Incidental Mutation 'IGL02946:Ccm2'
ID364731
Institutional Source Australian Phenomics Network (link to record)
Gene Symbol Ccm2
Ensembl Gene ENSMUSG00000000378
Gene Namecerebral cavernous malformation 2
Synonyms
Accession Numbers
Is this an essential gene? Essential (E-score: 1.000) question?
Stock #IGL02946
Quality Score
Status
Chromosome11
Chromosomal Location6546887-6596744 bp(+) (GRCm38)
Type of Mutationmissense
DNA Base Change (assembly) G to A at 6596195 bp
ZygosityHeterozygous
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]
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: ENSMUST00000177050
Predicted Effect probably benign
Transcript: ENSMUST00000177391
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: 110,028,215 probably benign Het
Actr3b T C 5: 25,848,483 I270T possibly damaging Het
Adgrf2 T C 17: 42,710,493 Y480C probably damaging Het
Arhgap27 T C 11: 103,338,348 T514A probably damaging Het
BC031181 C T 18: 75,008,665 probably benign Het
Cckbr C T 7: 105,434,031 A147V probably damaging Het
Ces1d C A 8: 93,169,718 probably null Het
Crabp1 T C 9: 54,764,948 F16S possibly damaging Het
Crmp1 C T 5: 37,284,080 A502V probably damaging Het
Ehhadh A T 16: 21,762,922 V440D probably damaging Het
Fam129a A T 1: 151,649,425 I194F probably damaging Het
Galnt3 T A 2: 66,095,218 I392L probably damaging Het
Gm12689 T A 4: 99,296,253 N114K unknown Het
Hspa2 A G 12: 76,405,173 T214A probably damaging Het
Itga7 T C 10: 128,934,083 I32T probably benign Het
Itgal A G 7: 127,314,368 S682G probably damaging Het
Kctd1 C T 18: 14,973,979 probably null Het
Lrp1b T A 2: 41,312,559 D439V probably damaging Het
Mdn1 A G 4: 32,734,366 K3258E probably damaging Het
Mgat4c T C 10: 102,389,253 S443P probably benign Het
Mylk G A 16: 34,921,788 G890E probably benign Het
Mylk2 T A 2: 152,919,210 L446* probably null Het
Olfr1395 T G 11: 49,148,892 F212V probably damaging Het
Pi4k2b T C 5: 52,753,207 F278L probably damaging Het
Pitpnm3 A G 11: 72,092,552 S84P probably benign Het
Plxna2 T C 1: 194,749,309 probably benign Het
Prr5l C A 2: 101,772,184 probably null Het
Ptprs T C 17: 56,424,032 T719A probably benign Het
Rasa3 T C 8: 13,598,280 H128R probably benign Het
Rhox13 A G X: 38,129,775 K205E probably damaging Het
Rif1 C A 2: 52,110,125 S1197* probably null Het
Sgta A G 10: 81,049,778 probably benign Het
Slc25a5 T A X: 36,797,853 M239K probably damaging Het
Stil T A 4: 115,029,913 H734Q probably benign Het
Stk32b T C 5: 37,531,539 probably benign Het
Ubr4 T G 4: 139,425,295 F1999C probably damaging Het
Wfdc2 A C 2: 164,564,089 T86P probably benign Het
Zfp407 T C 18: 84,560,709 S760G probably damaging Het
Zfp668 A T 7: 127,866,518 L498Q possibly damaging Het
Other mutations in Ccm2
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL02126:Ccm2 APN 11 6594154 missense probably damaging 0.97
IGL02274:Ccm2 APN 11 6590808 missense probably damaging 1.00
IGL02973:Ccm2 APN 11 6584544 missense probably damaging 1.00
R0521:Ccm2 UTSW 11 6590886 missense probably damaging 1.00
R1024:Ccm2 UTSW 11 6570119 nonsense probably null
R1201:Ccm2 UTSW 11 6593682 missense probably benign
R1687:Ccm2 UTSW 11 6585118 missense probably damaging 1.00
R2199:Ccm2 UTSW 11 6590790 missense probably damaging 1.00
R3237:Ccm2 UTSW 11 6570090 missense probably benign 0.43
R5196:Ccm2 UTSW 11 6561181 utr 5 prime probably benign
R6954:Ccm2 UTSW 11 6594239 missense probably damaging 0.98
R7195:Ccm2 UTSW 11 6596302 missense probably damaging 1.00
R7417:Ccm2 UTSW 11 6593091 missense probably benign 0.05
Posted On2015-12-18