Incidental Mutation 'R2874:Notch1'
ID 260445
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 040462-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R2874 (G1)
Quality Score 225
Status Validated
Chromosome 2
Chromosomal Location 26347914-26393834 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 26350247 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Cysteine to Arginine at position 2298 (C2298R)
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: C2298R

PolyPhen 2 Score 0.895 (Sensitivity: 0.82; Specificity: 0.94)
SMART Domains Protein: ENSMUSP00000028288
Gene: ENSMUSG00000026923
AA Change: C2298R

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: ENSMUST00000132941
Predicted Effect noncoding transcript
Transcript: ENSMUST00000133463
Predicted Effect noncoding transcript
Transcript: ENSMUST00000139144
Predicted Effect noncoding transcript
Transcript: ENSMUST00000151521
Predicted Effect noncoding transcript
Transcript: ENSMUST00000156099
Meta Mutation Damage Score 0.1305 question?
Coding Region Coverage
  • 1x: 99.2%
  • 3x: 98.6%
  • 10x: 97.4%
  • 20x: 95.3%
Validation Efficiency 100% (57/57)
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: 48 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
A930029G22Rik T A 17: 69,725,106 (GRCm39) noncoding transcript Het
Ankrd42 T C 7: 92,254,566 (GRCm39) K348E possibly damaging Het
Arhgef10 T C 8: 15,025,093 (GRCm39) probably null Het
Arhgef10 A G 8: 15,025,666 (GRCm39) I459V probably benign Het
Cd6 A G 19: 10,771,990 (GRCm39) I307T possibly damaging Het
Cebpz A T 17: 79,239,532 (GRCm39) probably benign Het
Clcn4 A G 7: 7,293,520 (GRCm39) I412T probably benign Het
Clstn3 T A 6: 124,415,294 (GRCm39) D690V probably damaging Het
Col12a1 A T 9: 79,606,831 (GRCm39) F531I probably damaging Het
Dennd2b A T 7: 109,156,637 (GRCm39) Y38N probably benign Het
Dhx57 A T 17: 80,558,805 (GRCm39) D1051E probably benign Het
Ext2 A G 2: 93,570,031 (GRCm39) V460A possibly damaging Het
Frmpd4 A T X: 166,260,243 (GRCm39) D1166E probably benign Het
Fscb T C 12: 64,520,210 (GRCm39) K419E probably benign Het
Ftdc1 A T 16: 58,434,342 (GRCm39) I125K probably benign Het
Ggct G T 6: 54,969,759 (GRCm39) A21D probably damaging Het
Gm10717 A G 9: 3,025,532 (GRCm39) Y39C probably benign Het
Grid2ip C A 5: 143,343,684 (GRCm39) Q127K probably benign Het
Ighv2-2 G A 12: 113,552,118 (GRCm39) T40I possibly damaging Het
Itpr2 T C 6: 146,327,996 (GRCm39) K79R possibly damaging Het
Klf8 A T X: 152,165,678 (GRCm39) E82D probably damaging Het
Kpna7 T C 5: 144,930,745 (GRCm39) T367A probably benign Het
Lactbl1 G A 4: 136,354,097 (GRCm39) C37Y probably damaging Het
Lrp1b A G 2: 40,741,705 (GRCm39) L3188P probably damaging Het
Matcap1 A G 8: 106,008,664 (GRCm39) M451T possibly damaging Het
Myo9b G A 8: 71,786,981 (GRCm39) R721Q probably benign Het
Noc4l A G 5: 110,796,969 (GRCm39) V465A probably benign Het
Or10z1 T C 1: 174,078,092 (GRCm39) S134G probably benign Het
Parp1 A G 1: 180,401,230 (GRCm39) D45G probably damaging Het
Plxna3 T A X: 73,383,002 (GRCm39) probably benign Het
Prdx4 A G X: 154,123,460 (GRCm39) V15A probably benign Het
Prps1 C T X: 139,372,743 (GRCm39) probably benign Het
Psmb8 T C 17: 34,419,144 (GRCm39) I146T probably damaging Het
Qng1 T A 13: 58,530,384 (GRCm39) I209F probably damaging Het
Ralgds A G 2: 28,438,781 (GRCm39) probably null Het
Rasl12 A G 9: 65,315,605 (GRCm39) N83S probably benign Het
Rnf6 T C 5: 146,147,215 (GRCm39) Y601C probably benign Het
Rreb1 T C 13: 38,100,484 (GRCm39) I205T probably benign Het
Sgk2 A G 2: 162,836,449 (GRCm39) probably benign Het
Spsb4 G T 9: 96,878,071 (GRCm39) T84K probably damaging Het
St7 C T 6: 17,819,276 (GRCm39) P60L probably damaging Het
Stx3 A T 19: 11,766,938 (GRCm39) V91D probably damaging Het
Tbc1d8 A G 1: 39,444,398 (GRCm39) F187S probably damaging Het
Tep1 A G 14: 51,088,107 (GRCm39) I85T possibly damaging Het
Trpa1 A G 1: 14,957,844 (GRCm39) C705R probably damaging Het
Vmn2r68 A C 7: 84,882,834 (GRCm39) M306R probably benign Het
Vwa7 G A 17: 35,240,218 (GRCm39) M395I probably damaging Het
Zfp53 A T 17: 21,728,340 (GRCm39) E124D 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
R2156:Notch1 UTSW 2 26,350,873 (GRCm39) missense possibly damaging 0.91
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
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'- AAGTTCTGTGGCTGCACCTG -3'
(R):5'- CTTGAATGTGGCAGCCAAG -3'

Sequencing Primer
(F):5'- GGCAGGCCCTGGTAAATAATC -3'
(R):5'- GCAGCCAAGCCTGAGATG -3'
Posted On 2015-01-23