Mutagenetix > Incidental Mutation

Incidental Mutation 'R1024:Ccm2'

98764

Institutional Source

Beutler Lab

Gene Symbol

Ccm2

Ensembl Gene

ENSMUSG00000000378

Gene Name

cerebral cavernous malformation 2

Synonyms

MMRRC Submission

039126-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R1024 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

6496887-6546744 bp(+) (GRCm39)

Type of Mutation

nonsense

DNA Base Change (assembly)

T to A at 6520119 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Tyrosine to Stop codon at position 56 (Y56*)

Ref Sequence

ENSEMBL: ENSMUSP00000123790 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000000388] [ENSMUST00000109721] [ENSMUST00000109722] [ENSMUST00000159007] [ENSMUST00000160633] [ENSMUST00000161501]

AlphaFold

Q8K2Y9

Predicted Effect

probably null
Transcript: ENSMUST00000000388
AA Change: Y62*

SMART Domains

Protein: ENSMUSP00000000388
Gene: ENSMUSG00000000378
AA Change: Y62*

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 benign
Transcript: ENSMUST00000109721

SMART Domains

Protein: ENSMUSP00000105343
Gene: ENSMUSG00000000378

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 benign
Transcript: ENSMUST00000109722

SMART Domains

Protein: ENSMUSP00000105344
Gene: ENSMUSG00000000378

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 benign
Transcript: ENSMUST00000159007

SMART Domains

Protein: ENSMUSP00000125608
Gene: ENSMUSG00000000378

Domain	Start	End	E-Value	Type
low complexity region	2	10	N/A	INTRINSIC
Blast:PTB	11	102	3e-20	BLAST

Predicted Effect

probably null
Transcript: ENSMUST00000160633
AA Change: Y56*

SMART Domains

Protein: ENSMUSP00000125072
Gene: ENSMUSG00000000378
AA Change: Y56*

Domain	Start	End	E-Value	Type
Blast:PTB	54	224	6e-38	BLAST

Predicted Effect

probably null
Transcript: ENSMUST00000161501
AA Change: Y56*

SMART Domains

Protein: ENSMUSP00000123790
Gene: ENSMUSG00000000378
AA Change: Y56*

Domain	Start	End	E-Value	Type
Blast:PTB	40	122	3e-10	BLAST

Meta Mutation Damage Score

0.9711

Coding Region Coverage

1x: 99.5%
3x: 98.4%
10x: 95.6%
20x: 90.2%

Validation Efficiency

90% (36/40)

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: 66 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Akap13	T	C	7: 75,327,157 (GRCm39)	S719P	probably damaging	Het
Atxn2l	A	T	7: 126,096,466 (GRCm39)	N425K	probably benign	Het
B3galt4	G	A	17: 34,169,813 (GRCm39)	R142C	probably damaging	Het
Cacna2d2	T	C	9: 107,404,249 (GRCm39)		probably null	Het
Ccar2	A	G	14: 70,377,964 (GRCm39)	S674P	probably damaging	Het
Cdc14b	A	T	13: 64,363,490 (GRCm39)	V257E	probably damaging	Het
Cdca8	A	C	4: 124,815,798 (GRCm39)	S171R	probably benign	Het
Cep192	C	T	18: 67,971,125 (GRCm39)	T1042I	probably benign	Het
Cfap100	T	A	6: 90,389,986 (GRCm39)	T101S	possibly damaging	Het
Cfap46	T	A	7: 139,222,513 (GRCm39)	M1155L	probably benign	Het
Cyp3a13	T	A	5: 137,892,626 (GRCm39)	I473F	possibly damaging	Het
Dclk3	A	G	9: 111,298,138 (GRCm39)	I561V	possibly damaging	Het
Dock6	A	T	9: 21,744,908 (GRCm39)	L556H	probably damaging	Het
Dqx1	G	A	6: 83,038,070 (GRCm39)	C486Y	probably damaging	Het
Drd1	T	A	13: 54,207,333 (GRCm39)	M294L	probably benign	Het
Dsel	A	G	1: 111,788,403 (GRCm39)	S711P	probably damaging	Het
Fcho2	A	T	13: 98,869,167 (GRCm39)	I568N	probably damaging	Het
Folr1	A	G	7: 101,507,810 (GRCm39)	M210T	probably damaging	Het
Gatc	T	A	5: 115,478,904 (GRCm39)		probably null	Het
Gja8	A	T	3: 96,826,740 (GRCm39)	F307L	probably benign	Het
H1f7	G	A	15: 98,154,636 (GRCm39)	T171I	unknown	Het
Hnrnpd	C	A	5: 100,114,016 (GRCm39)	*87L	probably null	Het
Hpd	C	T	5: 123,312,532 (GRCm39)	R279H	possibly damaging	Het
Igfals	G	A	17: 25,099,457 (GRCm39)	V183M	probably damaging	Het
Izumo1	A	G	7: 45,276,598 (GRCm39)	Y387C	probably benign	Het
Kdm5a	A	G	6: 120,375,999 (GRCm39)	N585S	probably null	Het
Marchf2	C	A	17: 33,928,762 (GRCm39)	G45C	probably damaging	Het
Myo15a	A	T	11: 60,370,442 (GRCm39)	R1067S	probably benign	Het
Naip2	T	C	13: 100,298,362 (GRCm39)	E558G	probably benign	Het
Naip2	C	T	13: 100,298,368 (GRCm39)	G556D	probably benign	Het
Nell1	A	G	7: 49,770,411 (GRCm39)	S157G	probably damaging	Het
Nf1	A	T	11: 79,437,859 (GRCm39)	E2072D	probably damaging	Het
Nipal1	CGGG	CGG	5: 72,825,334 (GRCm39)		probably null	Het
Nop2	T	A	6: 125,114,149 (GRCm39)	V205E	probably benign	Het
Nphs1	G	T	7: 30,173,702 (GRCm39)	S939I	probably damaging	Het
Nudt8	T	A	19: 4,051,925 (GRCm39)	W179R	probably damaging	Het
Nutm1	A	T	2: 112,080,274 (GRCm39)	I547N	probably benign	Het
Oog2	A	C	4: 143,922,856 (GRCm39)	T374P	probably damaging	Het
Or4k5	A	T	14: 50,385,384 (GRCm39)	F316I	probably benign	Het
Or8b54	C	A	9: 38,686,631 (GRCm39)	L27I	probably damaging	Het
Otud4	T	A	8: 80,390,722 (GRCm39)	M413K	probably benign	Het
Pear1	A	G	3: 87,667,606 (GRCm39)		probably benign	Het
Pla2g3	G	A	11: 3,438,551 (GRCm39)	C67Y	probably damaging	Het
Plxdc2	A	G	2: 16,716,917 (GRCm39)	T334A	probably benign	Het
Ppl	G	A	16: 4,917,864 (GRCm39)	R543W	probably damaging	Het
Prl5a1	G	A	13: 28,333,880 (GRCm39)	V128I	probably damaging	Het
Pth1r	A	T	9: 110,571,295 (GRCm39)	L25Q	probably damaging	Het
Pth1r	T	C	9: 110,558,689 (GRCm39)	D96G	probably benign	Het
Rfpl4	G	T	7: 5,113,517 (GRCm39)	D215E	probably damaging	Het
Rnf146	T	A	10: 29,223,092 (GRCm39)	R265*	probably null	Het
Rpe65	T	C	3: 159,312,122 (GRCm39)	I207T	probably benign	Het
Rptn	A	G	3: 93,305,532 (GRCm39)	E955G	possibly damaging	Het
Rwdd2b	A	T	16: 87,233,738 (GRCm39)	C121S	probably damaging	Het
Scn10a	A	G	9: 119,438,340 (GRCm39)	I1843T	probably damaging	Het
Sirt5	A	G	13: 43,524,245 (GRCm39)	I6V	probably benign	Het
Slc25a36	A	G	9: 96,961,254 (GRCm39)	Y261H	probably damaging	Het
Slc5a3	G	A	16: 91,874,383 (GRCm39)	A147T	probably damaging	Het
Stk39	T	C	2: 68,240,390 (GRCm39)	S114G	probably damaging	Het
Stxbp1	T	C	2: 32,704,979 (GRCm39)		probably null	Het
Syt3	G	T	7: 44,040,106 (GRCm39)	G113V	probably damaging	Het
Tatdn2	A	G	6: 113,686,506 (GRCm39)	T644A	probably damaging	Het
Trim9	T	A	12: 70,298,791 (GRCm39)		probably null	Het
Tut1	A	G	19: 8,936,719 (GRCm39)	N181S	probably benign	Het
Vill	T	C	9: 118,895,892 (GRCm39)	S151P	probably damaging	Het
Vmn2r90	A	T	17: 17,948,400 (GRCm39)	I549F	probably damaging	Het
Wdfy4	T	C	14: 32,801,923 (GRCm39)	T1912A	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
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

Predicted Primers

PCR Primer
(F):5'- TTCATGGCGACGGTGCTAACTC -3'
(R):5'- GCCTGCTGTCATCTGTCTGCAAATC -3'

Sequencing Primer
(F):5'- GTGAATAATGAACTCCAATCATTGCC -3'
(R):5'- GACAGAGTAGTCTTCTGCTACACAG -3'

Posted On

2014-01-09