Incidental Mutation 'R6162:Notch1'
ID 489905
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 044309-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R6162 (G1)
Quality Score 216.009
Status Validated
Chromosome 2
Chromosomal Location 26347914-26393834 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) C to T at 26352207 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Valine to Isoleucine at position 2035 (V2035I)
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 probably benign
Transcript: ENSMUST00000028288
AA Change: V2035I

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
SMART Domains Protein: ENSMUSP00000028288
Gene: ENSMUSG00000026923
AA Change: V2035I

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: ENSMUST00000140082
Predicted Effect noncoding transcript
Transcript: ENSMUST00000148948
Predicted Effect noncoding transcript
Transcript: ENSMUST00000151521
Predicted Effect noncoding transcript
Transcript: ENSMUST00000156099
Predicted Effect noncoding transcript
Transcript: ENSMUST00000147481
Meta Mutation Damage Score 0.1191 question?
Coding Region Coverage
  • 1x: 99.9%
  • 3x: 99.6%
  • 10x: 98.0%
  • 20x: 94.1%
Validation Efficiency 98% (40/41)
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: 42 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abca13 T G 11: 9,259,047 (GRCm39) C2924W probably damaging Het
Adh4 T A 3: 138,121,250 (GRCm39) probably null Het
Aox3 A T 1: 58,198,890 (GRCm39) D695V possibly damaging Het
Ccnj A G 19: 40,833,606 (GRCm39) Y221C probably damaging Het
Cct2 T A 10: 116,894,091 (GRCm39) D221V probably damaging Het
Cd5 G A 19: 10,703,244 (GRCm39) T138M probably damaging Het
Cep78 A T 19: 15,952,304 (GRCm39) M307K probably benign Het
Dclk1 C A 3: 55,163,575 (GRCm39) D222E probably benign Het
Dhrs11 C T 11: 84,719,605 (GRCm39) G40D probably damaging Het
Dnah10 A G 5: 124,900,382 (GRCm39) S3823G probably benign Het
Dnai3 T A 3: 145,750,617 (GRCm39) I821F probably damaging Het
Dock3 A T 9: 106,841,998 (GRCm39) Y944N possibly damaging Het
Dst A G 1: 34,045,318 (GRCm39) D17G probably damaging Het
Ehmt2 C T 17: 35,118,067 (GRCm39) R40* probably null Het
Fam20a G T 11: 109,573,696 (GRCm39) S229* probably null Het
Fbn1 T C 2: 125,202,147 (GRCm39) D1242G probably damaging Het
Ggt5 T A 10: 75,425,626 (GRCm39) V28D possibly damaging Het
Gimap4 A T 6: 48,667,655 (GRCm39) I137F probably damaging Het
Git2 T A 5: 114,899,717 (GRCm39) H212L probably damaging Het
Gprc6a T A 10: 51,491,008 (GRCm39) I739F probably benign Het
Il1rl2 A G 1: 40,391,038 (GRCm39) Y327C probably damaging Het
Lmf1 A G 17: 25,831,368 (GRCm39) I205V probably benign Het
Mipep C A 14: 61,024,853 (GRCm39) P98Q probably damaging Het
Mroh2b A G 15: 4,944,707 (GRCm39) D436G probably damaging Het
Mtcl2 T A 2: 156,881,784 (GRCm39) E756V possibly damaging Het
Myorg A G 4: 41,497,899 (GRCm39) V577A possibly damaging Het
Or1e28-ps1 T A 11: 73,615,713 (GRCm39) I46F probably damaging Het
Or2ag16 A T 7: 106,352,227 (GRCm39) Y123N probably damaging Het
Or4c118 G T 2: 88,975,114 (GRCm39) F84L probably benign Het
Oxa1l A G 14: 54,605,789 (GRCm39) T395A probably damaging Het
Phospho2 T A 2: 69,626,375 (GRCm39) I177K probably damaging Het
Prpf40a T C 2: 53,049,317 (GRCm39) T224A probably benign Het
Reln T A 5: 22,116,048 (GRCm39) T2987S probably damaging Het
Scn5a T A 9: 119,351,621 (GRCm39) I787F probably damaging Het
Sgsm2 A T 11: 74,782,847 (GRCm39) D36E probably damaging Het
Slc12a3 A G 8: 95,072,401 (GRCm39) probably null Het
Tas2r134 T C 2: 51,517,571 (GRCm39) S17P probably damaging Het
Top3a T C 11: 60,636,763 (GRCm39) Y609C probably damaging Het
Trem2 A G 17: 48,655,694 (GRCm39) I84V probably damaging Het
Vmn2r12 A G 5: 109,234,430 (GRCm39) L594P probably damaging Het
Zdbf2 A T 1: 63,319,977 (GRCm39) probably benign Het
Zfr C T 15: 12,146,331 (GRCm39) A294V unknown 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
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
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'- AGGCTCAAGTAACCGTGACATG -3'
(R):5'- ATGCTGACGTCAATGCCGTG -3'

Sequencing Primer
(F):5'- ACAGCTGCTTACGCCTCAG -3'
(R):5'- TCAATGCCGTGGATGACCTAG -3'
Posted On 2017-10-10