Incidental Mutation 'R8863:Ccm2'
| ID |
675779 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Ccm2
|
| Ensembl Gene |
ENSMUSG00000000378 |
| Gene Name |
cerebral cavernous malformation 2 |
| Synonyms |
|
| MMRRC Submission |
068679-MU
|
| Accession Numbers |
|
| Essential gene? |
Essential
(E-score: 1.000)
|
| Stock # |
R8863 (G1)
|
| Quality Score |
225.009 |
|
Status
|
Validated
|
| Chromosome |
11 |
| Chromosomal Location |
6496887-6546744 bp(+) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
A to G
at 6535211 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Lysine to Glutamic Acid
at position 156
(K156E)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000000388
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000000388]
[ENSMUST00000109721]
[ENSMUST00000109722]
[ENSMUST00000159007]
[ENSMUST00000160633]
[ENSMUST00000161501]
|
| AlphaFold |
Q8K2Y9 |
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000000388
AA Change: K156E
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
| SMART Domains |
Protein: ENSMUSP00000000388
Gene: ENSMUSG00000000378
AA Change: K156E
| Domain | Start | End | E-Value | Type |
|---|
|
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 damaging
Transcript: ENSMUST00000109721
AA Change: K92E
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
| SMART Domains |
Protein: ENSMUSP00000105343
Gene: ENSMUSG00000000378
AA Change: K92E
| Domain | Start | End | E-Value | Type |
|---|
|
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: K92E
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
| SMART Domains |
Protein: ENSMUSP00000105344
Gene: ENSMUSG00000000378
AA Change: K92E
| Domain | Start | End | E-Value | Type |
|---|
|
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: K98E
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
| SMART Domains |
Protein: ENSMUSP00000125608
Gene: ENSMUSG00000000378
AA Change: K98E
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
2 |
10 |
N/A |
INTRINSIC |
|
Blast:PTB
|
11 |
102 |
3e-20 |
BLAST |
|
| Predicted Effect |
|
| SMART Domains |
Protein: ENSMUSP00000125072
Gene: ENSMUSG00000000378
AA Change: K150E
| Domain | Start | End | E-Value | Type |
|---|
|
Blast:PTB
|
54 |
224 |
6e-38 |
BLAST |
|
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000161501
AA Change: K122E
PolyPhen 2
Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)
|
| SMART Domains |
Protein: ENSMUSP00000123790
Gene: ENSMUSG00000000378
AA Change: K122E
| Domain | Start | End | E-Value | Type |
|---|
|
Blast:PTB
|
40 |
122 |
3e-10 |
BLAST |
|
| Coding Region Coverage |
- 1x: 100.0%
- 3x: 99.9%
- 10x: 99.3%
- 20x: 97.3%
|
| Validation Efficiency |
100% (44/44) |
| 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: 44 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| 9130023H24Rik |
A |
G |
7: 127,836,123 (GRCm39) |
S157P |
possibly damaging |
Het |
| Aasdhppt |
C |
A |
9: 4,309,424 (GRCm39) |
A5S |
possibly damaging |
Het |
| Aoc1l2 |
T |
C |
6: 48,907,042 (GRCm39) |
L14P |
probably benign |
Het |
| Asb16 |
T |
C |
11: 102,168,058 (GRCm39) |
Y373H |
probably damaging |
Het |
| Axin1 |
T |
C |
17: 26,362,375 (GRCm39) |
S240P |
probably benign |
Het |
| C2cd5 |
T |
C |
6: 142,987,088 (GRCm39) |
I505V |
possibly damaging |
Het |
| Camk2g |
A |
G |
14: 20,810,244 (GRCm39) |
L305P |
probably damaging |
Het |
| Cdh23 |
G |
T |
10: 60,212,613 (GRCm39) |
Y1600* |
probably null |
Het |
| Cyp2c29 |
A |
G |
19: 39,261,810 (GRCm39) |
Q16R |
probably benign |
Het |
| Ebf1 |
T |
A |
11: 44,774,666 (GRCm39) |
V221E |
probably damaging |
Het |
| Fcgbpl1 |
A |
G |
7: 27,831,006 (GRCm39) |
D73G |
probably damaging |
Het |
| Gtpbp1 |
A |
G |
15: 79,591,262 (GRCm39) |
E125G |
possibly damaging |
Het |
| Idh2 |
TCCCAGG |
T |
7: 79,748,079 (GRCm39) |
|
probably benign |
Het |
| Igfbp3 |
A |
G |
11: 7,163,568 (GRCm39) |
C75R |
probably damaging |
Het |
| Itgb4 |
T |
A |
11: 115,875,898 (GRCm39) |
C478* |
probably null |
Het |
| L3mbtl4 |
T |
A |
17: 68,986,419 (GRCm39) |
C488S |
probably benign |
Het |
| Lysmd4 |
T |
C |
7: 66,873,493 (GRCm39) |
S43P |
probably damaging |
Het |
| Mocs2 |
A |
G |
13: 114,962,815 (GRCm39) |
K167E |
probably damaging |
Het |
| Mpl |
C |
A |
4: 118,314,602 (GRCm39) |
V23F |
|
Het |
| Muc4 |
A |
T |
16: 32,570,280 (GRCm39) |
I447F |
possibly damaging |
Het |
| Mxi1 |
G |
A |
19: 53,360,126 (GRCm39) |
G283S |
probably damaging |
Het |
| Ncf2 |
A |
G |
1: 152,711,864 (GRCm39) |
*526W |
probably null |
Het |
| Oas1a |
C |
T |
5: 121,043,943 (GRCm39) |
G63D |
probably damaging |
Het |
| Or2q1 |
A |
T |
6: 42,794,780 (GRCm39) |
Y125F |
probably damaging |
Het |
| Or5ac15 |
G |
T |
16: 58,939,712 (GRCm39) |
C240* |
probably null |
Het |
| Or8c17 |
T |
C |
9: 38,180,655 (GRCm39) |
V274A |
probably damaging |
Het |
| Piwil4 |
T |
C |
9: 14,631,383 (GRCm39) |
N409S |
probably benign |
Het |
| Pkhd1l1 |
C |
T |
15: 44,433,382 (GRCm39) |
Q3421* |
probably null |
Het |
| Plekha7 |
T |
A |
7: 115,753,875 (GRCm39) |
D664V |
probably damaging |
Het |
| Pole |
T |
C |
5: 110,437,233 (GRCm39) |
M66T |
possibly damaging |
Het |
| Pon2 |
C |
T |
6: 5,265,480 (GRCm39) |
|
probably null |
Het |
| Pop4 |
G |
A |
7: 37,962,649 (GRCm39) |
A205V |
possibly damaging |
Het |
| Ppp6r3 |
T |
A |
19: 3,521,030 (GRCm39) |
E590D |
probably damaging |
Het |
| Ptpn6 |
T |
A |
6: 124,709,309 (GRCm39) |
I96F |
probably damaging |
Het |
| Rfk |
T |
A |
19: 17,372,590 (GRCm39) |
N37K |
probably benign |
Het |
| Syne1 |
G |
T |
10: 5,049,527 (GRCm39) |
Q7535K |
probably damaging |
Het |
| Tcf15 |
A |
T |
2: 151,986,023 (GRCm39) |
I160F |
probably damaging |
Het |
| Thap1 |
CAGCATCTGCTCGGAGCA |
CAGCA |
8: 26,650,884 (GRCm39) |
|
probably null |
Het |
| Tmem160 |
T |
C |
7: 16,186,889 (GRCm39) |
M1T |
probably null |
Het |
| Tpp1 |
C |
T |
7: 105,398,814 (GRCm39) |
R205H |
probably benign |
Het |
| Trnt1 |
T |
C |
6: 106,751,443 (GRCm39) |
F140S |
probably damaging |
Het |
| Ttf1 |
T |
C |
2: 28,969,492 (GRCm39) |
|
probably null |
Het |
| Vmn1r172 |
A |
T |
7: 23,359,210 (GRCm39) |
I32F |
probably benign |
Het |
| Vwc2l |
T |
A |
1: 70,768,063 (GRCm39) |
N42K |
possibly damaging |
Het |
|
| Other mutations in Ccm2 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH 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 |
|
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 |
|
| Predicted Primers |
PCR Primer
(F):5'- GTGATTCTTTGCAGCGGTCC -3'
(R):5'- CTGACCCTGAATACTGTATTCCTCAAG -3'
Sequencing Primer
(F):5'- GGTCCCACCAGCTTCCTG -3'
(R):5'- AAGTCTCCAAAGGCCCTGAGTG -3'
|
| Posted On |
2021-07-15 |
Incidental Mutation