Mutagenetix > Incidental Mutation

Incidental Mutation 'R4504:Notch1'

331914

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

041755-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R4504 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

26347914-26393834 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 26362189 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Valine to Alanine at position 1022 (V1022A)

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 benign
Transcript: ENSMUST00000028288
AA Change: V1022A

PolyPhen 2 Score 0.162 (Sensitivity: 0.92; Specificity: 0.87)

SMART Domains

Protein: ENSMUSP00000028288
Gene: ENSMUSG00000026923
AA Change: V1022A

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

noncoding transcript
Transcript: ENSMUST00000123873

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000129506

Predicted Effect

unknown
Transcript: ENSMUST00000132820
AA Change: S48P

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000147481

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000183922

Meta Mutation Damage Score

0.1376

Coding Region Coverage

1x: 99.2%
3x: 98.6%
10x: 97.3%
20x: 95.4%

Validation Efficiency

100% (45/45)

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: 41 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4930503E14Rik	A	G	14: 44,407,899 (GRCm39)	S45P	probably damaging	Het
Adgrg4	C	T	X: 55,961,802 (GRCm39)	R1124C	possibly damaging	Het
Anxa13	T	C	15: 58,228,052 (GRCm39)		noncoding transcript	Het
Arhgap32	C	A	9: 32,093,135 (GRCm39)		probably null	Het
Carm1	T	C	9: 21,480,822 (GRCm39)	F99L	probably damaging	Het
Dennd1b	A	G	1: 139,013,665 (GRCm39)	E253G	possibly damaging	Het
Dsg4	A	G	18: 20,594,493 (GRCm39)	I541V	probably benign	Het
Dstyk	A	G	1: 132,362,127 (GRCm39)	T186A	possibly damaging	Het
Ear1	A	T	14: 44,056,721 (GRCm39)	V49D	probably benign	Het
Epha10	A	G	4: 124,809,480 (GRCm39)		probably benign	Het
Fbh1	A	G	2: 11,753,828 (GRCm39)	V838A	possibly damaging	Het
Fndc8	T	A	11: 82,783,226 (GRCm39)	M69K	probably benign	Het
Golga1	T	C	2: 38,913,466 (GRCm39)	I482V	probably benign	Het
Hivep3	G	A	4: 119,590,990 (GRCm39)		probably benign	Het
Igkv13-85	A	G	6: 68,907,356 (GRCm39)	F82L	probably damaging	Het
Itih1	G	A	14: 30,657,842 (GRCm39)	R410C	probably damaging	Het
Kcnc2	T	C	10: 112,291,699 (GRCm39)	W296R	probably damaging	Het
Kcnq3	A	T	15: 65,867,191 (GRCm39)	Y817*	probably null	Het
Kif3b	T	C	2: 153,165,564 (GRCm39)		probably null	Het
Krtcap2	A	G	3: 89,153,563 (GRCm39)		probably benign	Het
Lhx5	C	A	5: 120,578,073 (GRCm39)	H298N	possibly damaging	Het
Npc1l1	A	G	11: 6,178,741 (GRCm39)	L223S	possibly damaging	Het
Or11m3	T	C	15: 98,396,015 (GRCm39)	F221L	probably benign	Het
Or4c10	C	T	2: 89,760,695 (GRCm39)	P181S	possibly damaging	Het
Or8a1b	C	T	9: 37,622,760 (GRCm39)	V272I	probably benign	Het
Pbxip1	A	G	3: 89,353,690 (GRCm39)	D281G	possibly damaging	Het
Pcdhga8	G	C	18: 37,949,816 (GRCm39)	V411L	probably damaging	Het
Pcsk5	C	T	19: 17,429,319 (GRCm39)	C1553Y	probably damaging	Het
Pdgfc	A	C	3: 81,082,298 (GRCm39)	M164L	probably benign	Het
Pdzd8	T	C	19: 59,333,880 (GRCm39)	Y47C	probably damaging	Het
Pip5k1c	T	A	10: 81,150,945 (GRCm39)	I633N	probably damaging	Het
Pkn1	G	A	8: 84,419,556 (GRCm39)	R16*	probably null	Het
Pole2	A	G	12: 69,269,242 (GRCm39)	V85A	probably benign	Het
Ppp4c	A	C	7: 126,386,637 (GRCm39)	L150R	probably damaging	Het
Pramel25	G	C	4: 143,520,553 (GRCm39)	E102Q	probably benign	Het
Ric8a	A	G	7: 140,438,429 (GRCm39)	I223V	probably benign	Het
Rnf144a	T	A	12: 26,377,302 (GRCm39)	R92S	probably benign	Het
Sbno2	C	A	10: 79,896,326 (GRCm39)	R898L	possibly damaging	Het
Scnn1b	A	C	7: 121,511,698 (GRCm39)	N370T	probably damaging	Het
Taar3	A	G	10: 23,825,471 (GRCm39)	I6V	possibly damaging	Het
Vps13a	T	C	19: 16,672,866 (GRCm39)	E1302G	possibly 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
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'- CCAATGATGACACCAGGGAG -3'
(R):5'- CAGGTAGGCATGGAGTTGTCTC -3'

Sequencing Primer
(F):5'- CTCTGAAGGTAGTGTGGCCCAG -3'
(R):5'- AGTTGTCTCTCCTGGCAAGG -3'

Posted On

2015-07-21