Incidental Mutation 'IGL02946:Ccm2'
ID 364731
Institutional Source Australian Phenomics Network (link to record)
Gene Symbol Ccm2
Ensembl Gene ENSMUSG00000000378
Gene Name cerebral cavernous malformation 2
Synonyms
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # IGL02946
Quality Score
Status
Chromosome 11
Chromosomal Location 6496887-6546744 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) G to A at 6546195 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Arginine to Histidine at position 335 (R335H)
Ref Sequence ENSEMBL: ENSMUSP00000105344 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000000388] [ENSMUST00000045713] [ENSMUST00000109721] [ENSMUST00000109722] [ENSMUST00000160633] [ENSMUST00000161501]
AlphaFold Q8K2Y9
Predicted Effect probably damaging
Transcript: ENSMUST00000000388
AA Change: R399H

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000000388
Gene: ENSMUSG00000000378
AA Change: R399H

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: ENSMUST00000045713
SMART Domains Protein: ENSMUSP00000049490
Gene: ENSMUSG00000041073

DomainStartEndE-ValueType
low complexity region 2 28 N/A INTRINSIC
low complexity region 70 87 N/A INTRINSIC
low complexity region 228 235 N/A INTRINSIC
low complexity region 266 277 N/A INTRINSIC
low complexity region 294 306 N/A INTRINSIC
low complexity region 328 354 N/A INTRINSIC
low complexity region 391 422 N/A INTRINSIC
low complexity region 454 479 N/A INTRINSIC
internal_repeat_1 537 689 6.19e-8 PROSPERO
low complexity region 692 713 N/A INTRINSIC
internal_repeat_1 732 889 6.19e-8 PROSPERO
low complexity region 924 939 N/A INTRINSIC
low complexity region 1159 1170 N/A INTRINSIC
low complexity region 1308 1325 N/A INTRINSIC
Pfam:NAC 1357 1413 2.9e-24 PFAM
low complexity region 1449 1466 N/A INTRINSIC
Predicted Effect probably damaging
Transcript: ENSMUST00000109721
AA Change: R335H

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000105343
Gene: ENSMUSG00000000378
AA Change: R335H

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: ENSMUST00000109722
AA Change: R335H

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000105344
Gene: ENSMUSG00000000378
AA Change: R335H

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: ENSMUST00000160633
SMART Domains Protein: ENSMUSP00000125072
Gene: ENSMUSG00000000378

DomainStartEndE-ValueType
Blast:PTB 54 224 6e-38 BLAST
Predicted Effect probably benign
Transcript: ENSMUST00000161501
SMART Domains Protein: ENSMUSP00000123790
Gene: ENSMUSG00000000378

DomainStartEndE-ValueType
Blast:PTB 40 122 3e-10 BLAST
Predicted Effect noncoding transcript
Transcript: ENSMUST00000161667
Predicted Effect probably benign
Transcript: ENSMUST00000177391
Predicted Effect probably benign
Transcript: ENSMUST00000177050
Coding Region Coverage
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: 39 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abca8a G A 11: 109,919,041 (GRCm39) probably benign Het
Actr3b T C 5: 26,053,481 (GRCm39) I270T possibly damaging Het
Adgrf2 T C 17: 43,021,384 (GRCm39) Y480C probably damaging Het
Arhgap27 T C 11: 103,229,174 (GRCm39) T514A probably damaging Het
BC031181 C T 18: 75,141,736 (GRCm39) probably benign Het
Cckbr C T 7: 105,083,238 (GRCm39) A147V probably damaging Het
Ces1d C A 8: 93,896,346 (GRCm39) probably null Het
Crabp1 T C 9: 54,672,232 (GRCm39) F16S possibly damaging Het
Crmp1 C T 5: 37,441,424 (GRCm39) A502V probably damaging Het
Ehhadh A T 16: 21,581,672 (GRCm39) V440D probably damaging Het
Galnt3 T A 2: 65,925,562 (GRCm39) I392L probably damaging Het
Gm12689 T A 4: 99,184,490 (GRCm39) N114K unknown Het
Hspa2 A G 12: 76,451,947 (GRCm39) T214A probably damaging Het
Itga7 T C 10: 128,769,952 (GRCm39) I32T probably benign Het
Itgal A G 7: 126,913,540 (GRCm39) S682G probably damaging Het
Kctd1 C T 18: 15,107,036 (GRCm39) probably null Het
Lrp1b T A 2: 41,202,571 (GRCm39) D439V probably damaging Het
Mdn1 A G 4: 32,734,366 (GRCm39) K3258E probably damaging Het
Mgat4c T C 10: 102,225,114 (GRCm39) S443P probably benign Het
Mylk G A 16: 34,742,158 (GRCm39) G890E probably benign Het
Mylk2 T A 2: 152,761,130 (GRCm39) L446* probably null Het
Niban1 A T 1: 151,525,176 (GRCm39) I194F probably damaging Het
Or2t26 T G 11: 49,039,719 (GRCm39) F212V probably damaging Het
Pi4k2b T C 5: 52,910,549 (GRCm39) F278L probably damaging Het
Pitpnm3 A G 11: 71,983,378 (GRCm39) S84P probably benign Het
Plxna2 T C 1: 194,431,617 (GRCm39) probably benign Het
Prr5l C A 2: 101,602,529 (GRCm39) probably null Het
Ptprs T C 17: 56,731,032 (GRCm39) T719A probably benign Het
Rasa3 T C 8: 13,648,280 (GRCm39) H128R probably benign Het
Rhox13 A G X: 37,218,652 (GRCm39) K205E probably damaging Het
Rif1 C A 2: 52,000,137 (GRCm39) S1197* probably null Het
Sgta A G 10: 80,885,612 (GRCm39) probably benign Het
Slc25a5 T A X: 36,061,506 (GRCm39) M239K probably damaging Het
Stil T A 4: 114,887,110 (GRCm39) H734Q probably benign Het
Stk32b T C 5: 37,688,883 (GRCm39) probably benign Het
Ubr4 T G 4: 139,152,606 (GRCm39) F1999C probably damaging Het
Wfdc2 A C 2: 164,406,009 (GRCm39) T86P probably benign Het
Zfp407 T C 18: 84,578,834 (GRCm39) S760G probably damaging Het
Zfp668 A T 7: 127,465,690 (GRCm39) L498Q possibly 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
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
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
Posted On 2015-12-18