Incidental Mutation 'IGL02126:Ccm2'
ID 280871
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 # IGL02126
Quality Score
Status
Chromosome 11
Chromosomal Location 6496887-6546744 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 6544154 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Threonine to Alanine at position 317 (T317A)
Ref Sequence ENSEMBL: ENSMUSP00000000388 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000000388] [ENSMUST00000045713] [ENSMUST00000109721] [ENSMUST00000109722] [ENSMUST00000159007] [ENSMUST00000160633] [ENSMUST00000161501]
AlphaFold Q8K2Y9
Predicted Effect probably damaging
Transcript: ENSMUST00000000388
AA Change: T317A

PolyPhen 2 Score 0.974 (Sensitivity: 0.76; Specificity: 0.96)
SMART Domains Protein: ENSMUSP00000000388
Gene: ENSMUSG00000000378
AA Change: T317A

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 possibly damaging
Transcript: ENSMUST00000109721
AA Change: T253A

PolyPhen 2 Score 0.507 (Sensitivity: 0.88; Specificity: 0.90)
SMART Domains Protein: ENSMUSP00000105343
Gene: ENSMUSG00000000378
AA Change: T253A

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: T253A

PolyPhen 2 Score 0.507 (Sensitivity: 0.88; Specificity: 0.90)
SMART Domains Protein: ENSMUSP00000105344
Gene: ENSMUSG00000000378
AA Change: T253A

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
SMART Domains Protein: ENSMUSP00000125072
Gene: ENSMUSG00000000378

DomainStartEndE-ValueType
Blast:PTB 54 224 6e-38 BLAST
Predicted Effect noncoding transcript
Transcript: ENSMUST00000161667
Predicted Effect probably benign
Transcript: ENSMUST00000161501
SMART Domains Protein: ENSMUSP00000123790
Gene: ENSMUSG00000000378

DomainStartEndE-ValueType
Blast:PTB 40 122 3e-10 BLAST
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: 51 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Aldh16a1 G A 7: 44,795,459 (GRCm39) P400L probably damaging Het
Angptl3 T C 4: 98,919,738 (GRCm39) probably null Het
Atoh1 T C 6: 64,706,334 (GRCm39) W10R probably damaging Het
Brd8 C T 18: 34,735,780 (GRCm39) S899N probably damaging Het
Ccnt1 A T 15: 98,465,484 (GRCm39) W12R probably damaging Het
Celf1 T A 2: 90,831,408 (GRCm39) L79H probably damaging Het
Cmip T C 8: 118,175,770 (GRCm39) V423A probably damaging Het
Ddr1 T A 17: 35,999,481 (GRCm39) I431F probably damaging Het
Dnah6 A G 6: 73,080,149 (GRCm39) L2343P probably benign Het
Duox1 A G 2: 122,176,817 (GRCm39) D1446G probably benign Het
Erich3 A G 3: 154,419,599 (GRCm39) H231R possibly damaging Het
Fam221b T A 4: 43,666,450 (GRCm39) I54F probably benign Het
Fcgbpl1 G A 7: 27,839,281 (GRCm39) V365M probably damaging Het
Galntl5 T C 5: 25,394,839 (GRCm39) F69L possibly damaging Het
Gba2 T G 4: 43,567,918 (GRCm39) probably null Het
Gbf1 C A 19: 46,240,556 (GRCm39) P46Q probably damaging Het
Gimap6 T G 6: 48,679,635 (GRCm39) S134R probably damaging Het
Gm5424 A C 10: 61,907,377 (GRCm39) noncoding transcript Het
Hexb T C 13: 97,314,532 (GRCm39) K404E possibly damaging Het
Hs3st3a1 G A 11: 64,327,331 (GRCm39) V147M probably damaging Het
Hsd17b4 T C 18: 50,315,063 (GRCm39) V610A probably benign Het
Loxl3 T A 6: 83,025,628 (GRCm39) W329R probably damaging Het
Lrrc52 A G 1: 167,273,575 (GRCm39) F247S probably damaging Het
Naa38 C T 11: 69,287,045 (GRCm39) R42W probably damaging Het
Nadsyn1 G A 7: 143,357,753 (GRCm39) Q485* probably null Het
Nid1 A G 13: 13,663,743 (GRCm39) probably null Het
Ofcc1 T C 13: 40,362,251 (GRCm39) T224A probably benign Het
Or5m11b T G 2: 85,806,517 (GRCm39) I310S probably benign Het
Palld A G 8: 62,330,476 (GRCm39) Y134H possibly damaging Het
Pfkfb4 C T 9: 108,854,178 (GRCm39) R351W probably damaging Het
Pfn3 T C 13: 55,562,699 (GRCm39) D94G possibly damaging Het
Pkhd1 G A 1: 20,187,419 (GRCm39) R3630C probably damaging Het
Por T A 5: 135,744,829 (GRCm39) F31I probably benign Het
Ppp1r12c T C 7: 4,492,858 (GRCm39) E127G probably benign Het
Ppp1r9a T A 6: 5,156,229 (GRCm39) S1162T probably damaging Het
Psen2 C A 1: 180,057,488 (GRCm39) A297S probably benign Het
Rpusd2 G A 2: 118,869,119 (GRCm39) R514Q probably damaging Het
Rxrg A G 1: 167,462,029 (GRCm39) M235V probably damaging Het
Sash1 T C 10: 8,615,229 (GRCm39) M644V probably damaging Het
Sf3b3 T C 8: 111,550,075 (GRCm39) T648A probably benign Het
Slco1a7 T A 6: 141,684,739 (GRCm39) T239S probably benign Het
Ssu72 T C 4: 155,816,483 (GRCm39) I155T probably benign Het
Tas2r102 A G 6: 132,739,607 (GRCm39) R172G probably damaging Het
Tmem214 G A 5: 31,030,090 (GRCm39) A296T probably benign Het
Trav12-2 C A 14: 53,853,859 (GRCm39) N2K probably damaging Het
Tyrp1 C T 4: 80,755,845 (GRCm39) Q205* probably null Het
Ubr4 T A 4: 139,180,052 (GRCm39) probably null Het
Ush2a A G 1: 187,995,588 (GRCm39) S120G probably benign Het
Vmn2r100 T C 17: 19,741,504 (GRCm39) probably benign Het
Zer1 G T 2: 29,994,928 (GRCm39) T489K probably benign Het
Zfp955b G T 17: 33,521,238 (GRCm39) G236* probably null Het
Other mutations in Ccm2
AlleleSourceChrCoordTypePredicted EffectPPH Score
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
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 2015-04-16