CCM2 Gene (Protein Coding)

CCM2 Scaffold Protein

GC07P044999
GIFtS:
44
This gene encodes a scaffold protein that functions in the stress-activated p38 Mitogen-activated protein kinase (MAPK) signaling cascade. The protein interacts with SMAD specific E3 ubiquitin protein ligase 1 (also known as SMURF1) via a phosphotyrosine binding domain to promote RhoA degradation. The protein is required for normal cytoskeletal structure, cell-cell interactions... See more...

Aliases for CCM2 Gene

Aliases for CCM2 Gene

  • CCM2 Scaffold Protein 2 3 5
  • Malcavernin 2 3 4
  • Cerebral Cavernous Malformations 2 Protein 3 4
  • Cerebral Cavernous Malformation 2 2 3
  • Osmosensing Scaffold For MEKK3 2 3
  • CCM2 Scaffolding Protein 2 3
  • C7orf22 3 4
  • OSM 2 3
  • Chromosome 7 Open Reading Frame 22 2
  • PP10187 3
  • MGC4607 2
  • CCM2 5

External Ids for CCM2 Gene

Previous HGNC Symbols for CCM2 Gene

  • C7orf22

Previous GeneCards Identifiers for CCM2 Gene

  • GC07U990144
  • GC00U914335
  • GC07P044781
  • GC07P044813
  • GC07P045006
  • GC07P045039
  • GC07P044924

Summaries for CCM2 Gene

Entrez Gene Summary for CCM2 Gene

  • This gene encodes a scaffold protein that functions in the stress-activated p38 Mitogen-activated protein kinase (MAPK) signaling cascade. The protein interacts with SMAD specific E3 ubiquitin protein ligase 1 (also known as SMURF1) via a phosphotyrosine binding domain to promote RhoA degradation. The protein is required for normal cytoskeletal structure, cell-cell interactions, and lumen formation in endothelial cells. Mutations in this gene result in cerebral cavernous malformations. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Nov 2009]

GeneCards Summary for CCM2 Gene

CCM2 (CCM2 Scaffold Protein) is a Protein Coding gene. Diseases associated with CCM2 include Cerebral Cavernous Malformations 2 and Cerebral Cavernous Malformation, Familial. Among its related pathways are Regulation of p38-alpha and p38-beta and p38 MAPK signaling pathway (Pathway Interaction Database). An important paralog of this gene is CCM2L.

UniProtKB/Swiss-Prot Summary for CCM2 Gene

  • Component of the CCM signaling pathway which is a crucial regulator of heart and vessel formation and integrity. May act through the stabilization of endothelial cell junctions (By similarity). May function as a scaffold protein for MAP2K3-MAP3K3 signaling. Seems to play a major role in the modulation of MAP3K3-dependent p38 activation induced by hyperosmotic shock (By similarity).

Gene Wiki entry for CCM2 Gene

Additional gene information for CCM2 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for CCM2 Gene

Genomics for CCM2 Gene

GeneHancer (GH) Regulatory Elements Pubs

Download GeneHancer 2017 data
Promoters and enhancers for CCM2 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around CCM2 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for CCM2

Top Transcription factor binding sites by QIAGEN in the CCM2 gene promoter:
  • AML1a
  • Arnt
  • GATA-1
  • Ik-2
  • Lmo2
  • SRY
  • Tal-1beta
  • XBP-1

Genomic Locations for CCM2 Gene

Latest Assembly
chr7:44,999,475-45,076,470
(GRCh38/hg38)
Size:
76,996 bases
Orientation:
Plus strand

Previous Assembly
chr7:45,039,345-45,116,069
(GRCh37/hg19 by Entrez Gene)
Size:
76,725 bases
Orientation:
Plus strand

chr7:45,039,074-45,116,068
(GRCh37/hg19 by Ensembl)
Size:
76,995 bases
Orientation:
Plus strand

Genomic View for CCM2 Gene

Genes around CCM2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CCM2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CCM2 Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for CCM2 Gene

Proteins for CCM2 Gene

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  • Protein details for CCM2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9BSQ5-CCM2_HUMAN
    Recommended name:
    Cerebral cavernous malformations 2 protein
    Protein Accession:
    Q9BSQ5
    Secondary Accessions:
    • A4D2L4
    • B3KUV0
    • D3DVL4
    • E9PDJ3
    • F5H0E1
    • F5H551
    • Q71RE5
    • Q8TAT4

    Protein attributes for CCM2 Gene

    Size:
    444 amino acids
    Molecular mass:
    48837 Da
    Quaternary structure:
    • Part of a complex with MAP2K3, MAP3K3 and RAC1. Binds RAC1 directly and independently of its nucleotide-bound state (By similarity). Interacts with HEG1 and KRIT1; KRIT1 greatly facilitates the interaction with HEG1 (By similarity). Interacts with PDCD10.

    Three dimensional structures from OCA and Proteopedia for CCM2 Gene

    Alternative splice isoforms for CCM2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for CCM2 Gene

Protein Expression for CCM2 Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Post-translational modifications for CCM2 Gene

  • Ubiquitination at Lys96
  • Modification sites at PhosphoSitePlus

Other Protein References for CCM2 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for CCM2 Gene

Domains & Families for CCM2 Gene

Gene Families for CCM2 Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Predicted intracellular proteins

Protein Domains for CCM2 Gene

InterPro:
Blocks:
  • Phosphotyrosine interaction domain
ProtoNet:

Suggested Antigen Peptide Sequences for CCM2 Gene

GenScript: Design optimal peptide antigens:
  • Cerebral cavernous malformations 2 protein (CCM2_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9BSQ5

UniProtKB/Swiss-Prot:

CCM2_HUMAN :
  • The C-terminal region constitutes an independently folded domain that has structural similarity with the USH1C (harmonin) N-terminus, despite very low sequence similarity.
  • Belongs to the CCM2 family.
Domain:
  • The C-terminal region constitutes an independently folded domain that has structural similarity with the USH1C (harmonin) N-terminus, despite very low sequence similarity.
Family:
  • Belongs to the CCM2 family.
genes like me logo Genes that share domains with CCM2: view

Function for CCM2 Gene

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  6. Cell Lines for research

Molecular function for CCM2 Gene

UniProtKB/Swiss-Prot Function:
Component of the CCM signaling pathway which is a crucial regulator of heart and vessel formation and integrity. May act through the stabilization of endothelial cell junctions (By similarity). May function as a scaffold protein for MAP2K3-MAP3K3 signaling. Seems to play a major role in the modulation of MAP3K3-dependent p38 activation induced by hyperosmotic shock (By similarity).

Phenotypes From GWAS Catalog for CCM2 Gene

Gene Ontology (GO) - Molecular Function for CCM2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 16037064
genes like me logo Genes that share ontologies with CCM2: view
genes like me logo Genes that share phenotypes with CCM2: view

Human Phenotype Ontology for CCM2 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for CCM2 Gene

MGI Knock Outs for CCM2:
  • Ccm2 Ccm2<tm1.1Kwhi>
  • Ccm2 Ccm2<tm1.1Etl>
  • Ccm2 Ccm2<tm1Sbn>

Animal Models for research

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CCM2

Clone products for research

No data available for Enzyme Numbers (IUBMB) , miRNA , Transcription Factor Targets and HOMER Transcription for CCM2 Gene

Localization for CCM2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for CCM2 Gene

Cytoplasm.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for CCM2 gene
Compartment Confidence
mitochondrion 4
nucleus 4
cytosol 3
extracellular 2
cytoskeleton 2
plasma membrane 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Mitochondria (4)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for CCM2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IEA,IDA 16037064
GO:0005739 mitochondrion IDA --
GO:0032991 protein-containing complex IEA --
genes like me logo Genes that share ontologies with CCM2: view

Pathways & Interactions for CCM2 Gene

genes like me logo Genes that share pathways with CCM2: view

Pathways by source for CCM2 Gene

SIGNOR curated interactions for CCM2 Gene

Is activated by:

Gene Ontology (GO) - Biological Process for CCM2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001568 blood vessel development IEA --
GO:0001570 vasculogenesis IMP 14740320
GO:0001701 in utero embryonic development IEA --
GO:0001885 endothelial cell development IEA --
GO:0001944 vasculature development IEA --
genes like me logo Genes that share ontologies with CCM2: view

Drugs & Compounds for CCM2 Gene

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  1. Drug products for research
No Compound Related Data Available

Transcripts for CCM2 Gene

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mRNA/cDNA for CCM2 Gene

6 REFSEQ mRNAs :
19 NCBI additional mRNA sequence :
20 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CCM2

Clone products for research

Alternative Splicing Database (ASD) splice patterns (SP) for CCM2 Gene

ExUns: 1 ^ 2a · 2b · 2c · 2d ^ 3 ^ 4a · 4b ^ 5a · 5b ^ 6 ^ 7a · 7b ^ 8 ^ 9 ^ 10 ^ 11 ^ 12a · 12b · 12c · 12d ^ 13a · 13b ^ 14a · 14b · 14c ^
SP1: - - - - - - - - - -
SP2: - - - - -
SP3: - - - - - - - - - - - - - -
SP4: - - - - - - - - - - - - -
SP5: - - - - - - - - - - - -
SP6: - - - - - - -
SP7: - - - - - - - - - -
SP8: - - - - - - - - - -
SP9: - - - - - - -
SP10: - - - - - - - - - - - - - - -
SP11: - - - - - - - - - - -
SP12: - - - - - - - - - - - -
SP13: - - - - - - - - - - - - - - - -
SP14:
SP15: - - - - - - - - - - - - - -
SP16: - - - - - - - - - - - - - - - -
SP17: - - - - - - - - -
SP18:
SP19:
SP20: - - - - - - - - - - - - - - -
SP21: - - - - - - - -
SP22: - - - - - -
SP23: - - - - - -
SP24: - -
SP25: - - - - - -
SP26: - - - - - - - - - - - - - - - - - - -
SP27:
SP28:

ExUns: 15a · 15b · 15c ^ 16a · 16b ^ 17a · 17b ^ 18 ^ 19a · 19b · 19c ^ 20a · 20b · 20c · 20d ^ 21a · 21b · 21c · 21d · 21e · 21f · 21g
SP1: - - - - -
SP2: - - - - -
SP3: - - - - - - - -
SP4: - - - -
SP5: - - - - -
SP6: - - -
SP7: - - - - -
SP8: - - - - - - -
SP9: - - - - - - - - -
SP10: - - - -
SP11:
SP12:
SP13: - - - -
SP14: - - - - -
SP15:
SP16:
SP17: - - - - - - - - -
SP18: - - - - - -
SP19: - - -
SP20:
SP21:
SP22:
SP23:
SP24:
SP25:
SP26:
SP27:
SP28: -

Relevant External Links for CCM2 Gene

GeneLoc Exon Structure for
CCM2

Expression for CCM2 Gene

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  1. Primer products for research
  2. Gene Expression Assays for research

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for CCM2 Gene

mRNA expression in normal human tissues for CCM2 Gene
mRNA expression by GTEx for CCM2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for CCM2 Gene

This gene is overexpressed in Whole Blood (x4.9).

Protein differential expression in normal tissues from HIPED for CCM2 Gene

This gene is overexpressed in Peripheral blood mononuclear cells (23.6), CD8 Tcells (6.3), and Blymphocyte (6.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for CCM2 Gene



Protein tissue co-expression partners for CCM2 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for CCM2

SOURCE GeneReport for Unigene cluster for CCM2 Gene:

Hs.148272

Evidence on tissue expression from TISSUES for CCM2 Gene

  • Nervous system(4.8)
  • Liver(4.4)
  • Kidney(4.4)
  • Blood(3)
  • Heart(2.6)
  • Eye(2.3)
  • Muscle(2.1)
  • Skin(2.1)

Phenotype-based relationships between genes and organs from Gene ORGANizer for CCM2 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • integumentary
  • nervous
  • skeletal muscle
Regions:
Head and neck:
  • brain
  • eye
  • head
  • meninges
  • neck
Abdomen:
  • liver
General:
  • blood
  • blood vessel
  • coagulation system
  • skin
  • spinal cord
genes like me logo Genes that share expression patterns with CCM2: view

No data available for mRNA Expression by UniProt/SwissProt for CCM2 Gene

Orthologs for CCM2 Gene

This gene was present in the common ancestor of chordates.

Orthologs for CCM2 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
 Mammalia CCM2 30 31
  • 99.39 (n)
 OneToOne
Mouse
(Mus musculus)
 Mammalia Ccm2 30 17 31
  • 89.53 (n)
 OneToOne
Rat
(Rattus norvegicus)
 Mammalia Ccm2 30
  • 88.91 (n)
Cow
(Bos Taurus)
 Mammalia CCM2 30 31
  • 88.89 (n)
 OneToOne
Dog
(Canis familiaris)
 Mammalia LOC100856167 30
  • 87.23 (n)
CCM2 31
  • 87 (a)
 OneToOne
Oppossum
(Monodelphis domestica)
 Mammalia CCM2 31
  • 81 (a)
 OneToOne
Platypus
(Ornithorhynchus anatinus)
 Mammalia CCM2 31
  • 63 (a)
 OneToOne
Chicken
(Gallus gallus)
 Aves CCM2 30 31
  • 80.23 (n)
 OneToOne
Lizard
(Anolis carolinensis)
 Reptilia CCM2 31
  • 79 (a)
 OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
 Amphibia ccm2 30
  • 76.02 (n)
African clawed frog
(Xenopus laevis)
 Amphibia Xl.6991 30
Zebrafish
(Danio rerio)
 Actinopterygii ccm2 30 31
  • 70.99 (n)
 OneToOne
Sea Squirt
(Ciona savignyi)
 Ascidiacea -- 31
  • 34 (a)
 OneToMany
Species where no ortholog for CCM2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for CCM2 Gene

ENSEMBL:
Gene Tree for CCM2 (if available)
TreeFam:
Gene Tree for CCM2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for CCM2: view image

Paralogs for CCM2 Gene

Paralogs for CCM2 Gene

(1) SIMAP similar genes for CCM2 Gene using alignment to 5 proteins:

  • CCM2_HUMAN
  • C9JUH3_HUMAN
  • E9PEC4_HUMAN
  • H7C516_HUMAN
  • Q6P456_HUMAN
genes like me logo Genes that share paralogs with CCM2: view

Variants for CCM2 Gene

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Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for CCM2 Gene

SNP ID Clinical significance and condition Chr 07 pos Variation AA Info Type
838138 Pathogenic: Cerebral cavernous malformations 2 45,073,495(+) C/G
NM_031443.4(CCM2):c.839C>G (p.Ser280Ter) 		NONSENSE,NON_CODING_TRANSCRIPT
848889 Uncertain Significance: Cerebral cavernous malformations 2 45,069,914(+) T/C
NM_031443.4(CCM2):c.698T>C (p.Ile233Thr) 		MISSENSE_VARIANT,NON_CODING_TRANSCRIPT_VARIANT,INTRON
849329 Pathogenic: Cerebral cavernous malformations 2 45,075,800(+) A/T
NM_031443.4(CCM2):c.1078A>T (p.Lys360Ter) 		NONSENSE,NON_CODING_TRANSCRIPT
857759 Pathogenic: Cerebral cavernous malformations 2 45,064,528(+) C/A
NM_031443.4(CCM2):c.354C>A (p.Tyr118Ter) 		NONSENSE,NON_CODING_TRANSCRIPT
862971 Pathogenic: Cerebral cavernous malformations 2 45,074,324(+) G/T
NM_031443.4(CCM2):c.970G>T (p.Glu324Ter) 		NONSENSE,NON_CODING_TRANSCRIPT

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for CCM2 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for CCM2 Gene

Variant ID Type Subtype PubMed ID
nsv1117709 CNV deletion 24896259
nsv1144173 CNV deletion 24896259
nsv366390 CNV deletion 16902084
nsv473655 CNV novel sequence insertion 20440878
nsv951641 CNV deletion 24416366

Variation tolerance for CCM2 Gene

Residual Variation Intolerance Score: 27.1% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 6.60; 78.10% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for CCM2 Gene

Human Gene Mutation Database (HGMD)
CCM2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
CCM2

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for CCM2 Gene

Disorders for CCM2 Gene

MalaCards: The human disease database

(18) MalaCards diseases for CCM2 Gene - From: OMI, CVR, GTR, ORP, SWI, COP, and GCD

- elite association - COSMIC cancer census association via MalaCards
Search CCM2 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

CCM2_HUMAN
  • Cerebral cavernous malformations 2 (CCM2) [MIM:603284]: 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. {ECO:0000269 PubMed:14624391, ECO:0000269 PubMed:14740320, ECO:0000269 PubMed:22415356}. Note=The disease is caused by variants affecting the gene represented in this entry.

Additional Disease Information for CCM2

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with CCM2: view

No data available for Genatlas for CCM2 Gene

Publications for CCM2 Gene

  1. Mutations in a gene encoding a novel protein containing a phosphotyrosine-binding domain cause type 2 cerebral cavernous malformations. (PMID: 14624391) Liquori CL … Marchuk DA (American journal of human genetics 2003) 3 4 23 74
  2. Mutations within the MGC4607 gene cause cerebral cavernous malformations. (PMID: 14740320) Denier C … Société Française de Neurochirurgie (American journal of human genetics 2004) 3 4 23
  3. Structural studies of cerebral cavernous malformations 2 (CCM2) reveal a folded helical domain at its C-terminus. (PMID: 23266514) Fisher OS … Boggon TJ (FEBS letters 2013) 3 4
  4. De novo MGC4607 gene heterozygous missense variants in a child with multiple cerebral cavernous malformations. (PMID: 22415356) Mosca L … Penco S (Journal of molecular neuroscience : MN 2012) 3 4
  5. Crystal structure of CCM3, a cerebral cavernous malformation protein critical for vascular integrity. (PMID: 20489202) Li X … Boggon TJ (The Journal of biological chemistry 2010) 3 4

ExternalLinks

View latest publications for CCM2 gene in Mastermind

Products for CCM2 Gene

Sources for CCM2 Gene