Incidental Mutation 'R2156:Notch1'
ID 234780
Institutional Source Beutler Lab
Gene Symbol Notch1
Ensembl Gene ENSMUSG00000026923
Gene Name notch 1
Synonyms 9930111A19Rik, Motch A, Tan1, Mis6, lin-12, N1
MMRRC Submission 040159-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R2156 (G1)
Quality Score 225
Status Not validated
Chromosome 2
Chromosomal Location 26347914-26393834 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to C at 26350873 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Aspartic acid to Glycine at position 2089 (D2089G)
Ref Sequence ENSEMBL: ENSMUSP00000028288 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000028288]
AlphaFold Q01705
PDB Structure The Crystal Structure of a Partial Mouse Notch-1 Ankyrin Domain: Repeats 4 Through 7 Preserve an Ankyrin Fold [X-RAY DIFFRACTION]
Mouse Notch 1 Ankyrin Repeat Intracellular Domain [X-RAY DIFFRACTION]
Structure of sugar modified epidermal growth factor-like repeat 12 of mouse Notch-1 receptor [SOLUTION NMR]
Structure of epidermal growth factor-like repeat 12 of mouse Notch-1 receptor [SOLUTION NMR]
Structure of O-fucosylated epidermal growth factor-like repeat 12 of mouse Notch-1 receptor [SOLUTION NMR]
Factor inhibiting HIF-1 Alpha in complex with Notch 1 fragment mouse notch (1930-1949) peptide [X-RAY DIFFRACTION]
Factor inhibiting HIF-1 Alpha in complex with Notch 1 fragment mouse notch (1997-2016) peptide [X-RAY DIFFRACTION]
Predicted Effect possibly damaging
Transcript: ENSMUST00000028288
AA Change: D2089G

PolyPhen 2 Score 0.913 (Sensitivity: 0.81; Specificity: 0.94)
SMART Domains Protein: ENSMUSP00000028288
Gene: ENSMUSG00000026923
AA Change: D2089G

DomainStartEndE-ValueType
signal peptide 1 18 N/A INTRINSIC
EGF 23 58 1.63e1 SMART
EGF 62 99 4.29e-5 SMART
EGF 105 139 6.25e-7 SMART
EGF_CA 140 176 1.02e-6 SMART
EGF_CA 178 216 4.21e-13 SMART
EGF 221 255 6.7e-7 SMART
EGF_CA 257 293 6.8e-8 SMART
EGF_CA 295 333 1.16e-10 SMART
EGF_CA 335 371 3.17e-8 SMART
EGF 375 410 5.32e-1 SMART
EGF_CA 412 450 4.59e-14 SMART
EGF_CA 452 488 1.02e-11 SMART
EGF_CA 490 526 4.81e-8 SMART
EGF_CA 528 564 3.19e-13 SMART
EGF_CA 566 601 1.91e-11 SMART
EGF_CA 603 639 1.78e-11 SMART
EGF_CA 641 676 9.62e-8 SMART
EGF_CA 678 714 2.38e-12 SMART
EGF_CA 716 751 5.23e-9 SMART
EGF_CA 753 789 6.25e-7 SMART
EGF_CA 791 827 1.1e-11 SMART
EGF 832 867 2.03e-6 SMART
EGF_CA 869 905 5.73e-15 SMART
EGF_CA 907 943 4.56e-9 SMART
EGF_CA 945 981 1.64e-10 SMART
EGF_CA 983 1019 5.83e-7 SMART
EGF_CA 1021 1057 1.05e-13 SMART
EGF 1062 1095 8.12e-6 SMART
EGF 1100 1143 5.66e-5 SMART
EGF_CA 1145 1181 1.1e-11 SMART
EGF_CA 1183 1219 3.87e-12 SMART
EGF_CA 1221 1265 2.89e-11 SMART
EGF_CA 1267 1305 1.2e-8 SMART
EGF 1310 1346 5.74e-6 SMART
EGF 1351 1384 4.1e-2 SMART
EGF 1390 1426 2.66e-1 SMART
NL 1442 1480 4.08e-16 SMART
NL 1483 1522 1.08e-15 SMART
NL 1523 1562 7.39e-14 SMART
NOD 1566 1622 1.81e-32 SMART
NODP 1660 1722 3.27e-30 SMART
low complexity region 1729 1746 N/A INTRINSIC
ANK 1870 1912 1.07e2 SMART
ANK 1917 1946 4.82e-3 SMART
ANK 1950 1980 6.71e-2 SMART
ANK 1984 2013 1.23e0 SMART
ANK 2017 2046 9.13e-4 SMART
ANK 2050 2079 2.97e-3 SMART
low complexity region 2205 2222 N/A INTRINSIC
low complexity region 2364 2395 N/A INTRINSIC
DUF3454 2453 2517 2.01e-30 SMART
Predicted Effect noncoding transcript
Transcript: ENSMUST00000126872
Predicted Effect noncoding transcript
Transcript: ENSMUST00000132941
Predicted Effect noncoding transcript
Transcript: ENSMUST00000133463
Predicted Effect noncoding transcript
Transcript: ENSMUST00000138034
Predicted Effect noncoding transcript
Transcript: ENSMUST00000139144
Predicted Effect noncoding transcript
Transcript: ENSMUST00000151521
Predicted Effect noncoding transcript
Transcript: ENSMUST00000147481
Predicted Effect noncoding transcript
Transcript: ENSMUST00000140082
Predicted Effect noncoding transcript
Transcript: ENSMUST00000148948
Predicted Effect noncoding transcript
Transcript: ENSMUST00000156099
Coding Region Coverage
  • 1x: 99.2%
  • 3x: 98.7%
  • 10x: 97.5%
  • 20x: 95.6%
Validation Efficiency
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 plays a role in the development of numerous cell and tissue types. Mutations in this gene are associated with aortic valve disease, Adams-Oliver syndrome, T-cell acute lymphoblastic leukemia, chronic lymphocytic leukemia, and head and neck squamous cell carcinoma. [provided by RefSeq, Jan 2016]
PHENOTYPE: Homozygotes for null alleles exhibit defects in embryonic development resulting in lethality at some point in organogenesis. Lethal phenotype may be affected by genetic background. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 85 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
1810065E05Rik T A 11: 58,313,134 (GRCm39) probably null Het
Acaa2 T C 18: 74,926,476 (GRCm39) probably null Het
Adam7 T C 14: 68,748,792 (GRCm39) Q485R probably benign Het
Adcy4 T G 14: 56,006,627 (GRCm39) T1069P probably benign Het
Arsj T C 3: 126,232,337 (GRCm39) L361P probably damaging Het
Birc2 A C 9: 7,826,939 (GRCm39) L349R probably damaging Het
C1qa T C 4: 136,623,727 (GRCm39) Y159C probably damaging Het
Cdh13 A G 8: 119,963,703 (GRCm39) K428E probably damaging Het
Cenpe T C 3: 134,953,235 (GRCm39) M1563T probably benign Het
Col10a1 T C 10: 34,271,696 (GRCm39) V556A probably benign Het
Creg2 G A 1: 39,662,338 (GRCm39) L265F probably damaging Het
Cyp1a2 T A 9: 57,589,433 (GRCm39) D127V probably damaging Het
Cyp3a44 A T 5: 145,740,480 (GRCm39) Y53* probably null Het
Cyth1 C T 11: 118,073,634 (GRCm39) R233Q probably damaging Het
Dnmbp G A 19: 43,890,346 (GRCm39) H474Y possibly damaging Het
Dvl1 G A 4: 155,932,273 (GRCm39) V28I possibly damaging Het
Ercc2 G A 7: 19,120,717 (GRCm39) R206H possibly damaging Het
Evx2 T A 2: 74,486,360 (GRCm39) H343L probably damaging Het
Fcrl2 T A 3: 87,164,648 (GRCm39) I293F probably benign Het
Gcnt4 A G 13: 97,082,974 (GRCm39) E90G probably damaging Het
Gid8 T G 2: 180,358,751 (GRCm39) C139G probably benign Het
Gm11938 C A 11: 99,493,933 (GRCm39) C54F probably damaging Het
Gm3336 G A 8: 71,174,509 (GRCm39) V158I probably benign Het
Gucy1b1 T C 3: 81,968,327 (GRCm39) N60D probably benign Het
Hdac7 T C 15: 97,691,944 (GRCm39) K810E probably benign Het
Hsp90ab1 A G 17: 45,880,629 (GRCm39) F361L possibly damaging Het
Igf2bp3 A T 6: 49,085,858 (GRCm39) probably null Het
Inpp4b T A 8: 82,775,118 (GRCm39) I772N probably damaging Het
Iqca1 A G 1: 90,017,238 (GRCm39) L390P possibly damaging Het
Itgb2 C T 10: 77,396,082 (GRCm39) R586W probably benign Het
Itih1 A G 14: 30,655,432 (GRCm39) S588P possibly damaging Het
Iyd T A 10: 3,497,166 (GRCm39) probably null Het
Kl A G 5: 150,912,425 (GRCm39) K725E probably benign Het
Layn T A 9: 50,968,697 (GRCm39) M349L probably benign Het
Map3k5 T C 10: 19,900,683 (GRCm39) Y286H probably damaging Het
Med4 C T 14: 73,755,472 (GRCm39) probably benign Het
Mfn1 T A 3: 32,588,400 (GRCm39) N42K possibly damaging Het
Mindy2 T C 9: 70,563,874 (GRCm39) D152G probably benign Het
Mrc2 A G 11: 105,238,682 (GRCm39) probably null Het
Mrpl11 C A 19: 5,012,497 (GRCm39) A26E probably damaging Het
Msh6 G A 17: 88,293,568 (GRCm39) W774* probably null Het
Mtch1 A T 17: 29,561,841 (GRCm39) V121E probably damaging Het
Mtg2 G T 2: 179,725,923 (GRCm39) E178* probably null Het
Nbas A T 12: 13,491,510 (GRCm39) N1461Y probably damaging Het
Ndfip2 A G 14: 105,525,204 (GRCm39) T65A probably benign Het
Ninl G T 2: 150,786,503 (GRCm39) Q1146K probably damaging Het
Notch3 C T 17: 32,366,818 (GRCm39) V906M probably damaging Het
Or51l14 A G 7: 103,101,371 (GRCm39) I276V probably benign Het
Or6b6 A G 7: 106,570,775 (GRCm39) Y259H probably damaging Het
Osmr A T 15: 6,873,891 (GRCm39) Y169N probably benign Het
Ovgp1 T C 3: 105,885,033 (GRCm39) V124A possibly damaging Het
P2rx1 T C 11: 72,904,939 (GRCm39) M369T probably benign Het
Pde4dip T C 3: 97,631,534 (GRCm39) Q1125R probably damaging Het
Podn A T 4: 107,878,892 (GRCm39) V180E probably damaging Het
Pold1 A T 7: 44,188,542 (GRCm39) V475E probably damaging Het
Polg A G 7: 79,111,468 (GRCm39) I261T possibly damaging Het
Satb1 G T 17: 52,047,438 (GRCm39) Q595K probably benign Het
Scaf8 T A 17: 3,214,407 (GRCm39) probably null Het
Semp2l1 T A 1: 32,585,128 (GRCm39) M261L probably benign Het
Serpinb3a C T 1: 106,975,202 (GRCm39) probably null Het
Slc22a26 T C 19: 7,779,480 (GRCm39) D112G probably damaging Het
Slc25a23 A G 17: 57,352,562 (GRCm39) F441L probably benign Het
Slc25a53 T C X: 135,884,216 (GRCm39) T42A probably damaging Het
Slc6a15 T C 10: 103,229,269 (GRCm39) Y103H probably damaging Het
Slx4 A G 16: 3,804,223 (GRCm39) S864P probably benign Het
Snap91 T C 9: 86,707,130 (GRCm39) E220G probably damaging Het
Spam1 T C 6: 24,796,267 (GRCm39) F73L probably damaging Het
Sphkap C T 1: 83,255,710 (GRCm39) V393M probably benign Het
Spred2 T C 11: 19,971,241 (GRCm39) Y370H probably damaging Het
Sqle T C 15: 59,195,578 (GRCm39) probably null Het
Srrm2 A G 17: 24,037,237 (GRCm39) T1390A probably benign Het
Tas1r2 A G 4: 139,396,352 (GRCm39) R564G possibly damaging Het
Tbl2 G T 5: 135,185,374 (GRCm39) probably null Het
Tcof1 T C 18: 60,964,901 (GRCm39) D606G possibly damaging Het
Tdpoz3 T A 3: 93,734,087 (GRCm39) L254H probably damaging Het
Trpm1 A T 7: 63,884,736 (GRCm39) I806F probably damaging Het
Ttc22 A G 4: 106,496,237 (GRCm39) D429G probably benign Het
Ube2o C A 11: 116,471,972 (GRCm39) G90C probably damaging Het
Usp34 T A 11: 23,332,602 (GRCm39) F1110I probably damaging Het
Vmn2r82 T C 10: 79,214,722 (GRCm39) L235P probably damaging Het
Vps35 A G 8: 86,013,129 (GRCm39) V116A probably benign Het
Wdfy3 A G 5: 102,046,291 (GRCm39) probably null Het
Zeb2 T C 2: 44,878,821 (GRCm39) K1138E probably benign Het
Zfp513 G A 5: 31,357,866 (GRCm39) T169I probably benign Het
Zfp629 T C 7: 127,211,551 (GRCm39) D86G probably benign Het
Other mutations in Notch1
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00164:Notch1 APN 2 26,350,058 (GRCm39) missense probably damaging 0.98
IGL01343:Notch1 APN 2 26,362,917 (GRCm39) missense probably benign 0.25
IGL02066:Notch1 APN 2 26,350,408 (GRCm39) missense possibly damaging 0.71
IGL02158:Notch1 APN 2 26,350,351 (GRCm39) missense probably damaging 1.00
IGL02541:Notch1 APN 2 26,358,515 (GRCm39) missense probably benign 0.12
IGL03280:Notch1 APN 2 26,367,886 (GRCm39) intron probably benign
IGL03338:Notch1 APN 2 26,349,971 (GRCm39) missense probably benign
Antero UTSW 2 26,366,126 (GRCm39) missense possibly damaging 0.96
march UTSW 2 26,359,911 (GRCm39) missense probably damaging 0.98
PIT4494001:Notch1 UTSW 2 26,356,485 (GRCm39) missense probably damaging 1.00
R0013:Notch1 UTSW 2 26,363,830 (GRCm39) missense possibly damaging 0.64
R0025:Notch1 UTSW 2 26,360,943 (GRCm39) missense probably damaging 1.00
R0129:Notch1 UTSW 2 26,350,470 (GRCm39) missense probably benign 0.06
R0285:Notch1 UTSW 2 26,350,873 (GRCm39) missense possibly damaging 0.88
R0531:Notch1 UTSW 2 26,356,584 (GRCm39) missense probably benign 0.00
R0747:Notch1 UTSW 2 26,362,152 (GRCm39) missense unknown
R1440:Notch1 UTSW 2 26,370,976 (GRCm39) intron probably benign
R1502:Notch1 UTSW 2 26,374,335 (GRCm39) missense possibly damaging 0.95
R1539:Notch1 UTSW 2 26,362,125 (GRCm39) nonsense probably null
R1623:Notch1 UTSW 2 26,368,624 (GRCm39) missense possibly damaging 0.88
R1844:Notch1 UTSW 2 26,350,446 (GRCm39) missense probably benign 0.12
R1863:Notch1 UTSW 2 26,359,962 (GRCm39) missense probably damaging 1.00
R1874:Notch1 UTSW 2 26,371,591 (GRCm39) missense possibly damaging 0.89
R1926:Notch1 UTSW 2 26,371,669 (GRCm39) missense probably damaging 1.00
R2196:Notch1 UTSW 2 26,353,816 (GRCm39) nonsense probably null
R2209:Notch1 UTSW 2 26,350,019 (GRCm39) missense probably benign
R2382:Notch1 UTSW 2 26,363,793 (GRCm39) missense probably benign 0.40
R2508:Notch1 UTSW 2 26,355,485 (GRCm39) missense possibly damaging 0.80
R2873:Notch1 UTSW 2 26,350,247 (GRCm39) missense possibly damaging 0.89
R2874:Notch1 UTSW 2 26,350,247 (GRCm39) missense possibly damaging 0.89
R3798:Notch1 UTSW 2 26,368,630 (GRCm39) missense probably benign 0.00
R4019:Notch1 UTSW 2 26,371,154 (GRCm39) missense probably benign 0.03
R4305:Notch1 UTSW 2 26,367,936 (GRCm39) missense probably damaging 1.00
R4334:Notch1 UTSW 2 26,350,048 (GRCm39) missense probably benign 0.22
R4504:Notch1 UTSW 2 26,362,189 (GRCm39) missense probably benign 0.16
R4624:Notch1 UTSW 2 26,368,093 (GRCm39) missense possibly damaging 0.94
R4659:Notch1 UTSW 2 26,360,901 (GRCm39) missense probably damaging 0.99
R4703:Notch1 UTSW 2 26,361,170 (GRCm39) missense probably benign
R4869:Notch1 UTSW 2 26,361,191 (GRCm39) missense probably benign 0.21
R4938:Notch1 UTSW 2 26,364,136 (GRCm39) nonsense probably null
R4989:Notch1 UTSW 2 26,371,193 (GRCm39) missense probably damaging 1.00
R5010:Notch1 UTSW 2 26,366,126 (GRCm39) missense possibly damaging 0.96
R5283:Notch1 UTSW 2 26,358,638 (GRCm39) missense probably damaging 1.00
R5303:Notch1 UTSW 2 26,368,631 (GRCm39) missense probably benign 0.01
R5635:Notch1 UTSW 2 26,366,173 (GRCm39) missense probably damaging 1.00
R5755:Notch1 UTSW 2 26,363,704 (GRCm39) missense probably benign 0.12
R5926:Notch1 UTSW 2 26,366,116 (GRCm39) missense probably benign 0.35
R5947:Notch1 UTSW 2 26,352,540 (GRCm39) intron probably benign
R6053:Notch1 UTSW 2 26,362,924 (GRCm39) missense probably benign 0.06
R6161:Notch1 UTSW 2 26,358,743 (GRCm39) missense probably damaging 1.00
R6162:Notch1 UTSW 2 26,352,207 (GRCm39) missense probably benign
R6174:Notch1 UTSW 2 26,375,454 (GRCm39) missense possibly damaging 0.50
R6199:Notch1 UTSW 2 26,359,911 (GRCm39) missense probably damaging 0.98
R6209:Notch1 UTSW 2 26,362,817 (GRCm39) missense probably damaging 1.00
R6251:Notch1 UTSW 2 26,364,182 (GRCm39) missense possibly damaging 0.64
R6493:Notch1 UTSW 2 26,362,110 (GRCm39) missense unknown
R6723:Notch1 UTSW 2 26,368,118 (GRCm39) missense probably damaging 1.00
R6736:Notch1 UTSW 2 26,350,298 (GRCm39) missense probably benign 0.01
R7020:Notch1 UTSW 2 26,371,586 (GRCm39) missense possibly damaging 0.95
R7058:Notch1 UTSW 2 26,353,830 (GRCm39) missense probably benign 0.05
R7154:Notch1 UTSW 2 26,349,950 (GRCm39) missense probably benign
R7291:Notch1 UTSW 2 26,366,387 (GRCm39) missense probably benign 0.01
R7379:Notch1 UTSW 2 26,369,479 (GRCm39) missense probably damaging 1.00
R7560:Notch1 UTSW 2 26,350,177 (GRCm39) missense probably benign 0.43
R7610:Notch1 UTSW 2 26,368,191 (GRCm39) missense probably benign 0.13
R7833:Notch1 UTSW 2 26,349,545 (GRCm39) makesense probably null
R7988:Notch1 UTSW 2 26,361,013 (GRCm39) missense probably benign 0.00
R8493:Notch1 UTSW 2 26,362,251 (GRCm39) missense unknown
R8514:Notch1 UTSW 2 26,362,181 (GRCm39) missense probably damaging 1.00
R8523:Notch1 UTSW 2 26,354,917 (GRCm39) missense possibly damaging 0.82
R8677:Notch1 UTSW 2 26,359,936 (GRCm39) missense probably damaging 1.00
R8696:Notch1 UTSW 2 26,368,004 (GRCm39) critical splice acceptor site probably benign
R8833:Notch1 UTSW 2 26,371,615 (GRCm39) missense probably damaging 1.00
R8964:Notch1 UTSW 2 26,371,062 (GRCm39) missense possibly damaging 0.65
R9091:Notch1 UTSW 2 26,369,895 (GRCm39) missense probably damaging 0.99
R9144:Notch1 UTSW 2 26,349,587 (GRCm39) missense probably benign 0.00
R9145:Notch1 UTSW 2 26,349,587 (GRCm39) missense probably benign 0.00
R9151:Notch1 UTSW 2 26,367,939 (GRCm39) missense probably benign 0.01
R9270:Notch1 UTSW 2 26,369,895 (GRCm39) missense probably damaging 0.99
R9463:Notch1 UTSW 2 26,359,845 (GRCm39) missense probably benign 0.20
R9546:Notch1 UTSW 2 26,371,127 (GRCm39) missense probably damaging 0.97
R9674:Notch1 UTSW 2 26,361,308 (GRCm39) missense probably damaging 0.98
X0018:Notch1 UTSW 2 26,352,239 (GRCm39) nonsense probably null
X0066:Notch1 UTSW 2 26,360,347 (GRCm39) missense possibly damaging 0.90
Z1088:Notch1 UTSW 2 26,367,127 (GRCm39) missense probably damaging 0.99
Z1177:Notch1 UTSW 2 26,350,321 (GRCm39) missense possibly damaging 0.74
Predicted Primers PCR Primer
(F):5'- GCTTCCTTGCTACCACAAGC -3'
(R):5'- AATGACTCAGCAAATTCTACACCTG -3'

Sequencing Primer
(F):5'- ACAAGCCAGCCCTTTGGTG -3'
(R):5'- AAATTCTACACCTGCCCGCTC -3'
Posted On 2014-10-01