BRCC3

Summary

BRCC3 (BRCA1/BRCA2-containing complex subunit 3, HGNC:24185) is a protein-coding gene on chromosome Xq28, encoding Lys-63-specific deubiquitinase BRCC36 (P46736). Metalloprotease that specifically cleaves ‘Lys-63’-linked polyubiquitin chains.

This gene encodes a subunit of the BRCA1-BRCA2-containing complex (BRCC), which is an E3 ubiquitin ligase. This complex plays a role in the DNA damage response, where it is responsible for the stable accumulation of BRCA1 at DNA break sites. The component encoded by this gene can specifically cleave Lys 63-linked polyubiquitin chains, and it regulates the abundance of these polyubiquitin chains in chromatin. The loss of this gene results in abnormal angiogenesis and is associated with syndromic moyamoya, a cerebrovascular angiopathy. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 5.

Source: NCBI Gene 79184 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Moyamoya disease (Limited, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 126 total — 21 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 27
• Druggable target: yes
• MANE Select transcript: NM_001018055

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24185
Approved symbol	BRCC3
Name	BRCA1/BRCA2-containing complex subunit 3
Location	Xq28
Locus type	gene with protein product
Status	Approved
Aliases	C6.1A, BRCC36
Ensembl gene	ENSG00000185515
Ensembl biotype	protein_coding
OMIM	300617
Entrez	79184

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 nonsense_mediated_decay

ENST00000330045, ENST00000340647, ENST00000369459, ENST00000369462, ENST00000399026, ENST00000411985, ENST00000453705

RefSeq mRNA: 3 — MANE Select: NM_001018055 NM_001018055, NM_001242640, NM_024332

CCDS: CCDS56610, CCDS56611, CCDS56612

Canonical transcript exons

ENST00000330045 — 11 exons

Exon	Start	End
ENSE00001450104	155073377	155073431
ENSE00001761409	155072327	155072343
ENSE00001856280	155071508	155071650
ENSE00001950263	155121223	155123077
ENSE00003465734	155089263	155089351
ENSE00003549592	155116711	155116754
ENSE00003584139	155119999	155120168
ENSE00003590279	155090784	155090839
ENSE00003596470	155078616	155078703
ENSE00003627027	155116057	155116188
ENSE00003650453	155077170	155077289

Expression profiles

Bgee: expression breadth ubiquitous, 281 present calls, max score 95.36.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.2588 / max 199.4382, expressed in 1741 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
198215	8.9965	1716
198214	1.2623	825

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	95.36	gold quality
oral cavity	UBERON:0000167	93.57	gold quality
buccal mucosa cell	CL:0002336	93.19	gold quality
mucosa of sigmoid colon	UBERON:0004993	90.89	gold quality
colonic mucosa	UBERON:0000317	90.86	gold quality
corpus epididymis	UBERON:0004359	90.51	gold quality
biceps brachii	UBERON:0001507	90.06	gold quality
rectum	UBERON:0001052	89.96	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	89.81	gold quality
esophagus squamous epithelium	UBERON:0006920	89.40	gold quality
bronchial epithelial cell	CL:0002328	88.74	gold quality
islet of Langerhans	UBERON:0000006	88.68	gold quality
nasal cavity epithelium	UBERON:0005384	88.64	gold quality
heart right ventricle	UBERON:0002080	88.39	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	88.05	gold quality
upper arm skin	UBERON:0004263	87.93	gold quality
mucosa of paranasal sinus	UBERON:0005030	87.82	gold quality
cortical plate	UBERON:0005343	87.82	gold quality
nasal cavity mucosa	UBERON:0001826	87.72	gold quality
cauda epididymis	UBERON:0004360	87.65	gold quality
caput epididymis	UBERON:0004358	87.29	gold quality
epithelium of esophagus	UBERON:0001976	87.11	gold quality
jejunum	UBERON:0002115	86.78	gold quality
jejunal mucosa	UBERON:0000399	86.76	gold quality
vastus lateralis	UBERON:0001379	86.74	gold quality
duodenum	UBERON:0002114	86.74	gold quality
mammalian vulva	UBERON:0000997	86.65	gold quality
endometrium	UBERON:0001295	86.59	gold quality
trabecular bone tissue	UBERON:0002483	86.57	gold quality
monocyte	CL:0000576	86.56	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.33

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

89 targeting BRCC3, 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-1193	100.00	65.93	529
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-670-5P	99.67	69.94	1565
HSA-MIR-6757-3P	99.63	66.88	1089
HSA-MIR-4663	99.62	65.33	957
HSA-MIR-6832-5P	99.58	64.82	1132

Literature-anchored findings (GeneRIF, showing 31)

• These findings demonstrate that BRCC3 is a novel effector of Raf-1, and implicate a role of BRCC3 in modulation of p-ERK, cell survival and proliferation. (PMID:17143545)
• the human Ubc13/Rnf8 ubiquitin ligases control foci formation of the Rap80/Abraxas/Brca1/Brcc36 complex in response to DNA damage (PMID:18077395)
• Specificity for K63-linked polyubiquitin is a common property of the JAMM/MPN+ family of deubiquitinating enzymes. (PMID:19214193)
• scaffold proteins not only participate in the regulation of BRCC36 activity but also determine its subcellular localization and cellular functions. (PMID:20656690)
• NBA1/MERIT40 and BRE interaction is required for the integrity of two distinct deubiquitinating enzyme BRCC36-containing complexes (PMID:21282113)
• these data strongly suggest that BRCC3, a deubiquitinating enzyme that is part of the cellular BRCA1 and BRISC complexes, is an important player in angiogenesis and that BRCC3 loss-of-function mutations are associated with moyamoya angiopathy. (PMID:21596366)
• upregulation of BRCC3 expression is associated with glioma. (PMID:25337721)
• BRCC3 likely plays a role as tumor-associated gene in myelodysplastic syndromes and myelodysplastic/myeloproliferative neoplasms. (PMID:26001790)
• BRCC3 inversely correlated with NPC overall and relapse-free survival. Its expression was higher in radioresistant NPC cells, where BRCC3 knockdown increased the cell survival fraction, attenuated DNA damage repair and resulted in G2/M cell cycle arrest. (PMID:26024915)
• KIAA0157 allosterically activates a cognate deubiquitinating enzyme (DUB) partner and implicates super dimerization as a new regulatory mechanism underlying BRCC36 DUB activity. (PMID:26344097)
• BRCC3 may play a role in B7-H3-induced 5-Fu resistance. (PMID:27175567)
• findings uncover a pivotal role of BRCC36 DUB in limiting DSB processing and repair and illustrate how cells may physically couple ubiquitin recognition and metabolizing activities for fine tuning of DNA repair processes. (PMID:27288411)
• In late S/G2 phase, the DNA damage-responsive E3 ligase RNF8 conjugates K63-linked ubiquitin chains to tankyrase 1, while in G1 phase such ubiquitin chains are removed by BRISC, an ABRO1/BRCC36-containing deubiquitinase complex. (PMID:27993934)
• this study shows that mitochondrial DNA oxidation induces imbalanced activity of NLRP3/NLRP6 inflammasomes by activation of caspase-8 and BRCC36 in dry eye (PMID:28238526)
• Knockdown of BRCC3 in HeLa and SiHa cervical cancer cells revealed that BRCC3 interference inhibited the viability, in addition to the invasion and migration abilities, of cervical cancer cells via regulation of Snai family members and MMPs, which subsequently inhibit the progress of EMT. (PMID:30272359)
• Luciferase reporter assay and in vitro rescue experiment confirmed that ANRIL promoted NLRP3 inflammasome activation by up-regulating BRCC3 expression via sponging miR-122-5p. (PMID:30347231)
• a LNK-associated lysine-63 (K63)-deubiquitinating enzyme complex, Brcc36 isopeptidase complex (BRISC), attenuates HSC expansion through control of JAK2 signaling. (PMID:30755420)
• BRCC3 expressed in oligodendrocyte precursor cells in vitro is required for the oligodendrocyte lineage progression toward the mature stage. Lack of BRCC3 function could deteriorate demyelination at the lesion site. An increase in Lys63-linked ubiquitination levels induced by the deregulation of BRCC3 expression promotes the endosomal/lysosomal processing of myelin proteins. (PMID:31184779)
• Here we show that in the BRCA1-A complex structure, ABRAXAS integrates the DNA repair protein RAP80 and provides a high-affinity binding site that sequesters the tumor suppressor BRCA1 away from the break site. In the BRISC structure, ABRO1 binds SHMT2alpha, a metabolic enzyme enabling cancer growth in hypoxic environments, which we find prevents BRCC36 from binding and cleaving ubiquitin chains (PMID:31253574)
• Cell lines and primary mouse cells with inactivation of BRCC3 had a higher sensitivity to doxorubicin. (PMID:31576005)
• Vitamin D Receptor Inhibits NLRP3 Activation by Impeding Its BRCC3-Mediated Deubiquitination. (PMID:31866999)
• BRCC36 functions noncatalytically to promote antiviral response by maintaining STAT1 protein stability. (PMID:32673428)
• ABRO1 stabilizes the deubiquitinase BRCC3 through inhibiting its degradation mediated by the E3 ubiquitin ligase WWP2. (PMID:33107021)
• BRCA1-A and BRISC: Multifunctional Molecular Machines for Ubiquitin Signaling. (PMID:33142801)
• Identification and Verification of the Ability of Cdk5 to Phosphorylate Deubiquitinating Enzyme BRCC3 In Vitro. (PMID:35503584)
• Identification of BRCC3 and BRCA1 as Regulators of TAZ Stability and Activity. (PMID:37887275)
• The deubiquitinase BRCC3 increases the stability of ZEB1 and promotes the proliferation and metastasis of triple-negative breast cancer cells. (PMID:38449391)
• Deubiquitinase BRCC3 promotes the migration, invasion and EMT progression of colon adenocarcinoma by stabilizing MET expression. (PMID:38470543)
• BRCC3 mediates inflammation and pyroptosis in cerebral ischemia/reperfusion injury by activating the NLRP6 inflammasome. (PMID:38544474)
• BRCC3 Regulation of ALK2 in Vascular Smooth Muscle Cells: Implication in Pulmonary Hypertension. (PMID:38557054)
• BRCC36 regulates beta-catenin ubiquitination to alleviate vascular calcification in chronic kidney disease. (PMID:39227917)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	brcc3	ENSDARG00000098242
mus_musculus	Brcc3	ENSMUSG00000031201
mus_musculus	Brcc3dc	ENSMUSG00000112039
rattus_norvegicus	Brcc3dc	ENSRNOG00000070196

Paralogs (3): PSMD14 (ENSG00000115233), COPS5 (ENSG00000121022), EIF3H (ENSG00000147677)

Protein

Protein identifiers

Lys-63-specific deubiquitinase BRCC36 — P46736 (reviewed: P46736)

Alternative names: BRCA1-A complex subunit BRCC36, BRCA1/BRCA2-containing complex subunit 3, BRCA1/BRCA2-containing complex subunit 36, BRISC complex subunit BRCC36

All UniProt accessions (4): P46736, A0A0A0MS96, H7C413, X6RJS7

UniProt curated annotations — full annotation on UniProt →

Function. Metalloprotease that specifically cleaves ‘Lys-63’-linked polyubiquitin chains. Does not have activity toward ‘Lys-48’-linked polyubiquitin chains. Component of the BRCA1-A complex, a complex that specifically recognizes ‘Lys-63’-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks (DSBs). In the BRCA1-A complex, it specifically removes ‘Lys-63’-linked ubiquitin on histones H2A and H2AX, antagonizing the RNF8-dependent ubiquitination at double-strand breaks (DSBs). Catalytic subunit of the BRISC complex, a multiprotein complex that specifically cleaves ‘Lys-63’-linked ubiquitin in various substrates. Mediates the specific ‘Lys-63’-specific deubiquitination associated with the COP9 signalosome complex (CSN), via the interaction of the BRISC complex with the CSN complex. The BRISC complex is required for normal mitotic spindle assembly and microtubule attachment to kinetochores via its role in deubiquitinating NUMA1. Plays a role in interferon signaling via its role in the deubiquitination of the interferon receptor IFNAR1; deubiquitination increases IFNAR1 activity by enhancing its stability and cell surface expression. Acts as a regulator of the NLRP3 inflammasome by mediating deubiquitination of NLRP3, leading to NLRP3 inflammasome assembly. Down-regulates the response to bacterial lipopolysaccharide (LPS) via its role in IFNAR1 deubiquitination. Deubiquitinates HDAC1 and PWWP2B leading to their stabilization.

Subunit / interactions. Component of the ARISC complex, at least composed of UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1. Component of the BRCA1-A complex, at least composed of BRCA1, BARD1, UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36, babam2 and BABAM1/NBA1. In the BRCA1-A complex, interacts directly with ABRAXAS1 and babam2. Component of the BRISC complex, at least composed of ABRAXAS2, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1. Identified in a complex with SHMT2 and the other subunits of the BRISC complex. In the BRISC complex, interacts directly with ABRAXAS2. Identified in a complex with ABRAXAS2 and NUMA1. The BRISC complex interacts with the CSN complex. Component of the BRCA1/BRCA2 containing complex (BRCC), which also contains BRCA1, BRCA2, BARD1, BABAM2 and RAD51. BRCC is a ubiquitin E3 ligase complex that enhances cellular survival following DNA damage. Interacts with BRCA1. Binds polyubiquitin. Interacts with PWWP2B. Interacts with HDAC1; this interaction is enhanced in the presence of PWWP2B.

Subcellular location. Nucleus. Cytoplasm. Cytoskeleton. Spindle pole.

Tissue specificity. Heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. Aberrantly expressed in the vast majority of breast tumors.

Disease relevance. A chromosomal aberration involving BRCC3 is a cause of pro-lymphocytic T-cell leukemia (T-PLL). Translocation t(X;14)(q28;q11) with TCRA.

Cofactor. Binds 1 zinc ion per subunit.

Similarity. Belongs to the peptidase M67A family. BRCC36 subfamily.

Isoforms (5)

UniProt ID	Names	Canonical?
P46736-1	2	yes
P46736-2	1
P46736-3	3
P46736-4	4
P46736-5	5

RefSeq proteins (3): NP_001018065, NP_001229569, NP_077308 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000555	JAMM/MPN+_dom	Domain
IPR033860	MPN_BRCC36	Family
IPR037518	MPN	Domain
IPR040749	BRCC36_C	Domain
IPR050242	JAMM_MPN+_peptidase_M67A	Family

Pfam: PF01398, PF18110

UniProt features (36 total): strand 8, helix 7, mutagenesis site 5, splice variant 4, binding site 3, modified residue 2, initiator methionine 1, chain 1, sequence variant 1, sequence conflict 1, domain 1, turn 1, short sequence motif 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
8PVY	ELECTRON MICROSCOPY	3.02
8PY2	ELECTRON MICROSCOPY	3.32
6R8F	ELECTRON MICROSCOPY	3.8
6H3C	ELECTRON MICROSCOPY	3.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P46736-F1	84.68	0.73

Functional residue map

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

Ligand- & substrate-binding residues (3): 122; 124; 135

Post-translational modifications (2): 2, 258

Mutagenesis-validated functional residues (5):

Position	Phenotype
23	abolishes localization to sites of dna damage and interaction with abraxas2; uimc1; shmt2; baram2 and babam1; when assoc
27	abolishes localization to sites of dna damage and interaction with abraxas2; uimc1; shmt2; babam2 and babam1; when assoc
122–124	abolishes metalloprotease activity and function in dna repair.
122	loss of deubiquitinase activity.
278	abolishes interaction with uimc1 and shmt2.

Function

Pathways and Gene Ontology

Reactome pathways

16 pathways

ID	Pathway
R-HSA-5689901	Metalloprotease DUBs
R-HSA-5693565	Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks
R-HSA-5693571	Nonhomologous End-Joining (NHEJ)
R-HSA-5693607	Processing of DNA double-strand break ends
R-HSA-69473	G2/M DNA damage checkpoint
R-HSA-1640170	Cell Cycle
R-HSA-392499	Metabolism of proteins
R-HSA-5688426	Deubiquitination
R-HSA-5693532	DNA Double-Strand Break Repair
R-HSA-5693538	Homology Directed Repair
R-HSA-5693567	HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)
R-HSA-5693606	DNA Double Strand Break Response
R-HSA-597592	Post-translational protein modification
R-HSA-69481	G2/M Checkpoints
R-HSA-69620	Cell Cycle Checkpoints
R-HSA-73894	DNA Repair

MSigDB gene sets: 306 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_CELL_CYCLE_CHECKPOINT, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_RESPONSE_TO_IONIZING_RADIATION, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOMF_METALLOPEPTIDASE_ACTIVITY, GOBP_INFLAMMATORY_RESPONSE, REACTOME_G2_M_DNA_DAMAGE_CHECKPOINT, GOBP_CELL_CYCLE_PHASE_TRANSITION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_PROTEIN_MODIFICATION_BY_SMALL_PROTEIN_REMOVAL, GOBP_REGULATION_OF_DNA_REPAIR, GOBP_MITOTIC_G2_M_TRANSITION_CHECKPOINT, GOBP_REGULATION_OF_CELL_CYCLE_G2_M_PHASE_TRANSITION

GO Biological Process (19): regulation of DNA repair (GO:0006282), double-strand break repair (GO:0006302), proteolysis (GO:0006508), mitotic G2 DNA damage checkpoint signaling (GO:0007095), response to X-ray (GO:0010165), response to ionizing radiation (GO:0010212), protein deubiquitination (GO:0016579), mitotic G2/M transition checkpoint (GO:0044818), positive regulation of DNA repair (GO:0045739), cell division (GO:0051301), protein K63-linked deubiquitination (GO:0070536), cellular response to ionizing radiation (GO:0071479), DNA repair-dependent chromatin remodeling (GO:0140861), positive regulation of NLRP3 inflammasome complex assembly (GO:1900227), regulation of DNA damage checkpoint (GO:2000001), DNA repair (GO:0006281), chromatin organization (GO:0006325), DNA damage response (GO:0006974), NLRP3 inflammasome complex assembly (GO:0044546)

GO Molecular Function (10): cysteine-type deubiquitinase activity (GO:0004843), metallopeptidase activity (GO:0008237), enzyme regulator activity (GO:0030234), polyubiquitin modification-dependent protein binding (GO:0031593), metal ion binding (GO:0046872), K63-linked deubiquitinase activity (GO:0061578), metal-dependent deubiquitinase activity (GO:0140492), protein binding (GO:0005515), peptidase activity (GO:0008233), hydrolase activity (GO:0016787)

GO Cellular Component (10): ubiquitin ligase complex (GO:0000151), nuclear ubiquitin ligase complex (GO:0000152), spindle pole (GO:0000922), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), BRCA1-A complex (GO:0070531), BRISC complex (GO:0070552), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
DNA Double-Strand Break Repair	3
Deubiquitination	1
DNA Double Strand Break Response	1
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	1
G2/M Checkpoints	1
Post-translational protein modification	1
DNA Repair	1
Homology Directed Repair	1
Metabolism of proteins	1
Cell Cycle Checkpoints	1
Cell Cycle	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
DNA repair	3
deubiquitinase activity	3
nuclear protein-containing complex	3
regulation of cellular response to stress	2
response to ionizing radiation	2
DNA damage response	2
catalytic activity	2
regulation of DNA metabolic process	1
protein metabolic process	1
mitotic G2 phase	1
mitotic DNA damage checkpoint signaling	1
mitotic G2/M transition checkpoint	1
response to radiation	1
cysteine-type deubiquitinase activity	1
protein modification by small protein removal	1
mitotic cell cycle checkpoint signaling	1
negative regulation of G2/M transition of mitotic cell cycle	1
regulation of DNA repair	1
positive regulation of response to stimulus	1
positive regulation of DNA metabolic process	1
cellular process	1
protein deubiquitination	1
cellular response to radiation	1
chromatin remodeling	1
positive regulation of protein-containing complex assembly	1
NLRP3 inflammasome complex assembly	1
positive regulation of inflammasome-mediated signaling pathway	1
regulation of NLRP3 inflammasome complex assembly	1
DNA damage checkpoint signaling	1
regulation of cell cycle checkpoint	1
DNA metabolic process	1
cellular component organization	1
cellular response to stress	1
canonical inflammasome complex assembly	1
cysteine-type peptidase activity	1
peptidase activity	1
molecular function regulator activity	1
modification-dependent protein binding	1
cation binding	1

Protein interactions and networks

STRING

3074 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BRCC3	UIMC1	Q96RL1	999
BRCC3	BABAM2	Q9NXR7	998
BRCC3	BABAM1	Q9NWV8	998
BRCC3	ABRAXAS1	Q6UWZ7	998
BRCC3	BRCA1	P38398	995
BRCC3	BARD1	Q99728	994
BRCC3	ABRAXAS2	Q15018	992
BRCC3	BRCA2	P51587	858
BRCC3	RNF8	O76064	780
BRCC3	MDC1	Q14676	775
BRCC3	RAD51	Q06609	752
BRCC3	RBBP8	Q99708	733
BRCC3	ZUP1	Q96AP4	711
BRCC3	RNF168	Q8IYW5	659
BRCC3	STAMBPL1	Q96FJ0	654

IntAct

78 interactions, top by confidence:

A	B	Type	Score
JUNB	FOS	psi-mi:“MI:0914”(association)	0.950
SHMT2	BRCC3	psi-mi:“MI:0915”(physical association)	0.720
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
UIMC1	BRCC3	psi-mi:“MI:0915”(physical association)	0.690
BRCC3	UIMC1	psi-mi:“MI:0915”(physical association)	0.690
ABRAXAS2	BRCC3	psi-mi:“MI:2364”(proximity)	0.690
BRCC3	ABRAXAS2	psi-mi:“MI:2364”(proximity)	0.690
BRCC3	ABRAXAS2	psi-mi:“MI:0915”(physical association)	0.690
ABRAXAS2	BRCC3	psi-mi:“MI:0915”(physical association)	0.690
BABAM2	BRCC3	psi-mi:“MI:0914”(association)	0.670
ABRAXAS1	BRCC3	psi-mi:“MI:0915”(physical association)	0.640
BABAM1	TNKS	psi-mi:“MI:0914”(association)	0.640
BRCC3	BRCA1	psi-mi:“MI:0914”(association)	0.610
BRCA1	BRCC3	psi-mi:“MI:0914”(association)	0.610
ANKRD11	BRCC3	psi-mi:“MI:0915”(physical association)	0.560
BRCC3	ANKRD11	psi-mi:“MI:0915”(physical association)	0.560
YWHAG	SHTN1	psi-mi:“MI:0914”(association)	0.560
KSR2	POLR3A	psi-mi:“MI:0914”(association)	0.530
TNS1	SORBS3	psi-mi:“MI:0914”(association)	0.530
DEF6	ARHGAP42	psi-mi:“MI:0914”(association)	0.530
TFDP3	E2F3	psi-mi:“MI:0914”(association)	0.530

BioGRID (276): BRCC3 (Affinity Capture-Western), FANCG (Biochemical Activity), BRCC3 (Affinity Capture-Western), BRCC3 (Affinity Capture-MS), BRCC3 (Affinity Capture-MS), BRCC3 (Affinity Capture-MS), BRCC3 (Affinity Capture-MS), BRCC3 (Affinity Capture-MS), BRCC3 (Affinity Capture-MS), BRCC3 (Two-hybrid), BRCC3 (Affinity Capture-MS), BRCC3 (Affinity Capture-MS), BRCC3 (Affinity Capture-MS), BRCC3 (Affinity Capture-MS), BRCC3 (Affinity Capture-MS)

ESM2 similar proteins: A0A8M3B525, A2AHJ4, A5PJP6, B0KWU8, B2RYM5, B5X8M4, E1C3P4, E9Q4Z2, O00763, O42611, O94967, O95630, P46736, P46737, P48553, Q15386, Q15542, Q3TLI0, Q4VA72, Q5KSL6, Q5R558, Q5R9L6, Q5RAQ5, Q5VVJ2, Q641K1, Q66GV6, Q66H62, Q69Z66, Q6RI45, Q6WKZ8, Q76N33, Q7M757, Q80U95, Q8BPM2, Q8CGF6, Q8IVH8, Q8QFR2, Q8TAT6, Q8VDD9, Q8W206

Diamond homologs: A0A8M3B525, A5PJP6, B0KWU8, B2RYM5, B5X8M4, E2AXC7, O35864, P46736, P46737, Q3TV65, Q4VA72, Q5R9L6, Q66GV6, Q6GLM9, Q6P635, Q6PC30, Q7M757, Q8H936, Q8N594, Q92905, Q9LT08, A6ZXB7, B3LH96, O94454, P91001, Q12468, Q4IJM4, Q4P804, Q6BMQ3, Q6C703, Q7RXX8, Q9FVU9, O00487, O35593, O76577, P0CQ24, P0CQ25, P41878, P41883, P43588

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
BRCC3	down-regulates	H2AC11	deubiquitination
BRCC3	“form complex”	“BRCC ubiquitin ligase complex”	binding
BRCC3	“form complex”	“BRCA1-A complex”	binding
BRCC3	down-regulates	“Histone H2A”	deubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 80 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
Metalloprotease DUBs	8	40.1×	3e-09
DNA Double Strand Break Response	5	39.6×	1e-05
Homology Directed Repair	5	25.7×	7e-05
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	5	25.7×	7e-05
G2/M Checkpoints	11	24.6×	3e-10
G2/M DNA damage checkpoint	11	22.0×	5e-10
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks	9	22.0×	3e-08
DNA Double-Strand Break Repair	5	20.7×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
mitotic G2/M transition checkpoint	5	57.3×	4e-06
protein K63-linked deubiquitination	5	44.6×	1e-05
positive regulation of DNA repair	7	35.9×	5e-07
mitotic G2 DNA damage checkpoint signaling	5	31.7×	5e-05
response to ionizing radiation	5	29.4×	6e-05
regulation of DNA repair	6	23.7×	2e-05
double-strand break repair	8	23.2×	6e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	21
Likely pathogenic	6
Uncertain significance	27
Likely benign	12
Benign	1

Top pathogenic / likely-pathogenic (27)

Variant ID	HGVS	Classification
1340345	GRCh37/hg19 Xq28(chrX:154120629-154565718)x0	Pathogenic
1342389	NC_000023.11:g.(154612552_154656872)_(156005236_156038495)del	Pathogenic
146792	GRCh38/hg38 Xq28(chrX:154679854-156003229)x1	Pathogenic
1808575	GRCh37/hg19 Xq28(chrX:154110981-154565718)x2	Pathogenic
253454	GRCh37/hg19 Xq28(chrX:154115785-154528181)x1	Pathogenic
2583089	GRCh37/hg19 Xq28(chrX:154124352-154563736)x2	Pathogenic
3062537	GRCh37/hg19 Xq28(chrX:154260005-154739500)	Pathogenic
441839	GRCh37/hg19 Xq28(chrX:154120620-154565718)x1	Pathogenic
442510	GRCh37/hg19 Xq28(chrX:154250433-154317840)x0	Pathogenic
443466	GRCh37/hg19 Xq28(chrX:154117578-154553189)x2	Pathogenic
4796313	GRCh38/hg38 Xq28(chrX:154881139-155396181)x2	Pathogenic
564944	GRCh37/hg19 Xq28(chrX:154120640-154565718)x1	Pathogenic
58019	GRCh38/hg38 Xq28(chrX:154897608-155335682)x1	Pathogenic
58020	GRCh38/hg38 Xq28(chrX:154984506-155098444)x0	Pathogenic
625645	GRCh37/hg19 Xq28(chrX:154305031-154307464)	Pathogenic
684993	GRCh37/hg19 Xq28(chrX:154117563-154617602)x2	Pathogenic
687057	GRCh37/hg19 Xq28(chrX:154117563-154633634)x3	Pathogenic
687523	GRCh37/hg19 Xq28(chrX:154306330-154680053)x2	Pathogenic
929335	GRCh37/hg19 Xq28(chrX:154130223-154563104)x3	Pathogenic
929354	GRCh37/hg19 Xq28(chrX:154051891-155236747)x3	Pathogenic
980881	GRCh37/hg19 Xq28(chrX:154078238-154563469)x3	Pathogenic
144350	GRCh38/hg38 Xq28(chrX:154931352-155331063)x1	Likely pathogenic
150981	GRCh38/hg38 Xq28(chrX:154890313-155331062)x1	Likely pathogenic
1808711	GRCh37/hg19 Xq28(chrX:154120621-154565718)x1	Likely pathogenic
3906917	GRCh37/hg19 Xq28(chrX:154285587-154310562)x0	Likely pathogenic
560116	Single allele	Likely pathogenic
625803	GRCh37/hg19 Xq28(chrX:153761240-155227607)	Likely pathogenic

SpliceAI

1851 predictions. Top by Δscore:

Variant	Effect	Δscore
X:155071624:G:GT	donor_gain	1.0000
X:155071624:G:T	donor_gain	1.0000
X:155073361:A:AG	acceptor_gain	1.0000
X:155077284:G:GT	donor_gain	1.0000
X:155077285:C:T	donor_gain	1.0000
X:155089338:A:G	donor_gain	1.0000
X:155090782:A:AG	acceptor_gain	1.0000
X:155090783:G:GG	acceptor_gain	1.0000
X:155090838:GA:G	donor_gain	1.0000
X:155116709:A:AG	acceptor_gain	1.0000
X:155116710:G:GG	acceptor_gain	1.0000
X:155119997:A:AG	acceptor_gain	1.0000
X:155119998:G:GG	acceptor_gain	1.0000
X:155120115:G:GT	donor_gain	1.0000
X:155120630:G:T	donor_gain	1.0000
X:155071621:G:GT	donor_gain	0.9900
X:155071627:G:GG	donor_gain	0.9900
X:155071651:GTGA:G	donor_loss	0.9900
X:155072325:A:AG	acceptor_gain	0.9900
X:155072326:G:GA	acceptor_gain	0.9900
X:155073362:A:G	acceptor_gain	0.9900
X:155073366:A:AG	acceptor_gain	0.9900
X:155077164:CTTTA:C	acceptor_loss	0.9900
X:155077165:TTTA:T	acceptor_loss	0.9900
X:155077166:TTA:T	acceptor_loss	0.9900
X:155077167:TAGGT:T	acceptor_loss	0.9900
X:155077168:A:C	acceptor_loss	0.9900
X:155077232:G:GT	donor_gain	0.9900
X:155089347:CAAAG:C	donor_loss	0.9900
X:155089348:AAAGG:A	donor_loss	0.9900

AlphaMissense

1918 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:155071568:T:C	L14P	1.000
X:155071591:T:C	C22R	1.000
X:155071593:T:G	C22W	1.000
X:155071600:C:G	H25D	1.000
X:155071602:C:A	H25Q	1.000
X:155071602:C:G	H25Q	1.000
X:155071604:C:A	A26D	1.000
X:155071607:T:C	L27P	1.000
X:155071609:A:C	S28R	1.000
X:155071611:C:A	S28R	1.000
X:155071611:C:G	S28R	1.000
X:155071624:G:A	E33K	1.000
X:155071624:G:C	E33Q	1.000
X:155071625:A:C	E33A	1.000
X:155071625:A:G	E33G	1.000
X:155071625:A:T	E33V	1.000
X:155071626:A:C	E33D	1.000
X:155071626:A:T	E33D	1.000
X:155071633:G:A	G36R	1.000
X:155071633:G:C	G36R	1.000
X:155071633:G:T	G36W	1.000
X:155071634:G:A	G36E	1.000
X:155071634:G:T	G36V	1.000
X:155071637:T:C	L37P	1.000
X:155071639:T:C	C38R	1.000
X:155071645:G:T	G40W	1.000
X:155071646:G:A	G40E	1.000
X:155077218:C:A	R82S	1.000
X:155077218:C:G	R82G	1.000
X:155077229:G:C	K85N	1.000

dbSNP variants (sampled 300 via entrez): RS1000285506 (X:155070923 A>G), RS1000521820 (X:155087068 G>A,C), RS1000547692 (X:155105985 C>T), RS1000653258 (X:155098723 A>G), RS1000662050 (X:155078642 C>T), RS1000892706 (X:155119625 C>T), RS1000956402 (X:155086703 C>A,T), RS1001297703 (X:155075670 T>C), RS1001456016 (X:155114537 T>A), RS1001520543 (X:155107803 G>A), RS1001591818 (X:155114071 A>G), RS1001712295 (X:155093202 G>A), RS1001825476 (X:155104989 T>A), RS1001893280 (X:155084598 C>G,T), RS1002300198 (X:155076829 G>A)

Disease associations

OMIM: gene MIM:300617 | disease phenotypes: MIM:300815, MIM:300845

GenCC curated gene-disease

Disease	Classification	Inheritance
Moyamoya disease	Limited	Autosomal dominant

Mondo (4): chromosome Xq28 duplication syndrome (MONDO:0010436), hereditary neoplastic syndrome (MONDO:0015356), moyamoya angiopathy-short stature-facial dysmorphism-hypergonadotropic hypogonadism syndrome (MONDO:0010448), Moyamoya disease (MONDO:0016820)

Orphanet (3): Proximal Xq28 duplication syndrome (Orphanet:1762), Inherited cancer-predisposing syndrome (Orphanet:140162), Moyamoya angiopathy-short stature-facial dysmorphism-hypergonadotropic hypogonadism syndrome (Orphanet:280679)

HPO phenotypes

27 total (27 of 27 shown, HPO-id order):

HPO	Term
HP:0000027	Azoospermia
HP:0000278	Retrognathia
HP:0000316	Hypertelorism
HP:0000343	Long philtrum
HP:0000369	Low-set ears
HP:0000445	Wide nose
HP:0000454	Flared nostrils
HP:0000490	Deeply set eye
HP:0000518	Cataract
HP:0000707	Abnormality of the nervous system
HP:0000815	Hypergonadotropic hypogonadism
HP:0000822	Hypertension
HP:0000823	Delayed puberty
HP:0000824	Decreased response to growth hormone stimulation test
HP:0001263	Global developmental delay
HP:0001324	Muscle weakness
HP:0001342	Cerebral hemorrhage
HP:0001644	Dilated cardiomyopathy
HP:0001677	Coronary artery atherosclerosis
HP:0001999	Abnormal facial shape
HP:0002140	Ischemic stroke
HP:0002216	Premature graying of hair
HP:0004302	Functional motor deficit
HP:0004322	Short stature
HP:0007970	Congenital ptosis
HP:0008734	Decreased testicular size
HP:0011834	Moyamoya phenomenon

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009097_11	Venous thromboembolism	4.000000e-12

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D009072	Moyamoya Disease	C10.228.140.300.200.600; C10.228.140.300.510.200.737; C14.907.137.615; C14.907.253.123.620; C14.907.253.560.200.737
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
C567580	Chromosome Xq28 Duplication Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105965 (SINGLE PROTEIN)

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

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
Capzimin	IC50	340 nM	US-10005735: Inhibitors of RPN11

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
8-sulfanyl-N-[2-(1,3-thiazol-2-yl)ethyl]quinoline-3-carboxamide	1802703: In Vitro BRCC36 Activity Assay from Article 10.1038/nchembio.2326: “Capzimin is a potent and specific inhibitor of proteasome isopeptidase Rpn11.”	ic50	2.3000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression	2
sodium arsenite	affects cotreatment, increases expression, decreases expression	2
Plant Extracts	affects cotreatment, increases expression, decreases expression	2
TAK-243	decreases sumoylation	1
2,4,6-tribromophenol	increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
4-biphenylamine	decreases expression, decreases reaction	1
titanium dioxide	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
tetrabromobisphenol A	decreases expression	1
potassium chromate(VI)	decreases expression	1
nickel sulfate	decreases expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
torcetrapib	increases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
Bortezomib	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Amiodarone	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cannabidiol	decreases expression	1
Catechin	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4049715	Binding	Inhibition of BRCC36 (unknown origin) using DiUbK63TAMRA as substrate by fluorescence assay	Discovery of an Inhibitor of the Proteasome Subunit Rpn11. — J Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SF50	HAP1 BRCC3 (-) 1	Cancer cell line	Male
CVCL_SF51	HAP1 BRCC3 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04205578	PHASE3	UNKNOWN	NBP in Patients With Moyamoya Disease of High Risk for Ischemic Cerebrovascular Events
NCT07065409	PHASE1	RECRUITING	Treatment of Moyamoya Disease With iPSC-derived Exosomes
NCT07286110	PHASE1	NOT_YET_RECRUITING	Chinese Herbal Therapy (Qiqi Shengmai Formula) for Moyamoya Vasculopathy: The CHIMES Trial
NCT03162588	PHASE1/PHASE2	COMPLETED	Multiple Burrhole Therapy With Erythropoietin for Unstable Moyamoya
NCT01419275	Not specified	COMPLETED	Quantifying Collateral Perfusion in Cerebrovascular Disease-Moyamoya Disease and Stroke Patients
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT02074111	Not specified	UNKNOWN	Moyamoya Disease Biomarkers in Patients With Intracranial Atherosclerotic Stroke
NCT02305407	Not specified	UNKNOWN	Neurocognitive and Radiological Assessments in Adult Moyamoya Undergoing Surgery
NCT02510586	Not specified	UNKNOWN	Sevoflurane and Hyperperfusion Syndrome
NCT02982135	Not specified	UNKNOWN	Direct Bypass Versus Indirect Bypass in Treatment of Adults Hemorrhagic Moyamoya Disease
NCT03072914	Not specified	COMPLETED	Effects of Remote Ischemic Preconditioning With Postconditioning on Neurologic Outcome
NCT03516851	Not specified	WITHDRAWN	Precision Bypass in Patients With Moyamoya Disease
NCT03543748	Not specified	UNKNOWN	Efficacy and Safety of rTMS for Cognitive Rehabilitation in Moyamoya Disease
NCT03546309	Not specified	RECRUITING	Safety and Efficacy of RIC in Pediatric Moyamoya Disease Patients Treated With Revascularization Therapy
NCT03613701	Not specified	UNKNOWN	Relationship Between Endothelial Progenitor Cells and Revascularization Effect of Moyamoya Disease
NCT03627975	Not specified	UNKNOWN	Effect of Surgical Revascularization on Hemorrhagic Moyamoya Disease
NCT03785171	Not specified	UNKNOWN	Predicative Value of Multimodal MRI in Moyamoya Disease
NCT03821181	Not specified	UNKNOWN	The Effect of RIC on TIA/Stroke in Children With Moyamoya Disease
NCT03882060	Not specified	UNKNOWN	Effect of Recombinant Human EPO on the Postoperative Neurologic Outcome in Pediatric Moyamoya Patients
NCT04012268	Not specified	COMPLETED	The Safety and Efficacy of RIC on Adult Moyamoya Disease
NCT04064658	Not specified	SUSPENDED	Effects of Remote Ischemic Pre-Conditioning in Moyamoya Disease Patients
NCT04696094	Not specified	UNKNOWN	The Role of m6A RNA Modification in Moyamoya Disease
NCT04890782	Not specified	UNKNOWN	Gut Microbiota in Patients With Moyamoya Disease
NCT04906564	Not specified	COMPLETED	RNF213 Variants and Collateral Vessels in Moyamoya Disease
NCT04917003	Not specified	UNKNOWN	Safety and Efficacy of Remote Ischemic Conditioning Combined EDAS on Ischemic Moyamoya Disease
NCT05332756	Not specified	RECRUITING	Long-term Outcomes of Conservative Management in Patients with Moyamoya Disease and Their First-degree Relatives (LAMORA)
NCT05491980	Not specified	ACTIVE_NOT_RECRUITING	Florida Cerebrovascular Disease Biorepository and Genomics Center
NCT05619068	Not specified	RECRUITING	The Evolution and Prognosis of Moyamoya Disease
NCT05772572	Not specified	COMPLETED	Functional Disorders Moya Moya Young Patients
NCT05860946	Not specified	UNKNOWN	Remote Ischemic Conditioning in Adult Moyamoya Disease Patients
NCT05961748	Not specified	RECRUITING	Registry of Multicenter Brain-Heart Comorbidity in China
NCT06041659	Not specified	RECRUITING	Functional Magnetic Resonance-Based Observations of Brain Networks in Moyamoya Disease Patients Under Anesthesia
NCT06051552	Not specified	NOT_YET_RECRUITING	Prognostic Prediction Model in Patients With Moyamoya Disease Undergoing Revascularization Surgery
NCT06330818	Not specified	RECRUITING	Imaging in Moyamoya Disease - Study to Investigate Different Imaging Technologies for a Better Understanding of Various Imaging Techniques to Evaluate Cerebral Hemodynamics, Disease-activity and Possibly the Etiology in Moyamoya Patients
NCT06477107	Not specified	ENROLLING_BY_INVITATION	A Study of Cerebral Perfusion With tDCS in Chronic Hypoperfusion
NCT06634004	Not specified	ENROLLING_BY_INVITATION	Biomarker-Led Optimization of Successful Surgical Outcomes in Moyamoya
NCT06714097	Not specified	RECRUITING	Application of Digital Twins’ Technology in Patients Who Had a Stroke, With Moyamoya Disease and With Cerebral Amyloid Angiopathy (CAA) During the Secondary Prevention Phase: A Proof of Concept Using a Randomized Control Trial (Clinical Study 6, STRATIF-AI Project)
NCT06724029	Not specified	RECRUITING	Neurosurgical Outcome Network
NCT06817434	Not specified	RECRUITING	Study on Evaluating the Effectiveness of Statins in the Treatment of Moyamoya Disease
NCT06832839	Not specified	RECRUITING	Study on the Mechanism of Cognitive Impairment in Patients with Moyamoya Disease