Incidental Mutation 'R8306:Notch3'
ID 641104
Institutional Source Beutler Lab
Gene Symbol Notch3
Ensembl Gene ENSMUSG00000038146
Gene Name notch 3
Synonyms hpbk, N3
MMRRC Submission 067792-MU
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # R8306 (G1)
Quality Score 225.009
Status Not validated
Chromosome 17
Chromosomal Location 32339794-32385826 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) G to A at 32377086 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Threonine to Isoleucine at position 273 (T273I)
Ref Sequence ENSEMBL: ENSMUSP00000085016 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000087723]
AlphaFold Q61982
Predicted Effect probably damaging
Transcript: ENSMUST00000087723
AA Change: T273I

PolyPhen 2 Score 0.994 (Sensitivity: 0.69; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000085016
Gene: ENSMUSG00000038146
AA Change: T273I

DomainStartEndE-ValueType
signal peptide 1 39 N/A INTRINSIC
EGF 42 78 3.73e-5 SMART
EGF 82 119 1.78e-2 SMART
EGF 123 157 1.13e-4 SMART
EGF_CA 159 196 1.89e-15 SMART
EGF 201 235 3.85e-7 SMART
EGF_CA 237 273 3.97e-9 SMART
EGF_CA 275 313 4.63e-10 SMART
EGF_CA 315 351 1.05e-8 SMART
EGF 355 390 1.28e-3 SMART
EGF_CA 392 430 6.29e-12 SMART
EGF_CA 432 468 1.11e-12 SMART
EGF_CA 470 506 4.21e-13 SMART
EGF_CA 508 544 8.43e-13 SMART
EGF_CA 546 581 9.54e-12 SMART
EGF_CA 583 619 1.31e-9 SMART
EGF_CA 621 656 2.03e-6 SMART
EGF_CA 658 694 2.28e-9 SMART
EGF 699 731 7.18e-7 SMART
EGF 738 771 2.5e-6 SMART
EGF 775 809 8e-5 SMART
EGF_CA 811 848 4.77e-12 SMART
EGF_CA 850 886 3.81e-11 SMART
EGF_CA 888 923 1.47e-12 SMART
EGF_CA 925 961 3.4e-8 SMART
EGF 966 999 5.74e-6 SMART
EGF 1004 1035 7.18e-7 SMART
EGF 1040 1083 1.21e-4 SMART
EGF_CA 1085 1121 1.29e-8 SMART
EGF_CA 1123 1159 1.45e-11 SMART
EGF_CA 1161 1204 1.26e-11 SMART
EGF 1209 1245 1.53e-1 SMART
EGF 1250 1288 8e-5 SMART
EGF 1293 1326 1.13e1 SMART
EGF 1339 1374 5.36e-6 SMART
NL 1381 1419 1.63e-15 SMART
NL 1422 1460 1.78e-16 SMART
NL 1461 1502 1.75e-15 SMART
NOD 1506 1562 2.98e-24 SMART
NODP 1577 1641 1.34e-26 SMART
transmembrane domain 1644 1666 N/A INTRINSIC
low complexity region 1774 1783 N/A INTRINSIC
ANK 1789 1834 1.48e3 SMART
ANK 1839 1868 1.61e-4 SMART
ANK 1872 1902 1.42e0 SMART
ANK 1906 1935 1.77e-1 SMART
ANK 1939 1968 3.18e-3 SMART
ANK 1972 2001 5.16e-3 SMART
low complexity region 2028 2054 N/A INTRINSIC
low complexity region 2108 2123 N/A INTRINSIC
low complexity region 2169 2193 N/A INTRINSIC
DUF3454 2218 2275 2.81e-20 SMART
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 99.9%
  • 10x: 99.7%
  • 20x: 99.1%
Validation Efficiency
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes the third discovered human homologue of the Drosophilia melanogaster type I membrane protein notch. In Drosophilia, notch interaction with its cell-bound ligands (delta, serrate) establishes an intercellular signalling pathway that plays a key role in neural development. Homologues of the notch-ligands have also been identified in human, but precise interactions between these ligands and the human notch homologues remains to be determined. Mutations in NOTCH3 have been identified as the underlying cause of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). [provided by RefSeq, Jul 2008]
PHENOTYPE: Some, but not all, null alleles cause defects in artery morphology and in T cell development. Progressive emaciation and kyphosis with paraphimosis occurs in an intron 31 splice donor site point mutant. In conjunction with Notch1 deficiency, abnormalities in embryonic development have been observed. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 74 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Aarsd1 C A 11: 101,302,194 (GRCm39) V158F probably damaging Het
Abtb3 T A 10: 85,434,409 (GRCm39) C22* probably null Het
Adam1b T C 5: 121,641,212 (GRCm39) probably benign Het
Ambn G A 5: 88,607,281 (GRCm39) E50K possibly damaging Het
Ash1l A G 3: 88,873,259 (GRCm39) D14G probably benign Het
Asphd1 C T 7: 126,547,784 (GRCm39) R173H probably damaging Het
Atr A T 9: 95,802,423 (GRCm39) T1772S Het
Best3 T C 10: 116,838,515 (GRCm39) L191P probably damaging Het
Bola1 A T 3: 96,104,517 (GRCm39) S26T probably benign Het
Borcs6 T C 11: 68,950,646 (GRCm39) L8P probably benign Het
Brca1 T G 11: 101,416,463 (GRCm39) Q557P probably damaging Het
Brca2 G A 5: 150,460,128 (GRCm39) E468K possibly damaging Het
Capza2 T A 6: 17,637,131 (GRCm39) L4Q probably benign Het
Cc2d2b T A 19: 40,804,228 (GRCm39) Y918* probably null Het
Ccdc163 T C 4: 116,567,472 (GRCm39) L67P probably damaging Het
Ccdc172 C A 19: 58,525,022 (GRCm39) Q160K probably damaging Het
Ccp110 T A 7: 118,321,903 (GRCm39) D519E probably benign Het
Cd300ld2 T C 11: 114,904,648 (GRCm39) Q73R probably benign Het
Cfap46 T A 7: 139,236,496 (GRCm39) D608V Het
Cfap69 T G 5: 5,654,287 (GRCm39) Y549S probably benign Het
Cilp G A 9: 65,186,286 (GRCm39) G794S probably damaging Het
Clu A C 14: 66,217,211 (GRCm39) Q348P probably damaging Het
Cnot1 A T 8: 96,473,649 (GRCm39) N1153K probably benign Het
Col2a1 T C 15: 97,888,849 (GRCm39) probably null Het
Col6a6 A T 9: 105,661,272 (GRCm39) I279N probably damaging Het
Dop1a A G 9: 86,402,259 (GRCm39) D1153G possibly damaging Het
Dpyd A G 3: 119,205,822 (GRCm39) K888E probably benign Het
Eif2ak4 T C 2: 118,287,656 (GRCm39) I1208T possibly damaging Het
Epha1 T C 6: 42,335,722 (GRCm39) I972V probably damaging Het
Fam13c C T 10: 70,388,983 (GRCm39) T503I probably benign Het
Fbxo43 T A 15: 36,162,013 (GRCm39) Q398L probably benign Het
Fbxo44 A G 4: 148,243,089 (GRCm39) I57T probably benign Het
Flnc T C 6: 29,449,369 (GRCm39) I1422T probably benign Het
Flrt2 T C 12: 95,746,076 (GRCm39) L138P probably damaging Het
Frem3 A G 8: 81,338,840 (GRCm39) K378E possibly damaging Het
Ganc T A 2: 120,252,560 (GRCm39) D128E probably benign Het
Gm19965 T C 1: 116,749,515 (GRCm39) S399P Het
H2-Q1 A T 17: 35,539,997 (GRCm39) K89* probably null Het
H2-Q2 A T 17: 35,561,301 (GRCm39) probably benign Het
Hmmr G A 11: 40,612,499 (GRCm39) S206F probably damaging Het
Homer2 T A 7: 81,274,014 (GRCm39) S125C possibly damaging Het
Hormad2 T C 11: 4,358,714 (GRCm39) K231R probably benign Het
Kif17 A C 4: 138,005,220 (GRCm39) K262Q probably damaging Het
Kif20a G A 18: 34,761,444 (GRCm39) S279N probably benign Het
Lrp12 T C 15: 39,741,450 (GRCm39) N441D probably damaging Het
Lta4h G T 10: 93,318,126 (GRCm39) L515F possibly damaging Het
Mavs T C 2: 131,088,470 (GRCm39) S425P probably benign Het
Mcat A C 15: 83,439,592 (GRCm39) D99E probably damaging Het
Nav2 C A 7: 49,195,765 (GRCm39) T1047K probably benign Het
Neb T A 2: 52,099,657 (GRCm39) Y4731F probably damaging Het
Nectin4 G C 1: 171,211,325 (GRCm39) R283P probably null Het
Or4c11c G A 2: 88,661,633 (GRCm39) M57I possibly damaging Het
Or5i1 A T 2: 87,613,830 (GRCm39) *317C probably null Het
Or6b2b T G 1: 92,419,247 (GRCm39) I77L possibly damaging Het
Or6z7 T A 7: 6,483,868 (GRCm39) I96F possibly damaging Het
Pcdha12 A T 18: 37,155,638 (GRCm39) T786S probably benign Het
Pde9a A G 17: 31,692,186 (GRCm39) K520E probably benign Het
Piezo2 A C 18: 63,208,801 (GRCm39) L1404R probably damaging Het
Rrbp1 T C 2: 143,792,416 (GRCm39) S1321G probably benign Het
Rtkn T C 6: 83,128,897 (GRCm39) V464A probably damaging Het
Rtn4rl1 T C 11: 75,156,147 (GRCm39) F193S probably damaging Het
Samd4 G A 14: 47,122,374 (GRCm39) V33I probably damaging Het
Scn5a A G 9: 119,350,357 (GRCm39) L839P probably damaging Het
Slc6a17 C A 3: 107,380,985 (GRCm39) V507L probably benign Het
Stradb C A 1: 59,030,356 (GRCm39) N203K unknown Het
Tenm2 T C 11: 35,960,196 (GRCm39) T1044A possibly damaging Het
Tmem245 A C 4: 56,886,037 (GRCm39) W860G probably damaging Het
Tpst2 G A 5: 112,455,803 (GRCm39) R114H probably damaging Het
Trappc10 C T 10: 78,036,460 (GRCm39) D920N possibly damaging Het
Vmn1r59 T A 7: 5,456,966 (GRCm39) I265L probably benign Het
Zbtb20 A C 16: 43,439,100 (GRCm39) D667A probably damaging Het
Zbtb4 T A 11: 69,668,309 (GRCm39) I344N probably damaging Het
Zdbf2 T A 1: 63,343,234 (GRCm39) C538S possibly damaging Het
Zmym6 A T 4: 127,016,355 (GRCm39) H712L probably damaging Het
Other mutations in Notch3
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00161:Notch3 APN 17 32,377,088 (GRCm39) nonsense probably null
IGL01065:Notch3 APN 17 32,365,390 (GRCm39) nonsense probably null
IGL01296:Notch3 APN 17 32,385,731 (GRCm39) missense unknown
IGL01322:Notch3 APN 17 32,363,445 (GRCm39) missense probably damaging 1.00
IGL01343:Notch3 APN 17 32,362,410 (GRCm39) missense probably benign 0.10
IGL01358:Notch3 APN 17 32,363,721 (GRCm39) missense probably damaging 1.00
IGL01600:Notch3 APN 17 32,363,472 (GRCm39) missense probably damaging 1.00
IGL01622:Notch3 APN 17 32,377,844 (GRCm39) missense possibly damaging 0.50
IGL01623:Notch3 APN 17 32,377,844 (GRCm39) missense possibly damaging 0.50
IGL01971:Notch3 APN 17 32,343,321 (GRCm39) missense probably damaging 1.00
IGL02000:Notch3 APN 17 32,341,716 (GRCm39) missense probably damaging 0.99
IGL02072:Notch3 APN 17 32,366,048 (GRCm39) nonsense probably null
IGL02145:Notch3 APN 17 32,373,715 (GRCm39) missense probably benign 0.01
IGL02256:Notch3 APN 17 32,351,298 (GRCm39) missense probably damaging 1.00
IGL02366:Notch3 APN 17 32,363,179 (GRCm39) missense probably benign
IGL02476:Notch3 APN 17 32,377,612 (GRCm39) missense possibly damaging 0.67
IGL02502:Notch3 APN 17 32,377,252 (GRCm39) nonsense probably null
IGL02551:Notch3 APN 17 32,373,705 (GRCm39) splice site probably benign
divide UTSW 17 32,356,787 (GRCm39) splice site probably null
impressed UTSW 17 32,385,652 (GRCm39) missense probably benign
indented UTSW 17 32,366,937 (GRCm39) missense probably benign 0.00
Lopressor UTSW 17 32,372,858 (GRCm39) missense probably damaging 1.00
marginal UTSW 17 32,383,198 (GRCm39) missense probably benign
PIT4486001:Notch3 UTSW 17 32,373,737 (GRCm39) missense probably damaging 1.00
R0115:Notch3 UTSW 17 32,352,436 (GRCm39) missense possibly damaging 0.82
R0201:Notch3 UTSW 17 32,375,122 (GRCm39) splice site probably benign
R0630:Notch3 UTSW 17 32,366,446 (GRCm39) splice site probably benign
R1167:Notch3 UTSW 17 32,341,719 (GRCm39) missense possibly damaging 0.95
R1432:Notch3 UTSW 17 32,383,198 (GRCm39) missense probably benign
R1567:Notch3 UTSW 17 32,377,554 (GRCm39) missense possibly damaging 0.77
R1623:Notch3 UTSW 17 32,358,165 (GRCm39) missense probably benign 0.00
R1663:Notch3 UTSW 17 32,375,093 (GRCm39) missense probably damaging 1.00
R1668:Notch3 UTSW 17 32,377,563 (GRCm39) missense probably damaging 0.99
R1789:Notch3 UTSW 17 32,377,699 (GRCm39) missense probably damaging 1.00
R1813:Notch3 UTSW 17 32,362,402 (GRCm39) missense probably benign 0.08
R1837:Notch3 UTSW 17 32,343,296 (GRCm39) missense probably damaging 1.00
R1896:Notch3 UTSW 17 32,362,402 (GRCm39) missense probably benign 0.08
R1937:Notch3 UTSW 17 32,372,826 (GRCm39) missense probably benign 0.03
R1954:Notch3 UTSW 17 32,385,652 (GRCm39) missense probably benign
R2014:Notch3 UTSW 17 32,376,974 (GRCm39) missense probably benign 0.00
R2058:Notch3 UTSW 17 32,362,618 (GRCm39) missense probably benign
R2068:Notch3 UTSW 17 32,354,482 (GRCm39) missense probably benign 0.00
R2097:Notch3 UTSW 17 32,341,728 (GRCm39) missense probably damaging 1.00
R2112:Notch3 UTSW 17 32,363,584 (GRCm39) missense probably benign 0.19
R2156:Notch3 UTSW 17 32,366,818 (GRCm39) missense probably damaging 1.00
R2211:Notch3 UTSW 17 32,366,952 (GRCm39) missense probably benign 0.00
R2324:Notch3 UTSW 17 32,369,108 (GRCm39) splice site probably benign
R2432:Notch3 UTSW 17 32,372,778 (GRCm39) missense probably damaging 1.00
R3117:Notch3 UTSW 17 32,377,089 (GRCm39) missense probably damaging 1.00
R3236:Notch3 UTSW 17 32,377,435 (GRCm39) missense probably damaging 0.96
R3409:Notch3 UTSW 17 32,369,676 (GRCm39) missense possibly damaging 0.67
R3434:Notch3 UTSW 17 32,377,592 (GRCm39) missense possibly damaging 0.80
R3435:Notch3 UTSW 17 32,377,592 (GRCm39) missense possibly damaging 0.80
R3438:Notch3 UTSW 17 32,372,564 (GRCm39) missense probably damaging 1.00
R3926:Notch3 UTSW 17 32,372,531 (GRCm39) missense possibly damaging 0.92
R4087:Notch3 UTSW 17 32,377,087 (GRCm39) missense possibly damaging 0.60
R4115:Notch3 UTSW 17 32,377,407 (GRCm39) missense probably damaging 1.00
R4214:Notch3 UTSW 17 32,351,181 (GRCm39) missense possibly damaging 0.96
R4234:Notch3 UTSW 17 32,360,315 (GRCm39) missense probably damaging 0.97
R4242:Notch3 UTSW 17 32,362,719 (GRCm39) missense possibly damaging 0.74
R4658:Notch3 UTSW 17 32,373,737 (GRCm39) missense probably damaging 1.00
R4878:Notch3 UTSW 17 32,366,059 (GRCm39) missense probably damaging 1.00
R4879:Notch3 UTSW 17 32,366,937 (GRCm39) missense probably benign 0.00
R4885:Notch3 UTSW 17 32,360,351 (GRCm39) missense probably damaging 0.98
R4924:Notch3 UTSW 17 32,363,705 (GRCm39) missense probably damaging 1.00
R5084:Notch3 UTSW 17 32,376,864 (GRCm39) critical splice donor site probably null
R5086:Notch3 UTSW 17 32,362,308 (GRCm39) missense probably benign 0.13
R5343:Notch3 UTSW 17 32,362,257 (GRCm39) missense probably benign 0.03
R5389:Notch3 UTSW 17 32,358,163 (GRCm39) missense probably benign
R5503:Notch3 UTSW 17 32,366,029 (GRCm39) missense probably benign 0.00
R5698:Notch3 UTSW 17 32,376,961 (GRCm39) missense probably damaging 1.00
R5824:Notch3 UTSW 17 32,372,835 (GRCm39) missense possibly damaging 0.92
R5969:Notch3 UTSW 17 32,372,858 (GRCm39) missense probably damaging 1.00
R6050:Notch3 UTSW 17 32,362,501 (GRCm39) missense probably benign
R6274:Notch3 UTSW 17 32,366,264 (GRCm39) missense probably benign
R6276:Notch3 UTSW 17 32,373,723 (GRCm39) missense probably benign 0.10
R6313:Notch3 UTSW 17 32,370,128 (GRCm39) splice site probably null
R6316:Notch3 UTSW 17 32,356,787 (GRCm39) splice site probably null
R6380:Notch3 UTSW 17 32,363,533 (GRCm39) missense probably damaging 1.00
R6401:Notch3 UTSW 17 32,377,597 (GRCm39) missense probably benign 0.01
R6502:Notch3 UTSW 17 32,377,191 (GRCm39) missense probably damaging 1.00
R6741:Notch3 UTSW 17 32,362,458 (GRCm39) missense probably benign 0.16
R7131:Notch3 UTSW 17 32,363,191 (GRCm39) missense probably benign
R7140:Notch3 UTSW 17 32,375,351 (GRCm39) missense possibly damaging 0.84
R7162:Notch3 UTSW 17 32,365,423 (GRCm39) missense probably damaging 0.98
R7171:Notch3 UTSW 17 32,377,936 (GRCm39) missense probably damaging 1.00
R7449:Notch3 UTSW 17 32,376,940 (GRCm39) missense probably damaging 1.00
R7450:Notch3 UTSW 17 32,360,365 (GRCm39) missense possibly damaging 0.69
R7554:Notch3 UTSW 17 32,341,345 (GRCm39) missense probably benign 0.03
R7575:Notch3 UTSW 17 32,373,793 (GRCm39) missense possibly damaging 0.81
R7632:Notch3 UTSW 17 32,377,480 (GRCm39) missense probably benign
R7633:Notch3 UTSW 17 32,377,596 (GRCm39) missense probably benign 0.17
R7860:Notch3 UTSW 17 32,341,747 (GRCm39) missense possibly damaging 0.67
R8052:Notch3 UTSW 17 32,365,545 (GRCm39) missense probably damaging 1.00
R8250:Notch3 UTSW 17 32,351,310 (GRCm39) missense probably damaging 1.00
R8296:Notch3 UTSW 17 32,341,713 (GRCm39) missense probably damaging 1.00
R8458:Notch3 UTSW 17 32,375,024 (GRCm39) missense probably damaging 1.00
R8539:Notch3 UTSW 17 32,375,329 (GRCm39) missense possibly damaging 0.92
R8865:Notch3 UTSW 17 32,341,090 (GRCm39) missense probably benign 0.01
R8925:Notch3 UTSW 17 32,372,792 (GRCm39) missense probably benign 0.14
R8927:Notch3 UTSW 17 32,372,792 (GRCm39) missense probably benign 0.14
R9062:Notch3 UTSW 17 32,341,692 (GRCm39) missense possibly damaging 0.93
R9079:Notch3 UTSW 17 32,383,033 (GRCm39) intron probably benign
R9089:Notch3 UTSW 17 32,370,521 (GRCm39) missense probably benign 0.00
R9260:Notch3 UTSW 17 32,362,216 (GRCm39) critical splice donor site probably null
R9289:Notch3 UTSW 17 32,377,254 (GRCm39) missense probably damaging 1.00
R9294:Notch3 UTSW 17 32,362,665 (GRCm39) missense probably benign 0.03
R9661:Notch3 UTSW 17 32,373,792 (GRCm39) missense probably damaging 1.00
R9779:Notch3 UTSW 17 32,372,757 (GRCm39) missense probably damaging 1.00
T0975:Notch3 UTSW 17 32,365,391 (GRCm39) missense probably damaging 0.99
Z1088:Notch3 UTSW 17 32,377,626 (GRCm39) missense possibly damaging 0.94
Z1176:Notch3 UTSW 17 32,370,344 (GRCm39) missense probably damaging 1.00
Z1176:Notch3 UTSW 17 32,360,490 (GRCm39) missense probably benign 0.12
Z1177:Notch3 UTSW 17 32,385,668 (GRCm39) missense probably benign
Predicted Primers PCR Primer
(F):5'- AAAGAGGCCACACGGTCATG -3'
(R):5'- GGCCAGAACTGTGAAGTCAACG -3'

Sequencing Primer
(F):5'- ACACGGTCATGGCAGGTG -3'
(R):5'- TCAACGTGGATGACTGTCC -3'
Posted On 2020-07-28