Mutagenetix > Incidental Mutation

Incidental Mutation 'R1497:Shc1'

168939

Institutional Source

Beutler Lab

Gene Symbol

Shc1

Ensembl Gene

ENSMUSG00000042626

Gene Name

src homology 2 domain-containing transforming protein C1

Synonyms

ShcA, p66shc, p66

MMRRC Submission

039548-MU

Accession Numbers

Essential gene?

Probably essential (E-score: 0.969) question?

Stock #

R1497 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

89325858-89337336 bp(+) (GRCm39)

Type of Mutation

makesense

DNA Base Change (assembly)

A to G at 89335752 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Stop codon to Tryptophan at position 470 (*470W)

Ref Sequence

ENSEMBL: ENSMUSP00000140336 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000039110] [ENSMUST00000060061] [ENSMUST00000094378] [ENSMUST00000107413] [ENSMUST00000107417] [ENSMUST00000125036] [ENSMUST00000191485] [ENSMUST00000128238] [ENSMUST00000154791] [ENSMUST00000137793]

AlphaFold

P98083

Predicted Effect

probably null
Transcript: ENSMUST00000039110
AA Change: *470W

SMART Domains

Protein: ENSMUSP00000035361
Gene: ENSMUSG00000042626
AA Change: *470W

Domain	Start	End	E-Value	Type
low complexity region	6	17	N/A	INTRINSIC
PTB	47	211	2.15e-31	SMART
SH2	372	451	1.71e-26	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000060061

SMART Domains

Protein: ENSMUSP00000053672
Gene: ENSMUSG00000047824

Domain	Start	End	E-Value	Type
low complexity region	14	26	N/A	INTRINSIC
Blast:SH2	52	78	1e-9	BLAST
low complexity region	115	163	N/A	INTRINSIC
low complexity region	177	193	N/A	INTRINSIC
low complexity region	200	214	N/A	INTRINSIC
low complexity region	242	261	N/A	INTRINSIC
low complexity region	288	302	N/A	INTRINSIC
low complexity region	309	324	N/A	INTRINSIC
PHD	328	382	3.3e-5	SMART

Predicted Effect

probably null
Transcript: ENSMUST00000094378
AA Change: *580W

SMART Domains

Protein: ENSMUSP00000091940
Gene: ENSMUSG00000042626
AA Change: *580W

Domain	Start	End	E-Value	Type
low complexity region	16	55	N/A	INTRINSIC
low complexity region	85	98	N/A	INTRINSIC
low complexity region	116	127	N/A	INTRINSIC
PTB	157	321	2.15e-31	SMART
SH2	482	561	1.71e-26	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000107413

SMART Domains

Protein: ENSMUSP00000103036
Gene: ENSMUSG00000047824

Domain	Start	End	E-Value	Type
Blast:SH2	15	41	1e-9	BLAST
low complexity region	78	126	N/A	INTRINSIC
low complexity region	140	156	N/A	INTRINSIC
low complexity region	163	177	N/A	INTRINSIC
low complexity region	205	224	N/A	INTRINSIC
low complexity region	251	265	N/A	INTRINSIC
low complexity region	272	287	N/A	INTRINSIC
PHD	291	345	3.3e-5	SMART

Predicted Effect

probably null
Transcript: ENSMUST00000107417
AA Change: *425W

SMART Domains

Protein: ENSMUSP00000103040
Gene: ENSMUSG00000042626
AA Change: *425W

Domain	Start	End	E-Value	Type
PTB	2	166	2.15e-31	SMART
SH2	327	406	1.71e-26	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000125036

SMART Domains

Protein: ENSMUSP00000115509
Gene: ENSMUSG00000042626

Domain	Start	End	E-Value	Type
PTB	1	155	1.5e-21	SMART

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000125830

Predicted Effect

probably null
Transcript: ENSMUST00000191485
AA Change: *470W

SMART Domains

Protein: ENSMUSP00000140336
Gene: ENSMUSG00000042626
AA Change: *470W

Domain	Start	End	E-Value	Type
low complexity region	6	17	N/A	INTRINSIC
PTB	47	211	2.15e-31	SMART
SH2	372	451	1.71e-26	SMART

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000153334

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000136573

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000133680

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000146306

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000146037

Predicted Effect

probably benign
Transcript: ENSMUST00000128238

SMART Domains

Protein: ENSMUSP00000119293
Gene: ENSMUSG00000042626

Domain	Start	End	E-Value	Type
low complexity region	6	17	N/A	INTRINSIC
Pfam:PID	52	144	7.7e-19	PFAM
Pfam:PID	134	190	7.8e-16	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000154791

SMART Domains

Protein: ENSMUSP00000123635
Gene: ENSMUSG00000042626

Domain	Start	End	E-Value	Type
low complexity region	6	17	N/A	INTRINSIC
Pfam:PID	52	100	5.7e-13	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000137793

SMART Domains

Protein: ENSMUSP00000117190
Gene: ENSMUSG00000042626

Domain	Start	End	E-Value	Type
low complexity region	6	17	N/A	INTRINSIC
PTB	47	211	2.15e-31	SMART

Meta Mutation Damage Score

0.9372

Coding Region Coverage

1x: 99.2%
3x: 98.4%
10x: 96.8%
20x: 94.4%

Validation Efficiency

99% (79/80)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes three main isoforms that differ in activities and subcellular location. While all three are adapter proteins in signal transduction pathways, the longest (p66Shc) may be involved in regulating life span and the effects of reactive oxygen species. The other two isoforms, p52Shc and p46Shc, link activated receptor tyrosine kinases to the Ras pathway by recruitment of the GRB2/SOS complex. p66Shc is not involved in Ras activation. Unlike the other two isoforms, p46Shc is targeted to the mitochondrial matrix. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2011]
PHENOTYPE: Homozygotes with a targeted mutation of the exon encoding the CH2 region show an extended life span, reduced cellular sensitivity to oxidative stress and UV irradiation, and resistance to diet-induced atherogenesis. Homozygotes lacking all three isoformsdie around E11.5 with cardiovascular defects. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 79 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abca8b	G	T	11: 109,864,647 (GRCm39)		probably benign	Het
Abhd17a	A	G	10: 80,420,164 (GRCm39)		probably benign	Het
Acacb	G	A	5: 114,334,868 (GRCm39)	E646K	probably damaging	Het
Afap1l2	T	C	19: 56,916,743 (GRCm39)	M262V	probably benign	Het
Anapc7	T	A	5: 122,573,578 (GRCm39)		probably benign	Het
Car5b	T	A	X: 162,771,400 (GRCm39)	K188N	probably benign	Het
Caskin1	C	T	17: 24,723,515 (GRCm39)	R768*	probably null	Het
Casp8ap2	T	C	4: 32,639,938 (GRCm39)	S331P	probably benign	Het
Ccdc68	C	T	18: 70,093,585 (GRCm39)		probably benign	Het
Cd44	A	T	2: 102,673,300 (GRCm39)		probably null	Het
Celsr3	A	G	9: 108,726,064 (GRCm39)	S3090G	probably benign	Het
Clasp1	A	T	1: 118,479,788 (GRCm39)	M1023L	probably benign	Het
Clec16a	T	C	16: 10,453,123 (GRCm39)	F608S	probably damaging	Het
Col7a1	A	C	9: 108,807,893 (GRCm39)	E2531A	unknown	Het
Ctc1	T	A	11: 68,913,387 (GRCm39)	C128S	probably benign	Het
Cyp2d41-ps	T	C	15: 82,666,223 (GRCm39)		noncoding transcript	Het
Cyp2j6	T	A	4: 96,419,898 (GRCm39)	I278F	probably damaging	Het
Dhtkd1	A	T	2: 5,908,924 (GRCm39)	S723R	probably damaging	Het
Dhx8	A	G	11: 101,626,213 (GRCm39)		probably benign	Het
Dnah17	A	T	11: 118,005,059 (GRCm39)	L775Q	probably damaging	Het
Dnah8	C	A	17: 30,971,049 (GRCm39)	T2701K	probably damaging	Het
Eml3	T	A	19: 8,913,733 (GRCm39)	S424R	probably damaging	Het
Epm2aip1	A	G	9: 111,101,315 (GRCm39)	E96G	possibly damaging	Het
Ezr	T	C	17: 7,010,107 (GRCm39)	H314R	probably benign	Het
Fam193b	G	T	13: 55,702,247 (GRCm39)	H43Q	probably damaging	Het
Fam217a	T	A	13: 35,095,195 (GRCm39)	N340I	probably damaging	Het
Fcrl1	A	T	3: 87,292,109 (GRCm39)	Q89H	probably damaging	Het
Flg2	A	T	3: 93,127,076 (GRCm39)	H1996L	unknown	Het
Gabpb1	C	T	2: 126,481,169 (GRCm39)	V327M	possibly damaging	Het
Gtf3c3	A	G	1: 54,477,098 (GRCm39)	V36A	probably benign	Het
Hspg2	A	G	4: 137,275,407 (GRCm39)	N2739S	probably damaging	Het
Hyal1	A	G	9: 107,455,194 (GRCm39)		probably null	Het
Ipo13	T	C	4: 117,761,856 (GRCm39)	D448G	probably benign	Het
Kcnq5	T	C	1: 21,472,610 (GRCm39)	D860G	possibly damaging	Het
Kif13b	A	G	14: 64,973,715 (GRCm39)	N355S	probably damaging	Het
Kmt2c	T	A	5: 25,519,513 (GRCm39)	H2199L	possibly damaging	Het
Magi1	A	G	6: 93,724,310 (GRCm39)	F235S	probably damaging	Het
Maml1	A	C	11: 50,156,534 (GRCm39)	M547R	possibly damaging	Het
Mapk7	T	C	11: 61,384,689 (GRCm39)	K6E	possibly damaging	Het
Mbd5	T	A	2: 49,147,393 (GRCm39)	N534K	possibly damaging	Het
Mcat	G	A	15: 83,433,453 (GRCm39)	Q34*	probably null	Het
Mcu	T	A	10: 59,284,670 (GRCm39)	D180V	probably damaging	Het
Mettl21c	G	T	1: 44,048,951 (GRCm39)	P199T	probably benign	Het
Mndal	A	T	1: 173,700,441 (GRCm39)	S177T	probably benign	Het
Mpeg1	G	T	19: 12,438,611 (GRCm39)	C23F	probably benign	Het
Mup15	T	A	4: 61,356,471 (GRCm39)	Y98F	probably benign	Het
Myh8	T	C	11: 67,180,638 (GRCm39)	S625P	probably benign	Het
Nipsnap2	T	C	5: 129,830,282 (GRCm39)		probably benign	Het
Nlrp4e	T	C	7: 23,019,797 (GRCm39)	S95P	probably benign	Het
Or1e19	T	A	11: 73,316,653 (GRCm39)	D52V	possibly damaging	Het
Or4a66	T	C	2: 88,531,106 (GRCm39)	D189G	probably damaging	Het
Otop2	A	G	11: 115,220,675 (GRCm39)		probably null	Het
Pcnx4	G	C	12: 72,621,174 (GRCm39)	G998A	probably benign	Het
Pnkd	C	A	1: 74,390,681 (GRCm39)		probably null	Het
Ppp4r4	T	A	12: 103,573,204 (GRCm39)	V701E	probably benign	Het
Ryr2	A	G	13: 11,616,727 (GRCm39)	I3897T	probably damaging	Het
Scn1a	T	C	2: 66,162,631 (GRCm39)	E205G	probably damaging	Het
Sdk2	G	A	11: 113,784,401 (GRCm39)		probably benign	Het
Serpinb5	A	T	1: 106,803,782 (GRCm39)	Q156L	probably benign	Het
Setdb1	A	T	3: 95,234,778 (GRCm39)	V975D	probably benign	Het
Sik3	T	A	9: 46,113,320 (GRCm39)	V587E	probably damaging	Het
Sik3	C	A	9: 46,132,387 (GRCm39)	H1276Q	probably benign	Het
Spata7	T	C	12: 98,635,120 (GRCm39)	I384T	probably damaging	Het
Tanc2	T	A	11: 105,812,963 (GRCm39)	V1469D	probably benign	Het
Tasor2	T	C	13: 3,620,409 (GRCm39)	E2164G	probably damaging	Het
Tdrd5	A	T	1: 156,083,372 (GRCm39)	N888K	probably benign	Het
Tex22	T	C	12: 113,039,000 (GRCm39)	S34P	probably benign	Het
Tmed6	T	C	8: 107,790,754 (GRCm39)	T98A	probably benign	Het
Trim66	G	A	7: 109,083,826 (GRCm39)	P141L	probably benign	Het
Trpa1	T	C	1: 14,956,036 (GRCm39)	I778V	probably benign	Het
Urb2	T	A	8: 124,754,816 (GRCm39)	H174Q	probably damaging	Het
Usb1	T	C	8: 96,065,325 (GRCm39)	V59A	probably benign	Het
Vmn1r11	T	A	6: 57,114,394 (GRCm39)	N19K	probably damaging	Het
Vmn1r185	A	T	7: 26,311,219 (GRCm39)	F95L	probably benign	Het
Vmn1r206	C	T	13: 22,805,160 (GRCm39)	V16M	probably benign	Het
Vmn2r92	T	C	17: 18,387,625 (GRCm39)	V210A	probably benign	Het
Wdr17	A	T	8: 55,125,536 (GRCm39)	I448K	possibly damaging	Het
Zfp768	T	A	7: 126,942,733 (GRCm39)	Q465L	probably damaging	Het
Zfp804b	T	A	5: 6,821,105 (GRCm39)	N617Y	probably damaging	Het

Other mutations in Shc1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00990:Shc1	APN	3	89,331,536 (GRCm39)	missense	probably damaging	0.99
IGL01608:Shc1	APN	3	89,332,156 (GRCm39)	missense	probably damaging	0.96
IGL02710:Shc1	APN	3	89,331,917 (GRCm39)	splice site	probably null
PIT4382001:Shc1	UTSW	3	89,334,715 (GRCm39)	missense	probably benign	0.00
R0323:Shc1	UTSW	3	89,331,020 (GRCm39)	missense	probably damaging	0.98
R0445:Shc1	UTSW	3	89,333,844 (GRCm39)	missense	probably damaging	1.00
R0827:Shc1	UTSW	3	89,334,090 (GRCm39)	splice site	probably null
R0833:Shc1	UTSW	3	89,330,276 (GRCm39)	missense	probably damaging	1.00
R0836:Shc1	UTSW	3	89,330,276 (GRCm39)	missense	probably damaging	1.00
R1155:Shc1	UTSW	3	89,332,126 (GRCm39)	missense	probably benign	0.30
R1929:Shc1	UTSW	3	89,330,849 (GRCm39)	missense	probably damaging	1.00
R2271:Shc1	UTSW	3	89,330,849 (GRCm39)	missense	probably damaging	1.00
R4402:Shc1	UTSW	3	89,333,985 (GRCm39)	missense	probably benign
R4965:Shc1	UTSW	3	89,334,303 (GRCm39)	missense	probably damaging	0.98
R5898:Shc1	UTSW	3	89,334,274 (GRCm39)	nonsense	probably null
R6198:Shc1	UTSW	3	89,329,414 (GRCm39)	missense	probably benign
R6604:Shc1	UTSW	3	89,329,186 (GRCm39)	missense	probably damaging	1.00
R6673:Shc1	UTSW	3	89,329,269 (GRCm39)	missense	possibly damaging	0.93
R6705:Shc1	UTSW	3	89,330,266 (GRCm39)	nonsense	probably null
R7379:Shc1	UTSW	3	89,334,129 (GRCm39)	missense	probably benign	0.00
R8041:Shc1	UTSW	3	89,330,260 (GRCm39)	missense	probably damaging	1.00
R8284:Shc1	UTSW	3	89,329,215 (GRCm39)	missense	possibly damaging	0.70
R8700:Shc1	UTSW	3	89,334,740 (GRCm39)	missense	possibly damaging	0.92

Predicted Primers

PCR Primer
(F):5'- GAGACACCAGCTTCCTTCAAGTCAG -3'
(R):5'- GGCCTATCATCACAGGGCATTTTCC -3'

Sequencing Primer
(F):5'- CTGTAAAGATGCCTGGATAATCACG -3'
(R):5'- GGGCATTTTCCATTATAAGAACCCAC -3'

Posted On

2014-04-13