:0002728	84.79	gold quality
tonsil	UBERON:0002372	84.77	gold quality
amniotic fluid	UBERON:0000173	84.67	gold quality
mammary gland	UBERON:0001911	84.50	gold quality
thoracic mammary gland	UBERON:0005200	84.50	gold quality
skeletal muscle organ	UBERON:0014892	84.50	gold quality
muscle organ	UBERON:0001630	84.48	gold quality
penis	UBERON:0000989	84.42	gold quality
superior surface of tongue	UBERON:0007371	84.38	gold quality
granulocyte	CL:0000094	84.26	gold quality
ventricular zone	UBERON:0003053	84.21	gold quality
substantia nigra pars reticulata	UBERON:0001966	83.98	gold quality
endometrium	UBERON:0001295	83.84	gold quality
substantia nigra pars compacta	UBERON:0001965	83.82	gold quality
pericardium	UBERON:0002407	83.79	gold quality
dorsal plus ventral thalamus	UBERON:0001897	83.73	gold quality
middle temporal gyrus	UBERON:0002771	83.62	gold quality
monocyte	CL:0000576	83.53	gold quality
pharyngeal mucosa	UBERON:0000355	83.38	gold quality
deltoid	UBERON:0001476	83.30	silver quality
renal medulla	UBERON:0000362	83.24	gold quality
leukocyte	CL:0000738	83.23	gold quality
mononuclear cell	CL:0000842	83.22	gold quality
bronchial epithelial cell	CL:0002328	83.17	gold quality
buccal mucosa cell	CL:0002336	83.01	gold quality
bone marrow cell	CL:0002092	82.97	gold quality
pons	UBERON:0000988	82.95	gold quality
superior frontal gyrus	UBERON:0002661	82.76	gold quality
cortical plate	UBERON:0005343	82.63	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Nucleus accumbens	tissue	46.4
Locus coeruleus	tissue	44.5
Hippocampus	tissue	37.5	high
Choroid plexus	tissue	35.0
Postcentral gyrus	tissue	31.0
Corpus callosum	tissue	14.8
Caudate putamen	tissue	14.3
Cerebral cortex	tissue	14.0	high
Insular cortex	tissue	14.0
Prefrontal cortex	tissue	13.8
Motor cortex	tissue	13.6
Retrosplenial cortex	tissue	13.3
Somatosensory cortex	tissue	13.2
Amygdala	tissue	12.8
Hypothalamus	tissue	12.8
Hippocampal formation	tissue	12.8
Entorhinal cortex	tissue	12.8
Retrosplenial and cingulate cortex	tissue	12.8
Olfactory bulb	tissue	12.8
Temporal cortex	tissue	12.7
Occipital cortex	tissue	12.6
Ventral forebrain	tissue	12.5
Cerebellum	tissue	11.9	high
Frontal cortex	tissue	11.7
Septum	tissue	11.6
Midbrain	tissue	11.1
Putamen	tissue	11.0
Thalamus	tissue	11.0
Periaqueductal gray	tissue	11.0
Substantia nigra	tissue	10.8
Bone marrow	tissue	10.7	medium
Pons	tissue	10.5
Medulla oblongata	tissue	10.4
Superior colliculi	tissue	10.2
Basal ganglia	tissue	10.1	high
Spinal cord	tissue	9.7
Skeletal muscle	tissue	8.5	high
Tongue	tissue	8.5
Skin 1	tissue	8.0	high
Pituitary gland	tissue	7.5
Thymus	tissue	7.1
Parathyroid gland	tissue	6.6	high
Vagina	tissue	6.4	medium
Retina	tissue	6.3
Adipose tissue	tissue	6.2	not detected
Appendix	tissue	5.9	high
Lymph node	tissue	5.7	high
Epididymis	tissue	5.5	medium
Esophagus	tissue	5.4	high
Placenta	tissue	5.4	high
Endometrium 1	tissue	5.3	high
Tonsil	tissue	5.1	high
Smooth muscle	tissue	4.9	not detected
Ovary	tissue	4.8	low
Urinary bladder	tissue	4.8	medium
Gallbladder	tissue	4.8	high
Heart muscle	tissue	4.5	medium
Pancreas	tissue	4.5	high
Fallopian tube	tissue	4.5	low
Seminal vesicle	tissue	4.3	medium

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Parieto-temporal junction (white matter) (67.0), Temporal white matter (66.6), Area postrema (60.3), Nucleus raphe obscurus (59.1), Nucleus raphe pallidus (56.2).

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets:

Target	Regulation
IL2	Activation

Upstream regulators (CollecTRI, top): ESR1, FOXC1

miRNA regulators (miRDB)

Targeting AGO2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 43 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-202-5P	99.78	67.65	991
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-1197	99.70	67.75	1027
HSA-MIR-4527	99.66	67.43	714
HSA-MIR-4502	99.65	66.99	1021
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-6503-5P	99.62	66.96	597
HSA-MIR-4499	99.62	67.29	1470
HSA-MIR-12122	99.56	69.33	1672
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-942-5P	99.41	68.40	1977
HSA-MIR-5580-5P	99.38	66.96	1139
HSA-MIR-92B-5P	99.36	63.29	110
HSA-MIR-376A-3P	99.06	69.17	1128
HSA-MIR-376B-3P	99.06	69.17	1128

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.102, missense Z 6.98 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000220592 splits into 6 regions with different missense tolerance; 2 are missense-constrained (≈11% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
8:140,532,047–140,557,095	309 / 735.1	0.42	no
8:140,557,096–140,557,144	0 / 19.5	0.00	yes (p 1.0e-05)
8:140,557,145–140,558,530	38 / 68.1	0.56	no
8:140,558,531–140,560,455	21 / 105.0	0.20	yes (p 2.5e-16)
8:140,560,456–140,562,505	26 / 52.0	0.50	no
8:140,562,506–140,635,506	147 / 204.1	0.72	no

Literature-anchored findings (GeneRIF, showing 40)

• responsible for messenger RNA cleavage activity; evidence supports a model in which Argonaute contributes “Slicer” activity to RISC, providing the catalytic engine for RNAi (PMID:15284456)
• Argonaute proteins catalyze mRNA cleavage within RNA-Induced Silencing Complex (PMID:15800637)
• Argonaute 2, a key component of RISC, is not randomly distributed but concentrates in mRNA decay centres that are known as cytoplasmic bodies. (PMID:15908945)
• Activity of siRNA duplexes containing full 2’-OMe substitutions in the sense strand is mediated by the RNA-induced silencing complex and that strand-specific loading to hAgo2 may be modulated through selective incorporation of these modifications. (PMID:16301602)
• miRNA loading complex (miRLC) is formed by Ago2 and Dicer prior to their encounter with pre-miRNA. (PMID:16357216)
• Here, we show that the human slicer Argonaute2 (HsAgo2), but not HsAgo1, functions in RNAi in the early divergent protozoan Trypanosoma brucei, thus mimicking the situation in mammalian cells (PMID:16611939)
• AGO1 and AGO2 associate with promoter DNA in cells treated with antigene RNAs (agRNAs), and inhibiting expression of AGO1 or AGO2 reverses transcriptional and post-transcriptional silencing. (PMID:16936728)
• give a quantitative account of the Argonaute protein localization and dynamics in living cells in different cellular states (PMID:17116888)
• A crosslinking-coupled affinity purification method was used to isolate TNF-alpha AU-rich element-associated proteins: two microRNP-related proteins, FXR1 and AGO2 were found that associate during translation activation. (PMID:17382880)
• Ago2 represses the initiation of mRNA translation by binding to the m(7)G cap of mRNA targets, thus likely precluding the recruitment of eIF4E (PMID:17524464)
• The action of RNA-induced silencing complex (RISC) requires the endonucleolytic slicer activity of Argonaute2 (Ago2) (PMID:17531811)
• Local widening of the duplex formed by the siRNA guide strand and the targeted region of mRNA is a possible reason for the intolerance of human Ago2, the RISC endonuclease, toward internal mismatch pairs involving native or chemically modified RNA. (PMID:17881374)
• Results describe a repetitive motif within Tas3, termed the ‘Argonaute hook’, that is conserved from yeast to humans and binds Ago1 and 2 through their PIWI domains in vitro and in vivo. (PMID:17891150)
• Data show that Argonaute1 and 2 reside in three complexes with distinct Dicer and RNA-induced silencing complex activities, and that the putative RNA-binding protein RBM4 is required for microRNA-guided gene regulation. (PMID:17932509)
• Ago2, Dicer, and TRBP comprise the RISC-loading complex (RLC) and assembles spontaneously in vitro from purified components (PMID:18178619)
• These present data demonstrate that siAgo2 inhibited indispensable events of angiogenesis in vitro. (PMID:18222171)
• The results suggest a potential regulatory mechanism for RNA silencing acting through Ago2 serine-387 phosphorylation mediated by the p38 MAPK pathway. (PMID:18476811)
• Ectopic expression of the Argonaute-2 (Ago2, eIF2C2) dramatically enhances RNA interference specifically for mRNA targets with perfectly matched binding sites. (PMID:18591665)
• findings identify hydroxylation as a post-translational modification important for Ago2 stability and effective RNA interference (PMID:18690212)
• The specificity of RNA interference depends on the concentration of Ago1, Ago3, and Ago4 relative to Ago2. (PMID:18771919)
• Ago2 is regulated at both the transcriptional and posttranslational level, and Ago2 and enhanced micro-RNA activity is seen in the tumorigenic progression of breast cancer cell lines. (PMID:18787018)
• Data show that siRNA transfection induces up-regulated expression of both GW182, a key P-body component, and Ago2, indicating that P-body localization and interaction with GW182 and Ago2 are important in siRNA-mediated RNAi. (PMID:18946079)
• plays a roll in processes of tumor angiogenesis. (PMID:18981691)
• Mutant Ago2 protein containing 6 point mutations (G32W, F128L, R196Q, P458S, T741A, S752G) failed to accumulate in P-bodies. (PMID:19061863)
• Data report that stable, long-term overexpression of Argonaute2, an Argonaute isoform, induces the production of a number of microRNAs, such as the let-7 family of microRNAs, in 293T cells. (PMID:19064005)
• Mapping of the MC sequence to the mid domain structure reveals Ago2 aromatics that are incompatible with eIF4E-like mRNA cap-binding, yet display some limited local structure similarities that cause the chance sequence match to eIF4E (PMID:19159466)
• Study demonstrates that Imp8 is required for the recruitment of Ago protein complexes to a large set of Ago2-associated target mRNAs, allowing for efficient and specific gene silencing. (PMID:19167051)
• Tethering the C-terminal half of Ago2 to the 3’-UTR of reporter mRNA recapitulated translational repression comparable to that of tethered Ago2, and this repression was greatly impaired upon GW182 knockdown. (PMID:19324964)
• EIF2C2 protein shows an opposite trend, with an expression in N-type cells that is lower than in I-type cells (PMID:19393748)
• Hsp90 is a critical modulator of Argonaute function. (PMID:19458189)
• The interaction of Argonaute2 with the 5’ uracil base plays a critical role in the recruitment of mRNA. (PMID:19508234)
• High-throughput sequencing of Ago bound RNAs isolated by crosslinking immunoprecipitation (HITS-CLIP) identifies functional protein-RNA interaction sites in brain; validated miR-124 sites are also identified in HeLa cells. (PMID:19536157)
• Ago2 immunoprecipitated from HeLa cells contained the double strand RNA-binding protein human immunodeficiency virus, type 1, trans-activating response RNA-binding protein (PMID:19625255)
• Data show that Ago1 and Ago2 (which encode argonautes, the key proteins forming the RNA-induced silencing complex (RISC)) had significantly higher expression levels in ER- than in ER+ breast cancer. (PMID:19723326)
• Ago2 immunoprecipitation identifies predicted microRNAs in human embryonic stem cells and neural precursors (PMID:19784364)
• Data show that RBM4 interacts directly with Ago2 during muscle cell differentiation and may recruit Ago2 to suppress translation of target mRNAs. (PMID:19801630)
• The RLC Dicer’s N-terminal DExH/D domain, located in a short ‘base branch’, interacts with TRBP, whereas its C-terminal catalytic domains in the main body are proximal to AGO2. (PMID:19820710)
• The authors demonstrate that AGO1 uses only miRNA duplexes when assembling translational repression-competent complexes, whereas AGO2 can use both miRNA and siRNA duplexes. (PMID:19946268)
• EIF2C2-4 and PIWIL4 appear increased in advanced tumors with distant metastasis, suggesting they may promote tumor invasion (PMID:20146808)
• Data show that fibroblast growth factor-2 is regulated by an endogenous antisense RNA and by argonaute-2. (PMID:20197313)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ago2	ENSDARG00000061268
mus_musculus	Ago2	ENSMUSG00000036698
rattus_norvegicus	Ago2	ENSRNOG00000008533
drosophila_melanogaster	AGO1	FBGN0262739
caenorhabditis_elegans		WBGENE00000105
caenorhabditis_elegans		WBGENE00000106

Paralogs (3): AGO1 (ENSG00000092847), AGO3 (ENSG00000126070), AGO4 (ENSG00000134698)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2446632) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 26 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased erythrocyte cell number	2
decreased hematocrit	1
enlarged spleen	1
anemia	1
placental labyrinth hypoplasia	1
embryonic growth arrest	1
abnormal embryonic tissue morphology	1
abnormal proerythroblast morphology	1
abnormal erythrocyte morphology	1
decreased mean corpuscular volume	1
reticulocytosis	1
decreased hemoglobin content	1
decreased pancreatic beta cell number	1
abnormal erythrocyte physiology	1
pallor	1
small placenta	1
abnormal pancreatic beta cell morphology	1
improved glucose tolerance	1
decreased mean corpuscular hemoglobin	1
decreased pancreatic beta cell mass	1
increased red blood cell distribution width	1
neonatal lethality, complete penetrance	1
embryonic lethality between implantation and somite formation, complete penetrance	1
increased number of Heinz bodies	1
decreased pancreatic beta cell proliferation	1

+1 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	Q6QME8	99.7%	Diamond
Oryctolagus cuniculus	O77503	99.6%	Diamond
Gallus gallus	Q5ZMW0	99.5%	Diamond
Xenopus laevis	Q4KLV6	98.2%	Diamond
Xenopus tropicalis	Q6DJB9	97.4%	Diamond
Oryza sativa Japonica Group	Q851R2	88.1%	Diamond
Arabidopsis thaliana	Q9XGW1	82.0%	Diamond
Schizosaccharomyces pombe 972h-	O74957	34.3%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
MIR151A	ncRNA	442893
CHRAC1	protein-coding	54108
PTK2	protein-coding	5747
TRAPPC9	protein-coding	83696
ERICD	ncRNA	104355217

Protein

Protein identifiers

Protein argonaute-2 — Q9UKV8 (reviewed: Q9UKV8)

Alternative names: Argonaute RISC catalytic component 2, Eukaryotic translation initiation factor 2C 2, PAZ Piwi domain protein, Protein slicer

All UniProt accessions (3): E5RGG9, E5RJY2, Q9UKV8

UniProt curated annotations — full annotation on UniProt →

Function. Required for RNA-mediated gene silencing (RNAi) by the RNA-induced silencing complex (RISC). The ‘minimal RISC’ appears to include AGO2 bound to a short guide RNA such as a microRNA (miRNA) or short interfering RNA (siRNA). These guide RNAs direct RISC to complementary mRNAs that are targets for RISC-mediated gene silencing. The precise mechanism of gene silencing depends on the degree of complementarity between the miRNA or siRNA and its target. Binding of RISC to a perfectly complementary mRNA generally results in silencing due to endonucleolytic cleavage of the mRNA specifically by AGO2. Binding of RISC to a partially complementary mRNA results in silencing through inhibition of translation, and this is independent of endonuclease activity. May inhibit translation initiation by binding to the 7-methylguanosine cap, thereby preventing the recruitment of the translation initiation factor eIF4-E. May also inhibit translation initiation via interaction with EIF6, which itself binds to the 60S ribosomal subunit and prevents its association with the 40S ribosomal subunit. The inhibition of translational initiation leads to the accumulation of the affected mRNA in cytoplasmic processing bodies (P-bodies), where mRNA degradation may subsequently occur. In some cases RISC-mediated translational repression is also observed for miRNAs that perfectly match the 3’ untranslated region (3’-UTR). Can also up-regulate the translation of specific mRNAs under certain growth conditions. Binds to the AU element of the 3’-UTR of the TNF mRNA and up-regulates translation under conditions of serum starvation. Also required for transcriptional gene silencing (TGS), in which short RNAs known as antigene RNAs or agRNAs direct the transcriptional repression of complementary promoter regions. (Microbial infection) Upon Sars-CoV-2 infection, associates with viral miRNA-like small RNA, CoV2-miR-O7a, and may repress mRNAs, such as BATF2, to evade the IFN response.

Subunit / interactions. Interacts with DICER1 through its Piwi domain and with TARBP2 during assembly of the RNA-induced silencing complex (RISC). Together, DICER1, AGO2 and TARBP2 constitute the trimeric RISC loading complex (RLC), or micro-RNA (miRNA) loading complex (miRLC). Within the RLC/miRLC, DICER1 and TARBP2 are required to process precursor miRNAs (pre-miRNAs) to mature miRNAs and then load them onto AGO2. AGO2 bound to the mature miRNA constitutes the minimal RISC and may subsequently dissociate from DICER1 and TARBP2. Note however that the term RISC has also been used to describe the trimeric RLC/miRLC. The formation of RISC complexes containing siRNAs rather than miRNAs appears to occur independently of DICER1. Interacts with AGO1. Also interacts with DDB1, DDX5, DDX6, DDX20, DHX30, DHX36, DDX47, DHX9, ELAVL, FXR1, GEMIN4, HNRNPF, IGF2BP1, ILF3, IMP8, MATR3, PABPC1, PRMT5, P4HA1, P4HB, RBM4, SART3, TNRC6A, TNRC6B, UPF1 and YBX1. Interacts with the P-body components DCP1A and XRN1. Associates with polysomes and messenger ribonucleoproteins (mNRPs). Interacts with RBM4; the interaction is modulated under stress-induced conditions, occurs under both cell proliferation and differentiation conditions and in an RNA- and phosphorylation-independent manner. Interacts with LIMD1, WTIP and AJUBA. Interacts with TRIM71; the interaction increases in presence of RNA. Interacts with APOBEC3G in an RNA-dependent manner. Interacts with APOBEC3A, APOBEC3C, APOBEC3F and APOBEC3H. Interacts with DICER1, TARBP2, EIF6, MOV10 and RPL7A (60S ribosome subunit); they form a large RNA-induced silencing complex (RISC). Interacts with FMR1. Interacts with ZFP36. Found in a complex, composed of AGO2, CHD7 and ARB2A. Interacts with RC3H1; the interaction is RNA independent. Interacts with SND1. Interacts with SYT11. Interacts with CLNK. Interacts with GARRE1. Interacts with GRB2; this interaction is important for the formation of a ternary complex containing GRB2, AGO2 and DICER1. Interacts with FAM120A. (Microbial infection) Interacts with Epstein-Barr virus (EBV) tegument protein BGLF2; this interaction participates in the regulation of cellular miRNA by the virus, leading to enhanced SUMOylation. (Microbial infection) Interacts with rotavirus A non-structural protein 5; this interaction probably plays a role in the sequestration of AGO2 in viral factories. (Microbial infection) Interacts with human herpesvirus 8 protein MTA/ORF57; this interaction inhibits P-body formation.

Subcellular location. Cytoplasm. P-body. Nucleus.

Post-translational modifications. Hydroxylated. 4-hydroxylation appears to enhance protein stability but is not required for miRNA-binding or endonuclease activity. Ubiquitinated on surface-exposed lysines by a SCF-like E3 ubiquitin-protein ligase complex containing ZSWIM8 during target-directed microRNA degradation (TDMD), a process that mediates degradation of microRNAs (miRNAs). Ubiquitination by the SCF-like E3 ubiquitin-protein ligase complex containing ZSWIM8 leads to its subsequent degradation, thereby exposing miRNAs for degradation. ZSWIM8 recognizes and binds AGO2 when it is engaged with a TDMD target. Phosphorylated. A phosphorylation cycle of C-terminal serine cluster (Ser-824-Ser-834) regulates the release of target mRNAs. Target-binding leads to phosphorylation of these residues by CSNK1A1, which reduces the affinity of AGO2 for mRNA and enables target release. The ANKRD52-PPP6C phosphatase complex dephosphorylates the residues, which primes AGO2 for binding a new target. Phosphorylation at Ser-387 by AKT3; leads to up-regulate translational repression of microRNA target and down-regulate endonucleolytic cleavage.

Disease relevance. Lessel-Kreienkamp syndrome (LESKRES) [MIM:619149] An autosomal dominant disorder characterized by global developmental delay, intellectual disability of variable degree, and speech and language delay apparent from infancy or early childhood. Behavioral disorders are observed in most patients. Additional variable features include seizures, hypotonia, gait abnormalities, visual and cardiac defects, and non-specific facial dysmorphism. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by EDTA.

Domain organisation. The Piwi domain may perform RNA cleavage by a mechanism similar to that of RNase H. However, while RNase H utilizes a triad of Asp-Asp-Glu (DDE) for metal ion coordination, this protein appears to utilize a triad of Asp-Asp-His (DDH).

Similarity. Belongs to the argonaute family. Ago subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UKV8-1	1	yes
Q9UKV8-2	2

RefSeq proteins (2): NP_001158095, NP_036286* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003100	PAZ_dom	Domain
IPR003165	Piwi	Domain
IPR012337	RNaseH-like_sf	Homologous_superfamily
IPR014811	ArgoL1	Domain
IPR028602	AGO2	Family
IPR032472	ArgoL2	Domain
IPR032473	Argonaute_Mid_dom	Domain
IPR032474	Argonaute_N	Domain
IPR036085	PAZ_dom_sf	Homologous_superfamily
IPR036397	RNaseH_sf	Homologous_superfamily
IPR045246	Piwi_ago-like	Domain

Pfam: PF02170, PF02171, PF08699, PF16486, PF16487, PF16488

UniProt features (157 total): strand 47, helix 40, mutagenesis site 23, sequence variant 11, turn 9, region of interest 8, modified residue 7, sequence conflict 4, binding site 3, domain 2, chain 1, compositionally biased region 1, splice variant 1

Structure

Experimental structures (PDB)

showing 30 of 71 structures by resolution:

PDB	Title	Method	Resolution (Å)
9BF2	MID domain of Ago2 bound to UMP	X-RAY DIFFRACTION	1.59
4Z4D	Human Argonaute2 Bound to t1-G Target RNA	X-RAY DIFFRACTION	1.6
3LUC	Crystal structure of MID domain from hAGO2	X-RAY DIFFRACTION	1.69
3LUK	Crystal structure of MID domain from hAGO2	X-RAY DIFFRACTION	1.7
7C6B	Crystal structure of Ago2 MID domain in complex with 6-(3-(2-carboxyethyl)phenyl)purine …	X-RAY DIFFRACTION	1.7
9LSN	hAGO2-MID in complex with a chemical modified uridine monophosphate	X-RAY DIFFRACTION	1.75
9BF0	MID domain of human Argo2 bound to UTP	X-RAY DIFFRACTION	1.78
3LUJ	Crystal structure of MID domain from hAGO2 in complex with UMP	X-RAY DIFFRACTION	1.8
4Z4E	Human Argonaute2 Bound to t1-U Target RNA	X-RAY DIFFRACTION	1.8
9LMZ	hAGO2-MID in complex with a chemical modified uridine monophosphate	X-RAY DIFFRACTION	1.8
4W5O	The Crystal Structure of Human Argonaute2 Bound to a Guide and Target RNA Containing Seed …	X-RAY DIFFRACTION	1.8
3LUG	Crystal structure of MID domain from hAGO2 in complex with CMP	X-RAY DIFFRACTION	1.85
6RA4	Human ARGONAUTE-2 PAZ DOMAIN (214-347) IN COMPLEX WITH CGUGACUCU	X-RAY DIFFRACTION	1.9
9BEZ	MID domain of human Argo2 bound to RNA	X-RAY DIFFRACTION	1.9
9VLE	hAGO2-MID in complex with a chemical modified uridine monophosphate	X-RAY DIFFRACTION	1.99
3LUH	Crystal structure of MID domain from hAGO2 in complex with GMP	X-RAY DIFFRACTION	2
3QX9	Crystal structure of MID domain from hAGO2 in complex with ATP	X-RAY DIFFRACTION	2
7D7U	Crystal structure of Ago2 MID domain in complex with 8-Br-adenosin-5’-monophosphate	X-RAY DIFFRACTION	2
9OBD	Crystal structure of human Argonaute2 in complex with a fully modified siRNA with a …	X-RAY DIFFRACTION	2.02
9VLD	hAGO2-MID in complex with a chemical modified uridine monophosphate	X-RAY DIFFRACTION	2.05
9VLC	hAGO2-MID in complex with a chemical modified uridine monophosphate	X-RAY DIFFRACTION	2.09
3LUD	Crystal structure of MID domain from hAGO2 in complex with AMP	X-RAY DIFFRACTION	2.1
9LSO	hAGO2-MID in complex with a chemical modified uridine monophosphate	X-RAY DIFFRACTION	2.13
5KI6	Human Argonaute-2 bound to a guide RNA with a nucleobase modification at position 1	X-RAY DIFFRACTION	2.15
6CBD	Crystal Structure of Human Argonaute2 Bound to Three Tryptophans	X-RAY DIFFRACTION	2.2
4F3T	Human Argonaute-2 - miR-20a complex	X-RAY DIFFRACTION	2.25
3QX8	Crystal structure of MID domain from hAGO2 in complex with m7GpppG	X-RAY DIFFRACTION	2.3
4OLA	Crystal Structure of Human Argonaute2	X-RAY DIFFRACTION	2.3
9OBE	Crystal structure of human Argonaute2 in complex with a fully modified siRNA with a …	X-RAY DIFFRACTION	2.3
4Z4C	Human Argonaute2 Bound to t1-C Target RNA	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UKV8-F1	92.82	0.86

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Hydrolases, Predicted intracellular proteins, Plasma proteins, Disease related genes, Potential drug targets

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytoplasmic bodies; cytosol

Antibody reliability (HPA): IH approved · IF supported

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (3)

Position	Role
597	a divalent metal cation
669	a divalent metal cation
807	a divalent metal cation

Post-translational modifications (7)

Type	Positions
3’-nitrotyrosine	2
Phosphoserine	387, 824, 828, 831, 834
4-hydroxyproline	700

Mutagenesis-validated functional residues (23)

Position	Phenotype
140	no effect.
470	no effect on mirna-binding or target mrna cleavage. abrogates binding to the 7-methylguanosine cap of mrna and prevents inhibition of …
470	no effect on binding to the 7-methylguanosine cap of mrna or inhibition of translation.
505	no effect on mirna-binding or target mrna cleavage. abrogates binding to the 7-methylguanosine cap of mrna and prevents inhibition of …
505	no effect on binding to the 7-methylguanosine cap of mrna or inhibition of translation.
533	impairs rna cleavage.
545	impairs rna cleavage.
570	impairs rna cleavage.
597	abrogates rna cleavage but does not affect binding to sirna or translational repression.
633	no effect.
633	abrogates rna cleavage. binds sirna.
634	abrogates rna cleavage. binds sirna.
669	abrogates rna cleavage but does not affect binding to sirna.
673	impairs rna cleavage.
673	no effect on rna cleavage.
676	impairs rna cleavage.
676	abrogates rna cleavage.
682	no effect.
683	no effect on rna cleavage.
700	reduced protein stability.
704	no effect.
744	no effect.
807	abrogates rna cleavage.

Function

Pathways and Gene Ontology

Reactome pathways

21 curated (TAS) of 64; 5 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

showing 60 of 64 pathways:

ID	Pathway	Evidence
R-HSA-9725371	Nuclear events stimulated by ALK signaling in cancer ⚕	curated
R-HSA-4086398	Ca2+ pathway	curated
R-HSA-8948700	Competing endogenous RNAs (ceRNAs) regulate PTEN translation	curated
R-HSA-9018519	Estrogen-dependent gene expression	curated
R-HSA-5687128	MAPK6/MAPK4 signaling	curated
R-HSA-165159	MTOR signalling	curated
R-HSA-203927	MicroRNA (miRNA) biogenesis	curated
R-HSA-9029569	NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux	curated
R-HSA-426496	Post-transcriptional silencing by small RNAs	curated
R-HSA-1912408	Pre-NOTCH Transcription and Translation	curated
R-HSA-9764562	Regulation of CDH1 mRNA translation by microRNAs	curated
R-HSA-9824594	Regulation of MITF-M-dependent genes involved in apoptosis	curated
R-HSA-9768778	Regulation of NPAS4 mRNA translation	curated
R-HSA-9909620	Regulation of PD-L1(CD274) translation	curated
R-HSA-8943723	Regulation of PTEN mRNA translation	curated
R-HSA-8934593	Regulation of RUNX1 Expression and Activity	curated
R-HSA-426486	Small interfering RNA (siRNA) biogenesis	curated
R-HSA-9839394	TGFBR3 expression	curated
R-HSA-5628897	TP53 Regulates Metabolic Genes	curated
R-HSA-5578749	Transcriptional regulation by small RNAs	curated
R-HSA-9945556	Transcriptional regulation of multiciliogenesis	curated
R-HSA-1643685	Disease ⚕	—
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers ⚕	—
R-HSA-9725370	Signaling by ALK fusions and activated point mutants ⚕	—
R-HSA-9700206	Signaling by ALK in cancer ⚕	—
R-HSA-418990	Adherens junctions interactions	—
R-HSA-3858494	Beta-catenin independent WNT signaling	—
R-HSA-446728	Cell junction organization	—
R-HSA-1500931	Cell-Cell communication	—
R-HSA-421270	Cell-cell junction organization	—
R-HSA-1266738	Developmental Biology	—
R-HSA-8939211	ESR-mediated signaling	—
R-HSA-211000	Gene Silencing by RNA	—
R-HSA-74160	Gene expression (Transcription)	—
R-HSA-212436	Generic Transcription Pathway	—
R-HSA-9006925	Intracellular signaling by second messengers	—
R-HSA-9820841	M-decay: degradation of maternal mRNAs by maternally stored factors	electronic
R-HSA-5683057	MAPK family signaling cascades	—
R-HSA-9856651	MITF-M-dependent gene expression	—
R-HSA-9730414	MITF-M-regulated melanocyte development	—
R-HSA-9816359	Maternal to zygotic transition (MZT)	—
R-HSA-9024446	NR1H2 and NR1H3-mediated signaling	—
R-HSA-1257604	PIP3 activates AKT signaling	—
R-HSA-6807070	PTEN Regulation	—
R-HSA-1912422	Pre-NOTCH Expression and Processing	—
R-HSA-73857	RNA Polymerase II Transcription	—
R-HSA-9764265	Regulation of CDH1 Expression and Function	—
R-HSA-9759475	Regulation of CDH11 Expression and Function	—
R-HSA-9759811	Regulation of CDH11 mRNA translation by microRNAs	electronic
R-HSA-9764274	Regulation of Expression and Function of Type I Classical Cadherins	—
R-HSA-9764260	Regulation of Expression and Function of Type II Classical Cadherins	—
R-HSA-9759476	Regulation of Homotypic Cell-Cell Adhesion	—
R-HSA-9022692	Regulation of MECP2 expression and activity	electronic
R-HSA-9768759	Regulation of NPAS4 gene expression	—
R-HSA-162582	Signal Transduction	—
R-HSA-157118	Signaling by NOTCH	—
R-HSA-9006931	Signaling by Nuclear Receptors	—
R-HSA-9006936	Signaling by TGFB family members	—
R-HSA-9839373	Signaling by TGFBR3	—
R-HSA-195721	Signaling by WNT	—

MSigDB gene sets: 508 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, MODULE_97, REACTOME_SIGNALING_BY_NOTCH, GOBP_POSITIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, GOMF_ENDONUCLEASE_ACTIVITY, GOMF_RNA_NUCLEASE_ACTIVITY, WANG_CLIM2_TARGETS_UP, GOBP_P_BODY_ASSEMBLY, PAX4_01, DACOSTA_UV_RESPONSE_VIA_ERCC3_XPCS_DN, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GOMF_NUCLEASE_ACTIVITY, STEARMAN_LUNG_CANCER_EARLY_VS_LATE_DN

GO Biological Process (23): DNA-templated transcription (GO:0006351), translation (GO:0006412), regulatory ncRNA-mediated gene silencing (GO:0031047), pre-miRNA processing (GO:0031054), P-body assembly (GO:0033962), regulatory ncRNA-mediated post-transcriptional gene silencing (GO:0035194), miRNA processing (GO:0035196), miRNA-mediated gene silencing by inhibition of translation (GO:0035278), miRNA-mediated gene silencing by mRNA destabilization (GO:0035279), negative regulation of amyloid precursor protein biosynthetic process (GO:0042985), positive regulation of translation (GO:0045727), positive regulation of angiogenesis (GO:0045766), positive regulation of transcription by RNA polymerase II (GO:0045944), negative regulation of translational initiation (GO:0045947), positive regulation of nuclear-transcribed mRNA poly(A) tail shortening (GO:0060213), RISC complex assembly (GO:0070922), regulation of synapse maturation (GO:0090128), siRNA-mediated gene silencing by mRNA destabilization (GO:0090625), positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay (GO:1900153), positive regulation of trophoblast cell migration (GO:1901165), regulation of DNA-templated transcription (GO:0006355), translational initiation (GO:0006413), regulation of translation (GO:0006417)

GO Molecular Function (22): RNA 7-methylguanosine cap binding (GO:0000340), RNA polymerase II complex binding (GO:0000993), core promoter sequence-specific DNA binding (GO:0001046), RNA binding (GO:0003723), double-stranded RNA binding (GO:0003725), single-stranded RNA binding (GO:0003727), translation initiation factor activity (GO:0003743), RNA endonuclease activity (GO:0004521), siRNA binding (GO:0035197), miRNA binding (GO:0035198), mRNA 3’-UTR AU-rich region binding (GO:0035925), metal ion binding (GO:0046872), endoribonuclease activity, cleaving siRNA-paired mRNA (GO:0070551), endoribonuclease activity, cleaving miRNA-paired mRNA (GO:0090624), mRNA cap binding (GO:0098808), nucleic acid binding (GO:0003676), mRNA binding (GO:0003729), nuclease activity (GO:0004518), endonuclease activity (GO:0004519), protein binding (GO:0005515), hydrolase activity (GO:0016787), RNA endonuclease activity producing 5’-phosphomonoesters, hydrolytic mechanism (GO:0016891)

GO Cellular Component (14): P-body (GO:0000932), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), membrane (GO:0016020), RISC complex (GO:0016442), dendrite (GO:0030425), cytoplasmic ribonucleoprotein granule (GO:0036464), extracellular exosome (GO:0070062), RISC-loading complex (GO:0070578), postsynapse (GO:0098794), glutamatergic synapse (GO:0098978), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

17 top-level categories:

Category	Pathways
Gene Silencing by RNA	4
Signal Transduction	1
Pre-NOTCH Expression and Processing	1
Beta-catenin independent WNT signaling	1
Transcriptional Regulation by TP53	1
MAPK family signaling cascades	1
Transcriptional regulation by RUNX1	1
PTEN Regulation	1
Regulation of PTEN mRNA translation	1
Generic Transcription Pathway	1
ESR-mediated signaling	1
Transcriptional Regulation by MECP2	1
NR1H2 and NR1H3-mediated signaling	1
Signaling by ALK fusions and activated point mutants	1
Regulation of CDH11 Expression and Function	1
Regulation of CDH1 Expression and Function	1
Regulation of NPAS4 gene expression	1

GO top-level categories

showing 60 of 79 GO namespaces:

Category	Terms
cellular anatomical structure	5
translational initiation	3
RNA binding	3
regulatory ncRNA-mediated gene silencing	2
negative regulation of translation	2
miRNA-mediated post-transcriptional gene silencing	2
mRNA destabilization	2
positive regulation of mRNA catabolic process	2
RNA cap binding	2
regulatory RNA binding	2
RNA endonuclease activity producing 5’-phosphomonoesters, hydrolytic mechanism	2
binding	2
cytoplasm	2
synapse	2
gene expression	1
RNA biosynthetic process	1
peptidyltransferase activity	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
negative regulation of gene expression	1
miRNA processing	1
membraneless organelle assembly	1
post-transcriptional gene silencing	1
regulatory ncRNA processing	1
negative regulation of glycoprotein biosynthetic process	1
amyloid precursor protein biosynthetic process	1
regulation of amyloid precursor protein biosynthetic process	1
translation	1
regulation of translation	1
positive regulation of gene expression	1
positive regulation of protein metabolic process	1
angiogenesis	1
regulation of angiogenesis	1
positive regulation of vasculature development	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
regulation of translational initiation	1
nuclear-transcribed mRNA poly(A) tail shortening	1
regulation of nuclear-transcribed mRNA poly(A) tail shortening	1
protein-RNA complex assembly	1
regulation of developmental process	1
regulation of synapse organization	1
synapse maturation	1
siRNA-mediated post-transcriptional gene silencing	1
nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay	1
regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay	1
positive regulation of cell migration	1
positive regulation of developmental process	1
positive regulation of multicellular organismal process	1
trophoblast cell migration	1
regulation of trophoblast cell migration	1
positive regulation of reproductive process	1
RNA polymerase core enzyme binding	1
transcription cis-regulatory region binding	1
nucleic acid binding	1
translation factor activity	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 36 of 59 annotations. The rest are phylogenetic / computational / electronic (IEA).

36 experimentally-supported GO terms:

GO term	NS	Evidence
P-body assembly	BP	direct assay
RISC complex assembly	BP	direct assay
miRNA processing	BP	direct assay
miRNA-mediated gene silencing by inhibition of translation	BP	direct assay
miRNA-mediated gene silencing by mRNA destabilization	BP	direct assay
negative regulation of translational initiation	BP	direct assay
positive regulation of angiogenesis	BP	direct assay
positive regulation of transcription by RNA polymerase II	BP	mutant phenotype
positive regulation of translation	BP	direct assay
positive regulation of trophoblast cell migration	BP	mutant phenotype
pre-miRNA processing	BP	direct assay
regulation of synapse maturation	BP	direct assay
siRNA-mediated gene silencing by mRNA destabilization	BP	direct assay
P-body	CC	direct assay
RISC complex	CC	direct assay
RISC-loading complex	CC	direct assay
cytoplasm	CC	direct assay
cytoplasmic ribonucleoprotein granule	CC	direct assay
extracellular exosome	CC	direct assay
glutamatergic synapse	CC	direct assay
membrane	CC	high-throughput assay
nucleus	CC	direct assay
postsynapse	CC	direct assay
RNA 7-methylguanosine cap binding	MF	direct assay
RNA binding	MF	high-throughput assay
RNA endonuclease activity	MF	direct assay
RNA polymerase II complex binding	MF	direct assay
core promoter sequence-specific DNA binding	MF	mutant phenotype
double-stranded RNA binding	MF	direct assay
endoribonuclease activity, cleaving miRNA-paired mRNA	MF	direct assay
endoribonuclease activity, cleaving siRNA-paired mRNA	MF	direct assay
mRNA 3’-UTR AU-rich region binding	MF	direct assay
mRNA cap binding	MF	direct assay
miRNA binding	MF	direct assay
siRNA binding	MF	direct assay
single-stranded RNA binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 6,276 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AGO2	DICER1	Q9UPY3	976
AGO2	DROSHA	Q9NRR4	940
AGO2	TARBP2	Q15633	903
AGO2	GEMIN4	P57678	896
AGO2	TNRC6A	Q8NDV7	878
AGO2	DGCR8	Q8WYQ5	869
AGO2	DDX20	Q9UHI6	867
AGO2	MMUT	P22033	844
AGO2	XPO5	Q9HAV4	828
AGO2	TNRC6B	Q9UPQ9	809
AGO2	MOV10	Q9HCE1	787
AGO2	HENMT1	Q5T8I9	734
AGO2	TSN	Q15631	720
AGO2	IPO8	O15397	696
AGO2	MYC	P01106	693

IntAct

Human interaction partners of AGO2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 64 partners by confidence:

Partner	Interaction type	MIscore	Records
TNRC6A	association	0.960	16
DICER1	physical association	0.950	7
TNRC6B	physical association	0.930	15
TARBP2	physical association	0.930	7
DDX6	association	0.810	10
TNRC6C	physical association	0.780	4
AGO1	direct interaction	0.720	2
LIMD1	proximity	0.690	7
IPO8	physical association	0.690	3
EGFR	association	0.680	11
GNL3	physical association	0.640	2
PABPC1	association	0.640	2
ZMAT3	direct interaction	0.600	5
PLEKHA7	colocalization	0.570	4
DMWD	physical association	0.560	3
FGFR3	physical association	0.560	3
SPRED1	physical association	0.560	3
LRRK2	physical association	0.560	2
CNOT7	physical association	0.560	1
PRKRA	physical association	0.560	1
ADAR	association	0.530	3
FKBP5	association	0.530	1
EIF4EBP1	physical association	0.520	2
PRNP	association	0.500	3
RB1	physical association	0.500	3
MTDH	physical association	0.500	2
PTGES3	physical association	0.500	2
DHX58	physical association	0.500	1
FKBP4	physical association	0.500	1
RACK1	physical association	0.500	1

BioGRID (2,404 interactions; top human partners by supporting records in a sample of 600 records): TNRC6A (Affinity Capture-MS; 10 records), DICER1 (Affinity Capture-MS; 7 records), TNRC6B (Reconstituted Complex; 7 records), DDX20 (Affinity Capture-Western; 6 records), DDX6 (Affinity Capture-Western; 5 records), GEMIN4 (Affinity Capture-Western; 5 records), AGO1 (Proximity Label-MS; 4 records), DHX9 (Affinity Capture-Western; 4 records), MOV10 (Proximity Label-MS; 4 records), RNF31 (Affinity Capture-MS; 4 records), TNRC6C (Affinity Capture-Western; 4 records), CNOT1 (Affinity Capture-Western; 3 records), CNOT2 (Affinity Capture-Western; 3 records), CRBN (Affinity Capture-MS; 3 records), FKBP5 (Proximity Label-MS; 3 records)

SIGNOR signaling

showing 9 of 19 signaling interactions:

A	Effect	B	Mechanism
AGO2	“form complex”	RISC(DICER1/AGO2/TARBP2)	binding
AGO2	“form complex”	DICER1/hAgo2/PRKRA	binding
MAPKAPK2	up-regulates	AGO2	phosphorylation
AKT3	up-regulates	AGO2	phosphorylation
CSNK1A1	“down-regulates activity”	AGO2	phosphorylation
PPP6C	“up-regulates activity”	AGO2	dephosphorylation
PTPN1	“down-regulates activity”	AGO2	dephosphorylation
EGFR	“up-regulates activity”	AGO2	phosphorylation
TNRC6B	“up-regulates activity”	AGO2	binding

Protein complexes (CORUM) (7)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

7 complexes by size:

Complex	Subunits	Members
TRBP containing complex (DICER, TRBP, AGO2, RPL7A, EIF6, MOV10)	6	AGO2, DICER1, EIF6, MOV10, RPL7A, TARBP2
★ AGO2-DICER1-HSP90AB1-TARBP2 complex	4	AGO2, DICER1, HSP90AB1, TARBP2
RISC-loading complex	3	AGO2, DICER1, TARBP2
★ AGO2-KRAS complex	2	AGO2, KRAS
TTP-AGO2 complex	2	AGO2, ZFP36
AGO2-FXR1 complex	2	AGO2, FXR1
AGO2-PARN complex	2	AGO2, PARN

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 64 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Deadenylation of mRNA	8	67.6×	3e-11
Regulation of MITF-M-dependent genes involved in apoptosis	5	61.0×	8e-07
TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain	6	59.9×	4e-08
M-decay: degradation of maternal mRNAs by maternally stored factors	9	56.5×	9e-12
Oncogene Induced Senescence	5	32.3×	1e-05
MTOR signalling	5	25.5×	3e-05
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	5	18.6×	1e-04
MAPK6/MAPK4 signaling	5	13.1×	5e-04

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay	6	112.3×	1e-09
miRNA-mediated gene silencing by inhibition of translation	7	103.5×	2e-10
pre-miRNA processing	5	93.6×	1e-07
P-body assembly	5	87.8×	1e-07
nuclear-transcribed mRNA poly(A) tail shortening	6	80.2×	9e-09
regulatory ncRNA-mediated gene silencing	6	67.4×	2e-08
regulation of translation	6	21.9×	1e-05
negative regulation of translation	6	19.6×	3e-05

Disease & clinical

Genetic variants

Variant evidence for AGO2: 234 ClinVar records (17 pathogenic / likely pathogenic); 11 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

234 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	13
Uncertain significance	137
Likely benign	36
Benign	14

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 17 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
995791	NM_012154.5(AGO2):c.575T>C (p.Leu192Pro)	Pathogenic	criteria provided, single submitter	2
995795	NM_012154.5(AGO2):c.541TTC[1] (p.Phe182del)	Pathogenic	criteria provided, single submitter	2
1702822	NM_012154.5(AGO2):c.1444G>A (p.Gly482Ser)	Likely pathogenic	criteria provided, single submitter	1
1803264	NM_012154.5(AGO2):c.1619T>C (p.Leu540Pro)	Likely pathogenic	criteria provided, single submitter	1
1992346	NM_012154.5(AGO2):c.2389G>A (p.Val797Met)	Likely pathogenic	criteria provided, single submitter	1
2577022	NM_012154.5(AGO2):c.2479G>T (p.Gly827Ter)	Likely pathogenic	criteria provided, single submitter	1
2577829	NM_012154.5(AGO2):c.1093A>G (p.Ile365Val)	Likely pathogenic	criteria provided, single submitter	1
3064546	NM_012154.5(AGO2):c.1019C>A (p.Pro340His)	Likely pathogenic	criteria provided, single submitter	1
3595287	NM_012154.5(AGO2):c.1082_1090dup (p.Thr363_Met364insThrSerThr)	Likely pathogenic	criteria provided, single submitter	1
3602162	NM_012154.5(AGO2):c.1879G>A (p.Ala627Thr)	Likely pathogenic	criteria provided, single submitter	1
4278604	NM_012154.5(AGO2):c.1517G>A (p.Arg506Gln)	Likely pathogenic	criteria provided, single submitter	1
4852466	NM_012154.5(AGO2):c.589G>A (p.Glu197Lys)	Likely pathogenic	criteria provided, single submitter	1
4879427	NM_012154.5(AGO2):c.1080G>C (p.Gln360His)	Likely pathogenic	criteria provided, single submitter	1
4901677	NM_012154.5(AGO2):c.2201C>G (p.Thr734Arg)	Likely pathogenic	criteria provided, single submitter	1
4901680	NM_012154.5(AGO2):c.1092G>A (p.Met364Ile)	Likely pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore AGO2’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 35 predictions of 2,515):

Position(s)	Effect	Δscore	Sites
8:140532414–140532415	donor_loss	1.0000	4
8:140532616	acceptor_gain	1.0000
8:140532616–140532617	acceptor_loss	1.0000	4
8:140539318–140539319	donor_loss	1.0000	5
8:140539455–140539456	acceptor_loss	1.0000	5
8:140539461	acceptor_gain	1.0000
8:140541162–140541163	donor_loss	1.0000	4
8:140541176	donor_gain	1.0000
8:140541359–140541360	acceptor_loss	1.0000	5
8:140547466–140547467	donor_loss	1.0000	5

AlphaMissense

3,995 missense substitutions predicted likely pathogenic (of 5,668 scored), across 779 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M364	9	0.978	0.999
M856	9	0.952	0.997
M645	9	0.940	0.996
M437	9	0.933	0.996
M405	9	0.918	0.995
M213	9	0.906	0.998
M214	9	0.878	0.992
M483	9	0.838	0.996
D95	8	0.999	1.000
D218	8	0.999	1.000
H753	8	0.999	1.000
D597	8	0.998	0.999
D669	8	0.998	1.000
H711	8	0.998	1.000
N729	8	0.998	1.000
D163	8	0.997	0.999
H600	8	0.997	1.000
H712	8	0.997	1.000
N43	8	0.996	1.000
F224	8	0.996	1.000

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

4 prognostic cancer types:

Cancer	Prognostic	p-value
Pancreatic Adenocarcinoma (validation)	unfavorable	0.000148
Kidney Chromophobe (TCGA)	unfavorable	0.00025
Lung Squamous Cell Carcinoma (validation)	favorable	0.000807
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	0.000994

Disease associations

OMIM: gene MIM:606229 | disease phenotypes: MIM:619149, MIM:608996

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
Lessel-Kreienkamp syndrome	Definitive	Autosomal dominant	4

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

1 validity classifications:

Disease	Classification	Inheritance
Lessel-Kreienkamp syndrome	Definitive	AD

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (4 panels, 4 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

4 panels:

Panel	Rating
Hypotonic infant	green
Intellectual disability	green
Leukodystrophy, childhood onset	green
Paediatric disorders	green

Mondo (3): neurodevelopmental disorder (MONDO:0700092), Lessel-Kreienkamp syndrome (MONDO:0030897), premature ovarian failure 3 (MONDO:0012169)

HPO phenotypes

36 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000194	Open mouth
HP:0000219	Thin upper lip vermilion
HP:0000286	Epicanthus
HP:0000365	Hearing impairment
HP:0000396	Overfolded helix
HP:0000431	Wide nasal bridge
HP:0000486	Strabismus
HP:0000490	Deeply set eye
HP:0000505	Visual impairment
HP:0000582	Upslanted palpebral fissure
HP:0000689	Dental malocclusion
HP:0000718	Aggressive behavior
HP:0000729	Autistic behavior
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001270	Motor delay
HP:0001357	Plagiocephaly
HP:0001631	Atrial septal defect
HP:0001642	Pulmonic stenosis
HP:0001643	Patent ductus arteriosus
HP:0001647	Bicuspid aortic valve
HP:0001655	Patent foramen ovale
HP:0002007	Frontal bossing
HP:0002020	Gastroesophageal reflux
HP:0002793	Abnormal pattern of respiration
HP:0003593	Infantile onset
HP:0004209	Clinodactyly of the 5th finger
HP:0007018	Attention deficit hyperactivity disorder
HP:0008589	Hypoplastic helices
HP:0010537	Wide cranial sutures
HP:0010863	Receptive language delay
HP:0011968	Feeding difficulties
HP:0030799	Scaphocephaly

GWAS associations

11 associations:

Study	Trait	p-value
GCST90002390_544	Mean corpuscular hemoglobin	5e-24
GCST90002392_648	Mean corpuscular volume	4e-22
GCST90002397_304	Mean spheric corpuscular volume	5e-13
GCST007932_125	Medication use (thyroid preparations)	4e-11
GCST90002396_645	Mean reticulocyte volume	4e-10
GCST012442_1	Age-related hearing impairment	3e-9
GCST010796_2946	Electrocardiogram morphology (amplitude at temporal datapoints)	6e-9
GCST006940_46	Neurociticism	3e-8
GCST012332_65	Multisite chronic pain	3e-8
GCST90014023_19	Type 1 diabetes	3e-8
GCST001859_50	Thiazide-induced adverse metabolic effects in hypertensive patients	8e-6

EFO canonical traits (from GWAS)

6 canonical traits:

EFO ID	Trait name
EFO:0007660	neuroticism measurement
EFO:0009933	Thyroid preparation use measurement
EFO:0004327	electrocardiography
EFO:0010100	multisite chronic pain
EFO:0004527	mean corpuscular hemoglobin
EFO:0010701	mean reticulocyte volume

MeSH disease descriptors

2 disease descriptors:

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625
C563816	Premature Ovarian Failure 3 *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4680043 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 199,926 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

4 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL338802	SULFAGUANIDINE	4	4,993
CHEMBL21	SULFANILAMIDE	4	153,325
CHEMBL485696	SULFISOMIDINE	4	4,475
CHEMBL265502	SURAMIN	3	37,133

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

1 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs4961280		Other	Genotypes AA + AC is associated with decreased progression-free survival in people with Carcinoma, Renal Cell as compared to genotype CC.	PMID:34672687

Binding affinities (BindingDB)

6 measured of 8 human assays (9 total across all organisms); most potent 6 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL4439201	IC50	450 nM
5-(2-aminoethyl)benzene-1,2,4-triol;hydrobromide	IC50	1610 nM
CHEBI:32166	KD	4300 nM
CHEMBL3040216	IC50	11000 nM
CHEMBL1885327	KD	126000 nM
aromatic sulfonamide compound 5	IC50	145000 nM

ChEMBL bioactivities

4 potent at pChembl≥5 of 7 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.35	IC50	450	nM	CHEMBL4439201
6.16	IC50	690	nM	SURAMIN
5.79	IC50	1610	nM	OXIDOPAMINE HYDROCHLORIDE
5.37	Kd	4300	nM	SULFISOMIDINE

PubChem BioAssay actives

4 with measured affinity, of 21 total; 4 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
5-[(3-carboxy-4-hydroxyphenyl)-(3-carboxy-4-oxocyclohexa-2,5-dien-1-yl)methyl]-2-hydroxybenzoic acid	1930555: Inhibition of AGO2 (unknown origin)	ic50	0.4500	uM
8-[[4-methyl-3-[[3-[[3-[[2-methyl-5-[(4,6,8-trisulfonaphthalen-1-yl)carbamoyl]phenyl]carbamoyl]phenyl]carbamoylamino]benzoyl]amino]benzoyl]amino]naphthalene-1,3,5-trisulfonic acid	1930555: Inhibition of AGO2 (unknown origin)	ic50	0.6900	uM
5-(2-aminoethyl)benzene-1,2,4-triol;hydrochloride	1930555: Inhibition of AGO2 (unknown origin)	ic50	1.6100	uM
4-amino-N-(2,6-dimethylpyrimidin-4-yl)benzenesulfonamide	1682438: Binding affinity to human Argonaut protein 2 PAZ domain assessed as dissociation constant by using isothermal titration microcalorimetry	kd	4.3000	uM

CTD chemical–gene interactions

79 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects binding, increases reaction, increases abundance, increases expression, decreases reaction (+2 more)	6
Arsenic	increases abundance, affects methylation, increases expression	4
methylmercuric chloride	increases expression, affects cotreatment	3
bisphenol A	affects methylation, affects cotreatment, decreases expression	2
bisphenol S	decreases expression, decreases methylation, affects cotreatment	2
Arsenic Trioxide	affects binding, decreases reaction, decreases expression	2
Acetaminophen	affects binding, increases reaction, increases expression	2
Air Pollutants	decreases expression, increases abundance, affects expression, affects cotreatment	2
Cisplatin	affects cotreatment, decreases expression	2
Estradiol	increases expression	2
Ozone	affects cotreatment, decreases expression, increases abundance, affects expression	2
Tamoxifen	affects expression, affects cotreatment, decreases expression	2
Valproic Acid	decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cyclosporine	increases expression	2
Raloxifene Hydrochloride	affects expression, affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
FR900359	decreases phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
dicrotophos	increases expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
sodium arsenate	increases abundance, increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
zinc chloride	affects cotreatment, decreases expression	1
benzo(e)pyrene	decreases methylation	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	increases reaction, affects binding	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4677088	Binding	Binding affinity to human Argonaut protein 2 PAZ domain assessed as association constant by using isothermal titration microcalorimetry	Sulfonamide antibiotics inhibit RNAi by binding to human Argonaute protein 2 PAZ. — *Bioorg Med Chem Lett*

Cellosaurus cell lines

9 cell lines: 6 cancer cell line, 3 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A0DW	HeLa S3 AGO2KO	Cancer cell line	Female
CVCL_B8B3	Abcam HCT 116 AGO2 KO	Cancer cell line	Male
CVCL_B8S8	Abcam MCF-7 AGO2 KO	Cancer cell line	Female
CVCL_B9D5	Abcam A-549 AGO2 KO	Cancer cell line	Male
CVCL_D8YV	Ubigene HEK293 AGO2 KO	Transformed cell line	Female
CVCL_D9XD	Ubigene HeLa AGO2 KO	Cancer cell line	Female
CVCL_E1FM	Abcam HEK293 AGO2 KO	Transformed cell line	Female
CVCL_E8FP	HEK293T 3xFLAG-AGO2	Transformed cell line	Female
CVCL_KT32	HeLa SilenciX Argonaute 2	Cancer cell line	Female

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 212 trials:

NCT	Phase	Status	Title
NCT04586348	Phase 4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	Phase 4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	Phase 3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	Phase 3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	Phase 3	RECRUITING	Reducing Missed Appointments
NCT07377032	Phase 3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	Phase 2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	Phase 2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	Phase 2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	Phase 1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	Phase 1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	Phase 1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT03178695	Phase 1	COMPLETED	Inovium Ovarian Rejuvenation Trials
NCT01783041	Phase 2/3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	Phase 2/3	COMPLETED	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	Early Phase 1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	COMPLETED	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
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Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for AGO2 across ~30M SureChEMBL compounds — explore on Sugi Predict.