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Aliases for CCM2 Gene

Aliases for CCM2 Gene

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

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 Cavernous Hemangioma. 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 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 , fRNAdb sequence ontologies and piRNA Summary for CCM2 Gene

Genomics for CCM2 Gene

GeneHancer (GH) Regulatory Elements for CCM2 Gene

Promoters and enhancers for CCM2 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH07J044997 Promoter/Enhancer 2.5 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 663.2 +0.8 754 4.5 HDGF PKNOX1 ARNT ARID4B SIN3A YY1 POLR2B ZNF143 SP3 SP5 CCM2 LOC102723334 SNORA5C POLM ENSG00000260997 DDX56 SNORA5A SNORA5B ENSG00000228434 SNHG15
GH07J044975 Promoter/Enhancer 2.4 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 32.7 -20.6 -20553 6.5 PKNOX1 SMAD1 FEZF1 IRF4 POLR2B ZNF143 ATF7 RUNX3 JUNB REST MYO1G CCM2 ENSG00000260997 PURB RAMP3 SNHG15 OGDH ZMIZ2
GH07J045025 Promoter/Enhancer 1.4 Ensembl ENCODE dbSUPER 36.2 +28.6 28606 4.9 ELF3 MAX ERF EBF1 BATF POLR2A EED ZNF207 ETV6 IKZF2 CCM2 ENSG00000260997 MYO1G ENSG00000228596 SNHG15 LINC00957 GC07M045025 LOC102723334
GH07J044983 Promoter/Enhancer 1.8 Ensembl ENCODE dbSUPER 21.1 -13.8 -13836 5.2 HDGF PKNOX1 SMAD1 ARNT SIN3A ZNF2 IRF4 YY1 POLR2B ZNF766 SNHG15 SNORA9 GC07M044985 DDX56 CCM2 POLM SNORA5C ENSG00000260997 TMED4 SNORA5A
GH07J045108 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE 16.6 +111.5 111460 4 CLOCK ZFP64 DMAP1 YY1 E2F8 ZNF143 SP3 NFYC ZNF610 NBN TBRG4 SNHG15 NACAD CCM2 RAMP3 SNORA5B GC07P045063
- 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 UCSC Golden Path with GeneCards custom track

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

Genomic Locations for CCM2 Gene

Genomic Locations for CCM2 Gene
chr7:44,999,475-45,076,470
(GRCh38/hg38)
Size:
76,996 bases
Orientation:
Plus strand
chr7:45,039,074-45,116,069
(GRCh37/hg19)
Size:
76,996 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 StructureGene Density

RefSeq DNA sequence for CCM2 Gene

Proteins for CCM2 Gene

  • 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

Post-translational modifications for CCM2 Gene

  • Ubiquitination at Lys96
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for CCM2 Gene

Domains & Families for CCM2 Gene

Gene Families for CCM2 Gene

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

Protein Domains for CCM2 Gene

Suggested Antigen Peptide Sequences for CCM2 Gene

GenScript: Design optimal peptide antigens:

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

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<tm1.1Etl>
  • Ccm2 Ccm2<tm1Sbn>
  • Ccm2 Ccm2<tm1.1Kwhi>

Animal Model Products

Inhibitory RNA Products

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

Clone Products

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 5
nucleus 4
cytosol 3
extracellular 1
cytoskeleton 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for CCM2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IDA,IEA 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

Gene Ontology (GO) - Biological Process for CCM2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001570 vasculogenesis IMP 14740320
GO:0001701 in utero embryonic development IEA --
GO:0001885 endothelial cell development IEA --
GO:0001944 vasculature development IEA --
GO:0007229 integrin-mediated signaling pathway TAS 16037064
genes like me logo Genes that share ontologies with CCM2: view

No data available for SIGNOR curated interactions for CCM2 Gene

Drugs & Compounds for CCM2 Gene

No Compound Related Data Available

Transcripts for CCM2 Gene

Unigene Clusters for CCM2 Gene

Cerebral cavernous malformation 2:
Representative Sequences:

Inhibitory RNA Products

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

Clone Products

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
ECgene alternative splicing isoforms for
CCM2

Expression for CCM2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE 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

NURSA nuclear receptor signaling pathways regulating expression of CCM2 Gene:

CCM2

SOURCE GeneReport for Unigene cluster for CCM2 Gene:

Hs.148272

Evidence on tissue expression from TISSUES for CCM2 Gene

  • Nervous system(4.8)
  • Kidney(4.2)
  • Liver(4.2)
  • Heart(2.5)
  • Blood(2.4)

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 34 33
  • 99.39 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Ccm2 16 34 33
  • 89.53 (n)
rat
(Rattus norvegicus)
Mammalia Ccm2 33
  • 88.91 (n)
cow
(Bos Taurus)
Mammalia CCM2 34 33
  • 88.89 (n)
OneToOne
dog
(Canis familiaris)
Mammalia LOC100856167 33
  • 87.23 (n)
CCM2 34
  • 87 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia CCM2 34
  • 81 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia CCM2 34
  • 63 (a)
OneToOne
chicken
(Gallus gallus)
Aves CCM2 34 33
  • 80.23 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia CCM2 34
  • 79 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia ccm2 33
  • 76.02 (n)
African clawed frog
(Xenopus laevis)
Amphibia Xl.6991 33
zebrafish
(Danio rerio)
Actinopterygii ccm2 34 33
  • 70.99 (n)
OneToOne
sea squirt
(Ciona savignyi)
Ascidiacea -- 34
  • 34 (a)
OneToMany
Species where no ortholog for CCM2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya 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 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

Sequence variations from dbSNP and Humsavar for CCM2 Gene

SNP ID Clin Chr 07 pos Variation AA Info Type
rs137852841 pathogenic, Cerebral cavernous malformations 2, not provided 45,064,493(+) C/T coding_sequence_variant, non_coding_transcript_variant, stop_gained
rs137852842 pathogenic, Cerebral cavernous malformations 2, not provided 45,000,334(+) A/G genic_upstream_transcript_variant, initiator_codon_variant, intron_variant, missense_variant
rs137852843 pathogenic, Cerebral cavernous malformations 2, Cerebral cavernous malformations 2 (CCM2) [MIM:603284] 45,068,563(+) T/G coding_sequence_variant, intron_variant, missense_variant, non_coding_transcript_variant
rs181474100 likely-benign, Cerebral cavernous malformations 2 45,069,828(+) C/A/T coding_sequence_variant, intron_variant, non_coding_transcript_variant, synonymous_variant
rs190686229 likely-benign, not specified, not provided 45,074,420(+) C/T genic_downstream_transcript_variant, intron_variant

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 Assay Products

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

Disorders for CCM2 Gene

MalaCards: The human disease database

(13) MalaCards diseases for CCM2 Gene - From: HGMD, OMIM, ClinVar, GTR, Swiss-Prot, DISEASES, Novoseek, and GeneCards

- 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 mutations affecting the gene represented in this entry.

Additional Disease Information for CCM2

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
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 within the MGC4607 gene cause cerebral cavernous malformations. (PMID: 14740320) Denier C … Société Française de Neurochirurgie (American journal of human genetics 2004) 3 4 22 58
  2. 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 22 58
  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 58
  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 58
  5. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PMID: 20379614) Rose JE … Uhl GR (Molecular medicine (Cambridge, Mass.) 2010) 3 44 58

Products for CCM2 Gene

Sources for CCM2 Gene

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