RNF213

Summary

RNF213 (ring finger protein 213, HGNC:14539) is a protein-coding gene on chromosome 17q25.3, encoding E3 ubiquitin-protein ligase RNF213 (Q63HN8). Atypical E3 ubiquitin ligase that can catalyze ubiquitination of both proteins and lipids, and which is involved in various processes, such as lipid metabolism, angiogenesis and cell-autonomous immunity.

This gene encodes a protein containing a C3HC4-type RING finger domain, which is a specialized type of Zn-finger that binds two atoms of zinc and is thought to be involved in mediating protein-protein interactions. The protein also contains an AAA domain, which is associated with ATPase activity. This gene is a susceptibility gene for Moyamoya disease, a vascular disorder of intracranial arteries. This gene is also a translocation partner in anaplastic large cell lymphoma and inflammatory myofibroblastic tumor cases, where a t(2;17)(p23;q25) translocation has been identified with the anaplastic lymphoma kinase (ALK) gene on chromosome 2, and a t(8;17)(q24;q25) translocation has been identified with the MYC gene on chromosome 8. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 57674 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Moyamoya disease 2 (Strong, GenCC)
• GWAS associations: 13
• Clinical variants (ClinVar): 1,043 total — 6 pathogenic, 13 likely-pathogenic
• Phenotypes (HPO): 9
• Druggable target: yes
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 10 cancer types
• MANE Select transcript: NM_001256071

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14539
Approved symbol	RNF213
Name	ring finger protein 213
Location	17q25.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1554, NET57, ALO17
Ensembl gene	ENSG00000173821
Ensembl biotype	protein_coding
OMIM	613768
Entrez	57674

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 15 retained_intron, 4 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000319921, ENST00000411702, ENST00000427003, ENST00000508628, ENST00000558116, ENST00000558488, ENST00000559070, ENST00000559603, ENST00000559864, ENST00000560083, ENST00000560694, ENST00000570776, ENST00000571908, ENST00000572622, ENST00000573038, ENST00000573548, ENST00000573919, ENST00000574060, ENST00000574909, ENST00000582970

RefSeq mRNA: 4 — MANE Select: NM_001256071 NM_001256071, NM_001410195, NM_020914, NM_020954

CCDS: CCDS11772, CCDS32761, CCDS58606

Canonical transcript exons

ENST00000582970 — 68 exons

Exon	Start	End
ENSE00001191774	80381547	80381727
ENSE00001235391	80344678	80348286
ENSE00001260361	80273241	80273404
ENSE00001260391	80287815	80288363
ENSE00001390612	80260852	80260902
ENSE00001399527	80354019	80354166
ENSE00001400825	80351685	80351803
ENSE00001402870	80353512	80353666
ENSE00001403639	80350301	80350396
ENSE00001406208	80352940	80353059
ENSE00001410365	80349770	80349906
ENSE00001464743	80343857	80344015
ENSE00001464744	80343132	80343325
ENSE00002022415	80337586	80337726
ENSE00002041046	80339201	80340356
ENSE00002077270	80336161	80336378
ENSE00002677982	80263574	80263778
ENSE00002725005	80393345	80398794
ENSE00003460158	80386250	80386430
ENSE00003470916	80295557	80295813
ENSE00003476514	80374458	80374589
ENSE00003481372	80363609	80363790
ENSE00003481809	80317188	80317277
ENSE00003485264	80319190	80319312
ENSE00003490899	80354441	80354576
ENSE00003497941	80363102	80363314
ENSE00003500163	80376301	80376543
ENSE00003504455	80388612	80388689
ENSE00003506077	80377762	80377796
ENSE00003510221	80289659	80289837
ENSE00003511048	80375760	80375870
ENSE00003514026	80372521	80372734
ENSE00003520332	80367961	80368143
ENSE00003523788	80385538	80385621
ENSE00003524513	80380831	80380987
ENSE00003532369	80328328	80328477
ENSE00003539173	80371874	80371985
ENSE00003541281	80360061	80360206
ENSE00003542630	80379620	80379714
ENSE00003544359	80383677	80383928
ENSE00003544895	80298321	80298518
ENSE00003556604	80372975	80373165
ENSE00003562184	80325030	80325198
ENSE00003564454	80369768	80369867
ENSE00003579768	80327816	80327989
ENSE00003585975	80288633	80288755
ENSE00003586204	80334105	80334270
ENSE00003589610	80364433	80364553
ENSE00003592435	80367748	80367848
ENSE00003596621	80306252	80306468
ENSE00003597388	80382979	80383070
ENSE00003597920	80369502	80369671
ENSE00003600100	80290570	80290728
ENSE00003608782	80337833	80337997
ENSE00003620753	80313012	80313167
ENSE00003623256	80309018	80309171
ENSE00003624150	80291628	80291827
ENSE00003631769	80376882	80376963
ENSE00003639848	80307128	80307201
ENSE00003640143	80358288	80358479
ENSE00003643863	80390012	80390196
ENSE00003647714	80386690	80386891
ENSE00003652833	80294720	80295003
ENSE00003665518	80389828	80389917
ENSE00003668803	80361734	80361888
ENSE00003677343	80332006	80332631
ENSE00003678069	80385039	80385171
ENSE00003679533	80389173	80389367

Expression profiles

Bgee: expression breadth ubiquitous, 252 present calls, max score 99.03.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.3930 / max 216.9864, expressed in 1805 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
163230	15.5061	1803
163235	0.8148	201
163231	0.5817	308
163232	0.2738	96
163237	0.1055	34
163236	0.0891	36
163241	0.0221	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	99.03	gold quality
metanephros cortex	UBERON:0010533	98.69	gold quality
pancreatic ductal cell	CL:0002079	98.30	gold quality
spleen	UBERON:0002106	98.11	gold quality
sural nerve	UBERON:0015488	98.02	gold quality
bone marrow cell	CL:0002092	97.87	gold quality
upper lobe of left lung	UBERON:0008952	97.68	gold quality
leukocyte	CL:0000738	97.65	gold quality
monocyte	CL:0000576	97.56	gold quality
right lobe of thyroid gland	UBERON:0001119	97.55	gold quality
right uterine tube	UBERON:0001302	97.45	gold quality
mucosa of stomach	UBERON:0001199	97.41	gold quality
left lobe of thyroid gland	UBERON:0001120	97.36	gold quality
lymph node	UBERON:0000029	97.33	gold quality
upper lobe of lung	UBERON:0008948	97.23	gold quality
right adrenal gland	UBERON:0001233	97.21	gold quality
vermiform appendix	UBERON:0001154	97.18	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.13	gold quality
right adrenal gland cortex	UBERON:0035827	97.10	gold quality
right lung	UBERON:0002167	97.06	gold quality
thyroid gland	UBERON:0002046	96.84	gold quality
left adrenal gland	UBERON:0001234	96.81	gold quality
left adrenal gland cortex	UBERON:0035825	96.79	gold quality
blood	UBERON:0000178	96.64	gold quality
adrenal cortex	UBERON:0001235	96.51	gold quality
cortex of kidney	UBERON:0001225	96.40	gold quality
tibial nerve	UBERON:0001323	96.38	gold quality
caecum	UBERON:0001153	96.29	gold quality
descending thoracic aorta	UBERON:0002345	96.25	gold quality
gall bladder	UBERON:0002110	96.17	gold quality

Single-cell (SCXA)

Detected in 15 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-CURD-53	yes	1963.28
E-MTAB-6678	yes	1556.20
E-CURD-122	yes	44.69
E-HCAD-10	yes	6.96
E-MTAB-9801	yes	5.87
E-GEOD-130148	yes	4.86
E-MTAB-9067	yes	4.74
E-CURD-119	yes	4.53
E-MTAB-6379	no	1629.56
E-CURD-97	no	1341.06
E-CURD-89	no	1336.21
E-CURD-135	no	1102.64
E-MTAB-6075	no	709.39
E-CURD-112	no	3.45
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): STAT1

Literature-anchored findings (GeneRIF, showing 40)

• KIAA1618 (ALO17) ia a novel fusion partner of anaplastic lymphoma kinase in anaplastic large-cell lymphoma and inflammatory myofibroblastic tumor cases. (PMID:12112524)
• involvement of RNF213 in genetic susceptibility to moyamoya disease (PMID:21799892)
• The homozygous c.14576G>A variant in RNF213 could be a good DNA biomarker for predicting the severe type of moyamoya disease (PMID:22377813)
• Moyamoya disease is often accompanied by hypertension. RNF213 has been identified as a susceptibility gene for this disease. Associations of p.R4810K (rs112735431, ss179362673) of RNF213 with blood pressure were investigated in moyamoya disease patients. (PMID:22878964)
• A homozygous c.14576G>A variant of RNF213 gene is associated with neurological deficits with vasculopathy in moyamoya disease. (PMID:22931863)
• We propose the existence of a new entity of intracranial major artery stenosis/occlusion caused by the c.14576G>A variant in RNF213. (PMID:23010677)
• RNF213 mutations are associated with MMD susceptibility in Han Chinese. The ischemic type MMD is particularly related to the R4810K mutation. (PMID:23110205)
• There are strong associations between p.R4859K and p.R4810K polymorphisms of the RNF213 gene and Moyamoya disease (Meta-analysis). (PMID:23466837)
• the influences of PDGFRB, MMP-3, and TIMP-2 on MMD may be unremarkable in Chinese Hans. There may be no prominent interaction among these five gene polymorphisms on the occurrence of MMD. (PMID:23769926)
• RNF213 R4810K reduced angiogenic activities of iPSECs from patients with MMD, suggesting that it is a promising in vitro model for MMD. (PMID:23850618)
• A particular subset of patients with various phenotypes of ICASO has a common genetic variant, RNF213 c.14576G>A, indicating that RNF213 c.14576G>A variant is a high-risk allele for ICASO. (PMID:23970789)
• RNF213 R4810K induced mitotic abnormalities and increased risk of genomic instability. (PMID:23994138)
• the moyamoya disease-associated gene product is a unique protein that functions as ubiquitin ligase and AAA+ ATPase, which possibly contributes to vascular development through mechanical processes in the cell. (PMID:24658080)
• Study identified of a novel RNF213 variant in a three-generation family of European ancestry with intracerebral vasculopathy displaying variability in age of onset and clinical severity (PMID:25043520)
• RNF213 was not associated with bipolar disorder or schizophrenia. (PMID:25053281)
• Alterations in RNF213 predispose patients of diverse ethnicities to Moyamoya disease. (PMID:25278557)
• vascular wall was significantly thinner in RNF213-/- mice at 14 days (PMID:25383461)
• Nonatherosclerotic quasi-MMD did not have RNF213 c.14576G>A variant. (PMID:25817623)
• This study demonstrated that the RNF213 mutation should form part of the diagnostic workup for moyamoya in clinical practice. (PMID:25956231)
• Not only p.4810K but also other functional missense variants of RNF213 conferred susceptibility to moyamoya disease(MMD). (PMID:25964206)
• Gene-based association analyses shows nominal significant association with multifocal fibromuscular dysplasia for RNF213. (PMID:26147384)
• We herein report pediatric sibling patients of moyamoya disease who have homozygous wild-type c.14576G>A variant in RNF213, showing different clinical course and disease severity. (PMID:26277359)
• RNF213 plays unique roles in endothelial cells for proper gene expressions in response to inflammatory signals from environments. (PMID:26278786)
• This is the first report, to our knowledge, of different moyamoya disease phenotypes in a familial case involving the same heterozygous c.14429G > A variant in RNF213. (PMID:26315205)
• The findings indicate that the c.14429G>A (p.R4810K) allele of RNF213 is strongly associated with Korean patients with MMD. The homozygous c.14429G>A (p.R4810K) variant is particularly related to early-onset MMD. (PMID:26430847)
• results confirm that the RNF213 p.Arg4810Lys variant is not uncommon in the general Korean population and provide reference data for the association of this variant and MMD (PMID:26590131)
• Results suggested that rs112735431 in RNF213 was associated with increased risk of moyamoya disease, especially among Japanese and Korean compared with Chinese. [meta-analysis]. (PMID:26847828)
• The RNF213 c.14576G>A variant is more common in NF-1 patients who develop moyamoya syndrome than in NF-1 patients without moyamoya syndrome. (PMID:26849809)
• is a susceptibility gene not only for moyamoya disease but also for intracranial atherosclerotic stenosis in East Asians. (PMID:27253870)
• PTP1B/RNF213/alpha-KGDD pathway is critical for survival of HER2(+) breast cancer, and possibly other malignancies, in the hypoxic tumour microenvironment (PMID:27323329)
• Caveolin-1 level was decreased in patients with Moyamoya disease and markedly decreased in RNF213 variant carriers. Path analysis showed that the presence of the RNF213 variant was associated with caveolin-1 levels that could lead to Moyamoya disease. (PMID:27462098)
• RNF213 p.R4810K polymorphism was significantly associated with quasi-moyamoya disease. (PMID:27476341)
• Case-control study and meta-analysis both provide evidence of an association between the rs112735431 polymorphism in the RNF213 gene and moyamoya risk. (PMID:27515544)
• Both RNF213 D4013N and V4146A significantly decreased re-endothelialization in the migration assay compared with RNF213 WT and the control vector. (PMID:27736983)
• We found that RNF213 single nucleotide polymorphism rs6565666 was associated with intracranial aneurysms in French-Canadian individuals. (PMID:27745834)
• RNF213 is not only associated with MMD but also associated with intracranial major artery stenosis. The genotypes of RNF213 correlate with the phenotypes of MMD. (PMID:27748344)
• Moyamoya vasculopathy shows a genetic mutational gradient decreasing from East to West. (PMID:27787485)
• The p.R4810K variant was associated with atherosclerotic and autoimmune quasi-Moyamoya disease in a Chinese population, and a lower prevalence of this variant in patients with quasi-Moyamoya disease compared with patients with Moyamoya disease was observed. (PMID:28063898)
• Data indicate that mysterin/RNF213 is a substrate of ubiquitin specific protease 15 (USP15), and that the conserved skipping of exon 7 significantly decreases its specific affinity for mysterin. (PMID:28276505)
• This study suggests that the rs112735431 polymorphism of the RNF213 may be linked to the hypertension in moyamoya disease. (PMID:28320162)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	rnf213a	ENSDARG00000099465
danio_rerio		ENSDARG00000113458
mus_musculus	Rnf213	ENSMUSG00000070327
rattus_norvegicus	Rnf213	ENSRNOG00000029658

Protein

Protein identifiers

E3 ubiquitin-protein ligase RNF213 — Q63HN8 (reviewed: Q63HN8)

Alternative names: ALK lymphoma oligomerization partner on chromosome 17, E3 ubiquitin-lipopolysaccharide ligase RNF213, Mysterin, RING finger protein 213

All UniProt accessions (4): Q63HN8, A0A0A0MTC1, A0A0A0MTR7, I3L3H9

UniProt curated annotations — full annotation on UniProt →

Function. Atypical E3 ubiquitin ligase that can catalyze ubiquitination of both proteins and lipids, and which is involved in various processes, such as lipid metabolism, angiogenesis and cell-autonomous immunity. Acts as a key immune sensor by catalyzing ubiquitination of the lipid A moiety of bacterial lipopolysaccharide (LPS) via its RZ-type zinc-finger: restricts the proliferation of cytosolic bacteria, such as Salmonella, by generating the bacterial ubiquitin coat through the ubiquitination of LPS. Also acts indirectly by mediating the recruitment of the LUBAC complex, which conjugates linear polyubiquitin chains. Ubiquitination of LPS triggers cell-autonomous immunity, such as antibacterial autophagy, leading to degradation of the microbial invader. Involved in lipid metabolism by regulating fat storage and lipid droplet formation; act by inhibiting the lipolytic process. Also regulates lipotoxicity by inhibiting desaturation of fatty acids. Also acts as an E3 ubiquitin-protein ligase via its RING-type zinc finger: mediates ‘Lys-63’-linked ubiquitination of target proteins. Involved in the non-canonical Wnt signaling pathway in vascular development: acts by mediating ubiquitination and degradation of FLNA and NFATC2 downstream of RSPO3, leading to inhibit the non-canonical Wnt signaling pathway and promoting vessel regression. Also has ATPase activity; ATPase activity is required for ubiquitination of LPS.

Subunit / interactions. Monomer. Interacts with UBE2L3/UBCH7; UBE2L3/UBCH7 is the most efficient ubiquitin-conjugating enzyme E2 for the ubiquitin ligase activity. Interacts with UBE2N/UBC13; promoting ‘Lys-63’-linked ubiquitination of target proteins. (Microbial infection) Interacts with M.tuberculosis protein Rv3655c, which impairs caspase-8 activation and suppresses macrophage apoptosis by blocking the extrinsic pathway.

Subcellular location. Cytoplasm. Cytosol. Lipid droplet.

Tissue specificity. Widely expressed (at protein level). Major isoform detected in all tissues examined. Minor isoform with restricted expression.

Post-translational modifications. Autoubiquitinated.

Disease relevance. Moyamoya disease 2 (MYMY2) [MIM:607151] A progressive cerebral angiopathy characterized by bilateral intracranial carotid artery stenosis and telangiectatic vessels in the region of the basal ganglia. The abnormal vessels resemble a ‘puff of smoke’ (moyamoya) on cerebral angiogram. Affected individuals can develop transient ischemic attacks and/or cerebral infarction, and rupture of the collateral vessels can cause intracranial hemorrhage. Hemiplegia of sudden onset and epileptic seizures constitute the prevailing presentation in childhood, while subarachnoid bleeding occurs more frequently in adults. Disease susceptibility is associated with variants affecting the gene represented in this entry. A chromosomal aberration involving RNF213 is associated with anaplastic large-cell lymphoma (ALCL). Translocation t(2;17)(p23;q25) with ALK.

Domain organisation. Composed of an N-terminal stalk, a dynein-like core comprised of two catalytically active and four inactive ATPase domains, and a C-terminal E3 module. The ATPase regions do not generate movement but rather act like an intricate molecular ‘switch’. The RING-type zinc finger domain is required for the ubiquitin-protein ligase activity. The RZ-type (RNF213-ZNFX1) zinc-finger is required for the ubiquitination of the lipid A moiety of bacterial lipopolysaccharide (LPS).

Induction. Down-regulated by let-7c miRNA, which binds to the 3’-UTR transcript of RNF213. Induced by pro-inflammatory cytokines. (Microbial infection) Up-regulated in macrophages infected by M.tuberculosis.

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the AAA ATPase family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q63HN8-3	1	yes
Q63HN8-4	2
Q63HN8-5	3
Q63HN8-6	4

RefSeq proteins (4): NP_001243000, NP_001397124, NP_065965, NP_066005 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001841	Znf_RING	Domain
IPR003593	AAA+_ATPase	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR018957	Znf_C3HC4_RING-type	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR031248	RNF213	Family
IPR046439	ZF_RZ_dom	Domain

Pfam: PF00097, PF20173

Catalyzed reactions (Rhea), 1 shown:

• ATP + H2O = ADP + phosphate + H(+) (RHEA:13065)

UniProt features (484 total): helix 229, strand 88, sequence variant 64, turn 38, binding site 18, sequence conflict 15, compositionally biased region 9, mutagenesis site 6, splice variant 5, modified residue 4, zinc finger region 2, region of interest 2, chain 1, active site 1, cross-link 1, coiled-coil region 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
9JTA	X-RAY DIFFRACTION	1.7
8S24	ELECTRON MICROSCOPY	3
9G08	ELECTRON MICROSCOPY	3.3
9G09	ELECTRON MICROSCOPY	3.4

Predicted structure (AlphaFold)

No AlphaFold model available for Q63HN8 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

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): 4516 (nucleophile; for e3 ubiquitin-lipopolysaccharide ligase activity)

Ligand- & substrate-binding residues (18): 1995–2000; 2098; 2155; 2216; 2499; 2574; 3997; 4000; 4012; 4014; 4017; 4020 …

Post-translational modifications (5): 208, 217, 1258, 2273, 1151

Mutagenesis-validated functional residues (6):

Position	Phenotype
2426	impaired atp-binding leading to decreased atpase activity; abolished ubiquitination of lipopolysaccharide. in mutant a1a
2488	decreased atpase activity; abolished ubiquitination of lipopolysaccharide. in mutant b1b2; abolished atpase activity and
2488	loss of atpase hydrolysis.
2775	impaired atp-binding leading to decreased atpase activity; abolished ubiquitination of lipopolysaccharide. in mutant a1a
2845	decreased atpase activity; abolished ubiquitination of lipopolysaccharide. in mutant b1b2; abolished atpase activity and
4509	abolished ability to ubiquitinate lipopolysaccharide.

Function

Pathways and Gene Ontology

Reactome pathways

13 pathways

ID	Pathway
R-HSA-9635465	Suppression of apoptosis
R-HSA-9725370	Signaling by ALK fusions and activated point mutants
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation
R-HSA-1280218	Adaptive Immune System
R-HSA-1643685	Disease
R-HSA-168256	Immune System
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers
R-HSA-5663205	Infectious disease
R-HSA-9635486	Infection with Mycobacterium tuberculosis
R-HSA-9637690	Response of Mtb to phagocytosis
R-HSA-9700206	Signaling by ALK in cancer
R-HSA-9824439	Bacterial Infection Pathways
R-HSA-983169	Class I MHC mediated antigen processing & presentation

MSigDB gene sets: 305 (showing top): GOBP_LIPID_MODIFICATION, MYOGENIN_Q6, CCAWYNNGAAR_UNKNOWN, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, MODULE_255, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, GCANCTGNY_MYOD_Q6, GOBP_NON_CANONICAL_WNT_SIGNALING_PATHWAY, GOBP_REGULATION_OF_NON_CANONICAL_WNT_SIGNALING_PATHWAY, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, MODULE_317, JOHANSSON_GLIOMAGENESIS_BY_PDGFB_UP, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, GOBP_XENOPHAGY

GO Biological Process (14): angiogenesis (GO:0001525), sprouting angiogenesis (GO:0002040), immune system process (GO:0002376), ubiquitin-dependent protein catabolic process (GO:0006511), protein ubiquitination (GO:0016567), regulation of lipid metabolic process (GO:0019216), defense response to bacterium (GO:0042742), protein autoubiquitination (GO:0051865), protein K63-linked ubiquitination (GO:0070534), xenophagy (GO:0098792), lipid ubiquitination (GO:0120323), lipid droplet formation (GO:0140042), negative regulation of non-canonical Wnt signaling pathway (GO:2000051), lipid metabolic process (GO:0006629)

GO Molecular Function (10): ubiquitin-protein transferase activity (GO:0004842), ATP binding (GO:0005524), zinc ion binding (GO:0008270), ATP hydrolysis activity (GO:0016887), ubiquitin protein ligase activity (GO:0061630), nucleotide binding (GO:0000166), catalytic activity (GO:0003824), transferase activity (GO:0016740), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (5): nucleolus (GO:0005730), cytoplasm (GO:0005737), lipid droplet (GO:0005811), cytosol (GO:0005829), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
Disease	2
Response of Mtb to phagocytosis	1
Signaling by ALK in cancer	1
Class I MHC mediated antigen processing & presentation	1
Immune System	1
Bacterial Infection Pathways	1
Infection with Mycobacterium tuberculosis	1
Diseases of signal transduction by growth factor receptors and second messengers	1
Infectious disease	1
Adaptive Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
protein ubiquitination	2
catalytic activity	2
intracellular membraneless organelle	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
angiogenesis	1
biological_process	1
modification-dependent protein catabolic process	1
protein modification by small protein conjugation	1
lipid metabolic process	1
regulation of primary metabolic process	1
defense response	1
response to bacterium	1
protein polyubiquitination	1
macroautophagy	1
defense response to other organism	1
lipid modification by small protein conjugation	1
lipid storage	1
lipid droplet organization	1
membraneless organelle assembly	1
negative regulation of Wnt signaling pathway	1
non-canonical Wnt signaling pathway	1
regulation of non-canonical Wnt signaling pathway	1
primary metabolic process	1
ubiquitin-like protein transferase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
transition metal ion binding	1
ribonucleoside triphosphate phosphatase activity	1
ATP-dependent activity	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
molecular_function	1
cation binding	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

2034 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RNF213	NF1	P21359	629
RNF213	RAB40B	Q12829	584
RNF213	NPM1	P06748	557
RNF213	ALK	Q9UM73	546
RNF213	SLC26A11	Q86WA9	537
RNF213	MYH9	P35579	533
RNF213	UBXN11	Q5T124	500
RNF213	SDHD	O14521	493
RNF213	ATIC	P31939	487
RNF213	GUCY1A1	Q02108	474
RNF213	SDHB	P21912	450
RNF213	CMC4	P56277	448
RNF213	MYC	P01106	444
RNF213	CCER2	I3L3R5	439
RNF213	RET	P07949	436
RNF213	TPM4	P07226	436

IntAct

126 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
SCN2B	EXOC5	psi-mi:“MI:0914”(association)	0.640
SDC2	PDPK1	psi-mi:“MI:0914”(association)	0.640
LAMP3	METTL15	psi-mi:“MI:0914”(association)	0.530
PTPN1	GOLIM4	psi-mi:“MI:0914”(association)	0.530
FAM174A	BLTP3B	psi-mi:“MI:0914”(association)	0.530
NPDC1	TCAF2	psi-mi:“MI:0914”(association)	0.530
STK16	UNC119B	psi-mi:“MI:0914”(association)	0.530
CD40	EXOC5	psi-mi:“MI:0914”(association)	0.530
ANKRD22	ESYT2	psi-mi:“MI:0914”(association)	0.530
DNAJB8	DNAJB6	psi-mi:“MI:0914”(association)	0.530
ILVBL	SLC33A1	psi-mi:“MI:0914”(association)	0.530
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
vpu	SCAMP3	psi-mi:“MI:0914”(association)	0.460
RNF213	H1-1	psi-mi:“MI:0915”(physical association)	0.400
PLAC9	RNF213	psi-mi:“MI:0915”(physical association)	0.370
Rpl35	RPS6	psi-mi:“MI:0914”(association)	0.350
Ube2k		psi-mi:“MI:0914”(association)	0.350
Kif4	RNF213	psi-mi:“MI:0914”(association)	0.350
RNASEH2B	SAP18	psi-mi:“MI:0914”(association)	0.350
PTPN1		psi-mi:“MI:0914”(association)	0.350
MRPL50	MRPL43	psi-mi:“MI:0914”(association)	0.350
NUDCD1	TUBAL3	psi-mi:“MI:0914”(association)	0.350
NUDCD1	DNAJB2	psi-mi:“MI:0914”(association)	0.350
RNF213	GNB1	psi-mi:“MI:0914”(association)	0.350
UNC93B1		psi-mi:“MI:0914”(association)	0.350
DLK2	SLC22A23	psi-mi:“MI:0914”(association)	0.350

BioGRID (208): RNF213 (Two-hybrid), RNF213 (Two-hybrid), RNF213 (Two-hybrid), RNF213 (Two-hybrid), RNF213 (Two-hybrid), UBXN11 (Two-hybrid), KRT40 (Two-hybrid), RNF213 (Affinity Capture-MS), RNF213 (Affinity Capture-MS), RNF213 (Affinity Capture-MS), RNF213 (Affinity Capture-MS), RNF213 (Affinity Capture-MS), RNF213 (Affinity Capture-MS), RNF213 (Affinity Capture-MS), RNF213 (Affinity Capture-MS)

ESM2 similar proteins: A0A0M3U1B0, A0A1L8EYB2, A0JMF7, A1L2Y1, A2ALV5, A9JRX0, B2GUZ2, D3ZSP7, F1QB81, O35892, O70608, O75113, P23497, P70347, Q0P5X5, Q13129, Q16533, Q2T9I9, Q3U1D0, Q5CZC0, Q5H9M0, Q5REF4, Q5RHB5, Q5SW75, Q5T4T6, Q5T5J6, Q5XG69, Q5ZLE9, Q60664, Q63HN8, Q7M6U3, Q7Z4H7, Q80VH0, Q8BVK9, Q8C263, Q8CCC3, Q8NA03, Q90WN7, Q92844, Q96QP1

Diamond homologs: A0A0R4I9Y1, A0A0R4IBK5, A6NK02, B6VQ60, E9Q555, F4I443, Q63HN8, Q2TBT8, Q66JE4, Q6NZ21, Q6PJ69, Q8R151, Q96LD4, Q9P2E3, A0A1L8FG46, A8Y4B2, E7FDW2, O14212, O54952, O60106, P38398, P68907, Q00940, Q1XHU0, Q20798, Q2KHN1, Q3UF64, Q3ZCC3, Q4WZJ6, Q5A1M4, Q5RAG4, Q5ZM74, Q69ZS0, Q6FPI4, Q6J2U6, Q6J6I8, Q6J6I9, Q6J6J0, Q6MFZ5, Q6ZMN7

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	RNF213	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 175 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
Transport of vitamins, nucleosides, and related molecules	5	13.6×	9e-03
SLC-mediated transmembrane transport	9	5.3×	1e-02

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 10 cancer types — ANGS, BLCA, CCRCC, CHOL, ESCA, GBM, LUSC, MBL, PRAD, UCEC.

Clinical variants and AI predictions

ClinVar

1043 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	13
Uncertain significance	371
Likely benign	321
Benign	174

Top pathogenic / likely-pathogenic (19)

Variant ID	HGVS	Classification
1184843	NM_001256071.3(RNF213):c.11986_11989delinsGGGTTAG (p.Pro3996_Cys3997delinsGlyLeuGly)	Pathogenic
1490618	NM_001256071.3(RNF213):c.12355C>T (p.Pro4119Ser)	Pathogenic
1686128	NM_001256071.3(RNF213):c.12391C>T (p.Arg4131Cys)	Pathogenic
3252942	NM_001256071.3(RNF213):c.12352T>C (p.Ser4118Pro)	Pathogenic
3602934	NM_001256071.3(RNF213):c.12034T>C (p.Cys4012Arg)	Pathogenic
870408	NM_001256071.3(RNF213):c.12353C>T (p.Ser4118Phe)	Pathogenic
1708407	NM_001256071.3(RNF213):c.12028C>G (p.Leu4010Val)	Likely pathogenic
1710243	NM_001256071.3(RNF213):c.14822T>A (p.Val4941Glu)	Likely pathogenic
1804036	NM_001256071.3(RNF213):c.114C>G (p.Asn38Lys)	Likely pathogenic
210001	NM_001256071.3(RNF213):c.12343_12345del (p.Lys4115del)	Likely pathogenic
2430341	NM_001256071.3(RNF213):c.12050G>A (p.Cys4017Tyr)	Likely pathogenic
2721123	NM_001256071.3(RNF213):c.12050G>C (p.Cys4017Ser)	Likely pathogenic
2760912	NM_001256071.3(RNF213):c.1102G>A (p.Val368Met)	Likely pathogenic
3065130	NM_001256071.3(RNF213):c.13641-2A>G	Likely pathogenic
417846	NM_001256071.3(RNF213):c.12040C>A (p.His4014Asn)	Likely pathogenic
4687912	NM_001256071.3(RNF213):c.10947dup (p.Glu3650fs)	Likely pathogenic
637049	NM_001256071.3(RNF213):c.12059G>T (p.Cys4020Phe)	Likely pathogenic
982215	NM_001256071.3(RNF213):c.12360C>G (p.Phe4120Leu)	Likely pathogenic
985230	NM_001256071.3(RNF213):c.12365A>C (p.Asp4122Ala)	Likely pathogenic

SpliceAI

11259 predictions. Top by Δscore:

Variant	Effect	Δscore
17:80273239:A:AG	acceptor_gain	1.0000
17:80273240:G:GG	acceptor_gain	1.0000
17:80273402:G:GT	donor_gain	1.0000
17:80273402:GAA:G	donor_gain	1.0000
17:80273405:G:GG	donor_gain	1.0000
17:80280048:GTCT:G	donor_gain	1.0000
17:80280049:TCTT:T	donor_gain	1.0000
17:80287813:A:AG	acceptor_gain	1.0000
17:80287814:G:GG	acceptor_gain	1.0000
17:80289657:AGGA:A	acceptor_loss	1.0000
17:80289658:GGAA:G	acceptor_gain	1.0000
17:80289809:G:GT	donor_gain	1.0000
17:80289824:G:GT	donor_gain	1.0000
17:80290565:A:AG	acceptor_gain	1.0000
17:80290568:A:AG	acceptor_gain	1.0000
17:80290568:AGCAC:A	acceptor_gain	1.0000
17:80290569:G:GA	acceptor_gain	1.0000
17:80290569:GC:G	acceptor_gain	1.0000
17:80290569:GCA:G	acceptor_gain	1.0000
17:80290569:GCAC:G	acceptor_gain	1.0000
17:80290569:GCACG:G	acceptor_gain	1.0000
17:80290726:CAG:C	donor_loss	1.0000
17:80290727:AG:A	donor_loss	1.0000
17:80290728:GG:G	donor_loss	1.0000
17:80290729:G:C	donor_loss	1.0000
17:80294913:G:GG	donor_gain	1.0000
17:80295647:G:GG	donor_gain	1.0000
17:80295768:A:G	donor_gain	1.0000
17:80298315:TTCCA:T	acceptor_loss	1.0000
17:80298317:CCAGC:C	acceptor_loss	1.0000

AlphaMissense

34423 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:80346660:G:C	K2775N	0.999
17:80346660:G:T	K2775N	0.999
17:80347022:G:C	R2896P	0.999
17:80345612:A:T	K2426I	0.998
17:80346244:A:C	S2637R	0.998
17:80346246:C:A	S2637R	0.998
17:80346246:C:G	S2637R	0.998
17:80346926:T:C	L2864P	0.998
17:80346988:T:C	S2885P	0.998
17:80346989:C:T	S2885F	0.998
17:80346993:C:A	N2886K	0.998
17:80346993:C:G	N2886K	0.998
17:80347686:C:A	N3117K	0.998
17:80347686:C:G	N3117K	0.998
17:80347838:G:C	R3168P	0.998
17:80345593:G:A	G2420R	0.997
17:80345593:G:C	G2420R	0.997
17:80345910:T:A	N2525K	0.997
17:80345910:T:G	N2525K	0.997
17:80346658:A:C	K2775Q	0.997
17:80346659:A:T	K2775M	0.997
17:80346869:A:T	E2845V	0.997
17:80347198:G:C	D2955H	0.997
17:80347199:A:C	D2955A	0.997
17:80347199:A:T	D2955V	0.997
17:80347771:T:C	F3146L	0.997
17:80347773:C:A	F3146L	0.997
17:80347773:C:G	F3146L	0.997
17:80347837:C:G	R3168G	0.997
17:80345611:A:C	K2426Q	0.996

dbSNP variants (sampled 300 via entrez): RS1000018134 (17:80335882 C>A,T), RS1000022267 (17:80297882 A>T), RS1000042528 (17:80264785 G>A,C), RS1000047113 (17:80262668 C>T), RS1000075528 (17:80269883 A>G), RS1000090323 (17:80259456 G>A), RS1000132848 (17:80370810 G>A), RS1000157061 (17:80342041 A>C,G), RS1000158383 (17:80301662 G>A), RS1000159938 (17:80272558 C>T), RS1000160962 (17:80320201 C>A), RS1000172408 (17:80330139 C>T), RS1000193696 (17:80370551 T>C,G), RS1000215803 (17:80344730 G>A), RS1000219753 (17:80288542 G>A)

Disease associations

OMIM: gene MIM:613768 | disease phenotypes: MIM:607151, MIM:252350, MIM:252900

GenCC curated gene-disease

Disease	Classification	Inheritance
Moyamoya disease 2	Strong	Autosomal dominant

Mondo (12): Moyamoya disease 2 (MONDO:0011784), Moyamoya disease (MONDO:0016820), nephrocalcinosis (MONDO:0001567), stroke disorder (MONDO:0005098), hemangioma (MONDO:0006500), mucopolysaccharidosis type 3A (MONDO:0009655), anaplastic ependymoma (MONDO:0016700), carotid stenosis (MONDO:0001612), coronary artery disorder (MONDO:0005010), atrial septal aneurysm (MONDO:0020438), patent foramen ovale (MONDO:0020439), atypical coarctation of aorta (MONDO:0015446)

Orphanet (8): Moyamoya disease (Orphanet:2573), Moyamoya angiopathy (Orphanet:477768), Mucopolysaccharidosis type 3 (Orphanet:581), Sanfilippo syndrome type A (Orphanet:79269), Anaplastic ependymoma (Orphanet:251646), Atrial septal aneurysm (Orphanet:99107), Middle aortic syndrome (Orphanet:1456), NON RARE IN EUROPE: Patent foramen ovale (Orphanet:99108)

HPO phenotypes

9 total (13 of 9 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0001009	Telangiectasia
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0002119	Ventriculomegaly
HP:0002326	Transient ischemic attack
HP:0011834	Moyamoya phenomenon
HP:0100659	Abnormal cerebral vascular morphology
HP:0001297	Stroke
HP:0001028	Hemangioma
HP:0100546	Carotid artery stenosis
HP:0001655	Patent foramen ovale

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST000860_1	Moyamoya disease	2.000000e-08
GCST001726_7	Lipoprotein-associated phospholipase A2 activity change in response to statin therapy	3.000000e-06
GCST003720_36	Migraine	5.000000e-10
GCST003986_10	Migraine	5.000000e-10
GCST004250_30	Alanine aminotransferase (ALT) levels after remission induction therapy in actute lymphoblastic leukemia (ALL)	2.000000e-06
GCST005575_27	Moyamoya disease	5.000000e-54
GCST005575_28	Moyamoya disease	2.000000e-14
GCST005575_29	Moyamoya disease	7.000000e-38
GCST005575_30	Moyamoya disease	8.000000e-17
GCST005575_31	Moyamoya disease	2.000000e-44
GCST010867_18	Coronary artery disease	2.000000e-21
GCST011141_20	Hypertension	3.000000e-08
GCST90011899_107	Aspartate aminotransferase levels	5.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004746	lipoprotein-associated phospholipase A(2) measurement
EFO:0007965	response to combination chemotherapy
EFO:0004736	aspartate aminotransferase measurement

MeSH disease descriptors (8)

Descriptor	Name	Tree numbers
D016893	Carotid Stenosis	C10.228.140.300.200.360; C14.907.137.230; C14.907.253.123.360
D003324	Coronary Artery Disease	C14.280.647.250.260; C14.907.137.126.339; C14.907.585.250.260
D054092	Foramen Ovale, Patent	C14.240.400.560.375.258; C14.280.400.560.375.258; C16.131.240.400.560.375.258
D006391	Hemangioma	C04.557.645.375
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
D009397	Nephrocalcinosis	C12.050.351.968.419.590; C12.200.777.419.590; C12.950.419.590; C18.452.174.130.560
D020521	Stroke	C10.228.140.300.775; C14.907.253.855
C536992	Moyamoya disease 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067308 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.22	Kd	595.2	nM	CHEMBL5653589
6.22	ED50	595.2	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 4 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149231: Binding affinity to human RNF213 incubated for 45 mins by Kinobead based pull down assay	kd	0.5952	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, increases methylation	4
Tretinoin	decreases expression, increases expression	3
sodium arsenite	decreases expression	2
Benzo(a)pyrene	affects methylation, increases expression	2
Nickel	increases expression	2
Aflatoxin B1	decreases methylation, increases expression	2
GW 506033X	decreases reaction, increases expression	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
bisphenol A	increases expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, decreases reaction	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
nickel sulfate	increases expression	1
coumarin	increases phosphorylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
epigallocatechin gallate	increases expression, affects cotreatment, decreases expression	1
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	decreases reaction, increases expression	1
entinostat	increases expression	1
K 7174	increases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Sunitinib	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	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
CHEMBL5652273	Binding	Binding affinity to human RNF213 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

3 cell lines: 2 transformed cell line, 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_B3TA	HUSTTJi001-A	Induced pluripotent stem cell	Male
CVCL_E1K0	HyCyte hCMEC/D3 KO-hRNF213	Transformed cell line	Female
CVCL_E2Q2	HyCyte hCMEC/D3 hRNF213_p.R4810K_c.12429G>A	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00004727	PHASE4	COMPLETED	Antiplatelet Therapy to Prevent Stroke in African Americans
NCT00029172	PHASE4	COMPLETED	Treatment for Post-Stroke Depression
NCT00079638	PHASE4	COMPLETED	Comparative Efficacy Evaluation of Lipids When Treated With Niaspan & Statin or Other Lipid-Modifying Therapies-COMPELL
NCT00101543	PHASE4	COMPLETED	Gait Training For Acute Stroke: Functional Neuromuscular Stimulation (FNS) and Weight Supported Treadmill Training
NCT00102869	PHASE4	COMPLETED	Dopaminergic Enhancement of Learning and Memory in Aphasia
NCT00106886	PHASE4	UNKNOWN	HOPE-2 Study (Heart Outcomes Prevention Evaluation-2 Study)
NCT00108706	PHASE4	UNKNOWN	Acute Candesartan Cilexetil Outcomes Stroke Trial (ACCOST)
NCT00126087	PHASE4	TERMINATED	Potentiation of Procedural Motor Learning in Health and Disease
NCT00149227	PHASE4	COMPLETED	Add-on Effects of Valsartan on Morbi- Mortality (KYOTO HEART Study)
NCT00153062	PHASE4	COMPLETED	PRoFESS - Prevention Regimen For Effectively Avoiding Second Strokes
NCT00153946	PHASE4	COMPLETED	Edaravone and Argatroban Stroke Therapy Study for Acute Ischemic Stroke
NCT00163150	PHASE4	COMPLETED	Vasomotor Reactivity In Cerebral Small Vessel Disease And New Approach To Treat Lacunar Stroke
NCT00177424	PHASE4	TERMINATED	Sertraline for Preventing Post-stroke Depression and Improving Rehabilitation Outcomes
NCT00178646	PHASE4	COMPLETED	Comparative Efficacy of Three Preparations of Botox-A in Treating Spasticity
NCT00196690	PHASE4	COMPLETED	Donepezil in Chronic Poststroke Aphasia: a Randomized Controlled Trial
NCT00196703	PHASE4	UNKNOWN	Memantine and Constraint-Induced Language Therapy in Chronic Poststroke Aphasia:A Randomized Controlled Trial
NCT00216411	PHASE4	COMPLETED	Effects on Quality of Life Following Dysport Treatment in Post-stroke Spasticity of the Arm
NCT00227994	PHASE4	COMPLETED	Acetylcholinesterase Inhibitors to Improve Cognitive Function and Overall Rehabilitation After a Stroke
NCT00234546	PHASE4	COMPLETED	Asian Botulinum Clinical Trial Designed for Early Stroke Spasticity
NCT00247533	PHASE4	UNKNOWN	Cerebral Artery Stenosis, Coronary Artery Disease and Arrhythmia
NCT00263393	PHASE4	COMPLETED	Rural Andhra Pradesh Cardiovascular Prevention Study (RAPCAPS)
NCT00279149	PHASE4	COMPLETED	TRUST-tPA: Therapeutic Trial Evaluating Efficacy of Telemedicine (TELESTROKE) of Patients With Acute Stroke
NCT00287508	PHASE4	COMPLETED	Emboshield® and Xact® Post Approval Carotid Stent Trial (The EXACT Study)
NCT00327418	PHASE4	COMPLETED	CARDS Is Designed To Show If Lowering Cholesterol With Atorvastatin In Type 2 Diabetics Without CV Disease Reduces The Risk Of CV Events
NCT00327691	PHASE4	COMPLETED	A Study to Determine the Degree of Additional Reduction in CV Risk in Lowering LDL Below Minimum Target Levels
NCT00396058	PHASE4	TERMINATED	The Effect of Methylphenidate on Motor Learning in Stroke Patients
NCT00412867	PHASE4	COMPLETED	Post-marketing Clinical Study of Alteplase for Acute Ischemic Stroke （Japan Alteplase Clinical Trial Ⅱ：J-ACT Ⅱ）
NCT00442325	PHASE4	COMPLETED	Benefits Of Using Various Starting Doses Of Atorvastatin On Achievement Of Cholesterol Targets
NCT00442845	PHASE4	COMPLETED	Establish The Benefits Of Using Various Starting Doses Of Atorvastatin On Achievement Of Cholesterol Targets (ACTFAST)
NCT00468923	PHASE4	COMPLETED	Heart Outcomes Prevention Evaluation-3
NCT00548223	PHASE4	COMPLETED	The Secondary Prevention Trial for Ischemic Stroke With DengzhanShengmai Capsule
NCT00552916	PHASE4	UNKNOWN	Functional Electrical Stimulation (FES) Assisted Walking: Enhancement of Walking Function After Stroke
NCT00559988	PHASE4	TERMINATED	Combined Use of BIOTRONIK Home Monitoring and Predefined Anticoagulation to Reduce Stroke Risk
NCT00562588	PHASE4	COMPLETED	EARLY 3-months Aggrenox Treatment Started Within 24 Hrs of Ischemic Stroke Onset vs. After One Week 100 mg ASA
NCT00572767	PHASE4	TERMINATED	Evaluation of the Effect of Dextro-Amphetamin Added to Physiotherapy in Patients After Stroke
NCT00574457	PHASE4	COMPLETED	Improving Cardiovascular Risk Prediction Using Hand Held Carotid Ultrasonography Study
NCT00640198	PHASE4	COMPLETED	Memantine and Intensive Speech-Language Therapy in Aphasia
NCT00724724	PHASE4	UNKNOWN	The Effectiveness and Safety of Butylphthalide Soft Capsules in Secondary Prevention of Ischemic Stroke Trial
NCT00741585	PHASE4	COMPLETED	Prognostic Value of the Circadian Pattern of Ambulatory Blood Pressure for Multiple Risk Assessment
NCT00766896	PHASE4	COMPLETED	Platelet Hyperreactivity to Aspirin and Stroke