DICER1

Summary

DICER1 (dicer 1, ribonuclease III, HGNC:17098) is a protein-coding gene on chromosome 14q32.13, encoding Endoribonuclease Dicer (Q9UPY3). Double-stranded RNA (dsRNA) endoribonuclease playing a central role in short dsRNA-mediated post-transcriptional gene silencing. It is a selective cancer dependency (DepMap: 56.5% of cell lines) and haploinsufficient (ClinGen: sufficient evidence).

This gene encodes a protein possessing an RNA helicase motif containing a DEXH box in its amino terminus and an RNA motif in the carboxy terminus. The encoded protein functions as a ribonuclease and is required by the RNA interference and small temporal RNA (stRNA) pathways to produce the active small RNA component that represses gene expression. This protein also acts as a strong antiviral agent with activity against RNA viruses, including the Zika and SARS-CoV-2 viruses. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 23405 — RefSeq curated summary.

At a glance

• Gene–disease (curated): DICER1-related tumor predisposition (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 12
• Clinical variants (ClinVar): 7,690 total — 635 pathogenic, 146 likely-pathogenic
• Phenotypes (HPO): 46
• Druggable target: yes
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 4 cancer types
• Cancer dependency (DepMap): dependent in 56.5% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_177438

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17098
Approved symbol	DICER1
Name	dicer 1, ribonuclease III
Location	14q32.13
Locus type	gene with protein product
Status	Approved
Aliases	Dicer, KIAA0928, K12H4.8-LIKE, HERNA
Ensembl gene	ENSG00000100697
Ensembl biotype	protein_coding
OMIM	606241
Entrez	23405

Gene structure

Transcript identifiers

Ensembl transcripts: 40 — 19 protein_coding, 12 retained_intron, 7 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000343455, ENST00000393063, ENST00000526495, ENST00000527414, ENST00000527416, ENST00000527554, ENST00000529206, ENST00000529720, ENST00000531162, ENST00000532939, ENST00000541352, ENST00000556045, ENST00000556681, ENST00000674628, ENST00000675540, ENST00000675995, ENST00000696733, ENST00000696734, ENST00000696735, ENST00000696736, ENST00000696737, ENST00000696738, ENST00000696739, ENST00000696740, ENST00000696920, ENST00000696921, ENST00000696922, ENST00000696923, ENST00000696924, ENST00000696925, ENST00000696926, ENST00000696927, ENST00000696928, ENST00000860615, ENST00000860616, ENST00000860617, ENST00000860618, ENST00000860619, ENST00000860620, ENST00000924636

RefSeq mRNA: 26 — MANE Select: NM_177438 NM_001195573, NM_001271282, NM_001291628, NM_001395677, NM_001395678, NM_001395679, NM_001395680, NM_001395682, NM_001395683, NM_001395684, NM_001395686, NM_001395687, NM_001395688, NM_001395689, NM_001395690, NM_001395691, NM_001395692, NM_001395693, NM_001395694, NM_001395695, NM_001395696, NM_001395697, NM_001395698, NM_001395700, NM_030621, NM_177438

CCDS: CCDS55941, CCDS91926, CCDS9931

Canonical transcript exons

ENST00000343455 — 27 exons

Exon	Start	End
ENSE00002182304	95132515	95132677
ENSE00003487149	95133315	95133503
ENSE00003899455	95157230	95157529
ENSE00003967956	95117622	95117754
ENSE00003967957	95108324	95108503
ENSE00003967958	95095825	95096713
ENSE00003967959	95107608	95107761
ENSE00003967960	95131509	95131639
ENSE00003967961	95115667	95115821
ENSE00003967962	95086228	95090663
ENSE00003967963	95129472	95129632
ENSE00003967964	95111317	95111456
ENSE00003967965	95103346	95104126
ENSE00003967966	95124196	95124668
ENSE00003967967	95105678	95105783
ENSE00003967968	95116453	95116695
ENSE00003967969	95093888	95094156
ENSE00003967970	95105071	95105246
ENSE00003967971	95112172	95112247
ENSE00003967972	95106041	95106223
ENSE00003967973	95099780	95099935
ENSE00003967974	95091034	95091109
ENSE00003967975	95091203	95091365
ENSE00003967976	95126580	95126748
ENSE00003967977	95130058	95130192
ENSE00003967978	95113092	95113224
ENSE00003967979	95107880	95108093

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.47.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.8724 / max 443.6932, expressed in 1794 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
144767	14.3128	1724
144770	6.1046	1567
144768	3.2279	1371
144769	1.6959	740
144766	0.1721	20
144763	0.1506	6
144771	0.1284	48
144762	0.0800	17

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cauda epididymis	UBERON:0004360	99.47	gold quality
caput epididymis	UBERON:0004358	99.40	gold quality
tongue squamous epithelium	UBERON:0006919	99.37	gold quality
cranial nerve II	UBERON:0000941	99.29	gold quality
trabecular bone tissue	UBERON:0002483	99.28	gold quality
corpus epididymis	UBERON:0004359	99.27	gold quality
mucosa of paranasal sinus	UBERON:0005030	99.05	gold quality
visceral pleura	UBERON:0002401	99.02	gold quality
oral cavity	UBERON:0000167	98.90	gold quality
parietal pleura	UBERON:0002400	98.83	gold quality
inferior vagus X ganglion	UBERON:0005363	98.81	gold quality
nipple	UBERON:0002030	98.76	gold quality
corpus callosum	UBERON:0002336	98.74	gold quality
pigmented layer of retina	UBERON:0001782	98.67	gold quality
pylorus	UBERON:0001166	98.58	gold quality
pleura	UBERON:0000977	98.53	gold quality
superficial temporal artery	UBERON:0001614	98.44	gold quality
subthalamic nucleus	UBERON:0001906	98.43	gold quality
pancreatic ductal cell	CL:0002079	98.41	gold quality
epithelium of nasopharynx	UBERON:0001951	98.41	gold quality
renal medulla	UBERON:0000362	98.36	gold quality
mammary duct	UBERON:0001765	98.35	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	98.32	gold quality
substantia nigra pars reticulata	UBERON:0001966	98.27	gold quality
pharyngeal mucosa	UBERON:0000355	98.25	gold quality
superior surface of tongue	UBERON:0007371	98.25	gold quality
trigeminal ganglion	UBERON:0001675	98.19	gold quality
cardia of stomach	UBERON:0001162	98.16	gold quality
lateral globus pallidus	UBERON:0002476	98.12	gold quality
epithelium of mammary gland	UBERON:0003244	98.11	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	12.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
EFNA3	Repression
TLR2	Repression

Upstream regulators (CollecTRI, top): GATA1, MITF, PAX6, RELA, SOX4

miRNA regulators (miRDB)

227 targeting DICER1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-126-5P	100.00	72.71	3180
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-520D-5P	99.98	73.34	4883

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 56.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• cloning and expression of the 218 kDa human Dicer, and characterization of its ribonuclease activity and dsRNA-binding properties (PMID:12411504)
• purification and properties of a recombinant human Dicer (PMID:12411505)
• fragile X syndrome CGG repeats readily form RNA hairpins and is digested by the human Dicer enzyme, a step central to the RNA interference effect on gene expression (PMID:14576312)
• Dicer has a single RNA post-transcriptional processing center (PMID:15242644)
• Dicer is essential for formation of the heterochromatin structure in vertebrate cells. (PMID:15247924)
• various attributes of the 3’ end structure, including overhang length and sequence composition, play a primary role in determining the position of Dicer cleavage in both dsRNA and unimolecular, short hairpin RNA (PMID:15811921)
• RNA containing the AU-rich element of GM-CSF is destabilized by dicer and positive charge of proteins (PMID:16380083)
• The C-terminal RNase III domain (RNase IIIb) of human Dicer was expressed, purified and crystallized by the sitting-drop vapour-diffusion method (PMID:16582496)
• Dicer up-regulation may explain an almost global increase of microRNA expression in prostate adenocarcinoma. (PMID:17071602)
• Up-regulation of TSSC3 occurred in Dicer knockdown cells. (PMID:17303335)
• Transcripts containing long hairpin structures composed of CNG repeats are another class of Dicer targets. (PMID:17317629)
• Overexpression of Dicer correlates with precancerous conditions for Lung adenocarcinoma. (PMID:17332367)
• These results suggest that, in the context of HIV replication, TRBP contributes mainly to the enhancement of virus production and that Dicer does not mediate HIV restriction by RNAi. (PMID:17360756)
• Maintenance and regulation of endogenous microRNA levels via Dicer-mediated processing is critical for endothelial cell gene expression and functions in vitro. (PMID:17379831)
• Results indicate that human TRBP and PACT directly interact with each other and associate with Dicer to stimulate the cleavage of double-stranded or short hairpin RNA to siRNA. (PMID:17452327)
• a unique amino acid sequence in human DICER protein is essential for binding to Argonaute family proteins (PMID:17482383)
• Results show that recombinant Dicer is capable of cleaving the TAR element in vitro and that TAR derived miRNA is present in HIV-1 infected cell lines and primary T-cell blasts. (PMID:17663774)
• a role for the PAZ domain of Dicer in binding ssRNAs. (PMID:18023283)
• DICER1 may play an important role in the development of cancer and the epigenetical regulation involved. (PMID:18167183)
• Ago2, Dicer, and TRBP comprise the RISC-loading complex (RLC) and assembles spontaneously in vitro from purified components (PMID:18178619)
• Abnormal immunoexpression of Dicer in aggressive mucoepidermoid carcinoma suggests a role for microRNA and microRNA machinery in tumor progression. (PMID:18239938)
• the role of Dicer, one of the central proteins of the miRNA processing machinery during apoptosis, and show that down-regulation of Dicer results in accelerated apoptosis of HeLa cells, triggered by TNFalpha (tumour necrosis factor alpha). (PMID:18289125)
• Our results suggest that HCV core protein may abrogate host cell RNA silencing defense by suppressing the ability of Dicer to process precursor dsRNAs into siRNAs. (PMID:18325616)
• Intact DICER is required to maintain full promoter DNA hypermethylation of select epigenetically silenced loci in human cancer cells. (PMID:18413723)
• These results suggest that the DExD/H-box domain likely disrupts the functionality of the Dicer active site until a structural rearrangement occurs, perhaps upon assembly with its molecular partners. (PMID:18508075)
• Chemical modifications patterns compatible with high potency dicer-substrate small interfering RNAs are reported. (PMID:18637735)
• Up-regulation of MICA and MICB is the result of DNA damage response activation caused by Dicer knockdown. RNAi is indirectly linked to the human innate immune system via the DNA damage pathway. (PMID:18644891)
• luciferase assay using a reporter carrying a putative target site in the 3’ untranslated region of Dicer revealed that let-7 directly affects Dicer expression (PMID:18700235)
• Evidence that a Dicer helicase mutant is sensitive to the thermodynamic properties of the stems in microRNAs and short-hairpin RNAs, with thermodynamically unstable stems resulting in poor processing and a reduction in the levels of functional mi/siRNAs. (PMID:18927112)
• Downregulation of Dicer expression by serum withdrawal sensitizes human endothelial cells to apoptosis. (PMID:18978195)
• Dicer cleaved substrates containing short siRNA-like double-strand regions and extended 3’ or 5’ ssRNA overhangs in the adjacent ssRNA regions (PMID:19017633)
• Data delineated the smallest 5-lipoxygenase binding domain (5LObd) of Dicer to its C-terminal 140 amino acids comprising the double-stranded RNA (dsRNA) binding domain (dsRBD). (PMID:19022417)
• knockdown of Dicer inhibits human breast carcinoma cell growth (PMID:19082437)
• Our findings indicate that levels of Dicer and Drosha mRNA in ovarian-cancer cells have associations with outcomes in patients with ovarian cancer. (PMID:19092150)
• Dicer is a stress response component and interferons are potentially important regulators of Dicer expression. (PMID:19118902)
• Data demonstrated a direct interaction between Dicer and Wig-1 and both may play a common role in dsRNA-related gene regulation. (PMID:19127773)
• Phosphorylation of FMRP regulates its association with the miRNA pathway by modulating association with Dicer. (PMID:19155329)
• Dicer 1 gene is expressed in differentiating and terminally differentiated N-type cells. (PMID:19393748)
• Binding of Dicer to TRBPs is critical for RNAi function. (PMID:19422693)
• Results show that Dicer is responsible for the generation of the mature miR-222 and -339, which suppress ICAM-1 expression on tumor cells. (PMID:19520829)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	dicer1	ENSDARG00000001129
mus_musculus	Dicer1	ENSMUSG00000041415
rattus_norvegicus	Dicer1	ENSRNOG00000010711
drosophila_melanogaster	Dcr-1	FBGN0039016
caenorhabditis_elegans		WBGENE00000939

Protein

Protein identifiers

Endoribonuclease Dicer — Q9UPY3 (reviewed: Q9UPY3)

Alternative names: Helicase with RNase motif

All UniProt accessions (12): Q9UPY3, A0A6Q8PFV4, A0A6Q8PH99, A0A6Q8PHG6, A0A7I2YBM0, A0A8Q3SJI0, A0A8Q3WLH6, A0A8Q3WLH8, A0A8Q3WLJ5, F6SZ09, H0YJZ6, Q5D0K5

UniProt curated annotations — full annotation on UniProt →

Function. Double-stranded RNA (dsRNA) endoribonuclease playing a central role in short dsRNA-mediated post-transcriptional gene silencing. Cleaves naturally occurring long dsRNAs and short hairpin pre-microRNAs (miRNA) into fragments of twenty-one to twenty-three nucleotides with 3’ overhang of two nucleotides, producing respectively short interfering RNAs (siRNA) and mature microRNAs. SiRNAs and miRNAs serve as guide to direct the RNA-induced silencing complex (RISC) to complementary RNAs to degrade them or prevent their translation. Gene silencing mediated by siRNAs, also called RNA interference, controls the elimination of transcripts from mobile and repetitive DNA elements of the genome but also the degradation of exogenous RNA of viral origin for instance. The miRNA pathway on the other side is a mean to specifically regulate the expression of target genes.

Subunit / interactions. Component of the RISC loading complex (RLC), or micro-RNA (miRNA) loading complex (miRLC), which is composed of DICER1, AGO2 and TARBP2; DICER1 and TARBP2 are required to process precursor miRNAs (pre-miRNAs) to mature miRNAs and then load them onto AGO2. Note that the trimeric RLC/miRLC is also referred to as RISC. Interacts with DHX9, AGO1, PIWIL1 and PRKRA. Associates with the 60S ribosome. Interacts with BCDIN3D. Interacts with AGO2, TARBP2, EIF6, MOV10 and RPL7A (60S ribosome subunit); they form a large RNA-induced silencing complex (RISC). Interacts (via Dicer dsRNA-binding fold domain) with ALOX5 (via PLAT domain); this interaction enhances arachidonate 5-lipoxygenase activity and modifies the miRNA precursor processing activity of DICER1. (Microbial infection) Interacts with ebolavirus transcriptional activator VP30; this interaction prevents TARBP2/TRBP binding to DICER1 and thus allows the virus to counteract host RNA silencing. (Microbial infection) Interacts with ebolavirus transcriptional activator VP35; this interaction prevents TARBP2/TRBP binding to DICER1 and thus allows the virus to counteract host RNA silencing.

Subcellular location. Cytoplasm. Perinuclear region.

Disease relevance. Pleuropulmonary blastoma (PPB) [MIM:601200] A rare pediatric intrathoracic neoplasm. The tumor arises from the lung, pleura, or both, and appears to be purely mesenchymal in phenotype. It lacks malignant epithelial elements, a feature that distinguishes it from the classic adult-type pulmonary blastoma. It arises during fetal lung development and is often part of an inherited cancer syndrome. The tumor contain both epithelial and mesenchymal cells. Early in tumorigenesis, cysts form in lung airspaces, and these cysts are lined with benign-appearing epithelium. Mesenchymal cells susceptible to malignant transformation reside within the cyst walls and form a dense layer beneath the epithelial lining. In a subset of patients, overgrowth of the mesenchymal cells produces a sarcoma, a transition that is associated with a poorer prognosis. Some patients have multilocular cystic nephroma, a benign kidney tumor. The disease is caused by variants affecting the gene represented in this entry. Goiter multinodular 1, with or without Sertoli-Leydig cell tumors (MNG1) [MIM:138800] A common disorder characterized by nodular overgrowth of the thyroid gland. Some individuals may also develop Sertoli-Leydig cell tumors, usually of the ovary. The disease is caused by variants affecting the gene represented in this entry. Rhabdomyosarcoma, embryonal, 2 (RMSE2) [MIM:180295] A form of rhabdomyosarcoma, a highly malignant tumor of striated muscle derived from primitive mesenchymal cells and exhibiting differentiation along rhabdomyoblastic lines. Rhabdomyosarcoma is one of the most frequently occurring soft tissue sarcomas and the most common in children. It occurs in four forms: alveolar, pleomorphic, embryonal and botryoidal rhabdomyosarcomas. The disease is caused by variants affecting the gene represented in this entry. Global developmental delay, lung cysts, overgrowth, and Wilms tumor (GLOW) [MIM:618272] A disease characterized by the association of congenital nephromegaly, bilateral Wilms tumor, somatic overgrowth, developmental delay, macrocephaly, and bilateral lung cysts. The disease is caused by variants affecting the gene represented in this entry. DICER1 mutations have been found in uterine cervix embryonal rhabdomyosarcoma, primitive neuroectodermal tumor, Wilms tumor, pulmonary sequestration and juvenile intestinal polyp. Somatic missense mutations affecting the RNase IIIb domain of DICER1 are common in non-epithelial ovarian tumors. These mutations do not abolish DICER1 function but alter it in specific cell types, a novel mechanism through which perturbation of microRNA processing may be oncogenic.

Cofactor. Binds 2 magnesium or manganese ions per subunit.

Similarity. Belongs to the helicase family. Dicer subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9UPY3-1	1	yes
Q9UPY3-2	2, t-Dicer
Q9UPY3-3	3

RefSeq proteins (25): NP_001182502, NP_001258211, NP_001278557, NP_001382606, NP_001382607, NP_001382608, NP_001382609, NP_001382611, NP_001382612, NP_001382613, NP_001382615, NP_001382616, NP_001382617, NP_001382618, NP_001382619, NP_001382620, NP_001382621, NP_001382622, NP_001382623, NP_001382624, NP_001382625, NP_001382626, NP_001382629, NP_085124, NP_803187* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000999	RNase_III_dom	Domain
IPR001650	Helicase_C-like	Domain
IPR003100	PAZ_dom	Domain
IPR005034	Dicer_dimerisation	Domain
IPR011545	DEAD/DEAH_box_helicase_dom	Domain
IPR014001	Helicase_ATP-bd	Domain
IPR014720	dsRBD_dom	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR036085	PAZ_dom_sf	Homologous_superfamily
IPR036389	RNase_III_sf	Homologous_superfamily
IPR038248	Dicer_dimer_sf	Homologous_superfamily
IPR044441	DICER_DSRM	Domain
IPR048512	Dicer_platform	Domain
IPR048513	Dicer_PBD	Domain

Pfam: PF00270, PF00271, PF00636, PF02170, PF03368, PF20930, PF20931, PF20932

Enzyme classification (BRENDA):

• EC 3.1.26.3 — ribonuclease III (BRENDA: 65 organisms, 299 substrates, 50 inhibitors, 32 Km, 23 kcat entries)

Substrate kinetics (BRENDA)

6 substrates with measured Km, best-characterized 6. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
R1.1 RNA	—	15
RNA	0.0003–0.34	4
515 BP DSRNA	—	3
AA-[16S[MICRO-HP]RNA]	0.001	1
MN2+	38	1
POLY(IC)	0.4	1

UniProt features (134 total): helix 36, strand 25, sequence variant 17, mutagenesis site 12, sequence conflict 9, modified residue 8, domain 7, binding site 7, turn 4, splice variant 3, region of interest 2, chain 1, short sequence motif 1, compositionally biased region 1, site 1

Structure

Experimental structures (PDB)

21 structures.

PDB	Method	Resolution (Å)
4NGD	X-RAY DIFFRACTION	1.96
2EB1	X-RAY DIFFRACTION	2
4NGC	X-RAY DIFFRACTION	2.1
4NGB	X-RAY DIFFRACTION	2.25
4NH5	X-RAY DIFFRACTION	2.55
4NH6	X-RAY DIFFRACTION	2.55
4NGG	X-RAY DIFFRACTION	2.6
4NH3	X-RAY DIFFRACTION	2.62
21CB	ELECTRON MICROSCOPY	3
7XW2	ELECTRON MICROSCOPY	3.04
4NGF	X-RAY DIFFRACTION	3.1
4WYQ	X-RAY DIFFRACTION	3.2
21CN	ELECTRON MICROSCOPY	3.21
21CQ	ELECTRON MICROSCOPY	3.29
9V43	ELECTRON MICROSCOPY	3.34
9V42	ELECTRON MICROSCOPY	3.37
4NHA	X-RAY DIFFRACTION	3.4
7XW3	ELECTRON MICROSCOPY	4.04
5ZAK	ELECTRON MICROSCOPY	4.4
5ZAL	ELECTRON MICROSCOPY	4.7
5ZAM	ELECTRON MICROSCOPY	5.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UPY3-F1	67.89	0.17

Functional residue map

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

Catalytic / active sites (1): 1806 (important for activity)

Ligand- & substrate-binding residues (7): 64–71; 1316; 1395; 1398; 1705; 1810; 1813

Post-translational modifications (8): 413, 415, 1016, 1160, 1460, 1468, 1470, 1868

Mutagenesis-validated functional residues (12):

Position	Phenotype
960	2-fold decrease in activity.
971	10-fold decrease in activity; when associated with y-972.
972	10-fold decrease in activity; when associated with y-971.
1036	5-fold decrease in activity.
1313	no effect on activity.
1320	decreased activity. loss of activity; when associated with d-1709.
1340	no effect on activity.
1444	decreased activity. loss of activity; when associated with e-1813.
1702	no effect on activity.
1709	decreased activity. loss of activity; when associated with d-1320.
1729	no effect on activity.
1813	decreased activity. loss of activity; when associated with e-1444.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-203927	MicroRNA (miRNA) biogenesis
R-HSA-426486	Small interfering RNA (siRNA) biogenesis
R-HSA-9708296	tRNA-derived small RNA (tsRNA or tRNA-related fragment, tRF) biogenesis
R-HSA-9820841	M-decay: degradation of maternal mRNAs by maternally stored factors
R-HSA-9824594	Regulation of MITF-M-dependent genes involved in apoptosis

MSigDB gene sets: 546 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, GOMF_ENDONUCLEASE_ACTIVITY, ACTACCT_MIR196A_MIR196B, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOMF_RNA_NUCLEASE_ACTIVITY, TAATAAT_MIR126, GOBP_RESPONSE_TO_PEPTIDE, GOBP_NEGATIVE_REGULATION_OF_GLIOGENESIS, GOMF_NUCLEASE_ACTIVITY, ATACCTC_MIR202, GOBP_TRNA_METABOLIC_PROCESS, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, GOBP_POSITIVE_REGULATION_OF_GLIAL_CELL_DIFFERENTIATION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_GLIAL_CELL_DEVELOPMENT

GO Biological Process (22): negative regulation of transcription by RNA polymerase II (GO:0000122), apoptotic DNA fragmentation (GO:0006309), miRNA metabolic process (GO:0010586), negative regulation of Schwann cell proliferation (GO:0010626), negative regulation of gene expression (GO:0010629), negative regulation of tumor necrosis factor-mediated signaling pathway (GO:0010804), positive regulation of Schwann cell differentiation (GO:0014040), tRNA decay (GO:0016078), nerve development (GO:0021675), siRNA processing (GO:0030422), pre-miRNA processing (GO:0031054), positive regulation of myelination (GO:0031643), peripheral nervous system myelin formation (GO:0032290), negative regulation of tumor necrosis factor production (GO:0032720), miRNA processing (GO:0035196), neuron projection morphogenesis (GO:0048812), RISC complex assembly (GO:0070922), global gene silencing by mRNA cleavage (GO:0098795), RNA processing (GO:0006396), post-transcriptional gene silencing (GO:0016441), regulatory ncRNA-mediated gene silencing (GO:0031047), regulation of multicellular organismal process (GO:0051239)

GO Molecular Function (20): RNA binding (GO:0003723), double-stranded RNA binding (GO:0003725), helicase activity (GO:0004386), RNA endonuclease activity (GO:0004521), ribonuclease III activity (GO:0004525), deoxyribonuclease I activity (GO:0004530), ATP binding (GO:0005524), protein domain specific binding (GO:0019904), siRNA binding (GO:0035197), metal ion binding (GO:0046872), pre-miRNA binding (GO:0070883), nucleotide binding (GO:0000166), nucleic acid binding (GO:0003676), DNA binding (GO:0003677), 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), regulatory RNA binding (GO:0061980)

GO Cellular Component (7): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), RISC complex (GO:0016442), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), RISC-loading complex (GO:0070578)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Gene Silencing by RNA	3
Maternal to zygotic transition (MZT)	1
MITF-M-dependent gene expression	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA binding	3
cellular anatomical structure	3
gene expression	2
regulatory ncRNA processing	2
nucleic acid binding	2
catalytic activity, acting on a nucleic acid	2
binding	2
cytoplasm	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
DNA catabolic process	1
apoptotic nuclear changes	1
RNA metabolic process	1
regulation of Schwann cell proliferation	1
Schwann cell proliferation	1
negative regulation of glial cell proliferation	1
regulation of gene expression	1
negative regulation of macromolecule biosynthetic process	1
negative regulation of cytokine-mediated signaling pathway	1
regulation of tumor necrosis factor-mediated signaling pathway	1
tumor necrosis factor-mediated signaling pathway	1
Schwann cell differentiation	1
regulation of Schwann cell differentiation	1
positive regulation of glial cell differentiation	1
tRNA metabolic process	1
RNA catabolic process	1
nervous system development	1
anatomical structure development	1
miRNA processing	1
regulation of myelination	1
positive regulation of nervous system process	1
myelination	1
positive regulation of cellular process	1
myelination in peripheral nervous system	1
myelin assembly	1
tumor necrosis factor production	1
regulation of tumor necrosis factor production	1
negative regulation of tumor necrosis factor superfamily cytokine production	1
neuron projection development	1

Protein interactions and networks

STRING

7728 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DICER1	AGO2	Q9UKV8	999
DICER1	TARBP2	Q15633	999
DICER1	AGO1	Q9UL18	999
DICER1	PRKRA	O75569	994
DICER1	RBM8A	Q9Y5S9	994
DICER1	ADAR	P55265	991
DICER1	MOV10	Q9HCE1	991
DICER1	TNRC6A	Q8NDV7	989
DICER1	FMR1	Q06787	988
DICER1	TARDBP	Q13148	977
DICER1	DROSHA	Q9NRR4	973
DICER1	DGCR8	Q8WYQ5	972
DICER1	KHSRP	Q92945	959
DICER1	ERI1	Q8IV48	955
DICER1	XPO5	Q9HAV4	955

IntAct

256 interactions, top by confidence:

A	B	Type	Score
DICER1	TARBP2	psi-mi:“MI:0915”(physical association)	0.960
DICER1	AGO2	psi-mi:“MI:0915”(physical association)	0.950
MED29	MED19	psi-mi:“MI:0914”(association)	0.890
AGO1	DICER1	psi-mi:“MI:0915”(physical association)	0.830
DICER1	PRKRA	psi-mi:“MI:0407”(direct interaction)	0.800
DICER1	PRKRA	psi-mi:“MI:0914”(association)	0.800
MED9	MED19	psi-mi:“MI:0914”(association)	0.790
PLEKHA7	CTNND1	psi-mi:“MI:0914”(association)	0.640
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
Sh2d5	BCR	psi-mi:“MI:0914”(association)	0.580
PLEKHA7	AGO2	psi-mi:“MI:0914”(association)	0.570
PLK1	C1orf226	psi-mi:“MI:0914”(association)	0.560
	TARBP2	psi-mi:“MI:0915”(physical association)	0.540
	PRKRA	psi-mi:“MI:0915”(physical association)	0.540
DICER1		psi-mi:“MI:0915”(physical association)	0.540
DICER1		psi-mi:“MI:0902”(rna cleavage)	0.540

BioGRID (284): DICER1 (Affinity Capture-MS), DICER1 (Affinity Capture-MS), DICER1 (Affinity Capture-MS), DICER1 (Affinity Capture-MS), DICER1 (Affinity Capture-MS), DICER1 (Affinity Capture-MS), DICER1 (Affinity Capture-MS), DICER1 (Affinity Capture-MS), DICER1 (Affinity Capture-MS), DICER1 (Affinity Capture-MS), DICER1 (Affinity Capture-MS), DICER1 (Affinity Capture-MS), DICER1 (Co-fractionation), DICER1 (Affinity Capture-MS), DICER1 (Proximity Label-MS)

ESM2 similar proteins: A0A8J1LLF7, A0A974H8H3, A0MQH0, A4FUD6, A5HK05, B3DLA6, P11029, P11497, P42694, P54198, Q13085, Q25BN1, Q28559, Q4R4U1, Q504Q3, Q5R5F8, Q5R660, Q5R8I6, Q5RCC1, Q5SWU9, Q5ZIT8, Q6DFV5, Q6IE70, Q6NYU2, Q6P1X5, Q6TUI4, Q6TV19, Q80YV4, Q8BGF7, Q8BHL5, Q8BPU7, Q8C176, Q8CIQ7, Q8IZD9, Q8K0F1, Q8R418, Q8R5L3, Q8VHE0, Q923S8, Q92556

Diamond homologs: A0A1D5PRR9, A1CS00, A1D4V5, A2Q8R2, A3GH78, A3LP87, A4RGD1, A4RN08, A5AA68, A5DKW3, A5E0U9, A6M931, A6RIS1, A6SFV4, A6ZVS0, A7A0P8, A7E436, A7EFH4, A7TSV4, B0XMV6, B5DG42, B5FZY7, B7ZTW1, E7F8F4, I3XHK1, O42226, P0C2N8, P0CQ98, P0CQ99, P0CR00, P0CR01, P0CR02, P0CR03, P32892, P34689, P37954, P38919, P40562, P42305, P84634

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
DICER1	“form complex”	RISC(DICER1/AGO2/TARBP2)	binding
TARBP2	up-regulates	DICER1	binding
DICER1	“form complex”	DICER1/hAgo2/PRKRA	binding
SOX4	“up-regulates quantity”	DICER1	“transcriptional regulation”
TARDBP	“up-regulates quantity”	DICER1	“post transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 206 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
MicroRNA (miRNA) biogenesis	7	22.8×	6e-07
MTOR signalling	6	11.4×	3e-04
Transcriptional Regulation by MECP2	5	11.3×	1e-03
Peptide chain elongation	12	10.9×	1e-07
Viral mRNA Translation	12	10.9×	1e-07
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	12	10.8×	1e-07
Beta-catenin independent WNT signaling	5	10.5×	2e-03
Formation of a pool of free 40S subunits	13	10.4×	1e-07

GO biological processes:

GO term	Partners	Fold	FDR
pre-miRNA processing	8	49.4×	6e-10
miRNA processing	6	34.7×	3e-06
miRNA-mediated gene silencing by inhibition of translation	5	24.4×	3e-04
cytoplasmic translation	14	14.2×	6e-10
negative regulation of translation	10	10.8×	6e-06
translation	14	7.9×	9e-07

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 4 cancer types — COADREAD, CSCC, MEL, UCEC.

Clinical variants and AI predictions

ClinVar

7690 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	635
Likely pathogenic	146
Uncertain significance	3845
Likely benign	2453
Benign	116

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1065544	NM_177438.2:c.(734+1_735-1)_(2256+1_2257-1)dup	Pathogenic
1068739	NM_177438.3(DICER1):c.948G>A (p.Trp316Ter)	Pathogenic
1068814	NM_177438.3(DICER1):c.4837C>T (p.Gln1613Ter)	Pathogenic
1070158	NC_000014.8:g.(?95578499)(95579571_?)del	Pathogenic
1070159	NC_000014.8:g.(?95590523)(95599795_?)del	Pathogenic
1070440	NM_177438.3(DICER1):c.2853C>G (p.Tyr951Ter)	Pathogenic
1072920	NM_177438.3(DICER1):c.5046C>G (p.Tyr1682Ter)	Pathogenic
1073344	NM_177438.3(DICER1):c.367del (p.Glu123fs)	Pathogenic
1073421	NM_177438.3(DICER1):c.1635del (p.Tyr546fs)	Pathogenic
1073895	NM_177438.3(DICER1):c.636del (p.Lys213fs)	Pathogenic
1074335	NM_177438.3(DICER1):c.714_715dup (p.Asp239fs)	Pathogenic
1074364	NM_177438.3(DICER1):c.2492_2495del (p.Glu830_Leu831insTer)	Pathogenic
1074780	NM_177438.3(DICER1):c.4558G>T (p.Glu1520Ter)	Pathogenic
1075588	NM_177438.3(DICER1):c.3669_3670del (p.Tyr1223_Ser1224delinsTer)	Pathogenic
1075817	NM_177438.3(DICER1):c.4503del (p.Phe1501fs)	Pathogenic
1076550	NM_177438.3(DICER1):c.4763dup (p.Lys1589fs)	Pathogenic
1076731	NM_177438.3(DICER1):c.4318_4319del (p.Glu1439_Asp1440insTer)	Pathogenic
1209876	NM_177438.3(DICER1):c.2524del (p.Met842fs)	Pathogenic
1210818	NM_177438.3(DICER1):c.1724dup (p.Asp575fs)	Pathogenic
1217316	NM_177438.3(DICER1):c.3082C>T (p.Gln1028Ter)	Pathogenic
1217317	NM_177438.3(DICER1):c.1144_1148dup (p.Ile383fs)	Pathogenic
1217318	NM_177438.3(DICER1):c.1711del (p.Ser571fs)	Pathogenic
1327570	NM_177438.3(DICER1):c.2504_2505dup (p.Phe836fs)	Pathogenic
1351715	NM_177438.3(DICER1):c.4583G>A (p.Trp1528Ter)	Pathogenic
1358330	NM_177438.3(DICER1):c.1054del (p.Phe351_Leu352insTer)	Pathogenic
1368411	NM_177438.3(DICER1):c.2306dup (p.Tyr769Ter)	Pathogenic
1368482	NM_177438.3(DICER1):c.2531_2532del (p.Glu844fs)	Pathogenic
1369112	NM_177438.3(DICER1):c.682_724dup (p.Val242delinsGluAsnSerTer)	Pathogenic
1369695	NM_177438.3(DICER1):c.2330T>G (p.Leu777Ter)	Pathogenic
1372490	NM_177438.3(DICER1):c.2689del (p.Met897fs)	Pathogenic

SpliceAI

4996 predictions. Top by Δscore:

Variant	Effect	Δscore
14:95090526:G:C	donor_gain	1.0000
14:95091028:GCTTA:G	donor_loss	1.0000
14:95091029:CTTAC:C	donor_loss	1.0000
14:95091030:TTACC:T	donor_loss	1.0000
14:95091031:TACCT:T	donor_loss	1.0000
14:95091032:A:AC	donor_gain	1.0000
14:95091033:C:CC	donor_gain	1.0000
14:95091033:C:CG	donor_loss	1.0000
14:95091105:CTTTT:C	acceptor_gain	1.0000
14:95091106:TTTT:T	acceptor_gain	1.0000
14:95091107:TTT:T	acceptor_gain	1.0000
14:95091107:TTTC:T	acceptor_loss	1.0000
14:95091108:TT:T	acceptor_gain	1.0000
14:95091109:TC:T	acceptor_loss	1.0000
14:95091110:C:A	acceptor_loss	1.0000
14:95091110:C:CC	acceptor_gain	1.0000
14:95091111:T:C	acceptor_loss	1.0000
14:95091117:CAAAA:C	acceptor_gain	1.0000
14:95091118:A:T	acceptor_gain	1.0000
14:95091361:CTAAG:C	acceptor_gain	1.0000
14:95092611:C:CT	acceptor_gain	1.0000
14:95093883:CTAA:C	donor_loss	1.0000
14:95093884:TAACC:T	donor_loss	1.0000
14:95093885:AAC:A	donor_loss	1.0000
14:95093886:A:AG	donor_loss	1.0000
14:95094153:CAAT:C	acceptor_gain	1.0000
14:95096577:T:A	donor_gain	1.0000
14:95096590:C:CA	donor_gain	1.0000
14:95096709:TTTGT:T	acceptor_gain	1.0000
14:95096710:TTGT:T	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000022943 (14:95092479 T>C), RS1000032315 (14:95111510 G>A), RS1000182035 (14:95086872 T>C), RS1000198981 (14:95128425 G>T), RS1000271165 (14:95136061 T>C), RS1000442804 (14:95136330 C>A,T), RS1000458985 (14:95116089 A>ACACT), RS1000479318 (14:95098003 T>C), RS1000525745 (14:95153909 A>T), RS1000538856 (14:95102972 T>C), RS1000617793 (14:95110321 C>G,T), RS1000619129 (14:95153459 T>C), RS1000647361 (14:95116305 C>G,T), RS1000684157 (14:95158999 G>A), RS1000727435 (14:95122251 A>G)

Disease associations

OMIM: gene MIM:606241 | disease phenotypes: MIM:138800, MIM:601200, MIM:618272, MIM:180295, MIM:167000, MIM:618223, MIM:155255

GenCC curated gene-disease

Disease	Classification	Inheritance
DICER1-related tumor predisposition	Definitive	Autosomal dominant
pleuropulmonary blastoma	Strong	Autosomal dominant
DICER1 syndrome	Supportive	Autosomal dominant
global developmental delay - lung cysts - overgrowth - Wilms tumor syndrome	Limited	Unknown

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
DICER1-related tumor predisposition	Definitive	AD

Mondo (21): DICER1-related tumor predisposition (MONDO:0100216), hereditary neoplastic syndrome (MONDO:0015356), goiter, multinodular 1, with or without Sertoli-Leydig cell tumors (MONDO:0007681), pleuropulmonary blastoma (MONDO:0011014), global developmental delay - lung cysts - overgrowth - Wilms tumor syndrome (MONDO:0018445), rhabdomyosarcoma, embryonal, 2 (MONDO:0859046), breast neoplasm (MONDO:0021100), diffuse midline glioma, H3 K27-altered (MONDO:1060171), neurodevelopmental disorder (MONDO:0700092), pineoblastoma (MONDO:0016722), breast cancer (MONDO:0007254), rhabdomyosarcoma (MONDO:0005212), pediatric high-grade glioma (MONDO:1010030), cancer or benign tumor (MONDO:0045024), ovarian cancer (MONDO:0008170)

Orphanet (10): DICER1 tumor-predisposition syndrome (Orphanet:284343), Inherited cancer-predisposing syndrome (Orphanet:140162), Familial multinodular goiter (Orphanet:276399), Global developmental delay-lung cysts-overgrowth-Wilms tumor syndrome (Orphanet:404476), Pleuropulmonary blastoma (Orphanet:64742), Microphthalmia-anophthalmia-coloboma (Orphanet:98555), Pineoblastoma (Orphanet:251909), Rhabdomyosarcoma (Orphanet:780), Rare ovarian cancer (Orphanet:213500), Medulloblastoma (Orphanet:616)

HPO phenotypes

46 total (30 of 46 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000023	Inguinal hernia
HP:0000105	Enlarged kidney
HP:0000256	Macrocephaly
HP:0000260	Wide anterior fontanel
HP:0000316	Hypertelorism
HP:0000347	Micrognathia
HP:0000463	Anteverted nares
HP:0000717	Autism
HP:0000767	Pectus excavatum
HP:0000836	Hyperthyroidism
HP:0000853	Goiter
HP:0000866	Euthyroid multinodular goiter
HP:0000960	Sacral dimple
HP:0001263	Global developmental delay
HP:0001442	Typified by somatic mosaicism
HP:0001520	Large for gestational age
HP:0001537	Umbilical hernia
HP:0001538	Protuberant abdomen
HP:0001548	Overgrowth
HP:0002007	Frontal bossing
HP:0002667	Nephroblastoma
HP:0002671	Basal cell carcinoma
HP:0002808	Kyphosis
HP:0002859	Rhabdomyosarcoma
HP:0002885	Medulloblastoma
HP:0002890	Thyroid carcinoma
HP:0002895	Papillary thyroid carcinoma
HP:0003577	Congenital onset
HP:0004467	Preauricular pit

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST000635_26	Response to statin therapy	2.000000e-08
GCST002805_2	Body mass index	9.000000e-07
GCST003989_39	Chin dimples	1.000000e-09
GCST003999_10	Nose size	4.000000e-09
GCST004587_2	Body mass index (dietary energy interaction)	1.000000e-06
GCST004587_3	Body mass index (dietary energy interaction)	4.000000e-07
GCST006190_65	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	9.000000e-10
GCST006288_330	Heel bone mineral density	5.000000e-07
GCST006288_435	Heel bone mineral density	3.000000e-10
GCST006979_1014	Heel bone mineral density	3.000000e-18
GCST008368_18	Plasma anti-thyroid peroxidase levels	2.000000e-06
GCST009391_1067	Metabolite levels	6.000000e-06

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0005937	longitudinal BMI measurement
EFO:0004340	body mass index
EFO:0008111	diet measurement
EFO:0006336	diastolic blood pressure
EFO:0006527	smoking status measurement
EFO:0009270	heel bone mineral density
EFO:0010364	lysophosphatidylcholine 20:5 measurement

MeSH disease descriptors (8)

Descriptor	Name	Tree numbers
D001943	Breast Neoplasms	C04.588.180; C17.800.090.500
D008527	Medulloblastoma	C04.557.465.625.600.380.515; C04.557.465.625.600.590.500; C04.557.470.670.380.515; C04.557.470.670.590.500; C04.557.580.625.600.380.515; C04.557.580.625.600.590.500
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
D065886	Neurodevelopmental Disorders	F03.625
D010051	Ovarian Neoplasms	C04.588.322.455; C12.050.351.500.056.630.705; C12.050.351.937.418.685; C12.100.250.056.630.705; C12.900.418.685; C19.344.410; C19.391.630.705
D012208	Rhabdomyosarcoma	C04.557.450.590.550.660; C04.557.450.795.550.660
C562732	Euthyroid Goiter (supp.)
C537516	Pleuropulmonary blastoma (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2311232 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression, increases cleavage, increases reaction	5
Valproic Acid	affects expression, decreases expression, decreases methylation	4
Cisplatin	decreases expression, affects binding, increases phosphorylation, increases reaction, increases response to substance (+4 more)	3
Estradiol	decreases expression, increases expression	3
Particulate Matter	decreases expression, increases abundance	3
perfluorooctane sulfonic acid	decreases expression	2
Arsenic	affects methylation, increases expression	2
Vehicle Emissions	decreases expression, increases abundance	2
Benzo(a)pyrene	decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
FR900359	decreases phosphorylation	1
2,4,6-tribromophenol	decreases expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
bisphenol A	decreases expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, decreases reaction	1
mono-(2-ethylhexyl)phthalate	affects cotreatment, increases expression	1
zinc chloride	affects cotreatment, decreases expression	1
cobaltous chloride	decreases expression, increases reaction	1
butyraldehyde	decreases expression	1
nickel chloride	decreases expression	1
manganese chloride	decreases expression, increases abundance	1
monobutyl phthalate	affects cotreatment, increases expression	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
mono-benzyl phthalate	affects cotreatment, increases expression	1
monoisononylphthalate	affects cotreatment, increases expression	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2317834	Binding	Inhibition of human recombinant Dicer-mediated pre-miR-29a without bulge loop processing assessed as reduction of mature miR-29a formation by Northern blot analysis (Rvb = 51%)	Xanthone derivatives as potential inhibitors of miRNA processing by human Dicer: targeting secondary structures of pre-miRNA by small molecules. — Bioorg Med Chem Lett

Cellosaurus cell lines

9 cell lines: 9 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A1SF	VOA1066	Cancer cell line	Female
CVCL_D8K4	Ubigene HCT 116 DICER1 KO	Cancer cell line	Male
CVCL_E0BR	Ubigene HeLa DICER1 KO	Cancer cell line	Female
CVCL_HD59	DLD-1 DICER1(-/-)	Cancer cell line	Male
CVCL_HD76	HCT 116 DICER1(-/-)	Cancer cell line	Male
CVCL_HE18	RKO DICER1(-/-)	Cancer cell line	Sex unspecified
CVCL_SK84	HAP1 DICER1 (-) 1	Cancer cell line	Male
CVCL_SK85	HAP1 DICER1 (-) 2	Cancer cell line	Male
CVCL_SK86	HAP1 DICER1 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00092183	PHASE4	COMPLETED	An Investigational Drug for the Prevention of Chemotherapy-Induced Nausea and Vomiting (MK-0869-071)
NCT00128778	PHASE4	COMPLETED	Maintenance Treatment With Liposomal Doxorubicin (Caelyx) in Metastatic Breast Cancer Patients
NCT00302120	PHASE4	UNKNOWN	The MONET - Study: MR Mammography of Nonpalpable Breast Tumors
NCT00307606	PHASE4	UNKNOWN	Does a Single Steroid Injection Reduce the Formation of Postmastectomy Seroma
NCT00370240	PHASE4	COMPLETED	Chlorhydrate of Ropivacaine and Breast Cancer Surgery
NCT00375752	PHASE4	TERMINATED	Efficacy and Safety of Letrozole vs. Letrozole Plus Zoledronic Acid as Endocrine Therapy Before Surgery in Postmenopausal Patients With Breast Cancer
NCT00575354	PHASE4	COMPLETED	Comparison of Sevoflurane and Isoflurane Anesthesia for Benign Breast Tumor Excision
NCT00604968	PHASE4	TERMINATED	Pegylated Liposomal Doxorubicin (Caelyx(R)) as Monotherapy in Elderly Patients With Locally Advanced and/or Metastatic Breast Cancer (Study P05059)
NCT00616135	PHASE4	COMPLETED	Study of Autologous Fat Enhanced w/ Regenerative Cells Transplanted to Reconstruct Breast Deformities After Lumpectomy
NCT00649090	PHASE4	COMPLETED	A Study to Evaluate the Safety of Adjuvant Treatment With Exemestane Following Previous Treatment With Tamoxifen in Postmenopausal Women With Estrogen Sensitive Primary Breast Cancer
NCT00779285	PHASE4	TERMINATED	Safety Study of CAELYX in Patients With Metastatic Breast Cancer Previously Treated With Anthracyclines (Study P04057)(TERMINATED)
NCT01176916	PHASE4	COMPLETED	Aromasin® Interventional Study Of Early Invasive Breast Cancer Patients In China
NCT01427400	PHASE4	UNKNOWN	The Use of Botulinum Toxin A in Two-Stage Tissue Expander/ Implant Breast Reconstruction
NCT01849380	PHASE4	UNKNOWN	Neoadjuvant ECS Versus ECF in Local Advanced Breast Cancer
NCT01859936	PHASE4	COMPLETED	Will Preoperative MRI Breast in Women Under 56 Years With Breast Cancer Change Primary Treatment
NCT01948960	PHASE4	COMPLETED	Influence of Exceptional Patient Characteristics on Everolimus Exposure
NCT01961544	PHASE4	COMPLETED	Eribulin Mesylate Phase IV Clinical Trial in Korean Patients With Metastatic or Locally Advanced Breast Cancer
NCT01975064	PHASE4	COMPLETED	Cancer and Anesthesia: Survival After Radical Surgery - a Comparison Between Propofol or Sevoflurane Anesthesia
NCT02004834	PHASE4	ACTIVE_NOT_RECRUITING	Levobupivacaine and Lidocaine for Paravertebral Block Causes Greater Hemodynamic Oscillations Than Levobupivacaine
NCT02372305	PHASE4	WITHDRAWN	Comparison of FlexHD and Alloderm Outcomes in Breast Reconstructive Surgery
NCT02479347	PHASE4	COMPLETED	Wound Infections in Breast Cancer Surgery After Preoperative Skin Preparation With Chlorhexidine vs. Povidone-iodine
NCT02549677	PHASE4	COMPLETED	Epirubicin Versus Docetaxel Plus Cyclophosphamide in Lymph Node Negative, ER-positive, Her2-negative Breast Cancer
NCT02612870	PHASE4	UNKNOWN	Sienna+® Injection Time Study 4 Arms
NCT02627560	PHASE4	COMPLETED	The Effect of Topical Tranexamic Acid on Bleeding and Seroma Formation in After Undergoing Mastectomy
NCT02661932	PHASE4	COMPLETED	Fertility Preservation in Breast Cancer Patients
NCT02781259	PHASE4	UNKNOWN	Selective Lymph Node Dissection Using Fluorescent Dye in Node-positive Breast Cancer
NCT02819921	PHASE4	TERMINATED	Desvenlafaxine for Treatment of Hot Flashes in Women With Breast Cancer Taking Tamoxifen
NCT03220178	PHASE4	TERMINATED	Impact of eHealth-support on Quality of Life in Metastatic Breast Cancer Patients Treated With Palbociclib and Endocrine Therapy
NCT03583944	PHASE4	COMPLETED	A Study to Evaluate Safety, Tolerability and Efficacy of Eribulin Mesylate in Treating Adult Females With Locally Advanced or Metastatic Breast Cancer
NCT03586154	PHASE4	COMPLETED	Combined Intra-articular Shoulder Injection and Stellate Ganglion Block in Chronic Post-mastectomy Shoulder Pain
NCT04707196	PHASE4	COMPLETED	A Study of Abemaciclib in Indian Women With Advanced Breast Cancer
NCT04931615	PHASE4	COMPLETED	ARTISS a Single-centre Randomised Control Study
NCT05033769	PHASE4	UNKNOWN	Assessing ImmunoResponse Post Eribulin: Eribulin and Immunogenicity in Advanced Breast Cancer
NCT05036005	PHASE4	UNKNOWN	Neoadjuvant Ontruzant (SB3) in Patients With HER2-positive Early Breast Cancer: An Open-Label (NeoON)
NCT05452213	PHASE4	RECRUITING	Comprehensive Analysis of Spatial, Temporal and Molecular Patterns of Ribociclib Efficacy and Resistance in Advanced Breast Cancer Patients
NCT05465031	PHASE4	RECRUITING	Sacubitril/Valsartan in PriMAry preventIoN of the Cardiotoxicity of Systematic breaST canceR trEAtMent (MAINSTREAM)
NCT05949333	PHASE4	UNKNOWN	Reducing Neutropenia Incidence With Pegfilgrastim Administration on Day 3 After Chemotherapy
NCT07158164	PHASE4	RECRUITING	DPYD Pharmacogenomics and Fluoropyrimidine (FP) Dose-Adjustment
NCT07162259	PHASE4	NOT_YET_RECRUITING	Cohort Study on Sequential ADC Therapy in HR-positive/HER2-negative Advanced Breast Cancer
NCT06647953	PHASE3	RECRUITING	Testing a Standardized Approach to Surgery and Chemotherapy for Type I Pleuropulmonary Blastoma or the Addition of an Anti-cancer Drug, Topotecan, to the Usual Treatment for Types II and III Pleuropulmonary Blastoma