Mutagenetix > Incidental Mutation

Incidental Mutation 'PIT4494001:Notch1'

556138

Institutional Source

Beutler Lab

Gene Symbol

Notch1

Ensembl Gene

ENSMUSG00000026923

Gene Name

notch 1

Synonyms

9930111A19Rik, Motch A, Tan1, Mis6, lin-12, N1

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

PIT4494001 (G1)

Quality Score

132.008

Status

Not validated

Chromosome

Chromosomal Location

26347914-26393834 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

C to T at 26356485 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Valine to Methionine at position 1711 (V1711M)

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

probably damaging
Transcript: ENSMUST00000028288
AA Change: V1711M

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000028288
Gene: ENSMUSG00000026923
AA Change: V1711M

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: 93.8%
3x: 91.1%
10x: 85.6%
20x: 73.9%

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: 38 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4933427I04Rik	T	C	4: 123,754,698 (GRCm39)	I204T	probably benign	Het
Acnat2	T	C	4: 49,383,133 (GRCm39)	E140G	probably benign	Het
Arhgef10l	T	C	4: 140,292,522 (GRCm39)	E413G	probably damaging	Het
Atg9a	A	T	1: 75,164,597 (GRCm39)	C122*	probably null	Het
Birc6	T	C	17: 74,933,975 (GRCm39)	Y2544H	probably damaging	Het
C3	G	A	17: 57,516,263 (GRCm39)	T1383I	probably benign	Het
Cd2ap	C	T	17: 43,163,258 (GRCm39)		probably null	Het
Cdhr1	T	C	14: 36,804,813 (GRCm39)	T466A	probably benign	Het
Cdhr2	G	T	13: 54,866,255 (GRCm39)		probably null	Het
Eppk1	T	A	15: 75,990,272 (GRCm39)	Q2203L	probably benign	Het
F10	T	C	8: 13,103,423 (GRCm39)	L281P	probably damaging	Het
Farp2	A	G	1: 93,545,316 (GRCm39)	T825A	probably damaging	Het
Fbxw27	T	C	9: 109,601,178 (GRCm39)	E314G	probably benign	Het
Foxred1	T	C	9: 35,120,355 (GRCm39)	E173G	possibly damaging	Het
Gm4847	T	C	1: 166,467,587 (GRCm39)	E203G	probably damaging	Het
Gpat2	G	A	2: 127,275,800 (GRCm39)	R526H	probably benign	Het
Grin2a	T	C	16: 9,402,960 (GRCm39)	Y842C	probably damaging	Het
Hyal4	T	C	6: 24,755,833 (GRCm39)	V17A	probably benign	Het
Igkv4-68	T	C	6: 69,282,091 (GRCm39)	T27A	probably damaging	Het
Loxhd1	A	T	18: 77,529,464 (GRCm39)	N2036Y	probably damaging	Het
Lrp5	T	C	19: 3,660,091 (GRCm39)	Y991C	probably damaging	Het
Lrp6	T	C	6: 134,456,741 (GRCm39)	Y841C	probably damaging	Het
Medag	A	G	5: 149,350,765 (GRCm39)	Y194C	probably damaging	Het
Mynn	C	T	3: 30,661,871 (GRCm39)	R318*	probably null	Het
Nsun2	T	C	13: 69,766,311 (GRCm39)		probably null	Het
Pex7	A	G	10: 19,770,469 (GRCm39)		probably null	Het
Pkd1	A	G	17: 24,796,775 (GRCm39)	T2417A	probably damaging	Het
Pknox2	A	G	9: 36,865,987 (GRCm39)		probably null	Het
Plekha4	T	C	7: 45,197,503 (GRCm39)	S522P	probably damaging	Het
Ptcd1	A	T	5: 145,092,168 (GRCm39)	S310R	probably benign	Het
Rap2a	A	G	14: 120,716,319 (GRCm39)	T61A	possibly damaging	Het
Ryr3	G	T	2: 112,672,221 (GRCm39)	L1437M	probably damaging	Het
Slc25a40	T	G	5: 8,490,737 (GRCm39)	I95S	probably damaging	Het
Srbd1	C	T	17: 86,449,787 (GRCm39)		probably null	Het
Tox4	C	T	14: 52,529,260 (GRCm39)	T407I	possibly damaging	Het
Vmn1r8	A	G	6: 57,013,712 (GRCm39)	I254M	probably benign	Het
Wiz	G	A	17: 32,580,905 (GRCm39)	A182V	probably damaging	Het
Zfp60	T	C	7: 27,448,126 (GRCm39)	S265P	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
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
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'- TGAACCCATCCCTGAAGAGG -3'
(R):5'- TAATCTCACTGTGCCATGTGTG -3'

Sequencing Primer
(F):5'- ATGTACGTCAGGACCCTGTG -3'
(R):5'- CACTGTGCCATGTGTGTTCTCAG -3'

Posted On

2019-06-07