Incidental Mutation 'R3237:Ccm2'
ID 259105
Institutional Source Beutler Lab
Gene Symbol Ccm2
Ensembl Gene ENSMUSG00000000378
Gene Name cerebral cavernous malformation 2
Synonyms
MMRRC Submission 040619-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R3237 (G1)
Quality Score 225
Status Not validated
Chromosome 11
Chromosomal Location 6496887-6546744 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) G to A at 6520090 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Valine to Isoleucine at position 53 (V53I)
Ref Sequence ENSEMBL: ENSMUSP00000000388 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000000388] [ENSMUST00000109721] [ENSMUST00000109722] [ENSMUST00000159007] [ENSMUST00000160633] [ENSMUST00000161501]
AlphaFold Q8K2Y9
Predicted Effect probably benign
Transcript: ENSMUST00000000388
AA Change: V53I

PolyPhen 2 Score 0.432 (Sensitivity: 0.89; Specificity: 0.90)
SMART Domains Protein: ENSMUSP00000000388
Gene: ENSMUSG00000000378
AA Change: V53I

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 probably benign
Transcript: ENSMUST00000109721
SMART Domains Protein: ENSMUSP00000105343
Gene: ENSMUSG00000000378

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 benign
Transcript: ENSMUST00000109722
SMART Domains Protein: ENSMUSP00000105344
Gene: ENSMUSG00000000378

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 benign
Transcript: ENSMUST00000159007
SMART Domains Protein: ENSMUSP00000125608
Gene: ENSMUSG00000000378

DomainStartEndE-ValueType
low complexity region 2 10 N/A INTRINSIC
Blast:PTB 11 102 3e-20 BLAST
Predicted Effect probably benign
Transcript: ENSMUST00000160633
AA Change: V47I

PolyPhen 2 Score 0.124 (Sensitivity: 0.93; Specificity: 0.86)
SMART Domains Protein: ENSMUSP00000125072
Gene: ENSMUSG00000000378
AA Change: V47I

DomainStartEndE-ValueType
Blast:PTB 54 224 6e-38 BLAST
Predicted Effect probably benign
Transcript: ENSMUST00000161501
AA Change: V47I

PolyPhen 2 Score 0.061 (Sensitivity: 0.94; Specificity: 0.84)
SMART Domains Protein: ENSMUSP00000123790
Gene: ENSMUSG00000000378
AA Change: V47I

DomainStartEndE-ValueType
Blast:PTB 40 122 3e-10 BLAST
Coding Region Coverage
  • 1x: 99.1%
  • 3x: 98.4%
  • 10x: 96.8%
  • 20x: 93.4%
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: 52 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
2700049A03Rik G T 12: 71,211,320 (GRCm39) E685* probably null Het
2700049A03Rik A T 12: 71,211,321 (GRCm39) E685V possibly damaging Het
Aff2 T A X: 68,907,543 (GRCm39) V1175E possibly damaging Het
Agbl3 A G 6: 34,800,022 (GRCm39) probably null Het
Bcar3 C A 3: 122,318,645 (GRCm39) Q678K probably benign Het
Cd3e G T 9: 44,913,608 (GRCm39) C42* probably null Het
Cd4 A T 6: 124,844,633 (GRCm39) I384N probably benign Het
Ceacam11 T A 7: 17,707,379 (GRCm39) F54L probably benign Het
Cfap46 A G 7: 139,197,506 (GRCm39) S2122P probably damaging Het
Clptm1 A G 7: 19,369,271 (GRCm39) S461P probably damaging Het
Dlat T C 9: 50,549,331 (GRCm39) T518A possibly damaging Het
Dnah17 T C 11: 117,985,680 (GRCm39) T1466A probably benign Het
Dnah9 G A 11: 65,845,815 (GRCm39) T3023I probably benign Het
Fam181a T G 12: 103,282,348 (GRCm39) C84W possibly damaging Het
Gask1a C T 9: 121,793,935 (GRCm39) P30S possibly damaging Het
H2-Q6 C A 17: 35,644,676 (GRCm39) T155K probably damaging Het
Hlx G T 1: 184,464,184 (GRCm39) A52D probably damaging Het
Inpp5b A G 4: 124,674,279 (GRCm39) R329G probably benign Het
Klrb1f A T 6: 129,031,306 (GRCm39) I168L possibly damaging Het
Lama4 A T 10: 38,973,175 (GRCm39) I1581F probably damaging Het
Lipn A G 19: 34,046,138 (GRCm39) N37S probably benign Het
Lyzl4 T C 9: 121,413,233 (GRCm39) D65G probably benign Het
Med29 A G 7: 28,092,046 (GRCm39) probably benign Het
Myrip C A 9: 120,270,473 (GRCm39) D574E possibly damaging Het
N4bp3 A T 11: 51,536,761 (GRCm39) F104Y probably damaging Het
Nlrp9a A T 7: 26,270,810 (GRCm39) K892* probably null Het
Nsd1 T A 13: 55,460,701 (GRCm39) H2309Q possibly damaging Het
Obscn T C 11: 59,022,472 (GRCm39) R758G possibly damaging Het
Optn T C 2: 5,039,014 (GRCm39) S370G probably damaging Het
Pbrm1 T C 14: 30,754,432 (GRCm39) F151L probably damaging Het
Plekhs1 A T 19: 56,453,032 (GRCm39) probably null Het
Rpn1 A G 6: 88,080,396 (GRCm39) K565R probably benign Het
Rrh T C 3: 129,605,360 (GRCm39) Y110C probably damaging Het
Rufy4 T C 1: 74,186,822 (GRCm39) C537R probably damaging Het
Ryr1 C T 7: 28,769,075 (GRCm39) probably null Het
Scai C T 2: 39,040,326 (GRCm39) probably benign Het
Scap C G 9: 110,208,650 (GRCm39) P564A probably damaging Het
Setdb1 A G 3: 95,246,065 (GRCm39) V619A probably damaging Het
Slc41a3 T C 6: 90,613,847 (GRCm39) Y226H probably benign Het
Slf2 A G 19: 44,930,773 (GRCm39) I617V probably benign Het
Sned1 G A 1: 93,186,725 (GRCm39) R180Q probably benign Het
Spata22 T A 11: 73,236,713 (GRCm39) F340I probably damaging Het
St8sia3 T C 18: 64,402,886 (GRCm39) F175S probably damaging Het
Supt20 T C 3: 54,616,501 (GRCm39) S253P possibly damaging Het
Syngap1 T A 17: 27,176,067 (GRCm39) Y118* probably null Het
Szt2 A C 4: 118,240,231 (GRCm39) probably null Het
Tns2 C T 15: 102,017,369 (GRCm39) R281C probably damaging Het
Uba3 G T 6: 97,163,201 (GRCm39) T319K probably damaging Het
Vmn2r112 T A 17: 22,822,096 (GRCm39) V258E probably damaging Het
Zc3hav1 A G 6: 38,296,650 (GRCm39) L751S probably damaging Het
Zfp804b T C 5: 6,819,239 (GRCm39) M1275V probably benign Het
Zgrf1 A G 3: 127,407,024 (GRCm39) D1597G probably damaging 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
R1687:Ccm2 UTSW 11 6,535,118 (GRCm39) missense probably damaging 1.00
R2199:Ccm2 UTSW 11 6,540,790 (GRCm39) missense probably damaging 1.00
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'- ATTTTCATGGCGACGGTGC -3'
(R):5'- CCAAAGCTAAGGACTGGGACTG -3'

Sequencing Primer
(F):5'- TCATGGCGACGGTGCTAACTC -3'
(R):5'- CTAAGGACTGGGACTGGGTTTG -3'
Posted On 2015-01-23