CCM3
MCID: CRB094
MIFTS: 42

Cerebral Cavernous Malformations 3 (CCM3)

Categories: Cardiovascular diseases, Fetal diseases, Genetic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Cerebral Cavernous Malformations 3

MalaCards integrated aliases for Cerebral Cavernous Malformations 3:

Name: Cerebral Cavernous Malformations 3 56 73 29 13 6 71
Cerebral Cavernous Malformation 3 12 15
Ccm3 56 73
Cerebral Cavernous Malformations, Type 3 39
Cavernous Angiomatous Malformations 73
Cavernous Hemangioma of the Brain 73
Cerebral Capillary Malformations 73
Familial Cavernous Angioma 73
Cerebral Cavernoma 73

Characteristics:

HPO:

31
cerebral cavernous malformations 3:
Inheritance somatic mutation


Classifications:



External Ids:

Disease Ontology 12 DOID:0060671
OMIM 56 603285
MeSH 43 D020786
ICD10 32 Q28.3
MedGen 41 C1864040
UMLS 71 C1864040

Summaries for Cerebral Cavernous Malformations 3

UniProtKB/Swiss-Prot : 73 Cerebral cavernous malformations 3: A congenital vascular anomaly of the central nervous system that can result in hemorrhagic stroke, seizures, recurrent headaches, and focal neurologic deficits. The lesions are characterized by grossly enlarged blood vessels consisting of a single layer of endothelium and without any intervening neural tissue, ranging in diameter from a few millimeters to several centimeters.

MalaCards based summary : Cerebral Cavernous Malformations 3, also known as cerebral cavernous malformation 3, is related to hemangioma and cavernous hemangioma. An important gene associated with Cerebral Cavernous Malformations 3 is PDCD10 (Programmed Cell Death 10). Affiliated tissues include brain, endothelial and heart, and related phenotypes are abnormality of the cerebrum and seizures

Disease Ontology : 12 A cerebral cavernous malformation that has material basis in mutation in the PDCD10 gene on chromosome 3q26.1.

More information from OMIM: 603285

Related Diseases for Cerebral Cavernous Malformations 3

Diseases in the Cerebral Cavernous Malformations family:

Cerebral Cavernous Malformations 2 Cerebral Cavernous Malformations 3
Cerebral Cavernous Malformation, Familial

Diseases related to Cerebral Cavernous Malformations 3 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 72)
# Related Disease Score Top Affiliating Genes
1 hemangioma 29.8 PDCD10 KRIT1 CCM2
2 cavernous hemangioma 29.7 PDCD10 KRIT1 CCM2
3 cavernous malformation 29.6 STK25 PDCD10 KRIT1 CCM2
4 cerebral cavernous malformation, familial 29.4 PDCD10 KRIT1 CCM2
5 cerebral cavernous malformations 29.3 STK25 STK24 PDCD10 KRIT1 CCM2
6 cerebral cavernous malformations 2 28.6 STK25 PDCD10 MAP4K2 KRIT1 CCM2
7 congenital vascular cavernous malformations 11.2
8 familial hemangioma 11.2
9 vascular erectile tumor 11.2
10 cortical dysplasia, complex, with other brain malformations 7 10.2
11 varicocele 10.2
12 rare surgical neurologic disease 10.2
13 epilepsy 10.1
14 visual epilepsy 10.1
15 seizure disorder 10.1
16 monieziasis 10.1 STRIP2 STRIP1
17 headache 10.0
18 alzheimer disease 10.0
19 leukemia, acute lymphoblastic 10.0
20 hemorrhage, intracerebral 10.0
21 lymphocytic leukemia 10.0
22 neutropenia 10.0
23 thrombocytopenia 10.0
24 vascular disease 10.0
25 multiple sclerosis 10.0
26 arteriovenous malformation 10.0
27 retinal vascular disease 10.0
28 chiasmal syndrome 10.0
29 glial tumor 10.0
30 medulloblastoma 10.0
31 noonan syndrome 1 10.0
32 pseudo-turner syndrome 10.0
33 myeloproliferative syndrome, transient 10.0 STK25 STK24 MOB4
34 von hippel-lindau syndrome 9.9
35 alpha-ketoglutarate dehydrogenase deficiency 9.9
36 ocular motor apraxia 9.9
37 maturity-onset diabetes of the young 9.9
38 coronary heart disease 1 9.9
39 alacrima, achalasia, and mental retardation syndrome 9.9
40 pain agnosia 9.9
41 cysticercosis 9.9
42 hemiplegia 9.9
43 von willebrand's disease 9.9
44 leiomyoma 9.9
45 keratosis 9.9
46 kidney cancer 9.9
47 breast ductal carcinoma 9.9
48 glioblastoma multiforme 9.9
49 systemic scleroderma 9.9
50 hyperglycemia 9.9

Graphical network of the top 20 diseases related to Cerebral Cavernous Malformations 3:



Diseases related to Cerebral Cavernous Malformations 3

Symptoms & Phenotypes for Cerebral Cavernous Malformations 3

Human phenotypes related to Cerebral Cavernous Malformations 3:

31
# Description HPO Frequency HPO Source Accession
1 abnormality of the cerebrum 31 obligate (100%) HP:0002060
2 seizures 31 frequent (33%) HP:0001250
3 paralysis 31 frequent (33%) HP:0003470
4 headache 31 frequent (33%) HP:0002315
5 cerebral hemorrhage 31 frequent (33%) HP:0001342

Clinical features from OMIM:

603285

GenomeRNAi Phenotypes related to Cerebral Cavernous Malformations 3 according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00055-A-2 9.55 MAP4K2
2 Decreased viability GR00107-A-1 9.55 STK25
3 Decreased viability GR00221-A-1 9.55 MAP4K2 STK24
4 Decreased viability GR00221-A-2 9.55 MAP4K2 STK24 STK26
5 Decreased viability GR00221-A-3 9.55 MAP4K2
6 Decreased viability GR00221-A-4 9.55 MAP4K2 STK24 STK25 STK26
7 Decreased viability GR00301-A 9.55 STK25
8 Decreased viability GR00402-S-2 9.55 MAP4K2 STK24 STK25 STK26

Drugs & Therapeutics for Cerebral Cavernous Malformations 3

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Modifiers of Disease Severity and Progression in Cerebral Cavernous Malformations Recruiting NCT01764529

Search NIH Clinical Center for Cerebral Cavernous Malformations 3

Genetic Tests for Cerebral Cavernous Malformations 3

Genetic tests related to Cerebral Cavernous Malformations 3:

# Genetic test Affiliating Genes
1 Cerebral Cavernous Malformations 3 29 PDCD10

Anatomical Context for Cerebral Cavernous Malformations 3

MalaCards organs/tissues related to Cerebral Cavernous Malformations 3:

40
Brain, Endothelial, Heart, Kidney, Testes, Skin, Placenta

Publications for Cerebral Cavernous Malformations 3

Articles related to Cerebral Cavernous Malformations 3:

(show top 50) (show all 216)
# Title Authors PMID Year
1
Different spectra of genomic deletions within the CCM genes between Italian and American CCM patient cohorts. 61 56 6
18060436 2008
2
Mutations within the programmed cell death 10 gene cause cerebral cavernous malformations. 61 56 6
15543491 2005
3
Biallelic somatic and germline mutations in cerebral cavernous malformations (CCMs): evidence for a two-hit mechanism of CCM pathogenesis. 61 56
19088123 2009
4
A two-hit mechanism causes cerebral cavernous malformations: complete inactivation of CCM1, CCM2 or CCM3 in affected endothelial cells. 61 56
19088124 2009
5
Genotype-phenotype correlations in cerebral cavernous malformations patients. 61 56
17041941 2006
6
CCM3 mutations are uncommon in cerebral cavernous malformations. 61 56
16380626 2005
7
Multilocus linkage identifies two new loci for a mendelian form of stroke, cerebral cavernous malformation, at 7p15-13 and 3q25.2-27. 61 56
9811928 1998
8
Guidelines for the primary prevention of stroke: a statement for healthcare professionals from the American Heart Association/American Stroke Association. 6
25355838 2014
9
EFNS guidelines on the molecular diagnosis of channelopathies, epilepsies, migraine, stroke, and dementias. 6
20298421 2010
10
Cerebral Cavernous Malformation, Familial 6
20301470 2003
11
KRIT1 loss-mediated upregulation of NOX1 in stromal cells promotes paracrine pro-angiogenic responses. 61
31917192 2020
12
VEGF signalling enhances lesion burden in KRIT1 deficient mice. 61
31746130 2020
13
Spatial arrangement of LD motif-interacting residues on focal adhesion targeting domain of Focal Adhesion Kinase determine domain-motif interaction affinity and specificity. 61
31676296 2020
14
Systems-wide analysis unravels the new roles of CCM signal complex (CSC). 61
31872111 2019
15
Low fluid shear stress conditions contribute to activation of cerebral cavernous malformation signalling pathways. 61
31369819 2019
16
Alternatively spliced isoforms reveal a novel type of PTB domain in CCM2 protein. 61
31676827 2019
17
Blood Flow Suppresses Vascular Anomalies in a Zebrafish Model of Cerebral Cavernous Malformations. 61
31495257 2019
18
Transcriptome clarifies mechanisms of lesion genesis versus progression in models of Ccm3 cerebral cavernous malformations. 61
31426861 2019
19
Postzygotic mosaicism in cerebral cavernous malformation. 61
31446422 2019
20
A Brain-Targeted Orally Available ROCK2 Inhibitor Benefits Mild and Aggressive Cavernous Angioma Disease. 61
31446620 2019
21
CCM1 and CCM2 variants in patients with cerebral cavernous malformation in an ethnically Chinese population in Taiwan. 61
31455779 2019
22
Cavernous angiomas: deconstructing a neurosurgical disease. 61
31261134 2019
23
First case of neutropenia and thrombocytopenia in the setting of cerebral cavernous malformation 3. 61
30904992 2019
24
CCM3 and cerebral cavernous malformation disease. 61
31338212 2019
25
Endothelial cell clonal expansion in the development of cerebral cavernous malformations. 61
31235698 2019
26
CDC42 Deletion Elicits Cerebral Vascular Malformations via Increased MEKK3-Dependent KLF4 Expression. 61
30732528 2019
27
Emerging Pharmacologic Targets in Cerebral Cavernous Malformation and Potential Strategies to Alter the Natural History of a Difficult Disease: A Review. 61
30476961 2019
28
Biallelic CCM3 mutations cause a clonogenic survival advantage and endothelial cell stiffening. 61
30549232 2019
29
Phenotypic characterization of murine models of cerebral cavernous malformations. 61
29946133 2019
30
Two Novel CCM2 Heterozygous Mutations Associated with Cerebral Cavernous Malformation in a Chinese Family. 61
30701383 2019
31
A novel large deletion in CCM1 gene in a Tunisian family. 61
30314744 2019
32
Rho Kinase Inhibition Blunts Lesion Development and Hemorrhage in Murine Models of Aggressive Pdcd10/Ccm3 Disease. 61
30744543 2019
33
Comprehensive transcriptome analysis of cerebral cavernous malformation across multiple species and genotypes. 61
30728328 2019
34
"Radiologically Isolated" Spinal Cavernoma Associated with Familial Cerebral Cavernomatosis. 61
31466067 2019
35
Novel Pathogenic Variants in a Cassette Exon of CCM2 in Patients With Cerebral Cavernous Malformations. 61
31824402 2019
36
The STRIPAK complex components FAM40A and FAM40B regulate endothelial cell contractility via ROCKs. 61
30509168 2018
37
Ponatinib (AP24534) inhibits MEKK3-KLF signaling and prevents formation and progression of cerebral cavernous malformations. 61
30417093 2018
38
Cerebral Cavernous Malformations Develop Through Clonal Expansion of Mutant Endothelial Cells. 61
30359189 2018
39
Systematic pharmacological screens uncover novel pathways involved in cerebral cavernous malformations. 61
30181117 2018
40
Mutational analysis of CCM1, CCM2 and CCM3 in a Han Chinese cohort with multiple cerebral cavernous malformations in Taiwan. 61
29787619 2018
41
Vascular Endothelial (VE)-Cadherin, Endothelial Adherens Junctions, and Vascular Disease. 61
28851747 2018
42
Interrogating the ccm-3 Gene Network. 61
30208312 2018
43
Connexin 43 gap junctions contribute to brain endothelial barrier hyperpermeability in familial cerebral cavernous malformations type III by modulating tight junction structure. 61
29295866 2018
44
[Cerebral cavernous malformation 3 gene deficiency promotes early changes in Alzheimer disease-like lesions induced by low lead exposure]. 61
29747348 2018
45
Lead promotes abnormal angiogenesis induced by CCM3 gene defects via mitochondrial pathway. 61
29110746 2018
46
Cerebral Cavernous Malformations: An Update on Prevalence, Molecular Genetic Analyses, and Genetic Counselling. 61
29593473 2018
47
Heg1 and Ccm1/2 proteins control endocardial mechanosensitivity during zebrafish valvulogenesis. 61
29364115 2018
48
Arsenic exposure assists ccm3 genetic polymorphism in elevating blood pressure. 61
29435151 2018
49
A novel CCM1/KRIT1 heterozygous deletion mutation (c.1919delT) in a Chinese family with familial cerebral cavernous malformation. 61
29169046 2018
50
Novel KRIT1/CCM1 and MGC4607/CCM2 Gene Variants in Chinese Families With Cerebral Cavernous Malformations. 61
30622508 2018

Variations for Cerebral Cavernous Malformations 3

ClinVar genetic disease variations for Cerebral Cavernous Malformations 3:

6 (show all 30) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 PDCD10 PDCD10, 586C-TSNV Pathogenic 1864
2 PDCD10 NM_007217.4(PDCD10):c.385C>T (p.Gln129Ter)SNV Pathogenic 1865 3:167413394-167413394 3:167695606-167695606
3 PDCD10 PDCD10, 103C-TSNV Pathogenic 1866
4 PDCD10 PDCD10, 54-BP DELdeletion Pathogenic 1867
5 PDCD10 PDCD10, 4-BP DELdeletion Pathogenic 1868
6 PDCD10 NM_007217.4(PDCD10):c.475-1G>ASNV Pathogenic 1869 3:167405105-167405105 3:167687317-167687317
7 PDCD10 PDCD10, DELdeletion Pathogenic 1870
8 PDCD10 NM_007217.4(PDCD10):c.103C>T (p.Arg35Ter)SNV Pathogenic 372445 rs1057517786 3:167422677-167422677 3:167704889-167704889
9 PDCD10 NM_007217.4(PDCD10):c.160_163del (p.Glu54fs)deletion Pathogenic 468328 rs1553761266 3:167414902-167414905 3:167697114-167697117
10 PDCD10 NM_007217.4(PDCD10):c.322C>T (p.Arg108Ter)SNV Pathogenic 468330 rs1553760900 3:167413457-167413457 3:167695669-167695669
11 PDCD10 NM_007217.4(PDCD10):c.301C>T (p.Gln101Ter)SNV Pathogenic 468329 rs1303470125 3:167413478-167413478 3:167695690-167695690
12 PDCD10 NM_007217.4(PDCD10):c.557+4_557+7delshort repeat Pathogenic 468332 rs1553759042 3:167405015-167405018 3:167687227-167687230
13 PDCD10 NM_007217.4(PDCD10):c.333dup (p.Gln112fs)duplication Pathogenic 567872 rs1559952317 3:167413445-167413446 3:167695657-167695658
14 PDCD10 NM_007217.4(PDCD10):c.394A>T (p.Lys132Ter)SNV Pathogenic 649296 3:167413385-167413385 3:167695597-167695597
15 PDCD10 NC_000003.11:g.(?_167402076)_(167437965_?)deldeletion Pathogenic 639871 3:167402076-167437965 3:167684288-167720177
16 PDCD10 NM_007217.4(PDCD10):c.474+5G>ASNV Pathogenic/Likely pathogenic 468331 rs1553759139 3:167405398-167405398 3:167687610-167687610
17 PDCD10 NM_007217.4(PDCD10):c.510C>G (p.Tyr170Ter)SNV Pathogenic/Likely pathogenic 536234 rs1553759059 3:167405069-167405069 3:167687281-167687281
18 PDCD10 NM_007217.4(PDCD10):c.575dup (p.Ser193fs)duplication Likely pathogenic 562013 rs1559941951 3:167402159-167402160 3:167684371-167684372
19 PDCD10 NM_007217.4(PDCD10):c.584dup (p.Asn195fs)duplication Uncertain significance 574691 rs1559941903 3:167402150-167402151 3:167684362-167684363
20 PDCD10 NM_007217.4(PDCD10):c.474+4C>ASNV Uncertain significance 580503 rs1390197622 3:167405399-167405399 3:167687611-167687611
21 PDCD10 NM_007217.4(PDCD10):c.558-2A>CSNV Uncertain significance 468333 rs1553758385 3:167402179-167402179 3:167684391-167684391
22 PDCD10 NM_007217.4(PDCD10):c.96+865A>CSNV not provided 427909 rs779988645 3:167436985-167436985 3:167719197-167719197
23 PDCD10 NM_007217.4(PDCD10):c.96+5292dupduplication not provided 427913 rs890418416 3:167432554-167432555 3:167714766-167714767
24 PDCD10 NM_007217.4(PDCD10):c.150+2693T>CSNV not provided 427919 rs374384046 3:167419937-167419937 3:167702149-167702149
25 PDCD10 NM_007217.4(PDCD10):c.-116-2132T>GSNV not provided 427920 rs147072468 3:167440193-167440193 3:167722405-167722405
26 PDCD10 NM_007217.4(PDCD10):c.151-2025A>GSNV not provided 427921 rs773691623 3:167416939-167416939 3:167699151-167699151
27 PDCD10 NM_007217.4(PDCD10):c.96+6786_96+6787deldeletion not provided 427923 rs577939683 3:167431063-167431064 3:167713275-167713276
28 PDCD10 NM_007217.4(PDCD10):c.96+4988C>GSNV not provided 427924 rs748153515 3:167432862-167432862 3:167715074-167715074
29 PDCD10 NM_007217.4(PDCD10):c.-117+1010C>TSNV not provided 427926 rs912904786 3:167450992-167450992 3:167733204-167733204
30 PDCD10 NM_007217.4(PDCD10):c.96+4389A>GSNV not provided 427927 rs541610164 3:167433461-167433461 3:167715673-167715673

Expression for Cerebral Cavernous Malformations 3

Search GEO for disease gene expression data for Cerebral Cavernous Malformations 3.

Pathways for Cerebral Cavernous Malformations 3

GO Terms for Cerebral Cavernous Malformations 3

Cellular components related to Cerebral Cavernous Malformations 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 Golgi apparatus GO:0005794 9.63 STK26 STK25 STK24 PDCD10 MOB4 MAP4K2
2 Golgi membrane GO:0000139 9.62 STK26 STK25 PDCD10 MAP4K2
3 cytoplasm GO:0005737 9.47 STRN4 STRN STRIP2 STRIP1 STK26 STK25
4 dendritic spine GO:0043197 9.43 STRN4 STRN MOB4
5 FAR/SIN/STRIPAK complex GO:0090443 8.96 STRN4 STRN

Biological processes related to Cerebral Cavernous Malformations 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein phosphorylation GO:0006468 9.76 STK26 STK25 STK24 MAP4K2
2 protein autophosphorylation GO:0046777 9.61 STK26 STK25 STK24
3 activation of protein kinase activity GO:0032147 9.46 STK26 STK25 STK24 MAP4K2
4 positive regulation of stress-activated MAPK cascade GO:0032874 9.4 STK25 PDCD10
5 establishment of Golgi localization GO:0051683 9.37 STK25 PDCD10
6 Golgi reassembly GO:0090168 9.32 STK25 PDCD10
7 intrinsic apoptotic signaling pathway in response to hydrogen peroxide GO:0036481 9.26 STK25 PDCD10
8 response to hydrogen peroxide GO:0042542 9.26 STK26 STK25 STK24 PDCD10
9 signal transduction by protein phosphorylation GO:0023014 8.92 STK26 STK25 STK24 MAP4K2

Molecular functions related to Cerebral Cavernous Malformations 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein binding GO:0005515 10.07 STRN4 STRN STRIP1 STK26 STK25 STK24
2 protein kinase activity GO:0004672 9.67 STK26 STK25 STK24 MAP4K2
3 protein serine/threonine kinase activity GO:0004674 9.46 STK26 STK25 STK24 MAP4K2
4 protein phosphatase 2A binding GO:0051721 9.32 STRN4 STRN
5 armadillo repeat domain binding GO:0070016 8.96 STRN4 STRN
6 Rho GTPase binding GO:0017048 8.8 STRIP1 SLMAP SIKE1

Sources for Cerebral Cavernous Malformations 3

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
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35 IUPHAR
36 KEGG
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43 MeSH
44 MESH via Orphanet
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50 NDF-RT
53 NINDS
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56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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