DROSHA

Summary

DROSHA (drosha ribonuclease III, HGNC:17904) is a protein-coding gene on chromosome 5p13.3, encoding Ribonuclease 3 (Q9NRR4). Ribonuclease III double-stranded (ds) RNA-specific endoribonuclease that is involved in the initial step of microRNA (miRNA) biogenesis. It is a selective cancer dependency (DepMap: 35.6% of cell lines).

This gene encodes a ribonuclease (RNase) III double-stranded RNA-specific ribonuclease and subunit of the microprocessor protein complex, which catalyzes the initial processing step of microRNA (miRNA) synthesis. The encoded protein cleaves the stem loop structure from the primary microRNA (pri-miRNA) in the nucleus, yielding the precursor miRNA (pre-miRNA), which is then exported to the cytoplasm for further processing. In a human cell line lacking a functional copy of this gene, canonical miRNA synthesis is reduced. Somatic mutations in this gene have been observed in human patients with kidney cancer.

Source: NCBI Gene 29102 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Moderate, GenCC)
• GWAS associations: 6
• Clinical variants (ClinVar): 262 total — 9 pathogenic
• Phenotypes (HPO): 2
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 3 cancer types
• Cancer dependency (DepMap): dependent in 35.6% of screened cell lines
• MANE Select transcript: NM_001382508

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17904
Approved symbol	DROSHA
Name	drosha ribonuclease III
Location	5p13.3
Locus type	gene with protein product
Status	Approved
Aliases	RNASE3L, Etohi2, HSA242976, RN3
Ensembl gene	ENSG00000113360
Ensembl biotype	protein_coding
OMIM	608828
Entrez	29102

Gene structure

Transcript identifiers

Ensembl transcripts: 49 — 35 protein_coding, 8 retained_intron, 6 protein_coding_CDS_not_defined

ENST00000344624, ENST00000504133, ENST00000504361, ENST00000505601, ENST00000507174, ENST00000507438, ENST00000509067, ENST00000509608, ENST00000510178, ENST00000510375, ENST00000511367, ENST00000511778, ENST00000511803, ENST00000512076, ENST00000512124, ENST00000512166, ENST00000512302, ENST00000512885, ENST00000513349, ENST00000514927, ENST00000866936, ENST00000866937, ENST00000866938, ENST00000866939, ENST00000866940, ENST00000866941, ENST00000866942, ENST00000866943, ENST00000866944, ENST00000866945, ENST00000866946, ENST00000866947, ENST00000866948, ENST00000926013, ENST00000926014, ENST00000926015, ENST00000926016, ENST00000926017, ENST00000926018, ENST00000926019, ENST00000926020, ENST00000926021, ENST00000926022, ENST00000926023, ENST00000926024, ENST00000926025, ENST00000926026, ENST00000926027, ENST00000944647

RefSeq mRNA: 3 — MANE Select: NM_001382508 NM_001100412, NM_001382508, NM_013235

CCDS: CCDS47194, CCDS47195

Canonical transcript exons

ENST00000344624 — 36 exons

Exon	Start	End
ENSE00000734381	31511035	31511176
ENSE00000804475	31514988	31515219
ENSE00000971062	31504555	31504635
ENSE00001083029	31449281	31449419
ENSE00001083052	31448547	31448607
ENSE00001083063	31437239	31437298
ENSE00001155496	31400494	31401562
ENSE00001164856	31515454	31515564
ENSE00001164865	31521123	31521215
ENSE00001165063	31493207	31493293
ENSE00001165072	31495286	31495372
ENSE00001200656	31508621	31508775
ENSE00001382130	31526079	31526912
ENSE00002059584	31530798	31530924
ENSE00002078271	31531450	31531525
ENSE00003477768	31431576	31431678
ENSE00003479095	31406853	31406945
ENSE00003483056	31472063	31472232
ENSE00003488514	31484881	31484962
ENSE00003488777	31466182	31466281
ENSE00003492847	31422787	31422944
ENSE00003495301	31435765	31435864
ENSE00003497453	31467939	31468063
ENSE00003509487	31409056	31409159
ENSE00003513104	31429475	31429545
ENSE00003513167	31421272	31421377
ENSE00003535806	31483554	31483628
ENSE00003553515	31451533	31451640
ENSE00003559530	31529040	31529105
ENSE00003559690	31405677	31405723
ENSE00003568687	31424427	31424471
ENSE00003576274	31464236	31464343
ENSE00003578158	31486491	31486562
ENSE00003628897	31410746	31410887
ENSE00003641174	31409250	31409332
ENSE00003912705	31531990	31532093

Expression profiles

Bgee: expression breadth ubiquitous, 283 present calls, max score 98.18.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.3371 / max 387.1359, expressed in 1811 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
61158	30.8273	1809
61159	0.6521	357
61157	0.5012	212
61156	0.3565	172

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	98.18	gold quality
ventricular zone	UBERON:0003053	97.44	gold quality
germinal epithelium of ovary	UBERON:0001304	97.28	gold quality
cortical plate	UBERON:0005343	97.26	gold quality
Brodmann (1909) area 23	UBERON:0013554	97.02	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.87	gold quality
ganglionic eminence	UBERON:0004023	96.77	gold quality
cerebellar hemisphere	UBERON:0002245	96.75	gold quality
cerebellar cortex	UBERON:0002129	96.69	gold quality
middle temporal gyrus	UBERON:0002771	96.54	gold quality
sural nerve	UBERON:0015488	96.39	gold quality
colonic epithelium	UBERON:0000397	96.19	gold quality
adenohypophysis	UBERON:0002196	96.16	gold quality
parietal pleura	UBERON:0002400	96.03	gold quality
primary visual cortex	UBERON:0002436	95.97	gold quality
cerebellum	UBERON:0002037	95.94	gold quality
visceral pleura	UBERON:0002401	95.80	gold quality
pleura	UBERON:0000977	95.40	gold quality
pituitary gland	UBERON:0000007	95.39	gold quality
tibia	UBERON:0000979	95.37	gold quality
cervix squamous epithelium	UBERON:0006922	95.37	silver quality
left ovary	UBERON:0002119	95.31	gold quality
mucosa of transverse colon	UBERON:0004991	95.27	gold quality
right ovary	UBERON:0002118	95.20	gold quality
right frontal lobe	UBERON:0002810	95.18	gold quality
secondary oocyte	CL:0000655	95.15	gold quality
right uterine tube	UBERON:0001302	95.15	gold quality
tendon of biceps brachii	UBERON:0008188	95.15	gold quality
gingival epithelium	UBERON:0001949	94.80	gold quality
caudate nucleus	UBERON:0001873	94.77	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.68

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
CCNB1	Activation

Upstream regulators (CollecTRI, top): E2F1, E2F4

miRNA regulators (miRDB)

49 targeting DROSHA, 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-6758-5P	100.00	66.21	1470
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-103A-1-5P	99.39	67.78	1545
HSA-MIR-103A-2-5P	99.39	67.72	1577
HSA-MIR-1276	99.36	68.18	1642

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 35.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• identification of another RNase III, human Drosha, as the core nuclease that executes the initiation step of miRNA processing in the nucleus (PMID:14508493)
• human Drosha is a component of two multi-protein complexes; both components of the smaller complex, termed Microprocessor, are necessary and sufficient in mediating the genesis of miRNAs from the primary miRNA transcript (PMID:15531877)
• Data show that human Drosha selectively cleaves RNA hairpins bearing a large (>/=10 nucleotides) terminal loop. (PMID:15565168)
• nuclear RNase III Drosha cleaves primary miRNAs (pri-miRNAs) to release hairpin-shaped pre-miRNAs that are subsequently cut by the cytoplasmic RNase III Dicer to generate mature miRNAs (PMID:15574589)
• processing of primary microRNA hairpins by Drosha requires flanking nonstructured RNA sequences (PMID:15932881)
• Dicer gene expression in human breast cells is regulated by alternative promoter selection to alter the length and composition of the 5’-leader sequence of its mRNA (PMID:15987463)
• We found that RNASEN expression levels were enhanced in a fraction of esophageal cancers. (PMID:17121874)
• Drosha may cleave intronic miRNAs between the splicing commitment step and the excision step, thereby ensuring both miRNA biogenesis and protein synthesis from a single primary transcript. (PMID:17255951)
• identify specific miRNAs up-regulated in leukemias triggered by All1 fusions. All1 fusion protein-mediated recruitment of Drosha to target genes encoding miRNAs is demonstrated (PMID:17581865)
• miR-BHRF1-2 in 3’ cleavage of BHRF1 mRNA in the cytoplasm and Drosha in cleavage of latency III EBNA and EBV replication-associated BHRF1 transcripts in the nucleus. (PMID:17626073)
• Integrative genomics analysis of chromosome 5p gain in cervical cancer reveals target over-expressed genes, including Drosha. (PMID:18559093)
• 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)
• The Drosha-DGCR8 complex cleaves the hairpin in the DGCR8 mRNA and thus destabilizes the mRNA; DGCR8 stabilizes Drosha protein via protein interaction; this crossregulation between Drosha and DGCR8 may contribute to the control of miRNA biogenesis. (PMID:19135890)
• The mRNA for microprocessor component DROSHA was found to be significantly upregulated in the dorsolateral prefrontal cortex in tissues from schizophrenic patients. (PMID:19721432)
• a Microprocessor, containing the RNA binding protein Dgcr8 and RNase III enzyme Drosha, is responsible for processing primary microRNAs to precursor microRNAs (PMID:19759829)
• Report dysregulation of microRNA processing enzymes Drosha and Dicer in epithelial skin tumors when compared to healthy control samples. (PMID:20210522)
• Smad proteins bind a conserved RNA sequence to promote microRNA maturation by Drosha. (PMID:20705240)
• Findings of growth promotion by Drosher silencing implies its potential use as therapeutic targets for neuroblastoma. (PMID:20805302)
• This study revealed for the first time that expression alterations of Dicer and Drosha are present in endometrial cancer tissue and could be potentially responsible for altered microRNAs profiles observed in this malignancy. (PMID:21559780)
• the selectivity of Drosha action contributes greatly to the specificity and efficiency of miRNA biogenesis (PMID:21683814)
• Drosha, an endoribonuclease best known for its role in the biogenesis of microRNAs, can also function to directly regulate viral gene expression of Kaposi’s sarcoma-associated herpesvirus (PMID:21690333)
• The authors report that Drosha cleavage of latency III BHRF1 RNA and cis-acting splicing effects inhibit splicing and inhibit BHRF1 RNA and protein expression. (PMID:21697496)
• Our results suggest that Drosha, Dicer, and Ago2 are possibly implicated in colorectal carcinoma pathobiology (PMID:21769619)
• Drosha regulates human mesenchymal stem cells cell cycle progression through a miRNA independent mechanism, potentially by regulating rRNA processing. (PMID:21794839)
• Low drosha expression is associated with breast cancer. (PMID:21898071)
• Drosha and Dicer expression was dysregulation in nasopharyngeal carcinoma compared with healthy control samples. (PMID:21953080)
• PTEN-mediated miR-21 regulation is achieved by inhibiting the interaction between the Drosha complex and RNH1, revealing previously unidentified role of PTEN in the oncogenic miR-21 biogenesis (PMID:22162762)
• mesenchymal stromal cells from MDS patients show low gene and protein expression of DICER1 and DROSHA which are involved in the microRNA biogenesis, as well as their target gene SBDS. (PMID:22371183)
• The results showed that genetic variants of DROSHA may modify the risk of abnormal semen parameters, which could result in male infertility. (PMID:22381205)
• DGCR8 and Drosha are targeted post-transcriptionally to chromosome 19 microRNA cluster pri-miRNAs as a preformed complex but dissociate separately. (PMID:22393237)
• results provide novel evidence that Drosha, is probably involved in the pathobiology of human smooth muscle neoplasms (PMID:22394132)
• Data show that down-regulation of either Dicer or Drosha had no effect on the sensitivity of cells to irradiation. (PMID:22479364)
• Rare Drosha splice variants are deficient in microRNA processing but do not affect general microRNA expression in cancer cells (PMID:22496623)
• Gene silencing of hepatitis B virus X protein by RNA interference significantly restored the expression of Drosha. (PMID:22554933)
• Drosha, Dicer, Argonaute 1, and Argonaute 2 are differentially expressed at different metastatic sites in ovarian carcinoma compared with primary carcinomas. (PMID:22647351)
• Dicer, Drosha, and Exportin 5 genes were up-regulated in bladder urothelial carcinoma compared to normal urothelium. Silencing these genes induced cell proliferation inhibition and apoptosis in bladder urothelial carcinoma cells. (PMID:22766726)
• DGCR8-mediated cleavage of snoRNAs was independent of Drosha, suggesting the involvement of DGCR8 in cellular complexes with other endonucleases. Binding of DGCR8 to cassette exons is a new mechanism for regulation of alternatively spliced isoforms. (PMID:22796965)
• A subset of Lin28 mRNA targets are destabilized in a Drosha-dependent manner. (PMID:22935707)
• Drosha protein potentially plays an important role in breast cancer progression. (PMID:23225145)
• Data indicate that tumour sample showed a significantly higher Drosha expression versus normal mucosa, while Dicer levels did not differ. (PMID:23266047)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	drosha	ENSDARG00000055563
mus_musculus	Drosha	ENSMUSG00000022191
rattus_norvegicus	Drosha	ENSRNOG00000013451
drosophila_melanogaster	drosha	FBGN0026722
caenorhabditis_elegans	drsh-1	WBGENE00009163

Protein

Protein identifiers

Ribonuclease 3 — Q9NRR4 (reviewed: Q9NRR4)

Alternative names: Protein Drosha, Ribonuclease III, p241

All UniProt accessions (4): Q9NRR4, E5RHD1, H0YB67, H7C5U6

UniProt curated annotations — full annotation on UniProt →

Function. Ribonuclease III double-stranded (ds) RNA-specific endoribonuclease that is involved in the initial step of microRNA (miRNA) biogenesis. Component of the microprocessor complex that is required to process primary miRNA transcripts (pri-miRNAs) to release precursor miRNA (pre-miRNA) in the nucleus. Within the microprocessor complex, DROSHA cleaves the 3’ and 5’ strands of a stem-loop in pri-miRNAs (processing center 11 bp from the dsRNA-ssRNA junction) to release hairpin-shaped pre-miRNAs that are subsequently cut by the cytoplasmic DICER to generate mature miRNAs. Involved also in pre-rRNA processing. Cleaves double-strand RNA and does not cleave single-strand RNA. Involved in the formation of GW bodies. Plays a role in growth homeostasis in response to autophagy in motor neurons.

Subunit / interactions. Component of the microprocessor complex, or pri-miRNA processing protein complex, which is composed of DROSHA and DGCR8. The microprocessor complex is a heterotrimer; each of the two DROSHA RNase III domains binds one DGCR8 (via C-terminal region). Interacts with SP1 and SNIP1. Interacts with SRRT/ARS2. Interacts with CPSF3 and ISY1; this interaction is in an RNA dependent manner. Interacts with PUS10; interaction promotes pri-miRNAs processing.

Subcellular location. Nucleus. Nucleolus. Cytoplasm.

Tissue specificity. Ubiquitous.

Post-translational modifications. Degraded by autophagy in response to neuronal activity in motor neurons.

Cofactor. Each RNase III domain binds at least one Mg(2+) or Mn(2+) ion.

Domain organisation. The 2 RNase III domains form an intramolecular dimer where the domain 1 cuts the 3’strand while the domain 2 cleaves the 5’strand of pri-miRNAs, independently of each other.

Similarity. Belongs to the ribonuclease III family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9NRR4-1	1	yes
Q9NRR4-2	2
Q9NRR4-3	3
Q9NRR4-4	4

RefSeq proteins (3): NP_001093882, NP_001369437, NP_037367 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000999	RNase_III_dom	Domain
IPR011907	RNase_III	Family
IPR014720	dsRBD_dom	Domain
IPR036389	RNase_III_sf	Homologous_superfamily
IPR044442	RNAse_III_DSRM__animal	Domain
IPR058938	Helical_CED_Drosha	Domain

Pfam: PF00035, PF00636, PF14622, PF26050

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 (140 total): helix 43, strand 28, mutagenesis site 17, binding site 14, compositionally biased region 8, turn 7, splice variant 5, sequence conflict 5, region of interest 4, domain 3, modified residue 2, sequence variant 2, chain 1, site 1

Structure

Experimental structures (PDB)

12 structures.

PDB	Method	Resolution (Å)
9ASM	ELECTRON MICROSCOPY	2.8
9ASO	ELECTRON MICROSCOPY	2.9
9ASQ	ELECTRON MICROSCOPY	3
5B16	X-RAY DIFFRACTION	3.2
9ASN	ELECTRON MICROSCOPY	3.2
9ASP	ELECTRON MICROSCOPY	3.2
6V5B	ELECTRON MICROSCOPY	3.7
6LXD	ELECTRON MICROSCOPY	3.9
6LXE	ELECTRON MICROSCOPY	4.2
6V5C	ELECTRON MICROSCOPY	4.4
2KHX	SOLUTION NMR
2NA2	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NRR4-F1	70.94	0.40

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): 1215 (important for activity)

Ligand- & substrate-binding residues (14): 536; 538; 549; 561; 609; 676; 680; 969; 1026; 1042; 1045; 1147 …

Post-translational modifications (2): 355, 373

Mutagenesis-validated functional residues (17):

Position	Phenotype
536	impairs protein folding and stability; when associated with a-538.
538	impairs protein folding and stability; when associated with a-536.
561	impairs protein folding and stability.
622–623	abolishes rnase activity.
676	impairs protein folding and stability.
835–836	abolishes rnase activity.
914	impairs rnase activity.
923	abolishes rnase activity; when associated with a-927.
927	abolishes rnase activity; when associated with a-923.
938–940	abolishes rnase activity.
993	no effect on pri-mirna processing activity.
1045	impairs pri-mirna processing activity. abolishes cleavage of the 3’ strand. abolishes enzyme activity; when associated w
1077	loss of one dgcr8 interaction site; no effect on the second dgcr8 interaction site.
1171	no effect on pri-mirna processing activity.
1194	abolishes interaction with dgcr8.
1222	impairs pri-mirna processing activity. abolishes cleavage of the 5’ strand. abolishes enzyme activity; when associated w
1243	abolishes interaction with dgcr8.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-203927	MicroRNA (miRNA) biogenesis
R-HSA-211000	Gene Silencing by RNA
R-HSA-74160	Gene expression (Transcription)

MSigDB gene sets: 154 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_RIBOSOME_BIOGENESIS, GOMF_ENDONUCLEASE_ACTIVITY, GOMF_RNA_NUCLEASE_ACTIVITY, GOBP_INFLAMMATORY_RESPONSE, GOMF_NUCLEASE_ACTIVITY, HUMMERICH_BENIGN_SKIN_TUMOR_UP, MITSIADES_RESPONSE_TO_APLIDIN_DN, GOBP_REGULATION_OF_LEUKOCYTE_DIFFERENTIATION, GOBP_REGULATION_OF_HEMOPOIESIS, GOMF_RNA_ENDONUCLEASE_ACTIVITY, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_REGULATION_OF_LYMPHOCYTE_DIFFERENTIATION, GOBP_DEFENSE_RESPONSE_TO_GRAM_NEGATIVE_BACTERIUM, GOBP_DEFENSE_RESPONSE_TO_GRAM_POSITIVE_BACTERIUM

GO Biological Process (15): rRNA processing (GO:0006364), miRNA metabolic process (GO:0010586), positive regulation of gene expression (GO:0010628), primary miRNA processing (GO:0031053), pre-miRNA processing (GO:0031054), regulation of regulatory T cell differentiation (GO:0045589), regulation of inflammatory response (GO:0050727), defense response to Gram-negative bacterium (GO:0050829), defense response to Gram-positive bacterium (GO:0050830), regulation of miRNA metabolic process (GO:2000628), RNA processing (GO:0006396), regulation of gene expression (GO:0010468), regulatory ncRNA-mediated gene silencing (GO:0031047), miRNA processing (GO:0035196), ribosome biogenesis (GO:0042254)

GO Molecular Function (14): lipopolysaccharide binding (GO:0001530), RNA binding (GO:0003723), ribonuclease III activity (GO:0004525), DEAD/H-box RNA helicase binding (GO:0017151), protein homodimerization activity (GO:0042803), SMAD binding (GO:0046332), metal ion binding (GO:0046872), R-SMAD binding (GO:0070412), primary miRNA binding (GO:0070878), nuclease activity (GO:0004518), endonuclease activity (GO:0004519), RNA endonuclease activity (GO:0004521), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (9): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytosol (GO:0005829), postsynaptic density (GO:0014069), microprocessor complex (GO:0070877), glutamatergic synapse (GO:0098978), cytoplasm (GO:0005737), organelle (GO:0043226)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Gene Silencing by RNA	1
Gene expression (Transcription)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
gene expression	3
miRNA processing	2
defense response to bacterium	2
nuclear lumen	2
RNA processing	1
rRNA metabolic process	1
ribosome biogenesis	1
RNA metabolic process	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
regulatory T cell differentiation	1
regulation of T cell differentiation	1
inflammatory response	1
regulation of defense response	1
regulation of response to external stimulus	1
miRNA metabolic process	1
regulation of RNA metabolic process	1
RNA biosynthetic process	1
primary metabolic process	1
regulation of macromolecule biosynthetic process	1
negative regulation of gene expression	1
regulatory ncRNA processing	1
ribonucleoprotein complex biogenesis	1
lipid binding	1
carbohydrate derivative binding	1
nucleic acid binding	1
RNA endonuclease activity producing 5’-phosphomonoesters, hydrolytic mechanism	1
double-stranded RNA-specific ribonuclease activity	1
enzyme binding	1
identical protein binding	1
protein dimerization activity	1
protein binding	1
cation binding	1
SMAD binding	1
RNA binding	1
catalytic activity, acting on a nucleic acid	1
nuclease activity	1
endonuclease activity	1
RNA nuclease activity	1

Protein interactions and networks

STRING

6550 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DROSHA	DGCR8	Q8WYQ5	999
DROSHA	DDX5	P17844	998
DROSHA	DDX17	Q92841	995
DROSHA	TP53	P04637	992
DROSHA	TARDBP	Q13148	990
DROSHA	FUS	P35637	988
DROSHA	SMAD2	Q15796	978
DROSHA	AGO2	Q9UKV8	973
DROSHA	DICER1	Q9UPY3	973
DROSHA	KHSRP	Q92945	969
DROSHA	BRCA1	P38398	940
DROSHA	XPO5	Q9HAV4	939
DROSHA	TARBP2	Q15633	939
DROSHA	AGO1	Q9UL18	939
DROSHA	PDCD4	Q53EL6	918

IntAct

83 interactions, top by confidence:

A	B	Type	Score
DGCR8	DROSHA	psi-mi:“MI:0915”(physical association)	0.940
DROSHA	DGCR8	psi-mi:“MI:0915”(physical association)	0.940
DROSHA	DGCR8	psi-mi:“MI:0914”(association)	0.940
DROSHA	DDX5	psi-mi:“MI:0915”(physical association)	0.740
DROSHA	DDX5	psi-mi:“MI:0914”(association)	0.740
DDX17	DDX5	psi-mi:“MI:0914”(association)	0.740
TP53	DROSHA	psi-mi:“MI:0915”(physical association)	0.680
DROSHA	TP53	psi-mi:“MI:0914”(association)	0.680
DROSHA	TP53	psi-mi:“MI:0915”(physical association)	0.680
TP53	DDX5	psi-mi:“MI:0915”(physical association)	0.660
DDX17	YAP1	psi-mi:“MI:0914”(association)	0.650
LNPEP	CANX	psi-mi:“MI:0914”(association)	0.640
FXR2	CSNK2A1	psi-mi:“MI:0914”(association)	0.640
SMAD1	DDX5	psi-mi:“MI:0914”(association)	0.610
DDX5	SMAD1	psi-mi:“MI:0914”(association)	0.610
DGCR8	DGCR8	psi-mi:“MI:0914”(association)	0.590
SMAD1	DROSHA	psi-mi:“MI:0915”(physical association)	0.560
SMAD5	DDX5	psi-mi:“MI:0914”(association)	0.560
MAGEB2	POLRMT	psi-mi:“MI:0914”(association)	0.530
CHRNA9	CHEK1	psi-mi:“MI:0914”(association)	0.530
SRPK2	RRP9	psi-mi:“MI:0914”(association)	0.530
SRPK1	DROSHA	psi-mi:“MI:0914”(association)	0.530

BioGRID (213): DDX5 (Affinity Capture-Western), DROSHA (Affinity Capture-Western), DROSHA (Affinity Capture-RNA), DROSHA (Affinity Capture-MS), DROSHA (Affinity Capture-MS), EVPL (Co-fractionation), PPL (Co-fractionation), SMC2 (Co-fractionation), DROSHA (Affinity Capture-MS), DROSHA (Affinity Capture-MS), DROSHA (Affinity Capture-MS), DROSHA (Affinity Capture-MS), DROSHA (Affinity Capture-MS), DROSHA (Affinity Capture-MS), DROSHA (Affinity Capture-MS)

ESM2 similar proteins: A0A0K3AV08, A2CEX1, A8XU52, E1BLT8, E7FBS9, E9QCD3, E9QDC5, F5HB62, G5EDE9, G5EEK3, O01700, O14490, O62090, P62024, P97836, P97839, Q2M3X8, Q2THW0, Q2THW7, Q2THW8, Q2THW9, Q2THX0, Q2THX1, Q571K4, Q5HZJ0, Q5R838, Q5RFW2, Q5RJX2, Q5Y5T5, Q66624, Q6PEI3, Q7ZXH3, Q7ZYZ6, Q8BJ42, Q8BQQ1, Q8IZN3, Q8VDZ4, Q8WQC0, Q91ZP3, Q96SK2

Diamond homologs: A0A8J1LLF7, A0A974H8H3, A0MQH0, A1D4V5, A4J683, A5ID21, A5N807, A5UBC4, A5UFI8, A5VKP2, A5W8F2, A6Q1H0, A7H186, A7MZA8, A8EXI3, A8F0M2, A8GM79, A8GQT8, A8GYE2, A9WJ69, B0B7L3, B0BBS8, B0BUA6, B0BW84, B0KV27, B0XMV6, B1J4E0, B2A2N1, B2G826, B2UTG4, B3DLA6, B4F047, B4RJT7, B4U7T8, B5Z735, B7GGE9, B8D7F5, B8D951, B8F3C7, B9E1G8

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
p38	“down-regulates activity”	DROSHA	phosphorylation
DROSHA	“form complex”	“Microprocessor complex”	binding
GSK3B	“up-regulates activity”	DROSHA	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 81 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
Regulation of TP53 Activity through Phosphorylation	5	11.3×	9e-03
SARS-CoV Infections	8	8.5×	1e-03
Viral Infection Pathways	10	5.9×	1e-03
Infectious disease	10	4.8×	5e-03

GO biological processes:

GO term	Partners	Fold	FDR
regulation of alternative mRNA splicing, via spliceosome	5	17.0×	2e-03
RNA splicing	7	8.6×	2e-03
DNA damage response	8	5.9×	5e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 3 cancer types — LUSC, PAAD, WT.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	9
Likely pathogenic	0
Uncertain significance	138
Likely benign	50
Benign	15

Top pathogenic / likely-pathogenic (9)

Variant ID	HGVS	Classification
3393485	NM_001382508.1(DROSHA):c.811C>T (p.Arg271Ter)	Pathogenic
3393486	NM_001382508.1(DROSHA):c.2883-1G>A	Pathogenic
3393487	NM_001382508.1(DROSHA):c.403_409delinsCCACTT (p.Ala135fs)	Pathogenic
3393488	NM_001382508.1(DROSHA):c.3261+1G>C	Pathogenic
3393489	NM_001382508.1(DROSHA):c.3548del (p.Asn1183fs)	Pathogenic
3393490	NM_001382508.1(DROSHA):c.2436_2439del (p.Asp814fs)	Pathogenic
3393491	NM_001382508.1(DROSHA):c.2988A>C (p.Leu996Phe)	Pathogenic
4073702	NM_001382508.1(DROSHA):c.927dup (p.Glu310fs)	Pathogenic
981828	NM_001382508.1(DROSHA):c.1498G>T (p.Glu500Ter)	Pathogenic

SpliceAI

7051 predictions. Top by Δscore:

Variant	Effect	Δscore
5:31405675:A:AC	donor_gain	1.0000
5:31405676:C:CC	donor_gain	1.0000
5:31405722:TA:T	acceptor_gain	1.0000
5:31405724:C:CC	acceptor_gain	1.0000
5:31405731:A:AC	acceptor_gain	1.0000
5:31409157:CTC:C	acceptor_gain	1.0000
5:31409248:A:AC	donor_gain	1.0000
5:31409249:C:CC	donor_gain	1.0000
5:31409333:C:CC	acceptor_gain	1.0000
5:31410744:A:AC	donor_gain	1.0000
5:31410745:C:CC	donor_gain	1.0000
5:31421270:A:AC	donor_gain	1.0000
5:31421271:C:CC	donor_gain	1.0000
5:31422785:A:AC	donor_gain	1.0000
5:31422786:C:CC	donor_gain	1.0000
5:31422832:G:A	donor_gain	1.0000
5:31422859:A:AC	donor_gain	1.0000
5:31422860:C:CC	donor_gain	1.0000
5:31422862:C:CA	donor_gain	1.0000
5:31422942:TAG:T	acceptor_gain	1.0000
5:31422943:AGC:A	acceptor_loss	1.0000
5:31422944:GCT:G	acceptor_loss	1.0000
5:31422945:C:CC	acceptor_gain	1.0000
5:31422945:CTA:C	acceptor_loss	1.0000
5:31422949:A:T	acceptor_gain	1.0000
5:31435736:A:C	donor_gain	1.0000
5:31435863:CG:C	acceptor_gain	1.0000
5:31435865:C:CC	acceptor_gain	1.0000
5:31436201:T:A	donor_gain	1.0000
5:31437235:TTACC:T	donor_loss	1.0000

AlphaMissense

9127 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:31401520:C:G	R1346P	1.000
5:31401526:A:T	I1344N	1.000
5:31401528:G:C	F1343L	1.000
5:31401528:G:T	F1343L	1.000
5:31401529:A:G	F1343S	1.000
5:31401530:A:G	F1343L	1.000
5:31401532:C:G	R1342P	1.000
5:31401537:C:A	Q1340H	1.000
5:31401537:C:G	Q1340H	1.000
5:31401538:T:G	Q1340P	1.000
5:31401542:G:C	H1339D	1.000
5:31401555:A:C	F1334L	1.000
5:31401555:A:T	F1334L	1.000
5:31401556:A:C	F1334C	1.000
5:31401556:A:G	F1334S	1.000
5:31401557:A:C	F1334V	1.000
5:31401557:A:G	F1334L	1.000
5:31401557:A:T	F1334I	1.000
5:31405685:A:G	L1329P	1.000
5:31405685:A:T	L1329H	1.000
5:31405688:G:T	A1328E	1.000
5:31405689:C:G	A1328P	1.000
5:31405697:G:A	A1325V	1.000
5:31405697:G:T	A1325E	1.000
5:31405698:C:G	A1325P	1.000
5:31405698:C:T	A1325T	1.000
5:31405700:G:T	A1324E	1.000
5:31405701:C:G	A1324P	1.000
5:31405708:T:A	E1321D	1.000
5:31405708:T:G	E1321D	1.000

dbSNP variants (sampled 300 via entrez): RS1000004054 (5:31434005 T>C), RS1000012067 (5:31456674 T>G), RS1000015415 (5:31524005 A>C), RS1000085073 (5:31456340 T>G), RS1000115571 (5:31479058 A>T), RS1000118907 (5:31411634 CT>C,CTT), RS1000147304 (5:31497054 G>A), RS1000159002 (5:31431900 C>T), RS1000206320 (5:31406264 T>A,C,G), RS1000229300 (5:31523106 C>G), RS1000240643 (5:31458328 T>C), RS1000261522 (5:31411392 C>A), RS1000311875 (5:31439349 T>C), RS1000343307 (5:31426996 A>G), RS1000355661 (5:31458012 C>A)

Disease associations

OMIM: gene MIM:608828 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Moderate	Autosomal dominant

Mondo (6): hepatoblastoma (MONDO:0018666), pineoblastoma (MONDO:0016722), esophageal atresia (MONDO:0001044), pyloric stenosis (MONDO:0001561), hereditary breast ovarian cancer syndrome (MONDO:0003582), neurodevelopmental disorder (MONDO:0700092)

Orphanet (3): Hepatoblastoma (Orphanet:449), Pineoblastoma (Orphanet:251909), Hereditary breast and/or ovarian cancer syndrome (Orphanet:145)

HPO phenotypes

2 total (2 of 2 shown, HPO-id order):

HPO	Term
HP:0002032	Esophageal atresia
HP:0002021	Pyloric stenosis

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST006991_2	Cerebrospinal fluid t-tau levels in Alzheimer’s disease dementia	9.000000e-07
GCST007231_1	Tuberculosis	2.000000e-06
GCST008480_6	Lung function (FEV1)	3.000000e-06
GCST90013466_34	Height	3.000000e-08
GCST90013466_4	Height	2.000000e-09
GCST90013468_2	Height	3.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004760	t-tau measurement
EFO:0004314	forced expiratory volume

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D004933	Esophageal Atresia	C06.198.330; C06.405.117.260; C16.131.314.330
D017219	Gastric Outlet Obstruction	C06.405.748.340
D018197	Hepatoblastoma	C04.557.435.380
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431
D065886	Neurodevelopmental Disorders	F03.625
D011707	Pyloric Stenosis	C06.405.748.340.690

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs639174	Toxicity	3	cyclophosphamide;cytarabine;daunorubicin;mercaptopurine;methotrexate;prednisone;vincristine	Acute lymphoblastic leukemia

PharmGKB variants

4 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs639174	DROSHA	3	2.50	1	cyclophosphamide;cytarabine;daunorubicin;mercaptopurine;methotrexate;prednisone;vincristine
rs2287584	DROSHA		0.00	0
rs3805500	DROSHA		0.00	0
rs4867329	DROSHA		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression	2
sodium arsenite	decreases expression, increases abundance	2
potassium chromate(VI)	affects cotreatment, decreases expression, increases expression	2
methacrylaldehyde	increases oxidation, increases abundance, affects cotreatment	2
Acrolein	affects cotreatment, increases oxidation, increases abundance	2
Arsenic	decreases expression, increases abundance, affects methylation	2
Ozone	increases oxidation, increases abundance, affects cotreatment	2
Valproic Acid	affects expression, decreases expression	2
FR900359	increases phosphorylation	1
TAK-243	increases sumoylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
beta-lapachone	increases expression, decreases expression	1
arsenite	affects binding, decreases reaction	1
mono-(2-ethylhexyl)phthalate	affects cotreatment, increases expression	1
zinc chloride	affects cotreatment, affects expression	1
butyraldehyde	decreases expression	1
monobutyl phthalate	affects cotreatment, increases expression	1
coumarin	increases phosphorylation	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
chromium hexavalent ion	affects expression	1
mono-benzyl phthalate	increases expression, affects cotreatment	1
monoisononylphthalate	affects cotreatment, increases expression	1
ICG 001	decreases expression	1
abrine	decreases expression	1
mono-isobutyl phthalate	affects cotreatment, increases expression	1
monoethyl phthalate	increases expression, affects cotreatment	1
Resveratrol	affects cotreatment, increases expression	1

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2W3	Abcam HEK293T DROSHA KO	Transformed cell line	Female
CVCL_B8EW	Abcam HCT 116 DROSHA KO	Cancer cell line	Male
CVCL_B8UZ	Abcam MCF-7 DROSHA KO	Cancer cell line	Female
CVCL_B9H4	Abcam A-549 DROSHA KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	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,
NCT02933333	PHASE4	UNKNOWN	G-CSF Alone or Combination With GM-CSF on Prevention and Treatment of Infection in Children With Malignant Tumor
NCT00556283	PHASE4	COMPLETED	RCT: STARR vs Biofeedback
NCT02562170	PHASE4	COMPLETED	Protexa® Versus TiLoopBra® in Immediate Breast Reconstruction- A Pilot Study
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT03017326	PHASE3	ACTIVE_NOT_RECRUITING	Paediatric Hepatic International Tumour Trial
NCT03533582	PHASE3	ACTIVE_NOT_RECRUITING	Cisplatin and Combination Chemotherapy in Treating Children and Young Adults With Hepatoblastoma or Liver Cancer After Surgery
NCT04478292	PHASE3	RECRUITING	A Multi-institutional Study for Treatment of Children With Newly Diagnosed Hepatoblastoma Using a Modified PHITT Strategy
NCT00226044	PHASE3	COMPLETED	Rectal and Oral Omeprazole Treatment of Reflux Disease in Infants.
NCT00673335	PHASE3	COMPLETED	Letrozole in Preventing Breast Cancer in Postmenopausal Women With a BRCA1 or BRCA2 Mutation
NCT00685256	PHASE3	COMPLETED	Standard Genetic Counseling With or Without a Decision Guide in Improving Communication Between Mothers Undergoing BRCA1/2 Testing and Their Minor-Age Children
NCT03162276	PHASE3	UNKNOWN	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT01154816	PHASE2	COMPLETED	Alisertib in Treating Young Patients With Recurrent or Refractory Solid Tumors or Leukemia
NCT02011126	PHASE2	WITHDRAWN	Imetelstat Sodium in Treating Younger Patients With Relapsed or Refractory Solid Tumors
NCT02867592	PHASE2	ACTIVE_NOT_RECRUITING	Cabozantinib-S-Malate in Treating Younger Patients With Recurrent, Refractory, or Newly Diagnosed Sarcomas, Wilms Tumor, or Other Rare Tumors
NCT03155620	PHASE2	ACTIVE_NOT_RECRUITING	Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)
NCT03210714	PHASE2	ACTIVE_NOT_RECRUITING	Erdafitinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With FGFR Mutations (A Pediatric MATCH Treatment Trial)
NCT03213652	PHASE2	ACTIVE_NOT_RECRUITING	Ensartinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With ALK or ROS1 Genomic Alterations (A Pediatric MATCH Treatment Trial)
NCT03213665	PHASE2	COMPLETED	Tazemetostat in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With EZH2, SMARCB1, or SMARCA4 Gene Mutations (A Pediatric MATCH Treatment Trial)
NCT03213678	PHASE2	COMPLETED	Samotolisib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With TSC or PI3K/MTOR Mutations (A Pediatric MATCH Treatment Trial)
NCT03213704	PHASE2	ACTIVE_NOT_RECRUITING	Larotrectinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With NTRK Fusions (A Pediatric MATCH Treatment Trial)
NCT03220035	PHASE2	COMPLETED	Vemurafenib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With BRAF V600 Mutations (A Pediatric MATCH Treatment Trial)
NCT03233204	PHASE2	COMPLETED	Olaparib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Defects in DNA Damage Repair Genes (A Pediatric MATCH Treatment Trial)
NCT03526250	PHASE2	COMPLETED	Palbociclib in Treating Patients With Relapsed or Refractory Rb Positive Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Activating Alterations in Cell Cycle Genes (A Pediatric MATCH Treatment Trial)
NCT03698994	PHASE2	ACTIVE_NOT_RECRUITING	Ulixertinib in Treating Patients With Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With MAPK Pathway Mutations (A Pediatric MATCH Treatment Trial)
NCT04195555	PHASE2	ACTIVE_NOT_RECRUITING	Ivosidenib in Treating Patients With Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With IDH1 Mutations (A Pediatric MATCH Treatment Trial)
NCT04284774	PHASE2	ACTIVE_NOT_RECRUITING	Tipifarnib for the Treatment of Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With HRAS Gene Alterations, a Pediatric MATCH Treatment Trial
NCT04320888	PHASE2	ACTIVE_NOT_RECRUITING	Selpercatinib for the Treatment of Advanced Solid Tumors, Lymphomas, or Histiocytic Disorders With Activating RET Gene Alterations, a Pediatric MATCH Treatment Trial
NCT05302921	PHASE2	COMPLETED	Neoadjuvant Dual Checkpoint Inhibition and Cryoablation in Relapsed/Refractory Pediatric Solid Tumors
NCT06638931	PHASE2	RECRUITING	Agnostic Therapy in Rare Solid Tumors
NCT07300449	PHASE2	RECRUITING	A Prospective Multicenter Clinical Study of SCCG Protocol and ctDNA 5hmc in Predicting the Chemotherapy Sensitivity and Monitoring the Recurrence and Metastasis of Hepatoblastoma in Children and Adolescents
NCT00179803	PHASE2	COMPLETED	Stem Cell Transplant for High Risk Central Nervous System (CNS) Tumors
NCT01217437	PHASE2	COMPLETED	Temozolomide and Irinotecan Hydrochloride With or Without Bevacizumab in Treating Young Patients With Recurrent or Refractory Medulloblastoma or CNS Primitive Neuroectodermal Tumors