Incidental Mutation 'R4041:Krit1'
ID 313874
Institutional Source Beutler Lab
Gene Symbol Krit1
Ensembl Gene ENSMUSG00000000600
Gene Name KRIT1, ankyrin repeat containing
Synonyms A630036P20Rik, Krit1B, 2010007K12Rik, Ccm1, Krit1A, Krit1
MMRRC Submission 040966-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R4041 (G1)
Quality Score 225
Status Validated
Chromosome 5
Chromosomal Location 3853156-3894515 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) G to C at 3859642 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Arginine to Proline at position 110 (R110P)
Ref Sequence ENSEMBL: ENSMUSP00000142657 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000080085] [ENSMUST00000171023] [ENSMUST00000198079] [ENSMUST00000200386] [ENSMUST00000200577]
AlphaFold Q6S5J6
Predicted Effect probably damaging
Transcript: ENSMUST00000080085
AA Change: R90P

PolyPhen 2 Score 0.990 (Sensitivity: 0.72; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000078985
Gene: ENSMUSG00000000600
AA Change: R90P

DomainStartEndE-ValueType
Pfam:NUDIX_5 22 198 3.8e-88 PFAM
ANK 287 316 1.04e2 SMART
ANK 320 350 4.5e-3 SMART
ANK 354 382 1.17e-1 SMART
B41 416 640 1.39e-39 SMART
Blast:B41 673 702 6e-8 BLAST
Predicted Effect probably damaging
Transcript: ENSMUST00000171023
AA Change: R90P

PolyPhen 2 Score 0.990 (Sensitivity: 0.72; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000132375
Gene: ENSMUSG00000000600
AA Change: R90P

DomainStartEndE-ValueType
PDB:4DX8|K 1 198 1e-125 PDB
ANK 287 316 1.04e2 SMART
ANK 320 350 4.5e-3 SMART
ANK 354 382 1.17e-1 SMART
B41 416 640 1.39e-39 SMART
Predicted Effect noncoding transcript
Transcript: ENSMUST00000196098
Predicted Effect noncoding transcript
Transcript: ENSMUST00000197742
Predicted Effect probably damaging
Transcript: ENSMUST00000198079
AA Change: R110P

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000142657
Gene: ENSMUSG00000000600
AA Change: R110P

DomainStartEndE-ValueType
PDB:4DX8|K 20 132 4e-62 PDB
Predicted Effect noncoding transcript
Transcript: ENSMUST00000199475
Predicted Effect noncoding transcript
Transcript: ENSMUST00000199845
Predicted Effect probably damaging
Transcript: ENSMUST00000200386
AA Change: R90P

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000143559
Gene: ENSMUSG00000000600
AA Change: R90P

DomainStartEndE-ValueType
Pfam:NUDIX_5 22 198 8.1e-85 PFAM
ANK 306 334 7.5e-4 SMART
B41 368 592 9.1e-42 SMART
Predicted Effect probably damaging
Transcript: ENSMUST00000200577
AA Change: R90P

PolyPhen 2 Score 0.990 (Sensitivity: 0.72; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000143776
Gene: ENSMUSG00000000600
AA Change: R90P

DomainStartEndE-ValueType
Pfam:NUDIX_5 22 198 1.8e-85 PFAM
Blast:B41 200 329 1e-82 BLAST
SCOP:d1ycsb1 291 329 2e-8 SMART
Meta Mutation Damage Score 0.5146 question?
Coding Region Coverage
  • 1x: 99.1%
  • 3x: 98.5%
  • 10x: 97.1%
  • 20x: 94.4%
Validation Efficiency 100% (29/29)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a protein containing four ankyrin repeats, a band 4.1/ezrin/radixin/moesin (FERM) domain, and multiple NPXY sequences. The encoded protein is localized in the nucleus and cytoplasm. It binds to integrin cytoplasmic domain-associated protein-1 alpha (ICAP1alpha), and plays a critical role in beta1-integrin-mediated cell proliferation. It associates with junction proteins and RAS-related protein 1A (Rap1A), which requires the encoded protein for maintaining the integrity of endothelial junctions. It is also a microtubule-associated protein and may play a role in microtubule targeting. Mutations in this gene result in cerebral cavernous malformations. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2009]
PHENOTYPE: Targeted disruption of this gene results in embryonic lethality by E11. Embryos display prominent vascular defects that disrupt arterial modeling and phenocopy the human disorder of cerebral cavernous malformations. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 30 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Atf5 T C 7: 44,462,921 (GRCm39) T68A possibly damaging Het
Cage1 A G 13: 38,203,153 (GRCm39) L637P possibly damaging Het
Cfl1 T C 19: 5,542,556 (GRCm39) I12T probably benign Het
Clcn1 A G 6: 42,286,902 (GRCm39) E653G probably damaging Het
Cntnap5a C A 1: 116,112,129 (GRCm39) P473Q probably benign Het
Dnah7b T C 1: 46,120,655 (GRCm39) S91P probably benign Het
Fcgbp A G 7: 27,813,404 (GRCm39) Q2313R probably benign Het
Gpc5 A T 14: 115,370,628 (GRCm39) Q151L probably damaging Het
Hexim1 A G 11: 103,007,932 (GRCm39) E62G probably benign Het
Ifna13 A G 4: 88,562,228 (GRCm39) F132S probably benign Het
Irgm2 A G 11: 58,110,956 (GRCm39) M228V probably benign Het
Klhl41 A G 2: 69,501,054 (GRCm39) M172V probably benign Het
Klk1 A T 7: 43,878,986 (GRCm39) N260I probably damaging Het
Krt7 T A 15: 101,321,161 (GRCm39) probably null Het
Lrrn4cl T A 19: 8,829,468 (GRCm39) Y149N probably damaging Het
Ltbp3 G T 19: 5,801,899 (GRCm39) C739F possibly damaging Het
Mbnl2 C T 14: 120,626,486 (GRCm39) H239Y probably damaging Het
Obscn G A 11: 58,942,357 (GRCm39) R4942* probably null Het
Or2bd2 T C 7: 6,443,688 (GRCm39) L263P probably damaging Het
R3hcc1 A G 14: 69,944,111 (GRCm39) S45P probably damaging Het
Ryr1 A T 7: 28,785,356 (GRCm39) H1778Q possibly damaging Het
Scyl2 T A 10: 89,485,914 (GRCm39) K558N probably damaging Het
Shank1 G A 7: 43,991,586 (GRCm39) V677M unknown Het
Slc39a5 T C 10: 128,232,337 (GRCm39) M488V possibly damaging Het
Styk1 A T 6: 131,289,880 (GRCm39) probably null Het
Styxl2 T C 1: 165,927,680 (GRCm39) D644G probably benign Het
Usp32 A G 11: 84,908,565 (GRCm39) V1047A probably benign Het
Wnt3a G T 11: 59,140,470 (GRCm39) H349N probably damaging Het
Zbtb39 T C 10: 127,579,423 (GRCm39) C666R probably damaging Het
Zfp420 T C 7: 29,575,427 (GRCm39) M549T probably benign Het
Other mutations in Krit1
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL01088:Krit1 APN 5 3,862,844 (GRCm39) missense probably damaging 0.98
IGL02186:Krit1 APN 5 3,859,733 (GRCm39) splice site probably benign
IGL02526:Krit1 APN 5 3,872,103 (GRCm39) missense probably damaging 1.00
IGL03280:Krit1 APN 5 3,861,248 (GRCm39) splice site probably benign
IGL03385:Krit1 APN 5 3,857,452 (GRCm39) missense possibly damaging 0.51
Waspish UTSW 5 3,881,551 (GRCm39) missense probably damaging 1.00
R0127:Krit1 UTSW 5 3,872,178 (GRCm39) missense probably damaging 0.99
R0594:Krit1 UTSW 5 3,873,694 (GRCm39) missense possibly damaging 0.71
R1157:Krit1 UTSW 5 3,882,176 (GRCm39) missense probably damaging 1.00
R1777:Krit1 UTSW 5 3,886,799 (GRCm39) missense probably damaging 0.96
R2115:Krit1 UTSW 5 3,872,108 (GRCm39) nonsense probably null
R4021:Krit1 UTSW 5 3,882,132 (GRCm39) missense probably benign 0.21
R4786:Krit1 UTSW 5 3,862,467 (GRCm39) missense possibly damaging 0.86
R4989:Krit1 UTSW 5 3,872,238 (GRCm39) missense probably damaging 1.00
R5217:Krit1 UTSW 5 3,856,451 (GRCm39) nonsense probably null
R5304:Krit1 UTSW 5 3,869,326 (GRCm39) missense probably damaging 0.99
R5371:Krit1 UTSW 5 3,881,551 (GRCm39) missense probably damaging 1.00
R5682:Krit1 UTSW 5 3,880,737 (GRCm39) missense probably damaging 0.99
R6248:Krit1 UTSW 5 3,863,032 (GRCm39) splice site probably null
R6338:Krit1 UTSW 5 3,886,857 (GRCm39) missense probably benign 0.01
R7081:Krit1 UTSW 5 3,873,651 (GRCm39) missense possibly damaging 0.71
R7454:Krit1 UTSW 5 3,862,474 (GRCm39) missense probably damaging 0.99
R7497:Krit1 UTSW 5 3,862,349 (GRCm39) missense possibly damaging 0.93
R7684:Krit1 UTSW 5 3,880,723 (GRCm39) missense possibly damaging 0.75
R7780:Krit1 UTSW 5 3,862,772 (GRCm39) missense probably damaging 1.00
R7862:Krit1 UTSW 5 3,862,788 (GRCm39) missense probably damaging 0.99
R8041:Krit1 UTSW 5 3,857,309 (GRCm39) missense probably benign
R8882:Krit1 UTSW 5 3,886,864 (GRCm39) missense possibly damaging 0.72
R9034:Krit1 UTSW 5 3,862,996 (GRCm39) intron probably benign
R9098:Krit1 UTSW 5 3,863,135 (GRCm39) missense probably benign 0.00
R9328:Krit1 UTSW 5 3,862,577 (GRCm39) critical splice donor site probably null
R9402:Krit1 UTSW 5 3,872,210 (GRCm39) missense possibly damaging 0.95
Predicted Primers PCR Primer
(F):5'- CGACAACCTCTAAAATCTTGAAGG -3'
(R):5'- AGCCAAGAAGCCTATATATTACTTGGG -3'

Sequencing Primer
(F):5'- AATTGCTACACTTAGGAGGCTG -3'
(R):5'- TGGGGAAATTAAAAGATTTGACATCG -3'
Posted On 2015-04-30