Incidental Mutation 'R4728:Notch4'
ID 358640
Institutional Source Beutler Lab
Gene Symbol Notch4
Ensembl Gene ENSMUSG00000015468
Gene Name notch 4
Synonyms Int3, Int-3, N4
MMRRC Submission 042020-MU
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # R4728 (G1)
Quality Score 225
Status Validated
Chromosome 17
Chromosomal Location 34783242-34807477 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 34789179 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Threonine to Alanine at position 497 (T497A)
Ref Sequence ENSEMBL: ENSMUSP00000133574 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000015612] [ENSMUST00000173389]
AlphaFold P31695
Predicted Effect probably benign
Transcript: ENSMUST00000015612
AA Change: T493A

PolyPhen 2 Score 0.003 (Sensitivity: 0.98; Specificity: 0.44)
SMART Domains Protein: ENSMUSP00000015612
Gene: ENSMUSG00000015468
AA Change: T493A

DomainStartEndE-ValueType
signal peptide 1 20 N/A INTRINSIC
EGF 24 60 3.2e-4 SMART
EGF 64 112 1.07e-5 SMART
EGF 118 152 5.49e-3 SMART
EGF 156 189 9.33e-6 SMART
EGF_CA 191 229 1.42e-10 SMART
EGF 234 271 1.11e-3 SMART
EGF 276 309 1.84e-4 SMART
EGF_CA 311 350 2.52e-11 SMART
EGF_CA 352 388 1.85e-9 SMART
EGF 392 427 1.58e-3 SMART
EGF_CA 429 470 2.46e-14 SMART
EGF_CA 472 508 5.03e-11 SMART
EGF_CA 510 546 6.74e-12 SMART
EGF_CA 548 584 2.98e-13 SMART
EGF_CA 586 622 7.63e-11 SMART
EGF_like 645 686 2.86e1 SMART
EGF 691 724 3.48e-5 SMART
EGF 729 762 3.62e-3 SMART
EGF_CA 764 800 1.48e-8 SMART
EGF 806 839 1.74e-5 SMART
EGF 844 877 2.3e-5 SMART
EGF 881 924 3.59e-7 SMART
EGF_CA 926 962 7.29e-8 SMART
EGF_CA 965 1000 4.42e-7 SMART
EGF_CA 1002 1040 4.56e-9 SMART
EGF 1045 1081 6.16e-6 SMART
EGF 1086 1122 8.65e-1 SMART
EGF 1129 1167 1.45e-2 SMART
NL 1159 1200 6.79e-13 SMART
NL 1203 1242 2.01e-15 SMART
NL 1243 1281 1.85e-14 SMART
NOD 1287 1341 4.37e-8 SMART
NODP 1373 1437 2.12e-6 SMART
transmembrane domain 1441 1463 N/A INTRINSIC
low complexity region 1525 1539 N/A INTRINSIC
ANK 1578 1623 2.5e3 SMART
ANK 1628 1657 1.12e-3 SMART
ANK 1661 1691 5.01e-1 SMART
ANK 1695 1724 1.65e-1 SMART
ANK 1728 1757 4.56e-4 SMART
ANK 1761 1790 2.88e-1 SMART
low complexity region 1889 1906 N/A INTRINSIC
low complexity region 1925 1937 N/A INTRINSIC
Predicted Effect noncoding transcript
Transcript: ENSMUST00000126950
Predicted Effect noncoding transcript
Transcript: ENSMUST00000152714
Predicted Effect noncoding transcript
Transcript: ENSMUST00000172623
Predicted Effect probably benign
Transcript: ENSMUST00000173389
AA Change: T497A

PolyPhen 2 Score 0.003 (Sensitivity: 0.98; Specificity: 0.44)
SMART Domains Protein: ENSMUSP00000133574
Gene: ENSMUSG00000015468
AA Change: T497A

DomainStartEndE-ValueType
signal peptide 1 20 N/A INTRINSIC
EGF 28 64 3.2e-4 SMART
EGF 68 116 1.07e-5 SMART
EGF 122 156 5.49e-3 SMART
EGF 160 193 9.33e-6 SMART
EGF_CA 195 233 1.42e-10 SMART
EGF 238 275 1.11e-3 SMART
EGF 280 313 1.84e-4 SMART
EGF_CA 315 354 2.52e-11 SMART
EGF_CA 356 392 1.85e-9 SMART
EGF 396 431 1.58e-3 SMART
EGF_CA 433 474 2.46e-14 SMART
EGF_CA 476 512 5.03e-11 SMART
EGF_CA 514 550 6.74e-12 SMART
EGF_CA 552 588 2.98e-13 SMART
EGF_CA 590 626 7.63e-11 SMART
EGF_like 649 690 2.86e1 SMART
EGF 695 728 3.48e-5 SMART
EGF 733 766 3.62e-3 SMART
EGF_CA 768 804 1.48e-8 SMART
EGF 810 843 1.74e-5 SMART
EGF 848 881 2.3e-5 SMART
EGF 885 928 3.59e-7 SMART
EGF_like 930 955 7.02e-1 SMART
Meta Mutation Damage Score 0.0617 question?
Coding Region Coverage
  • 1x: 99.2%
  • 3x: 98.5%
  • 10x: 96.9%
  • 20x: 94.3%
Validation Efficiency 94% (73/78)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the NOTCH family of proteins. Members of this Type I transmembrane protein family share structural characteristics including an extracellular domain consisting of multiple epidermal growth factor-like (EGF) repeats, and an intracellular domain consisting of multiple different domain types. Notch signaling is an evolutionarily conserved intercellular signaling pathway that regulates interactions between physically adjacent cells through binding of Notch family receptors to their cognate ligands. The encoded preproprotein is proteolytically processed in the trans-Golgi network to generate two polypeptide chains that heterodimerize to form the mature cell-surface receptor. This receptor may play a role in vascular, renal and hepatic development. Mutations in this gene may be associated with schizophrenia. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Jan 2016]
PHENOTYPE: Mice homozygous for a knock-out allele are viable and fertile but exhibit a slight delay in postnatal retinal angiogenesis. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 65 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Bicc1 C T 10: 70,771,661 (GRCm39) probably null Het
Bpifc T A 10: 85,827,063 (GRCm39) H162L possibly damaging Het
Ccdc163 C T 4: 116,566,209 (GRCm39) probably benign Het
Cldn12 A G 5: 5,558,385 (GRCm39) F14S probably damaging Het
Cyth4 G A 15: 78,486,913 (GRCm39) G14R probably benign Het
Ddhd2 C T 8: 26,242,294 (GRCm39) V194I probably damaging Het
Ddx23 A T 15: 98,548,106 (GRCm39) V433E probably damaging Het
Defb34 A G 8: 19,176,434 (GRCm39) N42D possibly damaging Het
Dennd6a A G 14: 26,348,575 (GRCm39) E313G probably null Het
Dhx30 A G 9: 109,916,718 (GRCm39) F570S probably damaging Het
Dnah3 T C 7: 119,658,589 (GRCm39) E864G probably damaging Het
Eps8 G A 6: 137,486,160 (GRCm39) Q451* probably null Het
Fmo9 A T 1: 166,490,880 (GRCm39) Y533N possibly damaging Het
Fut8 T A 12: 77,521,973 (GRCm39) D537E probably damaging Het
Gm5407 T C 16: 49,117,283 (GRCm39) noncoding transcript Het
Gm9916 A G 3: 118,228,690 (GRCm39) noncoding transcript Het
Grm5 T A 7: 87,624,496 (GRCm39) F354L probably damaging Het
Hira C T 16: 18,741,654 (GRCm39) A353V probably damaging Het
Ifna4 C A 4: 88,760,519 (GRCm39) T141K probably benign Het
Igf1r T C 7: 67,839,372 (GRCm39) L628P probably damaging Het
Kcnh5 A T 12: 75,054,555 (GRCm39) I463N probably damaging Het
Kcnh8 C A 17: 53,032,898 (GRCm39) Q62K probably damaging Het
Kif3c A T 12: 3,415,873 (GRCm39) probably benign Het
Kmo A G 1: 175,484,329 (GRCm39) D353G possibly damaging Het
Lrp1 T C 10: 127,399,606 (GRCm39) T2301A probably damaging Het
Lrrc7 GAAGTTGTTTGGAGATTCTTATCTTA GA 3: 158,024,045 (GRCm39) probably benign Het
Map3k9 C T 12: 81,769,147 (GRCm39) R967Q probably damaging Het
Mcm8 A G 2: 132,674,774 (GRCm39) H414R probably damaging Het
Mier1 A G 4: 102,997,402 (GRCm39) E145G probably damaging Het
Mlc1 A T 15: 88,862,234 (GRCm39) probably null Het
Napb T C 2: 148,551,245 (GRCm39) D96G probably damaging Het
Nbas T A 12: 13,338,740 (GRCm39) S193R probably damaging Het
Nlrp4a T C 7: 26,174,515 (GRCm39) V967A probably benign Het
Nlrp4e T A 7: 23,020,989 (GRCm39) I492K probably benign Het
Npdc1 G A 2: 25,298,957 (GRCm39) D284N probably damaging Het
Ogdh T A 11: 6,292,549 (GRCm39) Y417N probably damaging Het
Or5w19 T C 2: 87,698,779 (GRCm39) V148A probably benign Het
Ovol1 A T 19: 5,603,690 (GRCm39) Y70* probably null Het
P2ry1 A G 3: 60,911,641 (GRCm39) Y260C probably damaging Het
Pcx G T 19: 4,653,124 (GRCm39) R263L probably damaging Het
Pla2g4f T A 2: 120,131,402 (GRCm39) T774S probably benign Het
Prdm15 T G 16: 97,622,986 (GRCm39) K289Q probably benign Het
Prl7c1 A T 13: 27,960,268 (GRCm39) H91Q probably benign Het
Prmt5 C T 14: 54,745,364 (GRCm39) R601H probably benign Het
Prrc2b T A 2: 32,120,637 (GRCm39) D2192E probably damaging Het
Ptdss2 A G 7: 140,734,372 (GRCm39) I299V probably benign Het
Rbm28 A G 6: 29,143,591 (GRCm39) V354A probably damaging Het
Rps6kb1 G C 11: 86,435,484 (GRCm39) probably null Het
Sema3f A G 9: 107,582,639 (GRCm39) S35P probably benign Het
Serpina3n A T 12: 104,375,422 (GRCm39) T165S probably benign Het
Serpinb13 C T 1: 106,910,574 (GRCm39) S66L probably damaging Het
Sh2d4b T A 14: 40,564,389 (GRCm39) R267* probably null Het
Slc5a12 A T 2: 110,474,769 (GRCm39) K554* probably null Het
Snrnp200 T C 2: 127,059,334 (GRCm39) L409P probably damaging Het
Snrnp200 T A 2: 127,069,798 (GRCm39) V981E possibly damaging Het
Spon2 T A 5: 33,374,682 (GRCm39) R41S probably benign Het
Sptb A T 12: 76,630,153 (GRCm39) M2279K probably benign Het
Srcap T G 7: 127,140,096 (GRCm39) probably null Het
Tctn3 A G 19: 40,594,186 (GRCm39) V409A probably damaging Het
Tg A C 15: 66,554,676 (GRCm39) Q697P probably damaging Het
Tmem181a A G 17: 6,340,874 (GRCm39) D141G probably benign Het
Tmem82 A G 4: 141,341,963 (GRCm39) S334P probably benign Het
Ubr4 A G 4: 139,151,190 (GRCm39) Y1875C probably damaging Het
Vmn1r63 C A 7: 5,806,362 (GRCm39) R90L probably damaging Het
Zfp330 A C 8: 83,497,475 (GRCm39) Y56D probably damaging Het
Other mutations in Notch4
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00904:Notch4 APN 17 34,794,535 (GRCm39) critical splice donor site probably null
IGL01022:Notch4 APN 17 34,784,671 (GRCm39) missense probably damaging 1.00
IGL01356:Notch4 APN 17 34,800,000 (GRCm39) missense possibly damaging 0.67
IGL01634:Notch4 APN 17 34,791,562 (GRCm39) missense probably damaging 1.00
IGL02150:Notch4 APN 17 34,803,587 (GRCm39) missense probably damaging 1.00
IGL02248:Notch4 APN 17 34,806,172 (GRCm39) missense probably damaging 1.00
IGL02271:Notch4 APN 17 34,787,445 (GRCm39) missense probably damaging 1.00
IGL02299:Notch4 APN 17 34,796,978 (GRCm39) missense probably damaging 1.00
IGL02561:Notch4 APN 17 34,787,134 (GRCm39) splice site probably benign
IGL02604:Notch4 APN 17 34,784,362 (GRCm39) splice site probably null
IGL03323:Notch4 APN 17 34,801,445 (GRCm39) missense probably damaging 1.00
IGL03366:Notch4 APN 17 34,791,542 (GRCm39) missense probably damaging 1.00
IGL03408:Notch4 APN 17 34,784,542 (GRCm39) missense probably benign 0.03
K3955:Notch4 UTSW 17 34,787,436 (GRCm39) missense probably damaging 1.00
R0123:Notch4 UTSW 17 34,784,337 (GRCm39) missense possibly damaging 0.85
R0366:Notch4 UTSW 17 34,800,473 (GRCm39) splice site probably benign
R0446:Notch4 UTSW 17 34,784,337 (GRCm39) missense possibly damaging 0.85
R0490:Notch4 UTSW 17 34,801,864 (GRCm39) missense probably damaging 1.00
R0504:Notch4 UTSW 17 34,794,065 (GRCm39) missense probably damaging 1.00
R0545:Notch4 UTSW 17 34,802,407 (GRCm39) missense probably damaging 1.00
R0702:Notch4 UTSW 17 34,794,177 (GRCm39) missense probably damaging 1.00
R0763:Notch4 UTSW 17 34,784,306 (GRCm39) nonsense probably null
R0854:Notch4 UTSW 17 34,787,546 (GRCm39) missense probably damaging 1.00
R1082:Notch4 UTSW 17 34,806,364 (GRCm39) missense probably damaging 1.00
R1196:Notch4 UTSW 17 34,787,837 (GRCm39) missense probably damaging 1.00
R1316:Notch4 UTSW 17 34,786,444 (GRCm39) missense probably damaging 1.00
R1493:Notch4 UTSW 17 34,786,656 (GRCm39) nonsense probably null
R1527:Notch4 UTSW 17 34,784,718 (GRCm39) missense probably damaging 1.00
R1548:Notch4 UTSW 17 34,787,396 (GRCm39) missense probably damaging 1.00
R1718:Notch4 UTSW 17 34,795,737 (GRCm39) splice site probably benign
R1855:Notch4 UTSW 17 34,799,936 (GRCm39) missense probably benign 0.05
R1988:Notch4 UTSW 17 34,806,562 (GRCm39) missense possibly damaging 0.59
R2022:Notch4 UTSW 17 34,806,502 (GRCm39) missense probably damaging 1.00
R2023:Notch4 UTSW 17 34,806,502 (GRCm39) missense probably damaging 1.00
R2078:Notch4 UTSW 17 34,787,689 (GRCm39) critical splice acceptor site probably null
R2369:Notch4 UTSW 17 34,804,924 (GRCm39) missense probably benign 0.15
R3846:Notch4 UTSW 17 34,797,071 (GRCm39) missense probably damaging 1.00
R3874:Notch4 UTSW 17 34,797,043 (GRCm39) nonsense probably null
R4087:Notch4 UTSW 17 34,803,409 (GRCm39) missense probably damaging 1.00
R4456:Notch4 UTSW 17 34,802,807 (GRCm39) missense probably damaging 0.99
R4628:Notch4 UTSW 17 34,789,159 (GRCm39) missense probably damaging 1.00
R4778:Notch4 UTSW 17 34,801,485 (GRCm39) missense possibly damaging 0.95
R4818:Notch4 UTSW 17 34,797,690 (GRCm39) splice site probably benign
R4828:Notch4 UTSW 17 34,789,034 (GRCm39) missense probably damaging 1.00
R4830:Notch4 UTSW 17 34,789,092 (GRCm39) missense probably damaging 1.00
R4859:Notch4 UTSW 17 34,806,154 (GRCm39) missense probably damaging 1.00
R4871:Notch4 UTSW 17 34,796,536 (GRCm39) missense possibly damaging 0.63
R5090:Notch4 UTSW 17 34,799,894 (GRCm39) missense probably damaging 0.99
R5290:Notch4 UTSW 17 34,784,263 (GRCm39) missense probably benign 0.01
R5363:Notch4 UTSW 17 34,806,097 (GRCm39) missense probably damaging 1.00
R5860:Notch4 UTSW 17 34,801,392 (GRCm39) missense probably damaging 1.00
R6352:Notch4 UTSW 17 34,786,435 (GRCm39) missense probably damaging 1.00
R6385:Notch4 UTSW 17 34,792,788 (GRCm39) missense probably null 0.16
R6422:Notch4 UTSW 17 34,803,533 (GRCm39) missense probably benign
R6645:Notch4 UTSW 17 34,806,790 (GRCm39) missense probably benign 0.00
R6836:Notch4 UTSW 17 34,805,074 (GRCm39) missense probably damaging 0.96
R6943:Notch4 UTSW 17 34,802,577 (GRCm39) missense probably benign
R6991:Notch4 UTSW 17 34,803,774 (GRCm39) nonsense probably null
R7078:Notch4 UTSW 17 34,801,520 (GRCm39) missense possibly damaging 0.94
R7168:Notch4 UTSW 17 34,791,667 (GRCm39) missense probably benign 0.05
R7182:Notch4 UTSW 17 34,802,473 (GRCm39) missense probably damaging 1.00
R7240:Notch4 UTSW 17 34,795,445 (GRCm39) missense probably benign 0.00
R7247:Notch4 UTSW 17 34,791,491 (GRCm39) missense probably damaging 1.00
R7556:Notch4 UTSW 17 34,794,444 (GRCm39) missense probably damaging 1.00
R7571:Notch4 UTSW 17 34,802,548 (GRCm39) missense probably damaging 0.99
R7697:Notch4 UTSW 17 34,789,159 (GRCm39) missense probably damaging 1.00
R7763:Notch4 UTSW 17 34,801,392 (GRCm39) missense probably damaging 1.00
R7994:Notch4 UTSW 17 34,797,064 (GRCm39) missense possibly damaging 0.82
R8139:Notch4 UTSW 17 34,803,774 (GRCm39) nonsense probably null
R8171:Notch4 UTSW 17 34,801,483 (GRCm39) nonsense probably null
R8375:Notch4 UTSW 17 34,787,228 (GRCm39) missense possibly damaging 0.90
R8448:Notch4 UTSW 17 34,805,763 (GRCm39) splice site probably null
R8543:Notch4 UTSW 17 34,787,394 (GRCm39) missense probably damaging 1.00
R8776:Notch4 UTSW 17 34,806,579 (GRCm39) missense probably damaging 1.00
R8776-TAIL:Notch4 UTSW 17 34,806,579 (GRCm39) missense probably damaging 1.00
R8847:Notch4 UTSW 17 34,803,962 (GRCm39) splice site probably benign
R8885:Notch4 UTSW 17 34,803,470 (GRCm39) missense possibly damaging 0.94
R9126:Notch4 UTSW 17 34,800,080 (GRCm39) missense probably benign 0.00
R9184:Notch4 UTSW 17 34,806,364 (GRCm39) missense probably damaging 1.00
R9425:Notch4 UTSW 17 34,795,801 (GRCm39) missense probably benign 0.42
R9434:Notch4 UTSW 17 34,801,673 (GRCm39) missense probably damaging 1.00
R9462:Notch4 UTSW 17 34,806,667 (GRCm39) missense probably benign 0.00
R9664:Notch4 UTSW 17 34,784,601 (GRCm39) missense probably benign 0.07
R9772:Notch4 UTSW 17 34,792,883 (GRCm39) critical splice donor site probably null
X0054:Notch4 UTSW 17 34,803,469 (GRCm39) missense probably damaging 1.00
X0067:Notch4 UTSW 17 34,805,058 (GRCm39) nonsense probably null
Z1088:Notch4 UTSW 17 34,806,889 (GRCm39) missense probably damaging 1.00
Z1177:Notch4 UTSW 17 34,806,883 (GRCm39) missense probably benign 0.04
Z1177:Notch4 UTSW 17 34,806,882 (GRCm39) missense probably damaging 0.97
Z1177:Notch4 UTSW 17 34,794,122 (GRCm39) missense probably damaging 1.00
Predicted Primers PCR Primer
(F):5'- CTGTCAGTCTAGCCTCCCTG -3'
(R):5'- CAGCTTGTCCTTCTAGGGGTG -3'

Sequencing Primer
(F):5'- AGCCCCCATGGACTCCC -3'
(R):5'- CTAGGGGTGGTGGGTTCCC -3'
Posted On 2015-11-11