Mutagenetix > Incidental Mutation

Incidental Mutation 'R5635:Notch1'

448623

Institutional Source

Beutler Lab

Gene Symbol

Notch1

Ensembl Gene

ENSMUSG00000026923

Gene Name

notch 1

Synonyms

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

MMRRC Submission

043286-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R5635 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

26457903-26516663 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

C to T at 26476161 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Glutamic Acid to Lysine at position 794 (E794K)

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: E794K

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

SMART Domains

Protein: ENSMUSP00000028288
Gene: ENSMUSG00000026923
AA Change: E794K

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

Meta Mutation Damage Score

0.5281

Coding Region Coverage

1x: 99.3%
3x: 98.8%
10x: 97.6%
20x: 96.0%

Validation Efficiency

99% (90/91)

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: 85 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
9330159F19Rik	T	A	10: 29,218,277	M53K	possibly damaging	Het
Aldh3b3	C	T	19: 3,968,512	T409I	probably benign	Het
Ankrd13a	C	A	5: 114,801,717	H468Q	possibly damaging	Het
Ap2a1	A	C	7: 44,923,901		probably benign	Het
Arfgef1	A	T	1: 10,188,860	S671T	possibly damaging	Het
C1ra	G	A	6: 124,516,724	C145Y	probably damaging	Het
Catsperd	G	A	17: 56,632,335	V55M	possibly damaging	Het
Ccdc30	T	C	4: 119,359,674	N123D	possibly damaging	Het
Cdc20	A	T	4: 118,436,027	V232E	possibly damaging	Het
Cfap58	T	A	19: 47,983,542	V637E	possibly damaging	Het
Coq4	T	A	2: 29,788,355	V24E	possibly damaging	Het
Crim1	T	A	17: 78,315,641	F423I	probably damaging	Het
Crls1	T	C	2: 132,864,142	V262A	possibly damaging	Het
Crybb1	T	C	5: 112,257,559		probably null	Het
Cutc	T	A	19: 43,755,630	N23K	probably benign	Het
Cxcl10	T	A	5: 92,347,839	I82F	probably damaging	Het
Cyp3a44	A	T	5: 145,801,314	F60L	possibly damaging	Het
Dhx9	A	G	1: 153,483,747	M35T	probably benign	Het
Dnah8	A	G	17: 30,706,386	E1265G	probably benign	Het
Dzank1	C	G	2: 144,483,407	D548H	probably damaging	Het
Eef2kmt	A	G	16: 5,249,029	V120A	probably damaging	Het
Elp4	A	G	2: 105,814,264		probably null	Het
Etl4	A	T	2: 20,807,035	I1310F	probably damaging	Het
Exoc6b	A	T	6: 84,851,927	F492I	probably damaging	Het
F2rl2	A	T	13: 95,700,782	I112F	possibly damaging	Het
Farp1	T	A	14: 121,276,304	I837N	possibly damaging	Het
Fars2	A	G	13: 36,410,146	E378G	probably damaging	Het
Fgg	A	G	3: 83,011,423	T248A	probably benign	Het
Flrt3	T	A	2: 140,660,500	T403S	probably damaging	Het
Fndc3b	C	T	3: 27,541,931	E170K	probably damaging	Het
Gm17728	A	G	17: 9,422,370	H104R	probably benign	Het
Hist2h2ab	C	A	3: 96,220,277	T121K	possibly damaging	Het
Hivep1	A	G	13: 42,160,127	T1948A	probably benign	Het
Hspa4l	T	A	3: 40,745,745	I23N	probably damaging	Het
Ighv1-75	A	G	12: 115,834,209	V31A	probably benign	Het
Kalrn	T	A	16: 34,014,084	N627I	probably damaging	Het
Lrp1b	T	G	2: 42,652,822		probably benign	Het
Lrrc36	G	A	8: 105,457,573	V480M	probably damaging	Het
Map4k3	A	T	17: 80,613,495	N534K	possibly damaging	Het
Mybpc3	C	T	2: 91,134,829	T1081I	probably benign	Het
Nfrkb	T	C	9: 31,399,298	S351P	probably damaging	Het
Nme4	A	T	17: 26,094,231	V43E	probably damaging	Het
Nufip1	A	T	14: 76,126,146	K270M	probably damaging	Het
Olfr1093	A	G	2: 86,785,726		probably null	Het
Olfr1330	G	T	4: 118,893,635	G184V	probably benign	Het
Olfr390	G	T	11: 73,787,634	R232L	probably benign	Het
Olfr65	G	A	7: 103,906,638	M66I	probably benign	Het
Olfr919	A	G	9: 38,698,159	I73T	possibly damaging	Het
Pcdhb15	T	A	18: 37,473,770	Y18*	probably null	Het
Pcdhb21	A	T	18: 37,513,917	Y33F	probably benign	Het
Pds5b	T	A	5: 150,778,221	H772Q	possibly damaging	Het
Pik3r4	C	A	9: 105,667,825	H168N	probably benign	Het
Pitpnm3	A	G	11: 72,067,160	S386P	possibly damaging	Het
Plg	A	G	17: 12,395,754	H307R	probably damaging	Het
Prdm9	A	C	17: 15,562,440	D96E	probably damaging	Het
Prmt8	A	G	6: 127,768,729	S7P	probably damaging	Het
Prune2	T	C	19: 17,118,209	V359A	probably benign	Het
Pxn	A	T	5: 115,551,492	Q279L	probably benign	Het
Rarb	A	T	14: 16,443,788	C167S	probably damaging	Het
Rps6kb2	T	A	19: 4,161,134	I131F	probably damaging	Het
Sec14l3	T	A	11: 4,071,484	V219E	probably damaging	Het
Simc1	A	G	13: 54,525,404	T522A	probably benign	Het
Slc1a6	T	C	10: 78,789,091	V110A	possibly damaging	Het
Slc38a11	T	G	2: 65,361,403		probably null	Het
Snx13	T	A	12: 35,140,171	D840E	probably benign	Het
Sp100	C	A	1: 85,682,264		probably benign	Het
Spc24	G	T	9: 21,757,390	L104I	probably damaging	Het
Surf4	T	C	2: 26,933,313	N4D	probably benign	Het
Tas2r131	A	T	6: 132,957,608	D79E	probably benign	Het
Tbc1d20	T	C	2: 152,311,461	S304P	probably benign	Het
Tbrg1	T	C	9: 37,654,991		probably benign	Het
Tmem214	A	G	5: 30,871,517	N150S	probably damaging	Het
Trappc13	A	T	13: 104,150,098	I217K	probably benign	Het
Ttc41	T	A	10: 86,736,977	C738S	probably benign	Het
Ttn	T	C	2: 76,709,724	Q25979R	probably benign	Het
Tubb2b	A	T	13: 34,128,197	N204K	probably damaging	Het
Ube3a	T	A	7: 59,288,488	M713K	probably damaging	Het
Usp37	T	C	1: 74,495,811		probably benign	Het
Vegfb	T	A	19: 6,982,846	*189C	probably null	Het
Vmn2r82	A	G	10: 79,378,818	N212D	probably benign	Het
Vta1	A	T	10: 14,668,122		probably null	Het
Wdr66	A	T	5: 123,322,572	Q225L	probably benign	Het
Xdh	T	G	17: 73,913,875	I620L	possibly damaging	Het
Xpnpep3	A	G	15: 81,436,769	Y283C	probably benign	Het
Zscan18	A	G	7: 12,770,864	S609P	probably benign	Het

Other mutations in Notch1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00164:Notch1	APN	2	26460046	missense	probably damaging	0.98
IGL01343:Notch1	APN	2	26472905	missense	probably benign	0.25
IGL02066:Notch1	APN	2	26460396	missense	possibly damaging	0.71
IGL02158:Notch1	APN	2	26460339	missense	probably damaging	1.00
IGL02541:Notch1	APN	2	26468503	missense	probably benign	0.12
IGL03280:Notch1	APN	2	26477874	intron	probably benign
IGL03338:Notch1	APN	2	26459959	missense	probably benign
Antero	UTSW	2	26476114	missense	possibly damaging	0.96
march	UTSW	2	26469899	missense	probably damaging	0.98
PIT4494001:Notch1	UTSW	2	26466473	missense	probably damaging	1.00
R0013:Notch1	UTSW	2	26473818	missense	possibly damaging	0.64
R0025:Notch1	UTSW	2	26470931	missense	probably damaging	1.00
R0129:Notch1	UTSW	2	26460458	missense	probably benign	0.06
R0285:Notch1	UTSW	2	26460861	missense	possibly damaging	0.88
R0531:Notch1	UTSW	2	26466572	missense	probably benign	0.00
R0747:Notch1	UTSW	2	26472140	missense	unknown
R1440:Notch1	UTSW	2	26480964	intron	probably benign
R1502:Notch1	UTSW	2	26484323	missense	possibly damaging	0.95
R1539:Notch1	UTSW	2	26472113	nonsense	probably null
R1623:Notch1	UTSW	2	26478612	missense	possibly damaging	0.88
R1844:Notch1	UTSW	2	26460434	missense	probably benign	0.12
R1863:Notch1	UTSW	2	26469950	missense	probably damaging	1.00
R1874:Notch1	UTSW	2	26481579	missense	possibly damaging	0.89
R1926:Notch1	UTSW	2	26481657	missense	probably damaging	1.00
R2156:Notch1	UTSW	2	26460861	missense	possibly damaging	0.91
R2196:Notch1	UTSW	2	26463804	nonsense	probably null
R2209:Notch1	UTSW	2	26460007	missense	probably benign
R2382:Notch1	UTSW	2	26473781	missense	probably benign	0.40
R2508:Notch1	UTSW	2	26465473	missense	possibly damaging	0.80
R2873:Notch1	UTSW	2	26460235	missense	possibly damaging	0.89
R2874:Notch1	UTSW	2	26460235	missense	possibly damaging	0.89
R3798:Notch1	UTSW	2	26478618	missense	probably benign	0.00
R4019:Notch1	UTSW	2	26481142	missense	probably benign	0.03
R4305:Notch1	UTSW	2	26477924	missense	probably damaging	1.00
R4334:Notch1	UTSW	2	26460036	missense	probably benign	0.22
R4504:Notch1	UTSW	2	26472177	missense	probably benign	0.16
R4624:Notch1	UTSW	2	26478081	missense	possibly damaging	0.94
R4659:Notch1	UTSW	2	26470889	missense	probably damaging	0.99
R4703:Notch1	UTSW	2	26471158	missense	probably benign
R4869:Notch1	UTSW	2	26471179	missense	probably benign	0.21
R4938:Notch1	UTSW	2	26474124	nonsense	probably null
R4989:Notch1	UTSW	2	26481181	missense	probably damaging	1.00
R5010:Notch1	UTSW	2	26476114	missense	possibly damaging	0.96
R5283:Notch1	UTSW	2	26468626	missense	probably damaging	1.00
R5303:Notch1	UTSW	2	26478619	missense	probably benign	0.01
R5755:Notch1	UTSW	2	26473692	missense	probably benign	0.12
R5926:Notch1	UTSW	2	26476104	missense	probably benign	0.35
R5947:Notch1	UTSW	2	26462528	intron	probably benign
R6053:Notch1	UTSW	2	26472912	missense	probably benign	0.06
R6161:Notch1	UTSW	2	26468731	missense	probably damaging	1.00
R6162:Notch1	UTSW	2	26462195	missense	probably benign
R6174:Notch1	UTSW	2	26485442	missense	possibly damaging	0.50
R6199:Notch1	UTSW	2	26469899	missense	probably damaging	0.98
R6209:Notch1	UTSW	2	26472805	missense	probably damaging	1.00
R6251:Notch1	UTSW	2	26474170	missense	possibly damaging	0.64
R6493:Notch1	UTSW	2	26472098	missense	unknown
R6723:Notch1	UTSW	2	26478106	missense	probably damaging	1.00
R6736:Notch1	UTSW	2	26460286	missense	probably benign	0.01
R7020:Notch1	UTSW	2	26481574	missense	possibly damaging	0.95
R7058:Notch1	UTSW	2	26463818	missense	probably benign	0.05
R7154:Notch1	UTSW	2	26459938	missense	probably benign
R7291:Notch1	UTSW	2	26476375	missense	probably benign	0.01
R7379:Notch1	UTSW	2	26479467	missense	probably damaging	1.00
R7560:Notch1	UTSW	2	26460165	missense	probably benign	0.43
R7610:Notch1	UTSW	2	26478179	missense	probably benign	0.13
R7833:Notch1	UTSW	2	26459533	makesense	probably null
R7988:Notch1	UTSW	2	26471001	missense	probably benign	0.00
R8493:Notch1	UTSW	2	26472239	missense	unknown
R8514:Notch1	UTSW	2	26472169	missense	probably damaging	1.00
R8523:Notch1	UTSW	2	26464905	missense	possibly damaging	0.82
R8677:Notch1	UTSW	2	26469924	missense	probably damaging	1.00
R8696:Notch1	UTSW	2	26477992	critical splice acceptor site	probably benign
R8833:Notch1	UTSW	2	26481603	missense	probably damaging	1.00
R8964:Notch1	UTSW	2	26481050	missense	possibly damaging	0.65
R9091:Notch1	UTSW	2	26479883	missense	probably damaging	0.99
R9144:Notch1	UTSW	2	26459575	missense	probably benign	0.00
R9145:Notch1	UTSW	2	26459575	missense	probably benign	0.00
R9151:Notch1	UTSW	2	26477927	missense	probably benign	0.01
R9270:Notch1	UTSW	2	26479883	missense	probably damaging	0.99
R9463:Notch1	UTSW	2	26469833	missense	probably benign	0.20
R9546:Notch1	UTSW	2	26481115	missense	probably damaging	0.97
R9674:Notch1	UTSW	2	26471296	missense	probably damaging	0.98
X0018:Notch1	UTSW	2	26462227	nonsense	probably null
X0066:Notch1	UTSW	2	26470335	missense	possibly damaging	0.90
Z1088:Notch1	UTSW	2	26477115	missense	probably damaging	0.99
Z1177:Notch1	UTSW	2	26460309	missense	possibly damaging	0.74

Predicted Primers

PCR Primer
(F):5'- TTCTTCAGTGCCTGGTAAGCC -3'
(R):5'- CATGACCAGTGGCTACGTATG -3'

Sequencing Primer
(F):5'- GTGCCTGGTAAGCCCATATAC -3'
(R):5'- TACGTATGCACCTGCCGAGAAG -3'

Posted On

2016-12-15