DGCR8

Summary

DGCR8 (DGCR8 microprocessor complex subunit, HGNC:2847) is a protein-coding gene on chromosome 22q11.21, encoding Microprocessor complex subunit DGCR8 (Q8WYQ5). Component of the microprocessor complex that acts as a RNA- and heme-binding protein that is involved in the initial step of microRNA (miRNA) biogenesis. It is a selective cancer dependency (DepMap: 56.5% of cell lines).

This gene encodes a subunit of the microprocessor complex which mediates the biogenesis of microRNAs from the primary microRNA transcript. The encoded protein is a double-stranded RNA binding protein that functions as the non-catalytic subunit of the microprocessor complex. This protein is required for binding the double-stranded RNA substrate and facilitates cleavage of the RNA by the ribonuclease III protein, Drosha. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 54487 — RefSeq curated summary.

At a glance

• Gene–disease (curated): schwannoma (Limited, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 129 total — 3 pathogenic
• Phenotypes (HPO): 39
• Cancer driver (intOGen): activating (oncogene-like) across 4 cancer types
• Cancer dependency (DepMap): dependent in 56.5% of screened cell lines
• MANE Select transcript: NM_022720

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2847
Approved symbol	DGCR8
Name	DGCR8 microprocessor complex subunit
Location	22q11.21
Locus type	gene with protein product
Status	Approved
Aliases	DGCRK6, Gy1, pasha
Ensembl gene	ENSG00000128191
Ensembl biotype	protein_coding
OMIM	609030
Entrez	54487

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 14 protein_coding, 6 retained_intron

ENST00000351989, ENST00000407755, ENST00000457069, ENST00000475941, ENST00000485802, ENST00000491892, ENST00000495351, ENST00000495826, ENST00000498171, ENST00000704820, ENST00000704821, ENST00000868483, ENST00000868484, ENST00000868485, ENST00000868486, ENST00000868487, ENST00000868488, ENST00000927223, ENST00000954973, ENST00000954974

RefSeq mRNA: 2 — MANE Select: NM_022720 NM_001190326, NM_022720

CCDS: CCDS13773, CCDS54501

Canonical transcript exons

ENST00000351989 — 14 exons

Exon	Start	End
ENSE00001056489	20087162	20087321
ENSE00003460151	20092809	20092907
ENSE00003489431	20106177	20106277
ENSE00003493614	20110025	20111872
ENSE00003517899	20089669	20089811
ENSE00003532312	20107271	20107398
ENSE00003545395	20091869	20091970
ENSE00003561981	20089976	20090258
ENSE00003570746	20094713	20094795
ENSE00003622027	20091435	20091632
ENSE00003630574	20106592	20106698
ENSE00003671712	20108890	20109003
ENSE00003992544	20085687	20086683
ENSE00003992545	20080241	20080383

Expression profiles

Bgee: expression breadth ubiquitous, 271 present calls, max score 94.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.1974 / max 442.2738, expressed in 1799 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
191103	8.9789	1750
191105	5.1870	1575
191104	4.4888	1494
191102	0.5426	232

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	94.97	gold quality
cerebellar hemisphere	UBERON:0002245	94.78	gold quality
cerebellar cortex	UBERON:0002129	94.62	gold quality
cerebellum	UBERON:0002037	92.91	gold quality
sural nerve	UBERON:0015488	91.93	gold quality
right testis	UBERON:0004534	91.85	gold quality
left testis	UBERON:0004533	91.43	gold quality
body of uterus	UBERON:0009853	91.31	gold quality
right ovary	UBERON:0002118	91.22	gold quality
right lobe of thyroid gland	UBERON:0001119	91.11	gold quality
body of pancreas	UBERON:0001150	91.06	gold quality
left ovary	UBERON:0002119	90.61	gold quality
apex of heart	UBERON:0002098	90.48	gold quality
body of stomach	UBERON:0001161	90.41	gold quality
left uterine tube	UBERON:0001303	90.35	gold quality
transverse colon	UBERON:0001157	90.33	gold quality
small intestine Peyer’s patch	UBERON:0003454	90.02	gold quality
stromal cell of endometrium	CL:0002255	89.95	gold quality
granulocyte	CL:0000094	89.83	gold quality
minor salivary gland	UBERON:0001830	89.82	gold quality
muscle layer of sigmoid colon	UBERON:0035805	89.63	gold quality
endocervix	UBERON:0000458	89.59	gold quality
right lobe of liver	UBERON:0001114	89.54	gold quality
mucosa of transverse colon	UBERON:0004991	89.47	gold quality
skin of abdomen	UBERON:0001416	89.46	gold quality
right uterine tube	UBERON:0001302	89.43	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	89.38	gold quality
metanephros cortex	UBERON:0010533	89.36	gold quality
left lobe of thyroid gland	UBERON:0001120	89.35	gold quality
lower esophagus muscularis layer	UBERON:0035833	89.29	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.10

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

46 targeting DGCR8, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-205-5P	99.81	70.05	1557
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-378A-5P	99.65	66.33	1311
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-3064-5P	99.26	66.13	1497
HSA-MIR-3085-3P	99.26	66.16	1490
HSA-MIR-6504-5P	99.26	65.95	1487
HSA-MIR-6797-3P	99.17	66.94	668

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 56.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Molecular cloning and expression analysis of DGCR8 (PMID:12705904)
• DGCR8 may be an essential component of the primary miRNA processing complex, along with Drosha. (PMID:15574589)
• DGCR8 is required for the maturation of miRNA primary transcripts. (PMID:15589161)
• Thus, DGCR8 may function as the molecular anchor that measures the distance from the dsRNA-ssRNA junction (PMID:16751099)
• Study show that the RNA-binding protein DiGeorge critical region-8 (DGCR8), which is essential for the first step of miRNA processing, is a heme-binding protein; the association with heme promotes dimerization of DGCR8. (PMID:17159994)
• DGCR8 core recognizes pri-miRNA in two possible orientations. We propose a model for DGCR8’s recognition of pri-miRNA (PMID:17704815)
• DGCR8 locates at the nucleolus and small foci adjacent to splicing speckles in the nucleoplasm. (PMID:17765891)
• 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 DGCR8 was found to be significantly upregulated in the dorsolateral prefrontal cortex and superior temporal gyrus 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)
• SRY is a hybrid of DGCR8 and SOX3, and is regulated by the transcription factor CP2. (PMID:19902333)
• The dimerization domain of DGCR8 is embedded in an independently folded heme-binding domain and directly contributes to association with heme. Heme-binding-deficient DGCR8 mutants have reduced pri-miRNA processing activity in vitro. (PMID:20506313)
• analysis of the function of the DGCR8-heme interaction in microRNA maturation (PMID:21454614)
• DGCR8, AGO1, AGO2, PACT, and TARBP1 expression levels were significantly higher in the epithelial skin cancer groups than the healthy controls (P > 0.05). (PMID:22025453)
• HDAC1 is an integral component of the Drosha/DGCR8 complex and enhances miRNA processing by increasing the affinity of DGCR8 to primary miRNA transcripts via deacetylation of critical lysine residues in the RNA-binding domains of DGCR8. (PMID:22222205)
• This study demonstrates binding specificity of DGCR8 for ferric heme, provides direct biochemical evidence for ferric heme serving as an activator for miRNA maturation. (PMID:22308374)
• DGCR8 and Drosha are targeted post-transcriptionally to chromosome 19 microRNA cluster pri-miRNAs as a preformed complex but dissociate separately. (PMID:22393237)
• DGCR8 is cleaved by caspases between Asp396 and Ser397 in HeLa cells. (PMID:22434730)
• 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)
• Single nucleotide polymorphisms in the DGCR8 3’-UTR that binds to miR-106b/miR-579 is associated with breast cancer. (PMID:23629745)
• It is a miRNA processing enzyme and altered in non-alcoholic fatty liver disease. (PMID:23663110)
• A subset of senescence-associated miRNAs with the potential to target p21CIP1 is downregulated during DGCR8-mediated senescence. (PMID:23773483)
• This study demonstrated for the first time that the DGCR8 mRNA expression level was up-regulated in colorectal carcinomas, suggesting its important role in pathobiology of colorectal carcinogenesis. (PMID:23775303)
• RNase III enzyme Drosha and the double-stranded RNA-binding protein DGCR8 binds and regulates a large variety of cellular RNAs (PMID:23863141)
• specific RNA processing is likely facilitated by preformed DGCR8-Drosha heterodimers that can discriminate between authentic substrates and other hairpins (PMID:23893406)
• multisite phosphorylation regulates DGCR8 protein stability, thereby raising microprocessor complex levels, changing the mature miRNA profile of the cell, and increasing cell proliferation and migration (PMID:24239349)
• These data reveal a role for DeltaNp63 in the transcriptional regulation of DGCR8 to reprogram adult somatic cells into multipotent stem cells. (PMID:24449888)
• The Microprocessor complex of Drosha and DGCR8 proteins, which is responsible for the processing of the primary transcripts during the generation of microRNAs, destabilizes the mRNA of Aurora kinase B. (PMID:24589731)
• Study reveals a unique protein-RNA interaction central to pri-miRNA recognition. We propose a unifying model in which two DGCR8 dimers clamp a pri-miRNA hairpin using their Rheds. (PMID:24910438)
• Data show decreased DGCR8 expression and miRNA dysregulation in individuals with 22q11.2 deletion syndrome (PMID:25084529)
• These data show that hepatitis B virus proteins repress DGCR8 promoter activity by upregulating the expression of transcription factor YY1. (PMID:25427980)
• We aimed to evaluate the expression of the major components of microRNA biogenesis machinery including Drosha, Dicer and DiGeorge syndrome critical region gene 8 (DGCR8) in multiple sclerosis patients (PMID:25439752)
• in tumors with DGCR8 E518K and DROSHA exon 29 (miRNAPG-HS) mutations … greater prevalence of tumors with blastemal predominant histology in patients with miRNAPG-HS and/or SIX1/2 Q177R mutations (PMID:25670082)
• Recurrent mutations included a hotspot mutation (Q177R) in the homeo-domain of SIX1 and SIX2 in tumors with high proliferative potential (18.1% of blastemal cases); mutations in the DROSHA/DGCR8 microprocessor genes (PMID:25670083)
• DGCR8 functions as an oncogene in ovarian cancer, which is in part mediated by miR-27b. (PMID:25823356)
• Together with a 23-amino acid peptide from DGCR8, DROSHA constitutes a minimal functional core. DROSHA serves as a “ruler” by measuring 11 bp from the basal ssRNA-dsRNA junction. DGCR8 interacts with the stem and apical elements through its dsRNA-binding domains and RNA-binding heme domain, respectively, allowing efficient and accurate processing. (PMID:26027739)
• These results reveal a new pathway in the DNA damage response wherein ABL-dependent tyrosine phosphorylation of DGCR8 stimulates the processing of selective primary miRNAs. (PMID:26126715)
• DGCR8 and Drosha assemble into a heterotrimeric complex on RNA, comprising two DGCR8 molecules and one Drosha molecule. (PMID:26683315)
• Results show that DGCR8 forms an alternative complex with the RRP6-containing form of the exosome, acts as an adaptor to recruit the exosome to target structured RNAs, and the DGCR8/hRRP6 complex controls the stability of human telomerase RNA. (PMID:26687677)
• Results demonstrated that DGCR8 is significantly upregulated in invasive ductal breast carcinoma, suggesting that increased expression of DGCR8 may play a fundamental role during the process of breast carcinogenesis. (PMID:26804549)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	dgcr8	ENSDARG00000035564
mus_musculus	Dgcr8	ENSMUSG00000022718
rattus_norvegicus	Dgcr8	ENSRNOG00000001886
drosophila_melanogaster	pasha	FBGN0039861
caenorhabditis_elegans	pash-1	WBGENE00011908

Protein

Protein identifiers

Microprocessor complex subunit DGCR8 — Q8WYQ5 (reviewed: Q8WYQ5)

Alternative names: DiGeorge syndrome critical region 8

All UniProt accessions (4): Q8WYQ5, A0A994J4Y2, A0A994J7P0, C9JSD5

UniProt curated annotations — full annotation on UniProt →

Function. Component of the microprocessor complex that acts as a RNA- and heme-binding protein 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, DGCR8 function as a molecular anchor necessary for the recognition of pri-miRNA at dsRNA-ssRNA junction and directs DROSHA to cleave 11 bp away form the junction to release hairpin-shaped pre-miRNAs that are subsequently cut by the cytoplasmic DICER to generate mature miRNAs. The heme-bound DGCR8 dimer binds pri-miRNAs as a cooperative trimer (of dimers) and is active in triggering pri-miRNA cleavage, whereas the heme-free DGCR8 monomer binds pri-miRNAs as a dimer and is much less active. Both double-stranded and single-stranded regions of a pri-miRNA are required for its binding. Specifically recognizes and binds N6-methyladenosine (m6A)-containing pri-miRNAs, a modification required for pri-miRNAs processing. Involved in the silencing of embryonic stem cell self-renewal. Also plays a role in DNA repair by promoting the recruitment of RNF168 to RNF8 and MDC1 at DNA double-strand breaks and subsequently the clearance of DNA breaks.

Subunit / interactions. Monomer; in absence of heme. Homodimer; the association with heme promotes its dimerization. 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 ILF3, NCL and DROSHA. 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.

Tissue specificity. Ubiquitously expressed.

Post-translational modifications. Phosphorylated at Ser-677 by ATM upon radiation, which is crucial for its stability. Ubiquitinated, leading to degradation in a proteasome-dependent manner. Deubiquitinated by USP51, leading to stabilization.

Cofactor. Binds 1 heme group per homodimer.

Domain organisation. Both DRBM domains are required for efficient binding to pri-miRNA. The region between residues 276 and 498 has an autoinhibitory function on pri-miRNA processing activity.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8WYQ5-1	1	yes
Q8WYQ5-2	2
Q8WYQ5-3	3

RefSeq proteins (2): NP_001177255, NP_073557* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001202	WW_dom	Domain
IPR014720	dsRBD_dom	Domain
IPR036020	WW_dom_sf	Homologous_superfamily
IPR040375	DGCR8	Family

Pfam: PF00035

UniProt features (73 total): strand 16, helix 11, modified residue 10, region of interest 8, mutagenesis site 6, sequence conflict 4, turn 4, domain 3, cross-link 3, splice variant 3, sequence variant 2, chain 1, compositionally biased region 1, binding site 1

Structure

Experimental structures (PDB)

14 structures.

PDB	Method	Resolution (Å)
7CNC	X-RAY DIFFRACTION	1.6
3LE4	X-RAY DIFFRACTION	1.7
2YT4	X-RAY DIFFRACTION	2.6
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
1X47	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WYQ5-F1	64.28	0.24

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 (1): 352 (axial binding residue)

Post-translational modifications (13): 35, 92, 95, 271, 275, 279, 371, 373, 377, 677, 424, 500, 707

Mutagenesis-validated functional residues (6):

Position	Phenotype
352	inhibits heme-binding and dimerization.
430	does not inhibit heme-binding and dimerization.
561–565	strongly reduces pri-mirna binding affinity.
568–569	reduces pri-mirna binding affinity and pri-mirna processing activity. does not inhibit interaction with drosha. when ass
669–673	strongly reduces pri-mirna binding affinity.
676–677	reduces pri-mirna binding affinity and pri-mirna processing activity. slightly inhibits interaction with drosha. when as

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-203927	MicroRNA (miRNA) biogenesis
R-HSA-8986944	Transcriptional Regulation by MECP2

MSigDB gene sets: 262 (showing top): STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, TGACCTY_ERR1_Q2, GOBP_STEM_CELL_PROLIFERATION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, AGTCTTA_MIR499, MCAATNNNNNGCG_UNKNOWN, WANG_LMO4_TARGETS_DN, GOBP_DNA_DAMAGE_RESPONSE, PID_P53_DOWNSTREAM_PATHWAY, GOBP_REGULATION_OF_STEM_CELL_PROLIFERATION, FISCHER_DREAM_TARGETS, GOBP_PRE_MIRNA_PROCESSING, AP2_Q6_01

GO Biological Process (4): DNA damage response (GO:0006974), primary miRNA processing (GO:0031053), regulation of stem cell proliferation (GO:0072091), positive regulation of pre-miRNA processing (GO:2000633)

GO Molecular Function (10): double-stranded RNA binding (GO:0003725), heme binding (GO:0020037), protein-macromolecule adaptor activity (GO:0030674), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), metal ion binding (GO:0046872), primary miRNA binding (GO:0070878), protein-RNA adaptor activity (GO:0140517), RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (10): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), postsynaptic density (GO:0014069), nuclear body (GO:0016604), site of double-strand break (GO:0035861), microprocessor complex (GO:0070877), glutamatergic synapse (GO:0098978)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Gene Silencing by RNA	1
Generic Transcription Pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
RNA binding	2
protein binding	2
nuclear lumen	2
intracellular membraneless organelle	2
cellular response to stress	1
miRNA processing	1
regulation of cell population proliferation	1
stem cell proliferation	1
pre-miRNA processing	1
positive regulation of miRNA processing	1
regulation of pre-miRNA processing	1
tetrapyrrole binding	1
molecular adaptor activity	1
identical protein binding	1
protein dimerization activity	1
cation binding	1
protein-macromolecule adaptor activity	1
nucleic acid binding	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1
asymmetric synapse	1
postsynaptic specialization	1
nucleoplasm	1
site of DNA damage	1
nuclear protein-containing complex	1
ribonuclease III complex	1
synapse	1

Protein interactions and networks

STRING

2316 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DGCR8	DROSHA	Q9NRR4	999
DGCR8	HNRNPA2B1	P22626	992
DGCR8	DDX17	Q92841	992
DGCR8	DDX5	P17844	990
DGCR8	METTL14	Q9HCE5	989
DGCR8	METTL3	Q86U44	985
DGCR8	DICER1	Q9UPY3	972
DGCR8	AGO2	Q9UKV8	945
DGCR8	XPO5	Q9HAV4	924
DGCR8	TP53	P04637	905
DGCR8	MECP2	P51608	892
DGCR8	TARBP2	Q15633	884
DGCR8	GNB1L	Q9BYB4	883
DGCR8	RNH1	P13489	859
DGCR8	FMR1	Q06787	830

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:0914”(association)	0.740
DROSHA	TP53	psi-mi:“MI:0914”(association)	0.680
DGCR8	SRPK1	psi-mi:“MI:0915”(physical association)	0.670
DDX17	YAP1	psi-mi:“MI:0914”(association)	0.650
FXR2	CSNK2A1	psi-mi:“MI:0914”(association)	0.640
DGCR8	DGCR8	psi-mi:“MI:0407”(direct interaction)	0.590
DGCR8	DGCR8	psi-mi:“MI:0914”(association)	0.590
DGCR8	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
MEOX2	DGCR8	psi-mi:“MI:0915”(physical association)	0.560
MECP2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
ZNF324B	ZNF316	psi-mi:“MI:0914”(association)	0.530
MAGEB2	POLRMT	psi-mi:“MI:0914”(association)	0.530
ZBTB48	ZBTB24	psi-mi:“MI:0914”(association)	0.530
LRRTM4	AP3B1	psi-mi:“MI:0914”(association)	0.530
NIFK	RSL1D1	psi-mi:“MI:0914”(association)	0.530
DDX17	DGCR8	psi-mi:“MI:0915”(physical association)	0.500
DROSHA	DYRK1A	psi-mi:“MI:0914”(association)	0.480
KHSRP	DGCR8	psi-mi:“MI:0915”(physical association)	0.400
DGCR8	HNRNPUL1	psi-mi:“MI:0914”(association)	0.350

BioGRID (353): DGCR8 (Two-hybrid), DGCR8 (Affinity Capture-MS), DGCR8 (Proximity Label-MS), HNRNPUL1 (Affinity Capture-MS), DROSHA (Affinity Capture-MS), DGCR8 (Affinity Capture-MS), DGCR8 (Affinity Capture-MS), DGCR8 (Affinity Capture-MS), DGCR8 (Affinity Capture-MS), DGCR8 (Affinity Capture-MS), DGCR8 (Affinity Capture-MS), DGCR8 (Affinity Capture-MS), DGCR8 (Affinity Capture-MS), DGCR8 (Affinity Capture-MS), KIF15 (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8HTT5, A0A2R6W1B1, A2XC52, A6QR44, B9F4I8, F4I9G2, F4JSE7, O88566, O94763, P35922, P53349, P55265, Q06787, Q13233, Q1EQW7, Q2R2B1, Q3UDK1, Q3ULM0, Q53NI2, Q5E9N5, Q5EAH9, Q5QLS7, Q62925, Q63505, Q651A1, Q6PHZ5, Q7T3U0, Q7TN31, Q80Z10, Q80ZW0, Q86UB2, Q8CBX9, Q8CDG3, Q8CF97, Q8CFE5, Q8H8C6, Q8IPH9, Q8IVF5, Q8K284, Q8N9B5

Diamond homologs: A6QR44, Q6YW64, Q8WYQ5, Q9EQM6

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
ABL1	“up-regulates activity”	DGCR8	phosphorylation
DGCR8	“form complex”	“Microprocessor complex”	binding
ATM	“up-regulates quantity by stabilization”	DGCR8	phosphorylation
USP1	“up-regulates quantity by stabilization”	DGCR8	deubiquitination
DGCR8	“up-regulates activity”	RNF168	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 89 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
mRNA Polyadenylation	9	13.2×	4e-06
Peptide chain elongation	6	12.7×	3e-04
Viral mRNA Translation	6	12.7×	3e-04
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	6	12.6×	3e-04
Selenocysteine synthesis	6	12.0×	3e-04
Eukaryotic Translation Termination	6	12.0×	3e-04
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	6	11.8×	3e-04
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	6	11.8×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
alternative mRNA splicing, via spliceosome	6	49.9×	1e-06
negative regulation of mRNA splicing, via spliceosome	5	47.3×	1e-05
regulation of alternative mRNA splicing, via spliceosome	7	21.1×	1e-05
cytoplasmic translation	7	16.0×	4e-05
ribosomal small subunit biogenesis	5	14.1×	2e-03
RNA processing	5	13.5×	2e-03
rRNA processing	6	10.5×	2e-03
mRNA splicing, via spliceosome	9	10.2×	4e-05

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 4 cancer types — DLBCLNOS, PLMESO, WDTC, WT.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	77
Likely benign	26
Benign	5

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
1180538	GRCh37/hg19 22q11.21(chr22:18889693-21465485)x1	Pathogenic
1684558	GRCh37/hg19 22q11.21(chr22:18718028-21326012)x1	Pathogenic
4279399	GRCh37/hg19 22q11.21(chr22:20030823-20068473)x1	Pathogenic

SpliceAI

2641 predictions. Top by Δscore:

Variant	Effect	Δscore
22:20080380:TCAG:T	donor_loss	1.0000
22:20080383:GGTA:G	donor_loss	1.0000
22:20080384:G:T	donor_loss	1.0000
22:20080385:T:G	donor_loss	1.0000
22:20085681:TTGCA:T	acceptor_loss	1.0000
22:20085682:TGCA:T	acceptor_loss	1.0000
22:20085684:CAGG:C	acceptor_loss	1.0000
22:20085685:A:AG	acceptor_gain	1.0000
22:20085685:A:T	acceptor_loss	1.0000
22:20085686:G:GA	acceptor_loss	1.0000
22:20085686:G:GG	acceptor_gain	1.0000
22:20085686:GGTA:G	acceptor_gain	1.0000
22:20085750:C:G	donor_gain	1.0000
22:20087319:AAA:A	donor_gain	1.0000
22:20087320:AA:A	donor_gain	1.0000
22:20087322:G:GG	donor_gain	1.0000
22:20089754:A:T	donor_gain	1.0000
22:20089801:G:T	donor_gain	1.0000
22:20091418:T:TA	acceptor_gain	1.0000
22:20091422:A:AG	acceptor_gain	1.0000
22:20091423:A:G	acceptor_gain	1.0000
22:20091427:T:A	acceptor_gain	1.0000
22:20091428:G:A	acceptor_gain	1.0000
22:20091628:GAAAG:G	donor_gain	1.0000
22:20091629:AAAGG:A	donor_loss	1.0000
22:20091630:AAGGT:A	donor_loss	1.0000
22:20091632:GGTA:G	donor_gain	1.0000
22:20091633:G:C	donor_loss	1.0000
22:20091634:T:A	donor_loss	1.0000
22:20091864:CACA:C	acceptor_loss	1.0000

AlphaMissense

5115 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:20087306:A:G	K289E	1.000
22:20087308:A:C	K289N	1.000
22:20087308:A:T	K289N	1.000
22:20089707:T:A	W307R	1.000
22:20089707:T:C	W307R	1.000
22:20089708:G:C	W307S	1.000
22:20089709:G:C	W307C	1.000
22:20089709:G:T	W307C	1.000
22:20089722:C:G	H312D	1.000
22:20089723:A:G	H312R	1.000
22:20089731:G:A	G315R	1.000
22:20089731:G:C	G315R	1.000
22:20089732:G:A	G315E	1.000
22:20089732:G:T	G315V	1.000
22:20089741:T:A	V318E	1.000
22:20089743:T:G	Y319D	1.000
22:20089747:T:C	L320P	1.000
22:20089768:T:A	V327D	1.000
22:20089773:T:A	W329R	1.000
22:20089773:T:C	W329R	1.000
22:20089776:T:C	S330P	1.000
22:20089780:G:C	R331T	1.000
22:20089780:G:T	R331M	1.000
22:20089781:G:C	R331S	1.000
22:20089781:G:T	R331S	1.000
22:20089782:C:A	P332T	1.000
22:20089782:C:T	P332S	1.000
22:20089783:C:A	P332Q	1.000
22:20089783:C:G	P332R	1.000
22:20089785:T:C	Y333H	1.000

dbSNP variants (sampled 300 via entrez): RS1000392251 (22:20084581 A>T), RS1000403480 (22:20108445 G>T), RS1000414591 (22:20102374 G>A), RS1000419308 (22:20108620 A>G), RS1000453742 (22:20108786 T>C,G), RS1000526957 (22:20093401 T>C), RS1000571492 (22:20101471 G>A), RS1000682663 (22:20087717 C>T), RS1000732919 (22:20087934 G>A), RS1000746315 (22:20101312 C>T), RS1000752245 (22:20082011 T>G), RS1000941515 (22:20093625 G>A), RS1001019617 (22:20098742 C>G), RS1001068662 (22:20111718 C>A,G,T), RS1001143815 (22:20106876 C>A,T)

Disease associations

OMIM: gene MIM:609030 | disease phenotypes: MIM:209850

GenCC curated gene-disease

Disease	Classification	Inheritance
schwannoma	Limited	Autosomal dominant

Mondo (3): autism spectrum disorder (MONDO:0005258), autism (MONDO:0005260), schwannoma (MONDO:0002546)

Orphanet (1): NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

39 total (30 of 39 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000175	Cleft palate
HP:0000176	Submucous cleft hard palate
HP:0000194	Open mouth
HP:0000201	Pierre-Robin sequence
HP:0000220	Velopharyngeal insufficiency
HP:0000252	Microcephaly
HP:0000278	Retrognathia
HP:0000414	Bulbous nose
HP:0000430	Underdeveloped nasal alae
HP:0000581	Blepharophimosis
HP:0000598	Abnormality of the ear
HP:0000627	Posterior embryotoxon
HP:0000712	Emotional lability
HP:0000718	Aggressive behavior
HP:0000829	Hypoparathyroidism
HP:0001155	Abnormality of the hand
HP:0001249	Intellectual disability
HP:0001252	Hypotonia
HP:0001328	Specific learning disability
HP:0001537	Umbilical hernia
HP:0001611	Hypernasal speech
HP:0001629	Ventricular septal defect
HP:0001636	Tetralogy of Fallot
HP:0001883	Talipes
HP:0002627	Right aortic arch with mirror image branching
HP:0002719	Recurrent infections
HP:0002901	Hypocalcemia

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST006249_109	Serum metabolite levels	3.000000e-13
GCST009391_2018	Metabolite levels	3.000000e-06
GCST010988_513	Adult body size	2.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010348	cholesteryl ester 20:4 measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	2
Acrolein	affects cotreatment, increases oxidation, increases abundance	2
Air Pollutants	affects expression, affects response to substance, affects cotreatment, increases abundance, increases oxidation	2
Ozone	affects cotreatment, increases oxidation, increases abundance	2
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
pirinixic acid	affects binding, decreases expression, increases activity	1
sulforaphane	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
cobaltous chloride	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
ferrous chloride	decreases expression	1
aflatoxin B2	increases methylation	1
beta-methylcholine	affects expression	1
CGP 52608	affects binding, increases reaction	1
ICG 001	increases expression	1
abrine	decreases expression	1
Irinotecan	decreases expression	1
Arsenic Trioxide	decreases expression	1
Leflunomide	decreases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Caffeine	increases phosphorylation	1
Cannabidiol	decreases expression	1
Demecolcine	decreases expression	1
Dexamethasone	affects binding, increases reaction, increases expression, decreases reaction	1
Diazinon	increases methylation	1

Cellosaurus cell lines

5 cell lines: 4 cancer cell line, 1 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A4DR	HVRDe009-A-1	Embryonic stem cell	Female
CVCL_B8EN	Abcam HCT 116 DGCR8 KO	Cancer cell line	Male
CVCL_B8UT	Abcam MCF-7 DGCR8 KO	Cancer cell line	Female
CVCL_B9GX	Abcam A-549 DGCR8 KO	Cancer cell line	Male
CVCL_F1LX	HyCyte A-549 KO-hDGCR8	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT01302964	PHASE3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	PHASE3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	PHASE3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	PHASE3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	PHASE3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	PHASE3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	PHASE3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	PHASE3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	PHASE3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
NCT03715166	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder
NCT04233502	PHASE3	WITHDRAWN	Efficacy and Safety of Slenyto for Insomnia in Children With ASD
NCT04578756	PHASE3	COMPLETED	Open-Label, Flexible-dose Study to Evaluate the Long-Term Safety and Tolerability of Cariprazine in the Treatment of Pediatric Participants With Schizophrenia, Bipolar I Disorder, or Autism Spectrum Disorder
NCT04623398	PHASE3	COMPLETED	Effect of Lithium in Patients With Autism Spectrum Disorder and Phelan-McDermid Syndrome (SHANK3 Haploinsufficiency)
NCT04725383	PHASE3	TERMINATED	Amitriptyline for Repetitive Behaviors in Autism Spectrum Disorders
NCT05212493	PHASE3	COMPLETED	The Effects of Medical Cannabis in Children With Autistic Spectrum Disorder
NCT05361707	PHASE3	UNKNOWN	Evaluating the Effects of Tasimelteon in Individuals With Autism Spectrum Disorder (ASD) and Sleep Disturbances
NCT05439616	PHASE3	COMPLETED	Study of Cariprazine Oral Capsules or Solution to Assess Adverse Events and Change in Irritability Due to Autism Spectrum Disorder (ASD) in Participants Aged 5-17 Years With ASD
NCT06229210	PHASE3	RECRUITING	Safety and Tolerability Trial of Lumateperone in Pediatric Patients With Schizophrenia, Bipolar Disorder or Autism Spectrum Disorder