Incidental Mutation 'R1687:Ccm2'
ID 189437
Institutional Source Beutler Lab
Gene Symbol Ccm2
Ensembl Gene ENSMUSG00000000378
Gene Name cerebral cavernous malformation 2
Synonyms
MMRRC Submission 039720-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R1687 (G1)
Quality Score 225
Status Not validated
Chromosome 11
Chromosomal Location 6496887-6546744 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 6535118 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Arginine to Glycine at position 67 (R67G)
Ref Sequence ENSEMBL: ENSMUSP00000125608 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000000388] [ENSMUST00000109721] [ENSMUST00000109722] [ENSMUST00000159007] [ENSMUST00000160633] [ENSMUST00000161501]
AlphaFold Q8K2Y9
Predicted Effect possibly damaging
Transcript: ENSMUST00000000388
AA Change: R125G

PolyPhen 2 Score 0.889 (Sensitivity: 0.82; Specificity: 0.94)
SMART Domains Protein: ENSMUSP00000000388
Gene: ENSMUSG00000000378
AA Change: R125G

DomainStartEndE-ValueType
low complexity region 2 12 N/A INTRINSIC
Blast:PTB 60 230 2e-35 BLAST
low complexity region 242 252 N/A INTRINSIC
Pfam:CCM2_C 296 396 8.9e-50 PFAM
Predicted Effect possibly damaging
Transcript: ENSMUST00000109721
AA Change: R61G

PolyPhen 2 Score 0.679 (Sensitivity: 0.86; Specificity: 0.92)
SMART Domains Protein: ENSMUSP00000105343
Gene: ENSMUSG00000000378
AA Change: R61G

DomainStartEndE-ValueType
Blast:PTB 2 166 2e-32 BLAST
low complexity region 178 188 N/A INTRINSIC
low complexity region 230 244 N/A INTRINSIC
PDB:4FQN|D 245 324 5e-52 PDB
Predicted Effect possibly damaging
Transcript: ENSMUST00000109722
AA Change: R61G

PolyPhen 2 Score 0.679 (Sensitivity: 0.86; Specificity: 0.92)
SMART Domains Protein: ENSMUSP00000105344
Gene: ENSMUSG00000000378
AA Change: R61G

DomainStartEndE-ValueType
Blast:PTB 2 166 2e-32 BLAST
low complexity region 178 188 N/A INTRINSIC
low complexity region 230 244 N/A INTRINSIC
PDB:4FQN|D 245 324 5e-52 PDB
Predicted Effect probably damaging
Transcript: ENSMUST00000159007
AA Change: R67G

PolyPhen 2 Score 0.995 (Sensitivity: 0.68; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000125608
Gene: ENSMUSG00000000378
AA Change: R67G

DomainStartEndE-ValueType
low complexity region 2 10 N/A INTRINSIC
Blast:PTB 11 102 3e-20 BLAST
Predicted Effect possibly damaging
Transcript: ENSMUST00000160633
AA Change: R119G

PolyPhen 2 Score 0.922 (Sensitivity: 0.81; Specificity: 0.94)
SMART Domains Protein: ENSMUSP00000125072
Gene: ENSMUSG00000000378
AA Change: R119G

DomainStartEndE-ValueType
Blast:PTB 54 224 6e-38 BLAST
Predicted Effect probably damaging
Transcript: ENSMUST00000161501
AA Change: R91G

PolyPhen 2 Score 0.993 (Sensitivity: 0.70; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000123790
Gene: ENSMUSG00000000378
AA Change: R91G

DomainStartEndE-ValueType
Blast:PTB 40 122 3e-10 BLAST
Coding Region Coverage
  • 1x: 99.2%
  • 3x: 98.5%
  • 10x: 96.7%
  • 20x: 93.8%
Validation Efficiency
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] 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]
PHENOTYPE: Homozygous null mice die during embryonic development with vasculature defects in the heart and placenta. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 70 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abca5 A T 11: 110,184,714 (GRCm39) F931I probably benign Het
Alox15 T A 11: 70,240,744 (GRCm39) H212L probably benign Het
Arhgap42 A T 9: 9,035,538 (GRCm39) V268D probably benign Het
Armc9 A G 1: 86,084,677 (GRCm39) M1V probably null Het
Brca1 C T 11: 101,380,666 (GRCm39) C1789Y probably benign Het
Cacng4 A G 11: 107,627,585 (GRCm39) V138A probably benign Het
Camsap1 A G 2: 25,829,627 (GRCm39) F699S probably damaging Het
Cdk16 G A X: 20,562,898 (GRCm39) probably null Het
Cep85 T C 4: 133,875,324 (GRCm39) H546R probably benign Het
Cfap54 T C 10: 92,768,502 (GRCm39) D207G probably damaging Het
Cldn9 G T 17: 23,902,050 (GRCm39) R192S probably benign Het
Crybb3 A G 5: 113,227,633 (GRCm39) S63P probably damaging Het
Cux1 A G 5: 136,341,523 (GRCm39) L615P probably damaging Het
Dctn3 A G 4: 41,715,407 (GRCm39) Y154H probably damaging Het
Depdc5 CTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCT CTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCT 5: 33,067,751 (GRCm39) probably benign Het
Dnah3 A T 7: 119,645,009 (GRCm39) probably null Het
Eif1ad2 A G 12: 87,786,488 (GRCm39) D133G unknown Het
Eml6 G A 11: 29,783,187 (GRCm39) H565Y probably damaging Het
Ephb6 T C 6: 41,594,300 (GRCm39) V610A probably benign Het
Fam234a T C 17: 26,434,282 (GRCm39) Y333C probably damaging Het
Fbln1 G A 15: 85,111,307 (GRCm39) V154I probably benign Het
Frem2 A T 3: 53,561,373 (GRCm39) W1045R probably benign Het
Fubp1 A G 3: 151,933,838 (GRCm39) probably benign Het
Gja3 T A 14: 57,274,333 (GRCm39) N13I probably damaging Het
Gpr20 C A 15: 73,567,751 (GRCm39) V213L probably benign Het
Grk5 T C 19: 61,065,221 (GRCm39) I295T probably damaging Het
Gucy1b1 A G 3: 81,945,349 (GRCm39) F430L probably damaging Het
Gzmk T A 13: 113,310,462 (GRCm39) I119L probably benign Het
Hadh T C 3: 131,038,898 (GRCm39) I153V probably benign Het
Hsfy2 T C 1: 56,676,012 (GRCm39) Y175C probably damaging Het
Hspa5 T C 2: 34,665,836 (GRCm39) I560T probably benign Het
Igdcc4 T C 9: 65,038,945 (GRCm39) V863A probably damaging Het
Il22ra2 A G 10: 19,508,620 (GRCm39) D216G probably benign Het
Klc2 G A 19: 5,161,682 (GRCm39) P303S probably damaging Het
Lama5 C T 2: 179,835,859 (GRCm39) V1192I probably benign Het
Mon2 A G 10: 122,862,029 (GRCm39) S772P probably damaging Het
Mphosph8 T A 14: 56,909,935 (GRCm39) L96Q probably damaging Het
Mzf1 C A 7: 12,786,698 (GRCm39) R124L possibly damaging Het
Nckap1 A G 2: 80,350,929 (GRCm39) I726T probably damaging Het
Ndnf A T 6: 65,680,407 (GRCm39) T229S probably benign Het
Npas3 A T 12: 54,095,658 (GRCm39) probably null Het
Nrap C T 19: 56,343,961 (GRCm39) E729K probably damaging Het
Nsun2 T A 13: 69,775,716 (GRCm39) F387I probably damaging Het
Or11g27 T C 14: 50,771,159 (GRCm39) S97P possibly damaging Het
Pabpc1l C T 2: 163,886,226 (GRCm39) T452M probably benign Het
Pcdh10 T C 3: 45,334,450 (GRCm39) Y255H probably damaging Het
Pdcd6ip A T 9: 113,529,087 (GRCm39) Y72N probably damaging Het
Pglyrp1 A T 7: 18,618,629 (GRCm39) probably benign Het
Pkp2 T C 16: 16,086,573 (GRCm39) probably null Het
Ppard A G 17: 28,516,154 (GRCm39) Y126C probably damaging Het
Prkcq T C 2: 11,295,344 (GRCm39) Y598H probably damaging Het
Rhobtb1 A G 10: 69,106,109 (GRCm39) T287A probably damaging Het
Sema4b T C 7: 79,869,010 (GRCm39) Y361H probably damaging Het
Slfn9 A T 11: 82,872,983 (GRCm39) I640N probably damaging Het
Smurf2 C A 11: 106,726,896 (GRCm39) probably null Het
Spag5 T C 11: 78,195,755 (GRCm39) V354A probably benign Het
Sptb T C 12: 76,650,473 (GRCm39) D1748G possibly damaging Het
St6galnac5 C A 3: 152,686,887 (GRCm39) L22F probably benign Het
Sugp2 T C 8: 70,695,284 (GRCm39) S86P probably damaging Het
Tnk1 T C 11: 69,747,299 (GRCm39) I111V possibly damaging Het
Tnni3k T A 3: 154,645,263 (GRCm39) I541F possibly damaging Het
Trim36 G T 18: 46,321,724 (GRCm39) H108N possibly damaging Het
Ttn T C 2: 76,701,251 (GRCm39) probably benign Het
Usp28 T A 9: 48,935,317 (GRCm39) S89R probably benign Het
Vmn2r121 T C X: 123,042,488 (GRCm39) D223G probably benign Het
Vmn2r65 T A 7: 84,590,026 (GRCm39) Y630F probably benign Het
Washc2 T A 6: 116,233,673 (GRCm39) S900T probably benign Het
Wdr72 A G 9: 74,117,481 (GRCm39) N731S probably benign Het
Xrra1 T A 7: 99,525,451 (GRCm39) F123L probably damaging Het
Zfp648 A G 1: 154,079,988 (GRCm39) D49G probably benign Het
Other mutations in Ccm2
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL02126:Ccm2 APN 11 6,544,154 (GRCm39) missense probably damaging 0.97
IGL02274:Ccm2 APN 11 6,540,808 (GRCm39) missense probably damaging 1.00
IGL02946:Ccm2 APN 11 6,546,195 (GRCm39) missense probably damaging 1.00
IGL02973:Ccm2 APN 11 6,534,544 (GRCm39) missense probably damaging 1.00
R0521:Ccm2 UTSW 11 6,540,886 (GRCm39) missense probably damaging 1.00
R1024:Ccm2 UTSW 11 6,520,119 (GRCm39) nonsense probably null
R1201:Ccm2 UTSW 11 6,543,682 (GRCm39) missense probably benign
R2199:Ccm2 UTSW 11 6,540,790 (GRCm39) missense probably damaging 1.00
R3237:Ccm2 UTSW 11 6,520,090 (GRCm39) missense probably benign 0.43
R5196:Ccm2 UTSW 11 6,511,181 (GRCm39) utr 5 prime probably benign
R6954:Ccm2 UTSW 11 6,544,239 (GRCm39) missense probably damaging 0.98
R7195:Ccm2 UTSW 11 6,546,302 (GRCm39) missense probably damaging 1.00
R7417:Ccm2 UTSW 11 6,543,091 (GRCm39) missense probably benign 0.05
R8706:Ccm2 UTSW 11 6,539,447 (GRCm39) missense possibly damaging 0.65
R8863:Ccm2 UTSW 11 6,535,211 (GRCm39) missense probably damaging 1.00
Predicted Primers PCR Primer
(F):5'- CTTTTAACCGAGGACTGTAGCCAGC -3'
(R):5'- AAGTCTCCAAAGGCCCTGAGTGTG -3'

Sequencing Primer
(F):5'- ACTGTAGCCAGCACAGTG -3'
(R):5'- CTAATTTATAGCCGTAGCAGGTG -3'
Posted On 2014-05-14