Mutagenetix > Incidental Mutation

Incidental Mutation 'R1813:Notch3'

202593

Institutional Source

Beutler Lab

Gene Symbol

Notch3

Ensembl Gene

ENSMUSG00000038146

Gene Name

notch 3

Synonyms

hpbk, N3

MMRRC Submission

039841-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R1813 (G1)

Quality Score

178

Status

Validated

Chromosome

Chromosomal Location

32339794-32385826 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 32362402 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Threonine to Alanine at position 1408 (T1408A)

Ref Sequence

ENSEMBL: ENSMUSP00000085016 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000087723]

AlphaFold

Q61982

Predicted Effect

probably benign
Transcript: ENSMUST00000087723
AA Change: T1408A

PolyPhen 2 Score 0.084 (Sensitivity: 0.93; Specificity: 0.85)

SMART Domains

Protein: ENSMUSP00000085016
Gene: ENSMUSG00000038146
AA Change: T1408A

Domain	Start	End	E-Value	Type
signal peptide	1	39	N/A	INTRINSIC
EGF	42	78	3.73e-5	SMART
EGF	82	119	1.78e-2	SMART
EGF	123	157	1.13e-4	SMART
EGF_CA	159	196	1.89e-15	SMART
EGF	201	235	3.85e-7	SMART
EGF_CA	237	273	3.97e-9	SMART
EGF_CA	275	313	4.63e-10	SMART
EGF_CA	315	351	1.05e-8	SMART
EGF	355	390	1.28e-3	SMART
EGF_CA	392	430	6.29e-12	SMART
EGF_CA	432	468	1.11e-12	SMART
EGF_CA	470	506	4.21e-13	SMART
EGF_CA	508	544	8.43e-13	SMART
EGF_CA	546	581	9.54e-12	SMART
EGF_CA	583	619	1.31e-9	SMART
EGF_CA	621	656	2.03e-6	SMART
EGF_CA	658	694	2.28e-9	SMART
EGF	699	731	7.18e-7	SMART
EGF	738	771	2.5e-6	SMART
EGF	775	809	8e-5	SMART
EGF_CA	811	848	4.77e-12	SMART
EGF_CA	850	886	3.81e-11	SMART
EGF_CA	888	923	1.47e-12	SMART
EGF_CA	925	961	3.4e-8	SMART
EGF	966	999	5.74e-6	SMART
EGF	1004	1035	7.18e-7	SMART
EGF	1040	1083	1.21e-4	SMART
EGF_CA	1085	1121	1.29e-8	SMART
EGF_CA	1123	1159	1.45e-11	SMART
EGF_CA	1161	1204	1.26e-11	SMART
EGF	1209	1245	1.53e-1	SMART
EGF	1250	1288	8e-5	SMART
EGF	1293	1326	1.13e1	SMART
EGF	1339	1374	5.36e-6	SMART
NL	1381	1419	1.63e-15	SMART
NL	1422	1460	1.78e-16	SMART
NL	1461	1502	1.75e-15	SMART
NOD	1506	1562	2.98e-24	SMART
NODP	1577	1641	1.34e-26	SMART
transmembrane domain	1644	1666	N/A	INTRINSIC
low complexity region	1774	1783	N/A	INTRINSIC
ANK	1789	1834	1.48e3	SMART
ANK	1839	1868	1.61e-4	SMART
ANK	1872	1902	1.42e0	SMART
ANK	1906	1935	1.77e-1	SMART
ANK	1939	1968	3.18e-3	SMART
ANK	1972	2001	5.16e-3	SMART
low complexity region	2028	2054	N/A	INTRINSIC
low complexity region	2108	2123	N/A	INTRINSIC
low complexity region	2169	2193	N/A	INTRINSIC
DUF3454	2218	2275	2.81e-20	SMART

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000180839

Meta Mutation Damage Score

0.0898

Coding Region Coverage

1x: 97.5%
3x: 96.8%
10x: 94.8%
20x: 90.3%

Validation Efficiency

96% (79/82)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes the third discovered human homologue of the Drosophilia melanogaster type I membrane protein notch. In Drosophilia, notch interaction with its cell-bound ligands (delta, serrate) establishes an intercellular signalling pathway that plays a key role in neural development. Homologues of the notch-ligands have also been identified in human, but precise interactions between these ligands and the human notch homologues remains to be determined. Mutations in NOTCH3 have been identified as the underlying cause of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). [provided by RefSeq, Jul 2008]
PHENOTYPE: Some, but not all, null alleles cause defects in artery morphology and in T cell development. Progressive emaciation and kyphosis with paraphimosis occurs in an intron 31 splice donor site point mutant. In conjunction with Notch1 deficiency, abnormalities in embryonic development have been observed. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 74 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
A2ml1	T	A	6: 128,543,236 (GRCm39)	N595Y	probably benign	Het
Abca6	A	G	11: 110,124,671 (GRCm39)		probably benign	Het
Abo	C	A	2: 26,733,609 (GRCm39)	D199Y	probably damaging	Het
Acvr1c	A	C	2: 58,170,306 (GRCm39)	V277G	probably damaging	Het
Adam23	G	A	1: 63,584,731 (GRCm39)	A380T	probably benign	Het
Art2b	A	G	7: 101,229,236 (GRCm39)	V221A	probably benign	Het
Bcam	A	G	7: 19,500,640 (GRCm39)	S153P	probably damaging	Het
Brip1	T	C	11: 86,077,906 (GRCm39)	H174R	possibly damaging	Het
Ccdc186	T	C	19: 56,788,601 (GRCm39)	D536G	probably benign	Het
Cd109	A	G	9: 78,524,287 (GRCm39)	N67S	probably benign	Het
Cd8a	G	T	6: 71,350,947 (GRCm39)	M137I	possibly damaging	Het
Ces2g	T	C	8: 105,693,569 (GRCm39)	F417L	probably benign	Het
Clec2g	A	G	6: 128,925,660 (GRCm39)	N23S	unknown	Het
Cntnap2	T	C	6: 46,507,567 (GRCm39)	Y61C	probably damaging	Het
Cog3	T	A	14: 75,979,784 (GRCm39)	E182D	probably benign	Het
Dbpht2	A	G	12: 74,342,624 (GRCm39)		noncoding transcript	Het
Dock4	A	T	12: 40,686,227 (GRCm39)	N154I	probably damaging	Het
Dysf	T	G	6: 84,128,906 (GRCm39)	V1422G	possibly damaging	Het
E2f3	T	C	13: 30,104,159 (GRCm39)	D140G	probably damaging	Het
Efcab3	A	G	11: 104,611,514 (GRCm39)	K452R	probably benign	Het
Epb41l2	T	A	10: 25,317,466 (GRCm39)		probably null	Het
Epha2	A	G	4: 141,035,857 (GRCm39)	K98E	possibly damaging	Het
Esyt1	T	C	10: 128,355,487 (GRCm39)	D444G	probably benign	Het
Fam163a	T	C	1: 155,955,787 (GRCm39)	T2A	probably damaging	Het
Foxp2	A	T	6: 15,379,767 (GRCm39)		probably benign	Het
Gcm2	T	C	13: 41,259,367 (GRCm39)	H34R	probably benign	Het
Gipr	A	G	7: 18,897,996 (GRCm39)	S79P	probably benign	Het
Gli3	T	C	13: 15,823,276 (GRCm39)	S333P	probably damaging	Het
Gm10717	T	G	9: 3,026,317 (GRCm39)	F205C	probably damaging	Het
Gzmk	A	G	13: 113,309,427 (GRCm39)	S208P	probably damaging	Het
Htra2	G	T	6: 83,028,583 (GRCm39)	A318D	probably damaging	Het
Itpkc	T	C	7: 26,907,805 (GRCm39)	D633G	probably damaging	Het
Lama1	G	A	17: 68,098,218 (GRCm39)	R1805H	probably benign	Het
Lama4	T	A	10: 38,909,121 (GRCm39)		probably benign	Het
Lama4	T	C	10: 38,936,182 (GRCm39)	V619A	probably damaging	Het
Nwd2	A	G	5: 63,962,753 (GRCm39)	D779G	probably benign	Het
Nxpe4	A	G	9: 48,304,678 (GRCm39)	Y255C	possibly damaging	Het
Obox6	A	T	7: 15,568,770 (GRCm39)	H35Q	possibly damaging	Het
Or2ab1	A	G	11: 58,489,133 (GRCm39)	I304V	probably damaging	Het
Or8b41	T	A	9: 38,055,025 (GRCm39)	I198N	possibly damaging	Het
Pkig	T	A	2: 163,563,147 (GRCm39)	I26N	possibly damaging	Het
Plekhm2	C	T	4: 141,369,750 (GRCm39)	V82M	possibly damaging	Het
Plppr2	G	A	9: 21,859,220 (GRCm39)	A446T	probably damaging	Het
Psme4	T	A	11: 30,754,353 (GRCm39)	F203L	probably benign	Het
Sh3bp1	A	G	15: 78,787,880 (GRCm39)	K137E	probably damaging	Het
Shisa5	T	A	9: 108,885,108 (GRCm39)	I126N	probably damaging	Het
Slc11a1	T	C	1: 74,414,931 (GRCm39)	L21P	probably benign	Het
Slc35f1	C	T	10: 52,809,291 (GRCm39)	P93S	probably damaging	Het
Slc4a4	A	G	5: 89,194,167 (GRCm39)	T172A	probably damaging	Het
Slc9c1	A	T	16: 45,393,710 (GRCm39)	Y551F	probably benign	Het
Spata31	T	C	13: 65,069,612 (GRCm39)	S587P	probably benign	Het
Syna	C	A	5: 134,588,006 (GRCm39)	M314I	probably benign	Het
Taf5l	A	G	8: 124,730,152 (GRCm39)	L144P	probably damaging	Het
Tbccd1	T	C	16: 22,641,271 (GRCm39)	T369A	probably benign	Het
Tnfrsf11b	A	T	15: 54,119,493 (GRCm39)	C160*	probably null	Het
Trim45	A	G	3: 100,830,283 (GRCm39)	N19S	probably benign	Het
Uba2	A	G	7: 33,850,455 (GRCm39)	F364S	probably damaging	Het
Unc50	T	A	1: 37,476,323 (GRCm39)	L161Q	probably damaging	Het
Uso1	A	T	5: 92,348,992 (GRCm39)		probably null	Het
Usp25	A	G	16: 76,911,838 (GRCm39)	I956V	probably benign	Het
Utf1	C	A	7: 139,524,213 (GRCm39)	L143I	probably damaging	Het
Vmn1r158	C	T	7: 22,490,143 (GRCm39)	C22Y	probably damaging	Het
Vmn1r36	T	A	6: 66,693,756 (GRCm39)	M40L	probably benign	Het
Vmn2r43	A	G	7: 8,258,055 (GRCm39)	V386A	possibly damaging	Het
Vps9d1	C	A	8: 123,973,778 (GRCm39)	R335L	probably damaging	Het
Wasf1	T	A	10: 40,802,585 (GRCm39)	V80D	probably damaging	Het
Wdr72	G	A	9: 74,183,298 (GRCm39)	V1077I	possibly damaging	Het
Wnt8a	A	G	18: 34,675,422 (GRCm39)	M1V	probably null	Het
Zbtb26	A	G	2: 37,326,347 (GRCm39)	S230P	possibly damaging	Het
Zfp335	A	G	2: 164,734,525 (GRCm39)	V1247A	probably damaging	Het
Zfp429	T	C	13: 67,538,505 (GRCm39)	N313S	possibly damaging	Het
Zfp74	A	T	7: 29,634,569 (GRCm39)	C380S	probably damaging	Het
Zfyve21	G	A	12: 111,791,328 (GRCm39)	E134K	probably damaging	Het
Zmynd11	T	C	13: 9,739,616 (GRCm39)	T474A	possibly damaging	Het

Other mutations in Notch3

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00161:Notch3	APN	17	32,377,088 (GRCm39)	nonsense	probably null
IGL01065:Notch3	APN	17	32,365,390 (GRCm39)	nonsense	probably null
IGL01296:Notch3	APN	17	32,385,731 (GRCm39)	missense	unknown
IGL01322:Notch3	APN	17	32,363,445 (GRCm39)	missense	probably damaging	1.00
IGL01343:Notch3	APN	17	32,362,410 (GRCm39)	missense	probably benign	0.10
IGL01358:Notch3	APN	17	32,363,721 (GRCm39)	missense	probably damaging	1.00
IGL01600:Notch3	APN	17	32,363,472 (GRCm39)	missense	probably damaging	1.00
IGL01622:Notch3	APN	17	32,377,844 (GRCm39)	missense	possibly damaging	0.50
IGL01623:Notch3	APN	17	32,377,844 (GRCm39)	missense	possibly damaging	0.50
IGL01971:Notch3	APN	17	32,343,321 (GRCm39)	missense	probably damaging	1.00
IGL02000:Notch3	APN	17	32,341,716 (GRCm39)	missense	probably damaging	0.99
IGL02072:Notch3	APN	17	32,366,048 (GRCm39)	nonsense	probably null
IGL02145:Notch3	APN	17	32,373,715 (GRCm39)	missense	probably benign	0.01
IGL02256:Notch3	APN	17	32,351,298 (GRCm39)	missense	probably damaging	1.00
IGL02366:Notch3	APN	17	32,363,179 (GRCm39)	missense	probably benign
IGL02476:Notch3	APN	17	32,377,612 (GRCm39)	missense	possibly damaging	0.67
IGL02502:Notch3	APN	17	32,377,252 (GRCm39)	nonsense	probably null
IGL02551:Notch3	APN	17	32,373,705 (GRCm39)	splice site	probably benign
divide	UTSW	17	32,356,787 (GRCm39)	splice site	probably null
impressed	UTSW	17	32,385,652 (GRCm39)	missense	probably benign
indented	UTSW	17	32,366,937 (GRCm39)	missense	probably benign	0.00
Lopressor	UTSW	17	32,372,858 (GRCm39)	missense	probably damaging	1.00
marginal	UTSW	17	32,383,198 (GRCm39)	missense	probably benign
PIT4486001:Notch3	UTSW	17	32,373,737 (GRCm39)	missense	probably damaging	1.00
R0115:Notch3	UTSW	17	32,352,436 (GRCm39)	missense	possibly damaging	0.82
R0201:Notch3	UTSW	17	32,375,122 (GRCm39)	splice site	probably benign
R0630:Notch3	UTSW	17	32,366,446 (GRCm39)	splice site	probably benign
R1167:Notch3	UTSW	17	32,341,719 (GRCm39)	missense	possibly damaging	0.95
R1432:Notch3	UTSW	17	32,383,198 (GRCm39)	missense	probably benign
R1567:Notch3	UTSW	17	32,377,554 (GRCm39)	missense	possibly damaging	0.77
R1623:Notch3	UTSW	17	32,358,165 (GRCm39)	missense	probably benign	0.00
R1663:Notch3	UTSW	17	32,375,093 (GRCm39)	missense	probably damaging	1.00
R1668:Notch3	UTSW	17	32,377,563 (GRCm39)	missense	probably damaging	0.99
R1789:Notch3	UTSW	17	32,377,699 (GRCm39)	missense	probably damaging	1.00
R1837:Notch3	UTSW	17	32,343,296 (GRCm39)	missense	probably damaging	1.00
R1896:Notch3	UTSW	17	32,362,402 (GRCm39)	missense	probably benign	0.08
R1937:Notch3	UTSW	17	32,372,826 (GRCm39)	missense	probably benign	0.03
R1954:Notch3	UTSW	17	32,385,652 (GRCm39)	missense	probably benign
R2014:Notch3	UTSW	17	32,376,974 (GRCm39)	missense	probably benign	0.00
R2058:Notch3	UTSW	17	32,362,618 (GRCm39)	missense	probably benign
R2068:Notch3	UTSW	17	32,354,482 (GRCm39)	missense	probably benign	0.00
R2097:Notch3	UTSW	17	32,341,728 (GRCm39)	missense	probably damaging	1.00
R2112:Notch3	UTSW	17	32,363,584 (GRCm39)	missense	probably benign	0.19
R2156:Notch3	UTSW	17	32,366,818 (GRCm39)	missense	probably damaging	1.00
R2211:Notch3	UTSW	17	32,366,952 (GRCm39)	missense	probably benign	0.00
R2324:Notch3	UTSW	17	32,369,108 (GRCm39)	splice site	probably benign
R2432:Notch3	UTSW	17	32,372,778 (GRCm39)	missense	probably damaging	1.00
R3117:Notch3	UTSW	17	32,377,089 (GRCm39)	missense	probably damaging	1.00
R3236:Notch3	UTSW	17	32,377,435 (GRCm39)	missense	probably damaging	0.96
R3409:Notch3	UTSW	17	32,369,676 (GRCm39)	missense	possibly damaging	0.67
R3434:Notch3	UTSW	17	32,377,592 (GRCm39)	missense	possibly damaging	0.80
R3435:Notch3	UTSW	17	32,377,592 (GRCm39)	missense	possibly damaging	0.80
R3438:Notch3	UTSW	17	32,372,564 (GRCm39)	missense	probably damaging	1.00
R3926:Notch3	UTSW	17	32,372,531 (GRCm39)	missense	possibly damaging	0.92
R4087:Notch3	UTSW	17	32,377,087 (GRCm39)	missense	possibly damaging	0.60
R4115:Notch3	UTSW	17	32,377,407 (GRCm39)	missense	probably damaging	1.00
R4214:Notch3	UTSW	17	32,351,181 (GRCm39)	missense	possibly damaging	0.96
R4234:Notch3	UTSW	17	32,360,315 (GRCm39)	missense	probably damaging	0.97
R4242:Notch3	UTSW	17	32,362,719 (GRCm39)	missense	possibly damaging	0.74
R4658:Notch3	UTSW	17	32,373,737 (GRCm39)	missense	probably damaging	1.00
R4878:Notch3	UTSW	17	32,366,059 (GRCm39)	missense	probably damaging	1.00
R4879:Notch3	UTSW	17	32,366,937 (GRCm39)	missense	probably benign	0.00
R4885:Notch3	UTSW	17	32,360,351 (GRCm39)	missense	probably damaging	0.98
R4924:Notch3	UTSW	17	32,363,705 (GRCm39)	missense	probably damaging	1.00
R5084:Notch3	UTSW	17	32,376,864 (GRCm39)	critical splice donor site	probably null
R5086:Notch3	UTSW	17	32,362,308 (GRCm39)	missense	probably benign	0.13
R5343:Notch3	UTSW	17	32,362,257 (GRCm39)	missense	probably benign	0.03
R5389:Notch3	UTSW	17	32,358,163 (GRCm39)	missense	probably benign
R5503:Notch3	UTSW	17	32,366,029 (GRCm39)	missense	probably benign	0.00
R5698:Notch3	UTSW	17	32,376,961 (GRCm39)	missense	probably damaging	1.00
R5824:Notch3	UTSW	17	32,372,835 (GRCm39)	missense	possibly damaging	0.92
R5969:Notch3	UTSW	17	32,372,858 (GRCm39)	missense	probably damaging	1.00
R6050:Notch3	UTSW	17	32,362,501 (GRCm39)	missense	probably benign
R6274:Notch3	UTSW	17	32,366,264 (GRCm39)	missense	probably benign
R6276:Notch3	UTSW	17	32,373,723 (GRCm39)	missense	probably benign	0.10
R6313:Notch3	UTSW	17	32,370,128 (GRCm39)	splice site	probably null
R6316:Notch3	UTSW	17	32,356,787 (GRCm39)	splice site	probably null
R6380:Notch3	UTSW	17	32,363,533 (GRCm39)	missense	probably damaging	1.00
R6401:Notch3	UTSW	17	32,377,597 (GRCm39)	missense	probably benign	0.01
R6502:Notch3	UTSW	17	32,377,191 (GRCm39)	missense	probably damaging	1.00
R6741:Notch3	UTSW	17	32,362,458 (GRCm39)	missense	probably benign	0.16
R7131:Notch3	UTSW	17	32,363,191 (GRCm39)	missense	probably benign
R7140:Notch3	UTSW	17	32,375,351 (GRCm39)	missense	possibly damaging	0.84
R7162:Notch3	UTSW	17	32,365,423 (GRCm39)	missense	probably damaging	0.98
R7171:Notch3	UTSW	17	32,377,936 (GRCm39)	missense	probably damaging	1.00
R7449:Notch3	UTSW	17	32,376,940 (GRCm39)	missense	probably damaging	1.00
R7450:Notch3	UTSW	17	32,360,365 (GRCm39)	missense	possibly damaging	0.69
R7554:Notch3	UTSW	17	32,341,345 (GRCm39)	missense	probably benign	0.03
R7575:Notch3	UTSW	17	32,373,793 (GRCm39)	missense	possibly damaging	0.81
R7632:Notch3	UTSW	17	32,377,480 (GRCm39)	missense	probably benign
R7633:Notch3	UTSW	17	32,377,596 (GRCm39)	missense	probably benign	0.17
R7860:Notch3	UTSW	17	32,341,747 (GRCm39)	missense	possibly damaging	0.67
R8052:Notch3	UTSW	17	32,365,545 (GRCm39)	missense	probably damaging	1.00
R8250:Notch3	UTSW	17	32,351,310 (GRCm39)	missense	probably damaging	1.00
R8296:Notch3	UTSW	17	32,341,713 (GRCm39)	missense	probably damaging	1.00
R8306:Notch3	UTSW	17	32,377,086 (GRCm39)	missense	probably damaging	0.99
R8458:Notch3	UTSW	17	32,375,024 (GRCm39)	missense	probably damaging	1.00
R8539:Notch3	UTSW	17	32,375,329 (GRCm39)	missense	possibly damaging	0.92
R8865:Notch3	UTSW	17	32,341,090 (GRCm39)	missense	probably benign	0.01
R8925:Notch3	UTSW	17	32,372,792 (GRCm39)	missense	probably benign	0.14
R8927:Notch3	UTSW	17	32,372,792 (GRCm39)	missense	probably benign	0.14
R9062:Notch3	UTSW	17	32,341,692 (GRCm39)	missense	possibly damaging	0.93
R9079:Notch3	UTSW	17	32,383,033 (GRCm39)	intron	probably benign
R9089:Notch3	UTSW	17	32,370,521 (GRCm39)	missense	probably benign	0.00
R9260:Notch3	UTSW	17	32,362,216 (GRCm39)	critical splice donor site	probably null
R9289:Notch3	UTSW	17	32,377,254 (GRCm39)	missense	probably damaging	1.00
R9294:Notch3	UTSW	17	32,362,665 (GRCm39)	missense	probably benign	0.03
R9661:Notch3	UTSW	17	32,373,792 (GRCm39)	missense	probably damaging	1.00
R9779:Notch3	UTSW	17	32,372,757 (GRCm39)	missense	probably damaging	1.00
T0975:Notch3	UTSW	17	32,365,391 (GRCm39)	missense	probably damaging	0.99
Z1088:Notch3	UTSW	17	32,377,626 (GRCm39)	missense	possibly damaging	0.94
Z1176:Notch3	UTSW	17	32,370,344 (GRCm39)	missense	probably damaging	1.00
Z1176:Notch3	UTSW	17	32,360,490 (GRCm39)	missense	probably benign	0.12
Z1177:Notch3	UTSW	17	32,385,668 (GRCm39)	missense	probably benign

Predicted Primers

PCR Primer
(F):5'- ACAGATGTGGCTCACTGACAG -3'
(R):5'- TGCCTACCTGTACAGAGTGTCC -3'

Sequencing Primer
(F):5'- AGAGTCAGGGGGCTCACTTG -3'
(R):5'- ACCTGTACAGAGTGTCCCTTTC -3'

Posted On

2014-06-23