Incidental Mutation 'R2432:Notch3'
ID 250474
Institutional Source Beutler Lab
Gene Symbol Notch3
Ensembl Gene ENSMUSG00000038146
Gene Name notch 3
Synonyms hpbk, N3
MMRRC Submission 040393-MU
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # R2432 (G1)
Quality Score 225
Status Validated
Chromosome 17
Chromosomal Location 32339794-32385826 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to T at 32372778 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Cysteine to Serine at position 598 (C598S)
Ref Sequence ENSEMBL: ENSMUSP00000085016 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000087723]
AlphaFold Q61982
Predicted Effect probably damaging
Transcript: ENSMUST00000087723
AA Change: C598S

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000085016
Gene: ENSMUSG00000038146
AA Change: C598S

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
Meta Mutation Damage Score 0.9750 question?
Coding Region Coverage
  • 1x: 99.2%
  • 3x: 98.5%
  • 10x: 97.1%
  • 20x: 94.5%
Validation Efficiency 100% (53/53)
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: 52 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abca13 T C 11: 9,401,333 (GRCm39) probably benign Het
Adamts6 A T 13: 104,563,485 (GRCm39) Y659F probably benign Het
Adamts9 C A 6: 92,834,881 (GRCm39) G750W probably damaging Het
Adgrv1 GA GAA 13: 81,688,251 (GRCm39) probably null Het
Aspscr1 A G 11: 120,593,392 (GRCm39) probably benign Het
Calr3 A G 8: 73,192,270 (GRCm39) probably benign Het
Cpt2 A T 4: 107,761,723 (GRCm39) Y126* probably null Het
Cyp2d34 A G 15: 82,503,212 (GRCm39) L94P probably damaging Het
Def6 A T 17: 28,447,043 (GRCm39) D558V probably benign Het
Dnase1l2 G A 17: 24,661,699 (GRCm39) T20I possibly damaging Het
Eif5b A G 1: 38,058,423 (GRCm39) K242E unknown Het
Golim4 T C 3: 75,799,249 (GRCm39) N478S possibly damaging Het
Helb A T 10: 119,941,442 (GRCm39) D415E probably benign Het
Ifna12 T A 4: 88,521,590 (GRCm39) probably benign Het
Jhy T A 9: 40,872,182 (GRCm39) H109L probably benign Het
Krt87 A T 15: 101,386,037 (GRCm39) Y241* probably null Het
Macf1 G T 4: 123,577,789 (GRCm39) A65E probably damaging Het
Mug2 C A 6: 122,061,335 (GRCm39) N1418K possibly damaging Het
Myo1f A G 17: 33,794,823 (GRCm39) D21G probably damaging Het
Myo5a T A 9: 75,120,155 (GRCm39) I1651N possibly damaging Het
Npat A T 9: 53,469,435 (GRCm39) H307L probably damaging Het
Nr1h2 T C 7: 44,200,791 (GRCm39) Q279R possibly damaging Het
Or4k52 T C 2: 111,611,016 (GRCm39) V117A probably benign Het
Or6c6c A G 10: 129,540,794 (GRCm39) T16A possibly damaging Het
Pcdhb16 A T 18: 37,612,983 (GRCm39) N648Y probably damaging Het
Pdzrn3 G T 6: 101,127,752 (GRCm39) S971R probably damaging Het
Plch2 A G 4: 155,070,621 (GRCm39) *494Q probably null Het
Plekhg4 T A 8: 106,108,468 (GRCm39) D1170E probably benign Het
Plekhm3 A G 1: 64,977,015 (GRCm39) S152P probably damaging Het
Ppargc1b G A 18: 61,440,870 (GRCm39) P683S possibly damaging Het
Prdm12 T G 2: 31,541,864 (GRCm39) M191R probably benign Het
Prdm14 T C 1: 13,195,857 (GRCm39) D68G probably benign Het
Prp2 C T 6: 132,576,874 (GRCm39) P54S unknown Het
Prpf4b A G 13: 35,067,324 (GRCm39) probably benign Het
Ptprk T A 10: 28,468,840 (GRCm39) V1408E probably damaging Het
Rap1gds1 A G 3: 138,662,011 (GRCm39) M415T probably damaging Het
Rps6ka5 A G 12: 100,520,664 (GRCm39) F621S probably damaging Het
Rrm1 T A 7: 102,092,279 (GRCm39) D35E probably benign Het
Rxfp3 T C 15: 11,036,226 (GRCm39) H382R probably damaging Het
Slc11a1 A G 1: 74,422,910 (GRCm39) probably benign Het
Slc25a13 A T 6: 6,114,017 (GRCm39) M285K probably benign Het
Slc30a3 T C 5: 31,246,038 (GRCm39) S231G probably damaging Het
Slc44a2 A T 9: 21,256,130 (GRCm39) I274F probably damaging Het
Tas2r119 A G 15: 32,178,165 (GRCm39) I244V possibly damaging Het
Tenm2 C A 11: 35,918,018 (GRCm39) R1914L probably damaging Het
Tfdp2 T C 9: 96,192,643 (GRCm39) M242T probably damaging Het
Tmprss6 A G 15: 78,349,304 (GRCm39) probably benign Het
Ttc6 C T 12: 57,668,821 (GRCm39) P421L possibly damaging Het
Usp16 T A 16: 87,263,246 (GRCm39) probably null Het
Usp40 T C 1: 87,909,804 (GRCm39) E550G probably benign Het
Vmn2r28 T C 7: 5,491,701 (GRCm39) Y182C probably damaging Het
Zfp382 A G 7: 29,833,174 (GRCm39) D275G probably benign 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
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
R8306:Notch3 UTSW 17 32,377,086 (GRCm39) missense probably damaging 0.99
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'- CCAAAGGTACAGGGGTTACTGG -3'
(R):5'- CCGTTCTTGCAGGCTTTGAG -3'

Sequencing Primer
(F):5'- GGCACAGTCATCAATGTTGAC -3'
(R):5'- CTTGCAGGCTTTGAGGGCAC -3'
Posted On 2014-11-12