CCM3
MCID: CRB094
MIFTS: 37

Cerebral Cavernous Malformations 3 (CCM3)

Categories: Cardiovascular 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 58 76 30 13 6 74
Cerebral Cavernous Malformation 3 12 15
Ccm3 58 76
Cerebral Cavernous Malformations, Type 3 41
Cavernous Angiomatous Malformations 76
Cavernous Hemangioma of the Brain 76
Cerebral Capillary Malformations 76
Familial Cavernous Angioma 76
Cerebral Cavernoma 76

Characteristics:

HPO:

33
cerebral cavernous malformations 3:
Inheritance somatic mutation


Classifications:



External Ids:

Disease Ontology 12 DOID:0060671
OMIM 58 603285
MeSH 45 D020786
ICD10 34 Q28.3
MedGen 43 C1864040
UMLS 74 C1864040

Summaries for Cerebral Cavernous Malformations 3

UniProtKB/Swiss-Prot : 76 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 cerebral cavernous malformations 2 and cavernous hemangioma. An important gene associated with Cerebral Cavernous Malformations 3 is PDCD10 (Programmed Cell Death 10). The drug Diazepam has been mentioned in the context of this disorder. Affiliated tissues include brain, endothelial and testes, 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.

Description 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 all 31)
# Related Disease Score Top Affiliating Genes
1 cerebral cavernous malformations 2 31.6 CCM2 KRIT1 PDCD10
2 cavernous hemangioma 31.0 CCM2 KRIT1 PDCD10
3 cerebral cavernous malformations 30.4 CCM2 KRIT1 PDCD10
4 cavernous malformation 30.4 CCM2 KRIT1 PDCD10
5 hemangioma 29.8 CCM2 KRIT1
6 human venous malformation 29.3 CCM2 KRIT1 PDCD10
7 cerebral cavernous malformation, familial 11.4
8 vascular erectile tumor 11.1
9 congenital vascular cavernous malformations 11.1
10 familial hemangioma 11.1
11 cerebral hemorrhage 10.1
12 vascular disease 10.1
13 heparin-induced thrombocytopenia 10.1
14 neutropenia 10.0
15 thrombocytopenia 10.0
16 chiasmal syndrome 10.0
17 medulloblastoma 10.0
18 noonan syndrome 1 10.0
19 pseudo-turner syndrome 10.0
20 von hippel-lindau syndrome 9.9
21 bornholm eye disease 9.9
22 cysticercosis 9.9
23 arteriovenous malformation 9.9
24 epilepsy 9.9
25 hyperglycemia 9.9
26 glioblastoma 9.9
27 central nervous system benign neoplasm 9.7 CCM2 KRIT1 PDCD10
28 klippel-trenaunay-weber syndrome 9.7 CCM2 KRIT1 PDCD10
29 venous malformations, multiple cutaneous and mucosal 9.7 CCM2 KRIT1 PDCD10
30 vascular hemostatic disease 9.6 CCM2 KRIT1
31 cell type benign neoplasm 9.5 CCM2 KRIT1 PDCD10

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:

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

Clinical features from OMIM:

603285

Drugs & Therapeutics for Cerebral Cavernous Malformations 3

Drugs for Cerebral Cavernous Malformations 3 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Diazepam Approved, Illicit, Investigational, Vet_approved Not Applicable 439-14-5 3016

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Modifiers of Disease Severity in Cerebral Cavernous Malformations Recruiting NCT01764529
2 Implementing Health Plan-Level Care Management for Solo & Small Practices Completed NCT02041962 Not Applicable
3 CASH (Cavernous Angiomas With Symptomatic Hemorrhage) Trial Readiness Recruiting NCT03652181
4 Covers to Improve Esthetic Outcome After Surgery for Chronic Subdural Hematoma Recruiting NCT03755349 Not Applicable

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 30 PDCD10

Anatomical Context for Cerebral Cavernous Malformations 3

MalaCards organs/tissues related to Cerebral Cavernous Malformations 3:

42
Brain, Endothelial, Testes, Neutrophil, Placenta, Eye, Heart

Publications for Cerebral Cavernous Malformations 3

Articles related to Cerebral Cavernous Malformations 3:

(show top 50) (show all 63)
# Title Authors Year
1
First case of neutropenia and thrombocytopenia in the setting of cerebral cavernous malformation 3. ( 30904992 )
2019
2
Rho Kinase Inhibition Blunts Lesion Development and Hemorrhage in Murine Models of Aggressive Pdcd10/Ccm3 Disease. ( 30744543 )
2019
3
Mutational analysis of CCM1, CCM2 and CCM3 in a Han Chinese cohort with multiple cerebral cavernous malformations in Taiwan. ( 29787619 )
2018
4
Lead promotes abnormal angiogenesis induced by CCM3 gene defects via mitochondrial pathway. ( 29110746 )
2018
5
Arsenic exposure assists ccm3 genetic polymorphism in elevating blood pressure. ( 29435151 )
2018
6
Biallelic CCM3 mutations cause a clonogenic survival advantage and endothelial cell stiffening. ( 30549232 )
2018
7
High-throughput sequencing of the entire genomic regions of CCM1/KRIT1, CCM2 and CCM3/PDCD10 to search for pathogenic deep-intronic splice mutations in cerebral cavernous malformations. ( 28645800 )
2017
8
EphB4 forward signalling mediates angiogenesis caused by CCM3/PDCD10-ablation. ( 28371279 )
2017
9
Endothelial exocytosis of angiopoietin-2 resulting from CCM3 deficiency contributes to cerebral cavernous malformation. ( 27548575 )
2016
10
Erratum: Endothelial exocytosis of angiopoietin-2 resulting from CCM3 deficiency contributes to cerebral cavernous malformation. ( 27923033 )
2016
11
CCM3/PDCD10 gene mutation in cerebral cavernous malformations associated with hyperkeratotic cutaneous capillary venous malformations. ( 26896283 )
2016
12
CCM3/SERPINI1 bidirectional promoter variants in patients with cerebral cavernous malformations: a molecular and functional study. ( 27737651 )
2016
13
Arsenic-induced anti-angiogenesis via miR-425-5p-regulated CCM3. ( 27132035 )
2016
14
The cerebral cavernous malformation 3 gene is necessary for senescence induction. ( 25655101 )
2015
15
PDCD10 (CCM3) regulates brain endothelial barrier integrity in cerebral cavernous malformation type 3: role of CCM3-ERK1/2-cortactin cross-talk. ( 26385474 )
2015
16
Detection of Novel Mutation in Ccm3 Causes Familial Cerebral Cavernous Malformations. ( 26115622 )
2015
17
Highly variable intrafamilial manifestations of a CCM3 mutation ranging from acute childhood cerebral haemorrhage to late-onset meningiomas. ( 25462093 )
2015
18
CCM2-CCM3 interaction stabilizes their protein expression and permits endothelial network formation. ( 25825518 )
2015
19
Sulindac metabolites decrease cerebrovascular malformations in CCM3-knockout mice. ( 26109568 )
2015
20
Expression of CCM2 and CCM3 during mouse gonadogenesis. ( 26386873 )
2015
21
Surveying genetic variants and molecular phylogeny of cerebral cavernous malformation gene, CCM3/PDCD10. ( 25451273 )
2014
22
Ccm3, a gene associated with cerebral cavernous malformations, is required for neuronal migration. ( 24595293 )
2014
23
Guidelines for the primary prevention of stroke: a statement for healthcare professionals from the American Heart Association/American Stroke Association. ( 25355838 )
2014
24
Structural basis for the unique heterodimeric assembly between cerebral cavernous malformation 3 and germinal center kinase III. ( 23665169 )
2013
25
Focal defects in single-celled tubes mutant for Cerebral cavernous malformation 3, GCKIII, or NSF2. ( 23763949 )
2013
26
Loss of CCM3 impairs DLL4-Notch signalling: implication in endothelial angiogenesis and in inherited cerebral cavernous malformations. ( 23388056 )
2013
27
CCM3 Mutations Are Associated with Early-Onset Cerebral Hemorrhage and Multiple Meningiomas. ( 23801932 )
2013
28
Structural mechanism of CCM3 heterodimerization with GCKIII kinases. ( 23541896 )
2013
29
The CCM3-GCKIII partnership. ( 23744102 )
2013
30
A network of interactions enables CCM3 and STK24 to coordinate UNC13D-driven vesicle exocytosis in neutrophils. ( 24176643 )
2013
31
Adaptor protein cerebral cavernous malformation 3 (CCM3) mediates phosphorylation of the cytoskeletal proteins ezrin/radixin/moesin by mammalian Ste20-4 to protect cells from oxidative stress. ( 22291017 )
2012
32
Ccm3 functions in a manner distinct from Ccm1 and Ccm2 in a zebrafish model of CCM vascular disease. ( 22182521 )
2012
33
Crystallization and preliminary crystallographic studies of CCM3 in complex with the C-terminal domain of MST4. ( 22750858 )
2012
34
Mutation analysis of CCM1, CCM2 and CCM3 genes in a cohort of Italian patients with cerebral cavernous malformation. ( 21029238 )
2011
35
Loss of cerebral cavernous malformation 3 (Ccm3) in neuroglia leads to CCM and vascular pathology. ( 21321212 )
2011
36
Molecular recognition of leucine-aspartate repeat (LD) motifs by the focal adhesion targeting homology domain of cerebral cavernous malformation 3 (CCM3). ( 21632544 )
2011
37
CCM3/PDCD10 heterodimerizes with germinal center kinase III (GCKIII) proteins using a mechanism analogous to CCM3 homodimerization. ( 21561863 )
2011
38
Presence of the brain proteins cerebral cavernous malformation-2 and cerebral cavernous malformation-3 in rat testes and their potential role in experimental varicocele. ( 19647235 )
2010
39
Stabilization of VEGFR2 signaling by cerebral cavernous malformation 3 is critical for vascular development. ( 20371769 )
2010
40
Crystal structure of CCM3, a cerebral cavernous malformation protein critical for vascular integrity. ( 20489202 )
2010
41
CCM3 signaling through sterile 20-like kinases plays an essential role during zebrafish cardiovascular development and cerebral cavernous malformations. ( 20592472 )
2010
42
Multiple cerebral cavernous malformations and a novel CCM3 germline deletion in a German family. ( 20623299 )
2010
43
Differential angiogenesis function of CCM2 and CCM3 in cerebral cavernous malformations. ( 20809750 )
2010
44
CCM3/PDCD10 stabilizes GCKIII proteins to promote Golgi assembly and cell orientation. ( 20332113 )
2010
45
Genetic variations within KRIT1/CCM1, MGC4607/CCM2 and PDCD10/CCM3 in a large Italian family harbouring a Krit1/CCM1 mutation. ( 20419355 )
2010
46
Gyrate: CCM3 dances with a different angiogenic partner. ( 20484115 )
2010
47
PDCD10/CCM3 acts downstream of {gamma}-protocadherins to regulate neuronal survival. ( 21041308 )
2010
48
EFNS guidelines on the molecular diagnosis of channelopathies, epilepsies, migraine, stroke, and dementias. ( 20298421 )
2010
49
Apoptotic functions of PDCD10/CCM3, the gene mutated in cerebral cavernous malformation 3. ( 19246713 )
2009
50
Functional analyses of human and zebrafish 18-amino acid in-frame deletion pave the way for domain mapping of the cerebral cavernous malformation 3 protein. ( 19370760 )
2009

Variations for Cerebral Cavernous Malformations 3

ClinVar genetic disease variations for Cerebral Cavernous Malformations 3:

6 (show all 47)
# Gene Variation Type Significance SNP ID Assembly Location
1 PDCD10 PDCD10, 586C-T single nucleotide variant Pathogenic
2 PDCD10 PDCD10, 385C-T single nucleotide variant Pathogenic
3 PDCD10 PDCD10, 103C-T single nucleotide variant Pathogenic
4 PDCD10 PDCD10, 54-BP DEL deletion Pathogenic
5 PDCD10 PDCD10, 4-BP DEL deletion Pathogenic
6 PDCD10 PDCD10, IVS8AS, G-A, -1 single nucleotide variant Pathogenic
7 PDCD10 PDCD10, DEL deletion Pathogenic
8 PDCD10 NM_007217.3(PDCD10): c.96+865A> C single nucleotide variant not provided rs779988645 GRCh37 Chromosome 3, 167436985: 167436985
9 PDCD10 NM_007217.3(PDCD10): c.96+865A> C single nucleotide variant not provided rs779988645 GRCh38 Chromosome 3, 167719197: 167719197
10 PDCD10 NM_007217.3(PDCD10): c.96+5295_96+5296insT insertion not provided rs890418416 GRCh37 Chromosome 3, 167432555: 167432555
11 PDCD10 NM_007217.3(PDCD10): c.96+5295_96+5296insT insertion not provided rs890418416 GRCh38 Chromosome 3, 167714766: 167714767
12 PDCD10 NM_007217.3(PDCD10): c.150+2693T> C single nucleotide variant not provided rs374384046 GRCh37 Chromosome 3, 167419937: 167419937
13 PDCD10 NM_007217.3(PDCD10): c.150+2693T> C single nucleotide variant not provided rs374384046 GRCh38 Chromosome 3, 167702149: 167702149
14 PDCD10 NM_007217.3(PDCD10): c.-116-2132T> G single nucleotide variant not provided rs147072468 GRCh37 Chromosome 3, 167440193: 167440193
15 PDCD10 NM_007217.3(PDCD10): c.-116-2132T> G single nucleotide variant not provided rs147072468 GRCh38 Chromosome 3, 167722405: 167722405
16 PDCD10 NM_007217.3(PDCD10): c.151-2025A> G single nucleotide variant not provided rs773691623 GRCh37 Chromosome 3, 167416939: 167416939
17 PDCD10 NM_007217.3(PDCD10): c.151-2025A> G single nucleotide variant not provided rs773691623 GRCh38 Chromosome 3, 167699151: 167699151
18 PDCD10 NM_007217.3(PDCD10): c.96+6786_96+6787delTT deletion not provided rs577939683 GRCh37 Chromosome 3, 167431063: 167431064
19 PDCD10 NM_007217.3(PDCD10): c.96+6786_96+6787delTT deletion not provided rs577939683 GRCh38 Chromosome 3, 167713275: 167713276
20 PDCD10 NM_007217.3(PDCD10): c.96+4988C> G single nucleotide variant not provided rs748153515 GRCh37 Chromosome 3, 167432862: 167432862
21 PDCD10 NM_007217.3(PDCD10): c.96+4988C> G single nucleotide variant not provided rs748153515 GRCh38 Chromosome 3, 167715074: 167715074
22 PDCD10 NM_007217.3(PDCD10): c.-117+1010C> T single nucleotide variant not provided rs912904786 GRCh37 Chromosome 3, 167450992: 167450992
23 PDCD10 NM_007217.3(PDCD10): c.-117+1010C> T single nucleotide variant not provided rs912904786 GRCh38 Chromosome 3, 167733204: 167733204
24 PDCD10 NM_007217.3(PDCD10): c.96+4389A> G single nucleotide variant not provided rs541610164 GRCh37 Chromosome 3, 167433461: 167433461
25 PDCD10 NM_007217.3(PDCD10): c.96+4389A> G single nucleotide variant not provided rs541610164 GRCh38 Chromosome 3, 167715673: 167715673
26 PDCD10 NM_145860.1(PDCD10): c.558-2A> C single nucleotide variant Uncertain significance rs1553758385 GRCh37 Chromosome 3, 167402179: 167402179
27 PDCD10 NM_145860.1(PDCD10): c.558-2A> C single nucleotide variant Uncertain significance rs1553758385 GRCh38 Chromosome 3, 167684391: 167684391
28 PDCD10 NM_145860.1(PDCD10): c.557+4_557+7delAGTA deletion Pathogenic rs1553759042 GRCh38 Chromosome 3, 167687227: 167687230
29 PDCD10 NM_145860.1(PDCD10): c.557+4_557+7delAGTA deletion Pathogenic rs1553759042 GRCh37 Chromosome 3, 167405015: 167405018
30 PDCD10 NM_145860.1(PDCD10): c.474+5G> A single nucleotide variant Pathogenic/Likely pathogenic rs1553759139 GRCh38 Chromosome 3, 167687610: 167687610
31 PDCD10 NM_145860.1(PDCD10): c.474+5G> A single nucleotide variant Pathogenic/Likely pathogenic rs1553759139 GRCh37 Chromosome 3, 167405398: 167405398
32 PDCD10 NM_145860.1(PDCD10): c.160_163delGAAA (p.Glu54Ilefs) deletion Pathogenic rs1553761266 GRCh38 Chromosome 3, 167697114: 167697117
33 PDCD10 NM_145860.1(PDCD10): c.160_163delGAAA (p.Glu54Ilefs) deletion Pathogenic rs1553761266 GRCh37 Chromosome 3, 167414902: 167414905
34 PDCD10 NM_145860.1(PDCD10): c.301C> T (p.Gln101Ter) single nucleotide variant Pathogenic rs1303470125 GRCh38 Chromosome 3, 167695690: 167695690
35 PDCD10 NM_145860.1(PDCD10): c.322C> T (p.Arg108Ter) single nucleotide variant Pathogenic rs1553760900 GRCh37 Chromosome 3, 167413457: 167413457
36 PDCD10 NM_145860.1(PDCD10): c.322C> T (p.Arg108Ter) single nucleotide variant Pathogenic rs1553760900 GRCh38 Chromosome 3, 167695669: 167695669
37 PDCD10 NM_145860.1(PDCD10): c.301C> T (p.Gln101Ter) single nucleotide variant Pathogenic rs1303470125 GRCh37 Chromosome 3, 167413478: 167413478
38 PDCD10 NM_145860.1(PDCD10): c.510C> G (p.Tyr170Ter) single nucleotide variant Pathogenic/Likely pathogenic rs1553759059 GRCh38 Chromosome 3, 167687281: 167687281
39 PDCD10 NM_145860.1(PDCD10): c.510C> G (p.Tyr170Ter) single nucleotide variant Pathogenic/Likely pathogenic rs1553759059 GRCh37 Chromosome 3, 167405069: 167405069
40 PDCD10 NM_007217.3(PDCD10): c.575dup (p.Ser193Lysfs) duplication Likely pathogenic GRCh37 Chromosome 3, 167402160: 167402160
41 PDCD10 NM_007217.3(PDCD10): c.575dup (p.Ser193Lysfs) duplication Likely pathogenic GRCh38 Chromosome 3, 167684372: 167684372
42 PDCD10 NM_007217.3(PDCD10): c.333dup (p.Gln112Thrfs) duplication Pathogenic GRCh37 Chromosome 3, 167413446: 167413446
43 PDCD10 NM_007217.3(PDCD10): c.333dup (p.Gln112Thrfs) duplication Pathogenic GRCh38 Chromosome 3, 167695658: 167695658
44 PDCD10 NM_007217.3(PDCD10): c.584dup (p.Asn195Lysfs) duplication Uncertain significance GRCh37 Chromosome 3, 167402151: 167402151
45 PDCD10 NM_007217.3(PDCD10): c.584dup (p.Asn195Lysfs) duplication Uncertain significance GRCh38 Chromosome 3, 167684363: 167684363
46 PDCD10 NM_145860.1(PDCD10): c.474+4C> A single nucleotide variant Uncertain significance GRCh37 Chromosome 3, 167405399: 167405399
47 PDCD10 NM_145860.1(PDCD10): c.474+4C> A single nucleotide variant Uncertain significance GRCh38 Chromosome 3, 167687611: 167687611

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 cytoplasm GO:0005737 9.17 CCM2 KRIT1 MOB4 PDCD10 RIPOR1 STRIP2

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

# Name GO ID Score Top Affiliating Genes
1 positive regulation of intracellular protein transport GO:0090316 8.96 PDCD10 RIPOR1
2 establishment of Golgi localization GO:0051683 8.62 PDCD10 RIPOR1

Sources for Cerebral Cavernous Malformations 3

3 CDC
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70 SNOMED-CT via HPO
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