CCM
MCID: CRB048
MIFTS: 67

Cerebral Cavernous Malformations (CCM)

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

Aliases & Classifications for Cerebral Cavernous Malformations

MalaCards integrated aliases for Cerebral Cavernous Malformations:

Name: Cerebral Cavernous Malformations 56 74 54 39
Cerebral Cavernous Malformation 12 74 52 25 53 36 29 6 15
Cerebral Cavernous Malformations 1 73 29 6 71
Cavernous Malformations of Cns and Retina 56 13 6
Familial Cerebral Cavernous Malformation 25 58 71
Cavernous Angiomatous Malformations 56 12 73
Cerebral Capillary Malformations 56 12 73
Ccm 56 52 25
Hyperkeratotic Cutaneous Capillary-Venous Malformations Associated with Cerebral Capillary Malformations 56 6
Hemangioma, Cavernous, Central Nervous System 43 17
Cerebral Cavernous Malformation 1 12 15
Cerebral Cavernous Hemangioma 52 25
Familial Cavernous Angioma 12 73
Cavernous Angioma 52 53
Central Nervous System Cavernous Hemangioma 25
Hereditary Cerebral Cavernous Malformation 58
Cavernous Angiomatous Malformations; Cam 56
Cerebral Cavernous Malformations, Type 1 39
Familial Cerebral Cavernous Angioma 25
Cerebral Cavernous Malformations-1 56
Hereditary Brain Cavernous Angioma 58
Intracerebral Cavernous Hemangioma 25
Cavernous Hemangioma of the Brain 73
Familial Brain Cavernous Angioma 58
Familial Cavernous Malformation 25
Familial Cavernous Hemangioma 25
Hereditary Cerebral Cavernoma 58
Cavernous Angioma, Familial 56
Familial Cerebral Cavernoma 58
Hemangioma, Cavernous 71
Cerebral Cavernoma 73
Angioma, Cavernous 71
Cavernomas 53
Cavernoma 52
Ccm1 73
Cam 56

Characteristics:

Orphanet epidemiological data:

58
familial cerebral cavernous malformation
Inheritance: Autosomal dominant; Prevalence: 1-5/10000 (Worldwide); Age of onset: All ages; Age of death: normal life expectancy;

OMIM:

56
Miscellaneous:
incomplete penetrance
most common age of clinical onset ranges from 16 to 33 years
multiple lesions in familial cases
single lesions in sporadic cases
genetic heterogeneity (ccm2 )

Inheritance:
autosomal dominant


HPO:

31
cerebral cavernous malformations:
Inheritance autosomal dominant inheritance heterogeneous
Onset and clinical course incomplete penetrance


Classifications:

Orphanet: 58  
Rare neurological diseases
Rare circulatory system diseases
Developmental anomalies during embryogenesis


Summaries for Cerebral Cavernous Malformations

Genetics Home Reference : 25 Cerebral cavernous malformations are collections of small blood vessels (capillaries) in the brain that are enlarged and irregular in structure. These capillaries have abnormally thin walls, and they lack other support tissues, such as elastic fibers, which normally make them stretchy. As a result, the blood vessels are prone to leakage, which can cause the health problems related to this condition. Cavernous malformations can occur anywhere in the body, but usually produce serious signs and symptoms only when they occur in the brain and spinal cord (which are described as cerebral). Approximately 25 percent of individuals with cerebral cavernous malformations never experience any related health problems. Other people with this condition may experience serious signs and symptoms such as headaches, seizures, paralysis, hearing or vision loss, and bleeding in the brain (cerebral hemorrhage). Severe brain hemorrhages can result in death. The location and number of cerebral cavernous malformations determine the severity of this disorder. These malformations can change in size and number over time. There are two forms of the condition: familial and sporadic. The familial form is passed from parent to child, and affected individuals typically have multiple cerebral cavernous malformations. The sporadic form occurs in people with no family history of the disorder. These individuals typically have only one malformation.

MalaCards based summary : Cerebral Cavernous Malformations, also known as cerebral cavernous malformation, is related to cerebral cavernous malformation, familial and cerebral cavernous malformations 3. An important gene associated with Cerebral Cavernous Malformations is KRIT1 (KRIT1 Ankyrin Repeat Containing), and among its related pathways/superpathways are Focal Adhesion and MAPK signaling pathway. The drugs Atorvastatin and Propranolol have been mentioned in the context of this disorder. Affiliated tissues include brain, spinal cord and endothelial, and related phenotypes are seizures and headache

Disease Ontology : 12 A cerebrovascular disease that is characterized by dilated blood-filled capillaries lacking structural support.

NIH Rare Diseases : 52 Cerebral cavernous malformations (CCMs) are collections of small blood vessels (capillaries) in the brain that are enlarged and irregular in structure which lead to altered blood flow. Cavernous malformations can occur anywhere in the body, but usually produce serious signs and symptoms only when they occur in the central nervous system (the brain and spinal cord). Cavernous malformations in the brain and/or spinal cord are called cerebral cavernous malformations. Approximately 25 percent of individuals with cerebral cavernous malformations never experience any related medical problems. Other people with cerebral cavernous malformations may experience serious symptoms such as headaches, seizures , paralysis, hearing or vision deficiencies, and bleeding in the brain (cerebral hemorrhage). These malformations can change in size and number over time, but they do not become cancerous. This condition can be sporadic or it can be inherited in an autosomal dominant pattern. Mutations in the KRIT1 (CCM1), CCM2 , and PDCD10 (CCM3) genes cause cerebral cavernous malformation. Treatment depends upon the symptoms. Seizures are usually treated with antiepileptic medications or surgery.

OMIM : 56 Cerebral cavernous angiomas are relatively rare vascular malformations that may involve any part of the central nervous system. Cerebral cavernous angiomas are to be distinguished from cerebral arteriovenous malformations (106070, 108010). CCMs are venous and not demonstrable by arteriography; hence they are referred to as angiographically silent. Capillary hemangiomas (602089) are classified as distinct from vascular malformations in that hemangiomas are benign, highly proliferative lesions involving aberrant localized growth of capillary endothelium. Hemangiomas develop shortly after birth. In contrast, vascular malformations are present from birth, tend to grow with the individual, do not regress, and show normal rates of endothelial cell turnover (Mulliken and Young, 1988). (116860)

NINDS : 53 Cerebral cavernous malformations (CCMs) are vascular lesions comprised of clusters of tightly packed, abnormally thin-walled small blood vessels (capillaries) that displace normal neurological tissue in the brain or spinal cord. The vessels are filled with slow-moving or stagnant blood that is usually clotted or in a state of decomposition. Cavernous malformations can occur in the brain, spinal cord, and some other body regions. In the brain and spinal cord these cavernous lesions are quite fragile and are prone to bleeding, causing hemorrhagic strokes (bleeding into the brain), seizures, and neurological deficits. CCMs can range in size from a few fractions of an inch to several inches in diameter, depending on the number of blood vessels involved. Some people develop multiple lesions while others never experience related medical problems. Hereditary forms of CCM are caused by mutations in one of three CCM disease genes: CCM1, CCM2, and CCM3. A large population with hereditary CCM disease is found in New Mexico and the Southwestern United States, in which the disease is caused by mutations in the gene CCM1 (or KRIT1).

KEGG : 36 Cerebral cavernous malformations (CCM) are vascular malformations of the central nervous system comprising enlarged caverns with a single layer of endothelium, which easily lead to cerebral hemorrhages. The disease present as either sporadic or autosomal dominant conditions and is linked to three genes KRIT1, MGC4607, and PDCD10. Mutations in KRIT1 impair its interaction with ICAP-1 alpha, and influence beta 1 integrin-dependent angiogenesis.

UniProtKB/Swiss-Prot : 73 Cerebral cavernous malformations 1: 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.

Wikipedia : 74 Cavernous hemangioma, also called cavernous angioma, cavernoma, or cerebral cavernoma (CCM) (when... more...

Related Diseases for Cerebral Cavernous Malformations

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 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 786)
# Related Disease Score Top Affiliating Genes
1 cerebral cavernous malformation, familial 35.2 PDCD10 KRIT1 CCM2
2 cerebral cavernous malformations 3 35.1 STK25 STK24 PDCD10 KRIT1 CCM2
3 cerebral cavernous malformations 2 34.3 STK25 RAP2A RAP1A PDCD10 MAP3K3 KRIT1
4 cavernous malformation 33.3 STK25 PDCD10 KRIT1 ITGB1BP1 CCM2L CCM2
5 venous malformations, multiple cutaneous and mucosal 32.7 TEK PDCD10 KRIT1 CCM2
6 arteriovenous malformation 31.2 TEK PTEN PDCD10
7 hemangioma 30.7 TEK PTEN PECAM1 PDCD10 KRIT1 KDR
8 cerebral angioma 30.7 PDCD10 KRIT1 CCM2
9 klippel-trenaunay-weber syndrome 30.7 TEK PDCD10 KRIT1 CCM2
10 angiosarcoma 30.6 TEK PECAM1 KDR
11 cavernous hemangioma 30.5 RAP2A PECAM1 PDCD10 KRIT1 KDR ITGB1BP1
12 meningioma, familial 30.3 PTEN PECAM1 PDCD10 KLF4
13 intussusception 30.1 TEK PECAM1 KDR
14 arteriovenous malformations of the brain 30.0 TEK PECAM1 PDCD10 KDR
15 exudative vitreoretinopathy 1 29.9 TEK PECAM1 KDR DLL4
16 dermal unilateral segmental cavernous angioma 12.4
17 cerebrocostomandibular syndrome 12.2
18 cataract 5, multiple types 12.2
19 cerebrofacial arteriovenous metameric syndrome 11.7
20 cobb syndrome 11.6
21 sengers syndrome 11.5
22 intracranial cavernous angioma 11.5
23 cavernous hemangioma of orbit 11.4
24 congenital vascular cavernous malformations 11.4
25 familial hemangioma 11.4
26 vascular erectile tumor 11.4
27 hemangioma, capillary infantile 11.1
28 hepatosplenic t-cell lymphoma 10.9
29 hair whorl 10.9
30 subacute delirium 10.5
31 hemangioma of liver 10.5 ZPLD1 KRIT1 CCM2
32 hemorrhagic disease 10.5 PDCD10 KRIT1 CCM2
33 portal hypertension 10.5
34 vascular disease 10.5
35 pulmonary vein stenosis 10.5 PECAM1 KDR
36 benign perivascular tumor 10.4 TEK PECAM1
37 kaposiform hemangioendothelioma 10.4 PECAM1 KDR
38 cerebrovascular disease 10.4
39 angiokeratoma circumscriptum 10.4 TEK PECAM1 KDR
40 capillary disease 10.4 TEK PECAM1 KDR
41 capillary hemangioma 10.4 TEK PECAM1 KDR
42 portal vein thrombosis 10.4
43 breast angiosarcoma 10.4 PECAM1 KDR
44 corneal neovascularization 10.4 TEK PECAM1 KDR
45 limb ischemia 10.4 TEK KLF2 KDR
46 varicose veins 10.4
47 bone epithelioid hemangioma 10.4 RAP1A PECAM1
48 radiation proctitis 10.4 PECAM1 KDR
49 hemangioma of orbit 10.3
50 epilepsy 10.3

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



Diseases related to Cerebral Cavernous Malformations

Symptoms & Phenotypes for Cerebral Cavernous Malformations

Human phenotypes related to Cerebral Cavernous Malformations:

58 31 (show all 23)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 seizures 58 31 hallmark (90%) Very frequent (99-80%) HP:0001250
2 headache 58 31 hallmark (90%) Very frequent (99-80%) HP:0002315
3 cerebral hemorrhage 58 31 hallmark (90%) Very frequent (99-80%) HP:0001342
4 scoliosis 58 31 frequent (33%) Frequent (79-30%) HP:0002650
5 increased intracranial pressure 58 31 frequent (33%) Frequent (79-30%) HP:0002516
6 meningioma 58 31 frequent (33%) Frequent (79-30%) HP:0002858
7 focal t2 hyperintense brainstem lesion 58 31 frequent (33%) Frequent (79-30%) HP:0012748
8 focal t2 hypointense brainstem lesion 58 31 frequent (33%) Frequent (79-30%) HP:0012749
9 neuroma 58 31 frequent (33%) Frequent (79-30%) HP:0030430
10 vascular skin abnormality 58 31 occasional (7.5%) Occasional (29-5%) HP:0011276
11 cognitive impairment 58 31 occasional (7.5%) Occasional (29-5%) HP:0100543
12 spinal cord lesion 58 31 occasional (7.5%) Occasional (29-5%) HP:0100561
13 venous malformation 58 31 occasional (7.5%) Occasional (29-5%) HP:0012721
14 episodic vomiting 58 31 occasional (7.5%) Occasional (29-5%) HP:0002572
15 choroidal hemangioma 58 31 occasional (7.5%) Occasional (29-5%) HP:0007872
16 retinal cavernous angioma 58 31 occasional (7.5%) Occasional (29-5%) HP:0011513
17 cerebral calcification 31 HP:0002514
18 intracranial hemorrhage 31 HP:0002170
19 abnormality of the musculature 31 HP:0003011
20 hemangioma 58 Frequent (79-30%)
21 abnormality of the skin 31 HP:0000951
22 retinal vascular malformation 31 HP:0007797
23 hepatic vascular malformations 31 HP:0006576

Symptoms via clinical synopsis from OMIM:

56
Neurologic Central Nervous System:
seizures
intracranial hemorrhage
headache
intracranial thin-walled sinusoidal vessel (cavernous) malformations
focal neurologic deficits
more
Head And Neck Eyes:
retinal vascular malformations

Muscle Soft Tissue:
soft tissue vascular malformations

Abdomen Liver:
hepatic vascular malformations

Skin Nails Hair Skin:
hyperkeratotic cutaneous vascular lesions

Clinical features from OMIM:

116860

MGI Mouse Phenotypes related to Cerebral Cavernous Malformations:

45 (show all 13)
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 10.4 CCM2 CCM2L DLL4 HEG1 KDR KLF2
2 growth/size/body region MP:0005378 10.27 CCM2 DLL4 HEG1 ITGB1BP1 KDR KLF2
3 cellular MP:0005384 10.25 CCM2 CCM2L DLL4 HEG1 KDR KLF4
4 hematopoietic system MP:0005397 10.25 CCM2 DLL4 KDR KLF2 KLF4 MAP3K3
5 mortality/aging MP:0010768 10.25 CCM2 CCM2L DLL4 HEG1 ITGB1BP1 KDR
6 homeostasis/metabolism MP:0005376 10.22 CCM2 CCM2L DLL4 HEG1 KDR KLF2
7 embryo MP:0005380 10.18 CCM2 DLL4 HEG1 KDR KLF2 KRIT1
8 immune system MP:0005387 10.15 CCM2 DLL4 HEG1 KDR KLF2 KLF4
9 craniofacial MP:0005382 10.04 CCM2 HEG1 ITGB1BP1 KDR KLF2 KLF4
10 muscle MP:0005369 10.03 CCM2 CCM2L DLL4 HEG1 KDR KLF2
11 nervous system MP:0003631 9.93 CCM2 KDR KLF2 KLF4 KRIT1 MAP3K3
12 normal MP:0002873 9.65 CCM2 CCM2L DLL4 ITGB1BP1 KDR KLF2
13 vision/eye MP:0005391 9.32 CCM2 DLL4 ITGB1BP1 KDR KLF4 KRIT1

Drugs & Therapeutics for Cerebral Cavernous Malformations

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

(show all 27)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Atorvastatin Approved Phase 1, Phase 2 134523-00-5 60823
2
Propranolol Approved, Investigational Phase 2 525-66-6 4946
3 Hypolipidemic Agents Phase 1, Phase 2
4 Anticholesteremic Agents Phase 1, Phase 2
5 Hydroxymethylglutaryl-CoA Reductase Inhibitors Phase 1, Phase 2
6 Antimetabolites Phase 1, Phase 2
7 Lipid Regulating Agents Phase 1, Phase 2
8 Neurotransmitter Agents Phase 2
9 Anti-Arrhythmia Agents Phase 2
10 Adrenergic Antagonists Phase 2
11 Adrenergic beta-Antagonists Phase 2
12 Vasodilator Agents Phase 2
13 Adrenergic Agents Phase 2
14 Antihypertensive Agents Phase 2
15
Doxycycline Approved, Investigational, Vet_approved Phase 1 564-25-0 54671203
16 Antimalarials Phase 1
17 Anti-Bacterial Agents Phase 1
18 Anti-Infective Agents Phase 1
19 Antiparasitic Agents Phase 1
20 Antiprotozoal Agents Phase 1
21
Simvastatin Approved Early Phase 1 79902-63-9 54454
22 Astragalus
23 Neuroserpin
24 Liver Extracts
25 Hematinics
26 Anticonvulsants
27 Analgesics

Interventional clinical trials:

(show all 16)
# Name Status NCT ID Phase Drugs
1 Phase I-II Randomized, Placebo-Controlled, Single-Blinded, Single-Site Clinical Trial of Atorvastatin in the Treatment of Cavernous Angiomas With Symptomatic Hemorrhage Exploratory Proof of Concept (AT CASH EPOC) Recruiting NCT02603328 Phase 1, Phase 2 Atorvastatin
2 Effect of Oral Propranolol on mRNA Expression in Symptomatice Caavernous Malformation Active, not recruiting NCT03474614 Phase 2 Propranolol
3 Treat_CCM Clinical Trial A Multicenter Randomized Clinical Trial on Propranolol in Cerebral Cavernous Malformation Active, not recruiting NCT03589014 Phase 2 Propranolol
4 Influence of Matrix Metalloproteinase on Brain Arteriovenous Malformation Hemorrhage Completed NCT00783523 Phase 1 Doxycycline or Placebo
5 Oral Propanolol for Surgically Inaccessible Cerebral and Spinal Cavernous Malformations Enrolling by invitation NCT03523650 Phase 1 Propranolol Oral Tablet;Placebo Oral Tablet
6 A Prospective Study on the Incidence and Related Risk Factors of Infantile Hemangioma in China Unknown status NCT03173352
7 Genetic Disease Gene Identification Unknown status NCT00916903
8 Cerebral Bases Bodily Representations: Imaging Approach by Functional Magnetic Resonance, Cortical Stimulation Corticographie and Surgery Awake Unknown status NCT02876016
9 Permeability MRI in Cerebral Cavernous Malformations Type 1 in New Mexico: Effects of Statins Completed NCT01764451 Early Phase 1 Simvastatin
10 A Prospective Controlled Study on Treatment of Giant Cavernous Hemangiomas of the Liver:RFA Versus Laparoscopic Hepatectomy. Completed NCT01471080
11 CASH (Cavernous Angiomas With Symptomatic Hemorrhage) Trial Readiness Recruiting NCT03652181
12 Modifiers of Disease Severity and Progression in Cerebral Cavernous Malformations Recruiting NCT01764529
13 Treatments and Outcomes of Untreated Cerebral Cavernous Malformations in CHINA (TOUCH): A Nationwide Multicenter Prospective Cohort Study. Recruiting NCT03467295
14 Quantitative Susceptibility Mapping Biomarker, Brain Structure and Connectome Associated With Cerebral Cavernous Malformation Related Epilepsy and Outcome After Surgery Recruiting NCT04076449
15 A Prospective Study for the Natural History and the Risk Factors of Prospective Symptomatic Hemorrhage in Adult Patients With Cerebral Cavernous Malformation Recruiting NCT02946866
16 Pattern and Management of Intracranial Cavernoma Not yet recruiting NCT04181086

Search NIH Clinical Center for Cerebral Cavernous Malformations

Cochrane evidence based reviews: hemangioma, cavernous, central nervous system

Genetic Tests for Cerebral Cavernous Malformations

Genetic tests related to Cerebral Cavernous Malformations:

# Genetic test Affiliating Genes
1 Cerebral Cavernous Malformation 29 KRIT1
2 Cerebral Cavernous Malformations 1 29 KRIT1

Anatomical Context for Cerebral Cavernous Malformations

MalaCards organs/tissues related to Cerebral Cavernous Malformations:

40
Brain, Spinal Cord, Endothelial, Retina, Smooth Muscle, Skin, Liver

Publications for Cerebral Cavernous Malformations

Articles related to Cerebral Cavernous Malformations:

(show top 50) (show all 782)
# Title Authors PMID Year
1
Cerebral cavernous malformations: mutations in Krit1. 6 54 61 56
11914398 2002
2
CCM1 gene mutations in families segregating cerebral cavernous malformations. 61 54 56 6
11222804 2001
3
C329X in KRIT1 is a founder mutation among CCM patients in Sardinia. 6 56 61
19454328 2009
4
Different spectra of genomic deletions within the CCM genes between Italian and American CCM patient cohorts. 56 6 61
18060436 2008
5
Clinical, magnetic resonance imaging, and genetic study of 5 Italian families with cerebral cavernous malformation. 6 56 61
17562932 2007
6
Truncating mutations in CCM1, encoding KRIT1, cause hereditary cavernous angiomas. 6 61 56
10508515 1999
7
Cerebral cavernous malformations. Incidence and familial occurrence. 61 6 56
3393196 1988
8
KRIT1 is mutated in hyperkeratotic cutaneous capillary-venous malformation associated with cerebral capillary malformation. 6 56
10814716 2000
9
A two-hit mechanism causes cerebral cavernous malformations: complete inactivation of CCM1, CCM2 or CCM3 in affected endothelial cells. 56 54 61
19088124 2009
10
Deletions in CCM2 are a common cause of cerebral cavernous malformations. 6 54 61
17160895 2007
11
CCM1 mutation screen of sporadic cases with cerebral cavernous malformations. 54 61 56
15079030 2004
12
Clinical features of cerebral cavernous malformations patients with KRIT1 mutations. 61 54 56
14755725 2004
13
Mutations within the MGC4607 gene cause cerebral cavernous malformations. 6 54 61
14740320 2004
14
Spectrum and expression analysis of KRIT1 mutations in 121 consecutive and unrelated patients with Cerebral Cavernous Malformations. 56 54 61
12404106 2002
15
Krit1 missense mutations lead to splicing errors in cerebral cavernous malformation. 6 54 61
11941540 2002
16
Germline mutations in the CCM1 gene, encoding Krit1, cause cerebral cavernous malformations. 6 54 61
11310633 2001
17
Mutations in the gene encoding KRIT1, a Krev-1/rap1a binding protein, cause cerebral cavernous malformations (CCM1). 54 61 6
10545614 1999
18
Refined localization of the cerebral cavernous malformation gene (CCM1) to a 4-cM interval of chromosome 7q contained in a well-defined YAC contig. 54 61 56
8750196 1995
19
Endothelial TLR4 and the microbiome drive cerebral cavernous malformations. 56 61
28489816 2017
20
Cerebral cavernous malformations arise from endothelial gain of MEKK3-KLF2/4 signalling. 56 61
27027284 2016
21
EndMT contributes to the onset and progression of cerebral cavernous malformations. 61 56
23748444 2013
22
Untreated clinical course of cerebral cavernous malformations: a prospective, population-based cohort study. 61 6
22297119 2012
23
A founder mutation in the Ashkenazi Jewish population affecting messenger RNA splicing of the CCM2 gene causes cerebral cavernous malformations. 6 61
21543988 2011
24
Biallelic somatic and germline mutations in cerebral cavernous malformations (CCMs): evidence for a two-hit mechanism of CCM pathogenesis. 61 56
19088123 2009
25
Large germline deletions and duplication in isolated cerebral cavernous malformation patients. 61 56
17211633 2007
26
Genotype-phenotype correlations in cerebral cavernous malformations patients. 61 56
17041941 2006
27
Cerebral cavernous malformation: new molecular and clinical insights. 61 56
16571644 2006
28
Value of gradient-echo magnetic resonance imaging in the diagnosis of familial cerebral cavernous malformation. 56 61
15824268 2005
29
Mutations within the programmed cell death 10 gene cause cerebral cavernous malformations. 6 61
15543491 2005
30
Mutations in a gene encoding a novel protein containing a phosphotyrosine-binding domain cause type 2 cerebral cavernous malformations. 61 6
14624391 2003
31
Cerebral Cavernous Malformation, Familial 61 6
20301470 2003
32
Multilocus linkage identifies two new loci for a mendelian form of stroke, cerebral cavernous malformation, at 7p15-13 and 3q25.2-27. 56 61
9811928 1998
33
A founder mutation as a cause of cerebral cavernous malformation in Hispanic Americans. 56 61
8596595 1996
34
A locus for cerebral cavernous malformations maps to chromosome 7q in two families. 56 61
8530042 1995
35
Mapping a gene causing cerebral cavernous malformation to 7q11.2-q21. 61 56
7604043 1995
36
Guidelines for the primary prevention of stroke: a statement for healthcare professionals from the American Heart Association/American Stroke Association. 6
25355838 2014
37
EFNS guidelines on the molecular diagnosis of channelopathies, epilepsies, migraine, stroke, and dementias. 6
20298421 2010
38
Hemorrhage from cavernous malformations of the brain: definition and reporting standards. Angioma Alliance Scientific Advisory Board. 6
18974380 2008
39
Novel CCM1 mutation in a patient with paraparesis and thoracic cord cavernous malformation. 56
16186553 2005
40
A novel KRIT1/CCM1 truncating mutation in a patient with cerebral and retinal cavernous angiomas. 6
11831930 2002
41
Genetic heterogeneity and absence of founder effect in a series of 36 French cerebral cavernous angiomas families. 56
10352941 1999
42
An association between autosomal dominant cerebral cavernomas and a distinctive hyperkeratotic cutaneous vascular malformation in 4 families. 56
9989629 1999
43
Hereditary cerebral cavernous angiomas: clinical and genetic features in 57 French families. Société Française de Neurochirurgie. 56
9863787 1998
44
Cutaneous and cerebral haemangiomas associated with eruptive angiokeratomas. 56
8776368 1996
45
A gene responsible for cavernous malformations of the brain maps to chromosome 7q. 56
7795602 1995
46
Familial cerebral cavernous angiomas: clinical and radiologic studies. 6
7898703 1995
47
Familial cerebral, hepatic, and retinal cavernous angiomas: a new syndrome. 56
7923228 1994
48
Cavernous angiomatosis of the central nervous system: usefulness of screening the family. 56
8256569 1993
49
Familial cavernous angiomas of the brain: observations in a four generation family. 56
1468464 1992
50
Terminal transverse limb defects associated with familial cavernous angiomatosis. 56
1536177 1992

Variations for Cerebral Cavernous Malformations

ClinVar genetic disease variations for Cerebral Cavernous Malformations:

6 (show top 50) (show all 137) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 KRIT1 KRIT1, 1283C-TSNV Pathogenic 5718
2 KRIT1 KRIT1, 1-BP DEL, 1342Adeletion Pathogenic 5719
3 KRIT1 KRIT1, 1-BP INS, 1271Cinsertion Pathogenic 5720
4 KRIT1 NM_194456.1(KRIT1):c.1363C>T (p.Gln455Ter)SNV Pathogenic 5721 rs267607203 7:91852184-91852184 7:92222870-92222870
5 KRIT1 KRIT1, 1-BP DEL, 103Gdeletion Pathogenic 5722
6 KRIT1 KRIT1, IVS2DS, T-C, +2SNV Pathogenic 5723
7 KRIT1 KRIT1, 2-BP DEL, 741TCdeletion Pathogenic 5724
8 KRIT1 NM_194456.1(KRIT1):c.410A>G (p.Asp137Gly)SNV Pathogenic 5725 rs137853139 7:91865802-91865802 7:92236488-92236488
9 KRIT1 NM_194456.1(KRIT1):c.601C>G (p.Gln201Glu)SNV Pathogenic 5726 rs137853140 7:91864845-91864845 7:92235531-92235531
10 KRIT1 KRIT1, 1-BP INS, 1374Cinsertion Pathogenic 5727
11 KRIT1 NM_194456.1(KRIT1):c.987C>A (p.Cys329Ter)SNV Pathogenic 5728 rs267607204 7:91863765-91863765 7:92234451-92234451
12 KRIT1 NM_194456.1(KRIT1):c.1267C>T (p.Arg423Ter)SNV Pathogenic 265216 rs886039402 7:91852280-91852280 7:92222966-92222966
13 KRIT1 NM_194456.1(KRIT1):c.152_155del (p.Lys51fs)deletion Pathogenic 265214 rs886039400 7:91870414-91870417 7:92241100-92241103
14 KRIT1 NM_004912.4(KRIT1):c.1197_1200CAAA[1] (p.Gln401fs)short repeat Pathogenic 372398 rs1057517753 7:91855084-91855087 7:92225770-92225773
15 KRIT1 NM_194456.1(KRIT1):c.729+2T>CSNV Pathogenic 427906 rs1554528541 7:91864715-91864715 7:92235401-92235401
16 KRIT1 NM_194456.1(KRIT1):c.1144dup (p.Arg382fs)duplication Pathogenic 427907 rs1554518386 7:91855842-91855842 7:92226528-92226528
17 KRIT1 NM_194456.1(KRIT1):c.1890G>A (p.Trp630Ter)SNV Pathogenic 439854 rs1554503009 7:91842644-91842644 7:92213330-92213330
18 KRIT1 deletion Pathogenic 468200 7:92213175-92242155
19 KRIT1 NM_194456.1(KRIT1):c.812G>A (p.Trp271Ter)SNV Pathogenic 468220 rs1554527779 7:91864155-91864155 7:92234841-92234841
20 KRIT1 NC_000007.13:g.(?_91863763)_(91871451_?)deldeletion Pathogenic 468201 7:91863763-91871451
21 KRIT1 NC_000007.13:g.(?_91870287)_(91871469_?)deldeletion Pathogenic 468203 7:91870287-91871469 7:92240973-92242155
22 KRIT1 NM_004912.4(KRIT1):c.1700_1701AG[1] (p.Glu567_Ser568insTer)short repeat Pathogenic 468212 rs1554504484 7:91843952-91843953 7:92214638-92214639
23 KRIT1 NM_194456.1(KRIT1):c.1417C>T (p.Gln473Ter)SNV Pathogenic 468209 rs1554513061 7:91851362-91851362 7:92222048-92222048
24 KRIT1 NM_194456.1(KRIT1):c.990G>A (p.Trp330Ter)SNV Pathogenic 468221 rs1554518783 7:91855996-91855996 7:92226682-92226682
25 KRIT1 NM_004912.4(KRIT1):c.1356_1357TC[3] (p.Gln455fs)short repeat Pathogenic 468207 rs1180476377 7:91852184-91852185 7:92222870-92222871
26 KRIT1 NM_194456.1(KRIT1):c.1201C>T (p.Gln401Ter)SNV Pathogenic 468205 rs1331502949 7:91855087-91855087 7:92225773-92225773
27 KRIT1 NM_194456.1(KRIT1):c.782C>G (p.Ser261Ter)SNV Pathogenic 468219 rs1554527817 7:91864185-91864185 7:92234871-92234871
28 KRIT1 NM_194456.1(KRIT1):c.730-2A>GSNV Pathogenic 468218 rs1554527925 7:91864239-91864239 7:92234925-92234925
29 KRIT1 NM_194456.1(KRIT1):c.1683_1695del (p.Val562fs)deletion Pathogenic 468211 rs1554504519 7:91843960-91843972 7:92214646-92214658
30 KRIT1 NM_194456.1(KRIT1):c.1545del (p.Leu516fs)deletion Pathogenic 468210 rs1554512658 7:91851234-91851234 7:92221920-92221920
31 KRIT1 NM_194456.1(KRIT1):c.1412-1G>TSNV Pathogenic 468208 rs1554513070 7:91851368-91851368 7:92222054-92222054
32 KRIT1 NM_194456.1(KRIT1):c.1255-1_1256delshort repeat Pathogenic 468206 rs1554514380 7:91852291-91852293 7:92222977-92222979
33 KRIT1 NM_194456.1(KRIT1):c.1400C>A (p.Ser467Ter)SNV Pathogenic 489287 rs1554513911 7:91852147-91852147 7:92222833-92222833
34 KRIT1 NM_194456.1(KRIT1):c.2119_2120del (p.Ser707fs)deletion Pathogenic 522190 rs1554490317 7:91830643-91830644 7:92201329-92201330
35 KRIT1 NM_194456.1(KRIT1):c.196C>T (p.Gln66Ter)SNV Pathogenic 522191 rs771656368 7:91870373-91870373 7:92241059-92241059
36 KRIT1 NC_000007.13:g.(?_91855014)_(91856016_?)deldeletion Pathogenic 536123 7:91855014-91856016 7:92225700-92226702
37 KRIT1 NM_194456.1(KRIT1):c.972_975CATT[3] (p.Tyr327fs)short repeat Pathogenic 536121 rs1326827713 7:91863773-91863776 7:92234459-92234462
38 KRIT1 NC_000007.13:g.(?_91829918)_(91871469_?)deldeletion Pathogenic 583667 7:91829918-91871469 7:92200604-92242155
39 KRIT1 NM_194456.1(KRIT1):c.1437_1438del (p.Lys479fs)deletion Pathogenic 576708 rs1563263905 7:91851341-91851342 7:92222027-92222028
40 KRIT1 NM_194456.1(KRIT1):c.1373del (p.Gln458fs)deletion Pathogenic 580059 rs1563266147 7:91852174-91852174 7:92222860-92222860
41 KRIT1 NM_194456.1(KRIT1):c.659dup (p.Leu220fs)duplication Pathogenic 660376 7:91864787-91864787 7:92235474-92235474
42 KRIT1 NM_194456.1(KRIT1):c.747_750del (p.Asn250fs)deletion Pathogenic 653169 7:91864217-91864220 7:92234906-92234909
43 KRIT1 NM_194456.1(KRIT1):c.810dup (p.Trp271fs)duplication Pathogenic 654640 7:91864157-91864157 7:92234847-92234847
44 KRIT1 NM_194456.1(KRIT1):c.1342del (p.Met448fs)deletion Pathogenic 649953 7:91852205-91852205 7:92222892-92222892
45 KRIT1 NM_194456.1(KRIT1):c.1558A>T (p.Lys520Ter)SNV Pathogenic 653656 7:91851221-91851221 7:92221907-92221907
46 KRIT1 NM_194456.1(KRIT1):c.1742_1748dup (p.Ile584fs)duplication Pathogenic 663252 7:91843275-91843276 7:92213968-92213974
47 KRIT1 NM_194456.1(KRIT1):c.268C>T (p.Arg90Ter)SNV Pathogenic 590740 rs1563313372 7:91867068-91867068 7:92237754-92237754
48 KRIT1 NM_004912.4(KRIT1):c.1301_1305TTGAA[1] (p.Leu436fs)short repeat Pathogenic 590697 rs1563266658 7:91852237-91852241 7:92222923-92222927
49 KRIT1 NM_004912.4(KRIT1):c.1199_1203AACAA[1] (p.Asn402fs)short repeat Pathogenic 566352 rs1563275562 7:91855080-91855084 7:92225766-92225770
50 KRIT1 NM_194456.1(KRIT1):c.730-1G>CSNV Pathogenic/Likely pathogenic 536122 rs1554527922 7:91864238-91864238 7:92234924-92234924

UniProtKB/Swiss-Prot genetic disease variations for Cerebral Cavernous Malformations:

73
# Symbol AA change Variation ID SNP ID
1 KRIT1 p.Phe97Ser VAR_023573
2 KRIT1 p.Lys569Glu VAR_023574

Expression for Cerebral Cavernous Malformations

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

Pathways for Cerebral Cavernous Malformations

Pathways related to Cerebral Cavernous Malformations according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.49 RAP1B RAP1A PTEN MAP3K3 KDR
2 12.32 TEK RAP1B RAP1A MAP3K3 KDR
3
Show member pathways
12 TEK RAP1B RAP1A KRIT1 KDR
4
Show member pathways
11.89 TEK PTEN KDR ITGB1BP1
5
Show member pathways
11.79 RAP1B RAP1A PTEN MAP3K3
6 10.87 TEK PECAM1 KDR DLL4
7 10.57 RAP1B RAP1A

GO Terms for Cerebral Cavernous Malformations

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

# Name GO ID Score Top Affiliating Genes
1 plasma membrane GO:0005886 10.1 TEK RAP2A RAP1B RAP1A PTEN PECAM1
2 cytoplasm GO:0005737 10.1 TEK STK25 STK24 RAP1B RAP1A PTEN
3 cell junction GO:0030054 9.5 TEK RAP1B RAP1A PECAM1 KRIT1 KDR
4 membrane raft GO:0045121 9.46 TEK RAP1B PECAM1 KDR
5 cell-cell junction GO:0005911 9.02 TEK RAP1B PECAM1 KRIT1 HEG1

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

(show top 50) (show all 51)
# Name GO ID Score Top Affiliating Genes
1 signal transduction GO:0007165 10.3 TEK STK25 STK24 RAP2A RAP1B RAP1A
2 protein phosphorylation GO:0006468 10.11 TEK STK25 STK24 MAP3K3 KDR
3 negative regulation of gene expression GO:0010629 9.99 PDCD10 KLF4 KDR DLL4
4 heart development GO:0007507 9.98 TEK PTEN HEG1 CCM2
5 positive regulation of protein phosphorylation GO:0001934 9.92 TEK RAP2A PECAM1 KDR
6 negative regulation of cell migration GO:0030336 9.89 STK24 RAP2A PTEN KLF4
7 positive regulation of ERK1 and ERK2 cascade GO:0070374 9.89 TEK RAP1B RAP1A PTEN KDR
8 small GTPase mediated signal transduction GO:0007264 9.88 RAP1B RAP1A KRIT1
9 activation of protein kinase activity GO:0032147 9.87 STK25 STK24 MAP3K3
10 response to organic substance GO:0010033 9.86 TEK PTEN KLF4
11 multicellular organism growth GO:0035264 9.86 KLF2 HEG1 CCM2
12 negative regulation of ERK1 and ERK2 cascade GO:0070373 9.84 PTEN KLF4 ITGB1BP1
13 cellular response to drug GO:0035690 9.83 RAP2A RAP1B RAP1A
14 vasculogenesis GO:0001570 9.82 KDR HEG1 CCM2
15 response to hydrogen peroxide GO:0042542 9.81 STK25 STK24 PDCD10
16 positive regulation of endothelial cell migration GO:0010595 9.8 TEK KDR ITGB1BP1
17 positive regulation of Notch signaling pathway GO:0045747 9.79 PDCD10 ITGB1BP1 DLL4
18 signal transduction by protein phosphorylation GO:0023014 9.78 STK25 STK24 MAP3K3
19 protein autophosphorylation GO:0046777 9.77 TEK STK25 STK24 MAP3K3 KDR
20 negative regulation of endothelial cell apoptotic process GO:2000352 9.74 TEK KRIT1 KDR
21 cellular response to vascular endothelial growth factor stimulus GO:0035924 9.73 KDR ITGB1BP1 DLL4
22 regulation of establishment of cell polarity GO:2000114 9.71 RAP1B KRIT1
23 cellular response to organic cyclic compound GO:0071407 9.71 RAP1B RAP1A KLF4 KLF2
24 negative regulation of focal adhesion assembly GO:0051895 9.7 PTEN ITGB1BP1
25 cellular response to peptide GO:1901653 9.7 KLF4 KLF2
26 negative regulation of phosphatidylinositol 3-kinase signaling GO:0014067 9.7 PTEN KLF4
27 positive regulation of focal adhesion assembly GO:0051894 9.69 TEK KDR ITGB1BP1
28 response to carbohydrate GO:0009743 9.68 RAP1B RAP1A
29 endothelial cell morphogenesis GO:0001886 9.68 PECAM1 HEG1
30 positive regulation of vasculogenesis GO:2001214 9.67 RAP1A KDR
31 positive regulation of protein metabolic process GO:0051247 9.67 KLF4 KLF2
32 pericardium development GO:0060039 9.66 HEG1 CCM2
33 cellular response to laminar fluid shear stress GO:0071499 9.65 KLF4 KLF2
34 establishment of Golgi localization GO:0051683 9.65 STK25 PDCD10
35 establishment of endothelial barrier GO:0061028 9.65 RAP1B RAP1A PECAM1
36 regulation of cell junction assembly GO:1901888 9.64 RAP1B RAP1A
37 venous blood vessel morphogenesis GO:0048845 9.64 HEG1 CCM2
38 microvillus assembly GO:0030033 9.63 RAP2A RAP1B RAP1A
39 negative regulation of synaptic vesicle exocytosis GO:2000301 9.62 RAP1B RAP1A
40 ventricular trabecula myocardium morphogenesis GO:0003222 9.61 HEG1 DLL4 CCM2L
41 positive regulation of fibroblast growth factor production GO:0090271 9.6 HEG1 CCM2L
42 Golgi reassembly GO:0090168 9.58 STK25 PDCD10
43 endothelial cell development GO:0001885 9.58 HEG1 CCM2
44 negative regulation of cell migration involved in sprouting angiogenesis GO:0090051 9.56 PDCD10 KLF4 ITGB1BP1 DLL4
45 cellular response to cycloheximide GO:0071409 9.55 KLF4 KLF2
46 cardiac muscle tissue growth GO:0055017 9.54 HEG1 CCM2L
47 intrinsic apoptotic signaling pathway in response to hydrogen peroxide GO:0036481 9.52 STK25 PDCD10
48 Rap protein signal transduction GO:0032486 9.5 RAP2A RAP1B RAP1A
49 regulation of axon regeneration GO:0048679 9.33 STK24 PTEN KLF4
50 angiogenesis GO:0001525 9.17 TEK PTEN PECAM1 PDCD10 KRIT1 KDR

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

# Name GO ID Score Top Affiliating Genes
1 protein binding GO:0005515 9.58 TEK STK25 STK24 RAP2A RAP1B RAP1A
2 protein kinase activity GO:0004672 9.55 TEK STK25 STK24 MAP3K3 KDR
3 GDP binding GO:0019003 9.13 RAP2A RAP1B RAP1A

Sources for Cerebral Cavernous Malformations

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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43 MeSH
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50 NDF-RT
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56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
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