Details of Disease

General Information of Disease (ID: DISLKNYA)

Disease Name	Cerebral cavernous malformation
Synonyms	familial cavernous angioma; cerebral cavernous malformation; cerebral capillary malformations; cavernous angiomatous malformations; brain cavernous hemangioma; CCM
Disease Class	8B22: Intracranial embolism
Definition	A disorder characterized by malformations in the structure of the capillaries in the brain. It is caused by mutations in the CCM2, KRIT1 and PDCD10 genes. The capillaries fill with blood and stretch, thereby creating cavernous spaces. Some patients experience headaches, seizures, or visual and hearing disturbances. Cerebral hemorrhage may also occur.
Disease Hierarchy	DIS2BIP8: Congenital nervous system disorder DISLKNYA: Cerebral cavernous malformation
ICD Code	ICD-11 ICD-11: 8B22.41
Disease Identifiers	MONDO ID MONDO_0000820 MESH ID D020786 UMLS CUI C2919945 OMIM ID 116860 MedGen ID 418825 HPO ID HP:0033522 Orphanet ID 164 SNOMED CT ID 444869007

Drug-Interaction Atlas (DIA) of This Disease

Drug-Interaction Atlas (DIA)

This Disease is Treated as An Indication in 1 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
REC-994	DM1V25N	Phase 2	Small molecule	[1]
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Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 7 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
GLMN	TT2UV5C	Limited	Biomarker	[2]
MAP2K5	TTV3O87	Limited	Altered Expression	[3]
MAP3K3	TTJZNIG	Limited	Altered Expression	[3]
AOC1	TTM3B5R	Strong	Biomarker	[4]
CD58	TT5KSBY	Strong	Biomarker	[5]
DLL4	TTV23LH	Strong	Biomarker	[6]
PECAM1	TT4EZB2	Strong	Altered Expression	[7]
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⏷ Show the Full List of 7 DTT(s)

This Disease Is Related to 18 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ALX3	OTXZ25PZ	Strong	Biomarker	[8]
CALM2	OTNYA92F	Strong	Biomarker	[9]
CAMKMT	OTLJBRUW	Strong	Biomarker	[9]
DBNL	OTT2OQOV	Strong	Biomarker	[4]
EMP1	OTSZHUHQ	Strong	Biomarker	[10]
EXOSC3	OTNCF906	Strong	Biomarker	[11]
HEG1	OT3CUXA7	Strong	Biomarker	[12]
ITGB1BP1	OTVQFNGS	Strong	Biomarker	[13]
KLF2	OTIP1UFX	Strong	Biomarker	[3]
OCLN	OTSUTVWL	Strong	Altered Expression	[14]
PDCD10	OTCHJTSF	Strong	Altered Expression	[3]
POU3F3	OT6BBXPD	Strong	Biomarker	[15]
RABGEF1	OTWC3Z3R	Strong	Biomarker	[16]
RAP1A	OT5RH6TI	Strong	Biomarker	[16]
RAP1B	OTHEIIMM	Strong	Biomarker	[17]
SERPINI1	OTUJHIJW	Strong	Genetic Variation	[18]
TERF2IP	OT3M5P3G	Strong	Biomarker	[16]
TNFAIP6	OT1SLUZH	Strong	Biomarker	[19]
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⏷ Show the Full List of 18 DOT(s)

References

1	ClinicalTrials.gov (NCT05085561) A Two-Part Study of REC-994 in the Treatment of Adults With Symptomatic Cerebral Cavernous Malformation (CCM); Part 1: A Phase 2 Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Evaluate the Safety, Efficacy and Pharmacokinetics of Two Doses of REC-994; Part 2: A Long-Term Blinded Extension Clinical Trial to Evaluate Long-Term Safety Tolerability and Efficacy of REC-994. U.S.National Institutes of Health.
2	Hereditary intraosseous vascular malformation of the craniofacial region: an apparently novel disorder.Am J Med Genet. 2002 Apr 15;109(1):22-35. doi: 10.1002/ajmg.10282.
3	CDC42 Deletion Elicits Cerebral Vascular Malformations via Increased MEKK3-Dependent KLF4 Expression.Circ Res. 2019 Apr 12;124(8):1240-1252. doi: 10.1161/CIRCRESAHA.118.314300.
4	Cobl-like promotes actin filament formation and dendritic branching using only a single WH2 domain.J Cell Biol. 2018 Jan 2;217(1):211-230. doi: 10.1083/jcb.201704071. Epub 2017 Dec 12.
5	The role of adhesion molecules in multiple myeloma.Leuk Lymphoma. 1992 Oct;8(3):189-96. doi: 10.3109/10428199209054904.
6	EphB4 forward signalling mediates angiogenesis caused by CCM3/PDCD10-ablation.J Cell Mol Med. 2017 Sep;21(9):1848-1858. doi: 10.1111/jcmm.13105. Epub 2017 Apr 1.
7	Upregulation of transmembrane endothelial junction proteins in human cerebral cavernous malformations.Neurosurg Focus. 2010 Sep;29(3):E3. doi: 10.3171/2010.6.FOCUS10125.
8	Stereotactic radiosurgery for cerebral cavernous malformations: A systematic review.Neurology. 2019 Nov 19;93(21):e1971-e1979. doi: 10.1212/WNL.0000000000008521. Epub 2019 Oct 28.
9	Chemoenzymatic Synthesis of O-Mannose Glycans Containing Sulfated or Nonsulfated HNK-1 Epitope.J Am Chem Soc. 2019 Dec 11;141(49):19351-19359. doi: 10.1021/jacs.9b08964. Epub 2019 Dec 2.
10	p53, miR-34a and EMP1-Newly Identified Targets of TFF3 Signaling in Y79 Retinoblastoma Cells.Int J Mol Sci. 2019 Aug 24;20(17):4129. doi: 10.3390/ijms20174129.
11	Extended Combined Neonatal Treatment With Erythropoietin Plus Melatonin Prevents Posthemorrhagic Hydrocephalus of Prematurity in Rats.Front Cell Neurosci. 2018 Sep 25;12:322. doi: 10.3389/fncel.2018.00322. eCollection 2018.
12	Cerebral cavernous malformations arise independent of the heart of glass receptor.Stroke. 2014 May;45(5):1505-1509. doi: 10.1161/STROKEAHA.114.004809. Epub 2014 Mar 18.
13	Nuclear Localization of Integrin Cytoplasmic Domain-associated Protein-1 (ICAP1) Influences 1 Integrin Activation and Recruits Krev/Interaction Trapped-1 (KRIT1) to the Nucleus.J Biol Chem. 2017 Feb 3;292(5):1884-1898. doi: 10.1074/jbc.M116.762393. Epub 2016 Dec 21.
14	Impairment of tight junctions and glucose transport in endothelial cells of human cerebral cavernous malformations.J Neuropathol Exp Neurol. 2011 Jun;70(6):417-29. doi: 10.1097/NEN.0b013e31821bc40e.
15	CCM-3 Promotes C.elegans Germline Development by Regulating Vesicle Trafficking Cytokinesis and Polarity.Curr Biol. 2017 Mar 20;27(6):868-876. doi: 10.1016/j.cub.2017.02.028. Epub 2017 Mar 9.
16	miR-21 coordinates tumor growth and modulates KRIT1 levels.Biochem Biophys Res Commun. 2013 Aug 16;438(1):90-6. doi: 10.1016/j.bbrc.2013.07.031. Epub 2013 Jul 18.
17	Combinatorial interaction between CCM pathway genes precipitates hemorrhagic stroke.Dis Model Mech. 2008 Nov-Dec;1(4-5):275-81. doi: 10.1242/dmm.000513. Epub 2008 Oct 28.
18	CCM3/SERPINI1 bidirectional promoter variants in patients with cerebral cavernous malformations: a molecular and functional study.BMC Med Genet. 2016 Oct 13;17(1):74. doi: 10.1186/s12881-016-0332-0.
19	TSG-6 in conditioned media from adipose mesenchymal stem cells protects against visual deficits in mild traumatic brain injury model through neurovascular modulation.Stem Cell Res Ther. 2019 Nov 5;10(1):318. doi: 10.1186/s13287-019-1436-1.