Mutagenetix > Incidental Mutation

Incidental Mutation 'R7020:Notch1'

545549

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

045121-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R7020 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

26347914-26393834 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 26371586 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Threonine to Alanine at position 288 (T288A)

Ref Sequence

ENSEMBL: ENSMUSP00000028288 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000028288] [ENSMUST00000132820]

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: T288A

PolyPhen 2 Score 0.953 (Sensitivity: 0.79; Specificity: 0.95)

SMART Domains

Protein: ENSMUSP00000028288
Gene: ENSMUSG00000026923
AA Change: T288A

Domain	Start	End	E-Value	Type
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

probably benign
Transcript: ENSMUST00000132820

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.6%
20x: 98.7%

Validation Efficiency

100% (52/52)

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: 49 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700001K19Rik	C	T	12: 110,634,975 (GRCm39)	G188R	probably damaging	Het
Abhd3	T	C	18: 10,645,127 (GRCm39)	Y384C	probably damaging	Het
Cd209b	T	A	8: 3,968,783 (GRCm39)	E282V	probably damaging	Het
Cep350	A	C	1: 155,804,077 (GRCm39)	L1002W	probably damaging	Het
Clcn1	T	C	6: 42,275,754 (GRCm39)	V292A	probably damaging	Het
Clcn7	T	C	17: 25,365,325 (GRCm39)	I107T	possibly damaging	Het
Cntrob	A	G	11: 69,193,918 (GRCm39)		probably null	Het
Crb1	A	T	1: 139,159,341 (GRCm39)	S1294T	possibly damaging	Het
Cst13	T	G	2: 148,665,129 (GRCm39)	Y41*	probably null	Het
Gp1ba	A	G	11: 70,531,139 (GRCm39)		probably benign	Het
Gucy2e	A	T	11: 69,123,619 (GRCm39)	L427I	probably benign	Het
Gucy2g	A	G	19: 55,221,482 (GRCm39)	S340P	probably damaging	Het
Herc1	A	G	9: 66,393,360 (GRCm39)	T4080A	probably benign	Het
Iglon5	A	T	7: 43,126,319 (GRCm39)	C195S	probably damaging	Het
Itgae	A	G	11: 73,002,195 (GRCm39)	T100A	probably damaging	Het
Jarid2	C	T	13: 45,038,300 (GRCm39)	S205L	probably damaging	Het
Macrod2	A	T	2: 142,231,795 (GRCm39)	*424C	probably null	Het
Map2k6	A	T	11: 110,397,540 (GRCm39)		probably benign	Het
Muc4	A	T	16: 32,570,628 (GRCm39)	K563*	probably null	Het
Myh7b	T	C	2: 155,473,671 (GRCm39)	I1568T	possibly damaging	Het
Myo15b	G	A	11: 115,757,493 (GRCm39)	W1114*	probably null	Het
Mypn	T	C	10: 63,028,289 (GRCm39)	Y258C	probably damaging	Het
Npc1	C	T	18: 12,331,594 (GRCm39)	G859R	probably damaging	Het
Olfm2	T	A	9: 20,579,864 (GRCm39)	R326W	probably damaging	Het
Or2a7	T	C	6: 43,151,096 (GRCm39)	Y59H	possibly damaging	Het
Or5al7	A	G	2: 85,992,363 (GRCm39)	I310T	probably benign	Het
Or5g23	A	G	2: 85,438,976 (GRCm39)	S93P	probably benign	Het
Ovol1	G	A	19: 5,610,261 (GRCm39)	P23L	probably damaging	Het
Pappa2	C	A	1: 158,675,579 (GRCm39)	V1056F	probably damaging	Het
Pik3ca	T	C	3: 32,490,428 (GRCm39)	L25S	probably damaging	Het
Pla2r1	T	C	2: 60,277,743 (GRCm39)	H860R	possibly damaging	Het
Pms1	A	T	1: 53,228,541 (GRCm39)	H902Q	probably damaging	Het
Ptgs1	T	G	2: 36,141,041 (GRCm39)	L496R	probably damaging	Het
Ralgapa2	A	T	2: 146,188,638 (GRCm39)	Y1381*	probably null	Het
Rtl1	T	C	12: 109,558,749 (GRCm39)	Q1030R	possibly damaging	Het
Ryr3	T	A	2: 112,583,423 (GRCm39)	Y2816F	probably benign	Het
Sh2b2	T	C	5: 136,253,153 (GRCm39)	T340A	possibly damaging	Het
Slc30a5	T	A	13: 100,961,421 (GRCm39)		probably null	Het
Spta1	T	C	1: 174,036,918 (GRCm39)	L1143P	probably damaging	Het
St8sia5	T	C	18: 77,333,876 (GRCm39)	I178T	probably damaging	Het
Tap2	A	G	17: 34,433,388 (GRCm39)	N517S	possibly damaging	Het
Tcp11	A	G	17: 28,290,679 (GRCm39)	Y227H	possibly damaging	Het
Usp34	A	G	11: 23,343,954 (GRCm39)	D1411G	probably benign	Het
Vmn2r105	A	G	17: 20,429,336 (GRCm39)	L580P	probably damaging	Het
Wdr19	A	G	5: 65,413,657 (GRCm39)	E1200G	probably damaging	Het
Xirp2	T	C	2: 67,355,913 (GRCm39)	V3558A	probably benign	Het
Xpo7	T	C	14: 70,903,463 (GRCm39)	N1082S	probably benign	Het
Zbtb49	A	T	5: 38,370,711 (GRCm39)	L390*	probably null	Het
Zfp639	C	A	3: 32,574,261 (GRCm39)	D295E	probably damaging	Het

Other mutations in Notch1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH 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
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
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'- ATGCTGAGCTGTGCTGACTC -3'
(R):5'- CAGGTCCACCCAGAATCTGAAG -3'

Sequencing Primer
(F):5'- TGTGCTGACTCCAACTGGAAG -3'
(R):5'- TCTGAAGATACCGGAGCCC -3'

Posted On

2019-05-13