Incidental Mutation 'R2873:Notch1'
ID 260377
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 040461-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R2873 (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: 97.3%
  • 20x: 95.2%
Validation Efficiency 100% (81/81)
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: 73 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abca8b A G 11: 109,846,002 (GRCm39) C811R possibly damaging Het
Acvr1 G A 2: 58,367,808 (GRCm39) Q118* probably null Het
Als2 A G 1: 59,250,296 (GRCm39) S483P probably damaging Het
Ankrd40 T C 11: 94,224,771 (GRCm39) V60A possibly damaging Het
Armc2 C T 10: 41,842,696 (GRCm39) probably null Het
Atp12a A G 14: 56,624,407 (GRCm39) R952G possibly damaging Het
Atp13a2 T C 4: 140,730,294 (GRCm39) I773T probably benign Het
Atp6v1g1 A G 4: 63,468,258 (GRCm39) Y87C probably benign Het
Ccdc162 G T 10: 41,531,095 (GRCm39) T537N possibly damaging Het
Ccdc59 A T 10: 105,677,388 (GRCm39) K9M possibly damaging Het
Cd101 A T 3: 100,911,164 (GRCm39) D831E probably benign Het
Ch25h T A 19: 34,452,210 (GRCm39) H106L probably benign Het
Chek2 C A 5: 111,011,202 (GRCm39) Y333* probably null Het
Cimap1d G A 10: 79,481,487 (GRCm39) T14I probably benign Het
Csmd2 T C 4: 128,451,511 (GRCm39) F113S unknown Het
Cyp4a14 C A 4: 115,344,498 (GRCm39) G456W probably damaging Het
Cyp4a30b A G 4: 115,315,559 (GRCm39) H260R possibly damaging Het
Dennd2b A T 7: 109,156,637 (GRCm39) Y38N probably benign Het
Eif4enif1 C T 11: 3,192,586 (GRCm39) P805S probably damaging Het
Fan1 A G 7: 64,012,938 (GRCm39) I668T probably benign Het
Flnc A G 6: 29,447,542 (GRCm39) D1115G probably damaging Het
Ftdc1 A T 16: 58,434,342 (GRCm39) I125K probably benign Het
Gbp11 C T 5: 105,478,866 (GRCm39) D191N probably benign Het
Gm5519 A C 19: 33,802,410 (GRCm39) D151A possibly damaging Het
Grid2ip C A 5: 143,343,684 (GRCm39) Q127K probably benign Het
Hdhd2 T C 18: 77,042,702 (GRCm39) F44L probably damaging Het
Hmcn1 A T 1: 150,614,467 (GRCm39) V1313D possibly damaging Het
Kpna7 T C 5: 144,930,745 (GRCm39) T367A probably benign Het
Matr3 T A 18: 35,705,349 (GRCm39) S91R probably benign Het
Mdm1 A G 10: 117,986,847 (GRCm39) T267A probably benign Het
Mlxip A G 5: 123,590,730 (GRCm39) M878V probably benign Het
Mtor T A 4: 148,624,487 (GRCm39) M2089K probably benign Het
Myo9b G A 8: 71,786,981 (GRCm39) R721Q probably benign Het
Ndufs1 A G 1: 63,203,882 (GRCm39) probably benign Het
Nlrp4b C T 7: 10,444,170 (GRCm39) Q40* probably null Het
Nomo1 C A 7: 45,696,361 (GRCm39) T293N probably damaging Het
Notum A G 11: 120,551,022 (GRCm39) V48A probably benign Het
Or10g1 T G 14: 52,648,318 (GRCm39) T4P probably benign Het
Or10z1 T C 1: 174,078,092 (GRCm39) S134G probably benign Het
Or6c211 A T 10: 129,505,628 (GRCm39) C253* probably null Het
Ostc T C 3: 130,497,157 (GRCm39) N80S probably damaging Het
Palmd T C 3: 116,717,400 (GRCm39) R366G possibly damaging Het
Parp1 A G 1: 180,401,230 (GRCm39) D45G probably damaging Het
Pcdhga9 T A 18: 37,870,524 (GRCm39) Y118N possibly damaging Het
Pes1 C A 11: 3,926,834 (GRCm39) T372K probably benign Het
Plcl1 A T 1: 55,736,309 (GRCm39) D550V probably benign Het
Plekhg5 T A 4: 152,191,960 (GRCm39) C433S probably benign Het
Plin2 A G 4: 86,586,915 (GRCm39) M1T probably null Het
Pms2 G A 5: 143,848,732 (GRCm39) probably benign Het
Ppp1r7 T A 1: 93,285,585 (GRCm39) probably null Het
Psmb8 T C 17: 34,419,144 (GRCm39) I146T probably damaging Het
Ptger4 T C 15: 5,264,286 (GRCm39) R457G probably benign Het
Pzp A T 6: 128,462,519 (GRCm39) probably null Het
Ralgds A G 2: 28,438,781 (GRCm39) probably null Het
Rnf6 T C 5: 146,147,215 (GRCm39) Y601C probably benign Het
Sgk2 A G 2: 162,836,449 (GRCm39) probably benign Het
Shoc1 A C 4: 59,093,850 (GRCm39) L226R probably damaging Het
Slc39a8 T A 3: 135,592,554 (GRCm39) probably null Het
Slc4a4 G T 5: 89,283,623 (GRCm39) V481L probably damaging Het
Slc5a8 A G 10: 88,740,825 (GRCm39) I247V probably benign Het
Slit3 G T 11: 35,435,620 (GRCm39) E184* probably null Het
Sppl2c C T 11: 104,078,141 (GRCm39) P314S probably benign Het
St7 C T 6: 17,819,276 (GRCm39) P60L probably damaging Het
Tafa2 A T 10: 123,540,270 (GRCm39) H42L possibly damaging Het
Tbc1d8 A G 1: 39,444,398 (GRCm39) F187S probably damaging Het
Tet2 C T 3: 133,192,715 (GRCm39) G573E probably damaging Het
Tnni3k C T 3: 154,644,387 (GRCm39) probably null Het
Trpa1 A G 1: 14,957,844 (GRCm39) C705R probably damaging Het
Usp9y T A Y: 1,310,502 (GRCm39) probably benign 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
Ybx3 G A 6: 131,347,376 (GRCm39) A253V 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
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'- GTAAGTTCTGTGGCTGCACCTG -3'
(R):5'- CTTGAATGTGGCAGCCAAGC -3'

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