Mutagenetix > Incidental Mutation

Incidental Mutation 'R2271:Shc1'

242451

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

040271-MU

Accession Numbers

Essential gene?

Probably essential (E-score: 0.969) question?

Stock #

R2271 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

89325858-89337336 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 89330849 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Glycine to Serine at position 91 (G91S)

Ref Sequence

ENSEMBL: ENSMUSP00000123635 (fasta)

Gene Model

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

AlphaFold

P98083

Predicted Effect

probably benign
Transcript: ENSMUST00000039110
AA Change: G91S

PolyPhen 2 Score 0.003 (Sensitivity: 0.98; Specificity: 0.44)

SMART Domains

Protein: ENSMUSP00000035361
Gene: ENSMUSG00000042626
AA Change: G91S

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 damaging
Transcript: ENSMUST00000094378
AA Change: G201S

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000091940
Gene: ENSMUSG00000042626
AA Change: G201S

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 damaging
Transcript: ENSMUST00000107417
AA Change: G46S

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000103040
Gene: ENSMUSG00000042626
AA Change: G46S

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

Predicted Effect

probably damaging
Transcript: ENSMUST00000125036
AA Change: G35S

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

SMART Domains

Protein: ENSMUSP00000115509
Gene: ENSMUSG00000042626
AA Change: G35S

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

Predicted Effect

probably damaging
Transcript: ENSMUST00000128238
AA Change: G91S

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000119293
Gene: ENSMUSG00000042626
AA Change: G91S

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 damaging
Transcript: ENSMUST00000137793
AA Change: G91S

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000117190
Gene: ENSMUSG00000042626
AA Change: G91S

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

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000146306

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000153334

Predicted Effect

probably damaging
Transcript: ENSMUST00000191485
AA Change: G91S

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000140336
Gene: ENSMUSG00000042626
AA Change: G91S

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 damaging
Transcript: ENSMUST00000154791
AA Change: G91S

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

SMART Domains

Protein: ENSMUSP00000123635
Gene: ENSMUSG00000042626
AA Change: G91S

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

Meta Mutation Damage Score

0.7054

Coding Region Coverage

1x: 99.2%
3x: 98.6%
10x: 97.3%
20x: 95.1%

Validation Efficiency

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: 82 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2310057J18Rik	T	A	10: 28,857,575 (GRCm39)	Q194L	probably damaging	Het
Acsf2	T	A	11: 94,449,699 (GRCm39)	K574*	probably null	Het
Adam22	T	C	5: 8,171,108 (GRCm39)	E614G	probably damaging	Het
Ap4e1	T	C	2: 126,889,083 (GRCm39)		probably null	Het
Arid3c	T	A	4: 41,724,744 (GRCm39)	I364F	probably damaging	Het
Bcan	T	A	3: 87,900,401 (GRCm39)	S611C	probably damaging	Het
Birc6	T	C	17: 74,909,966 (GRCm39)	V1453A	probably benign	Het
Carnmt1	T	C	19: 18,680,734 (GRCm39)	L336P	probably damaging	Het
Ccdc146	C	A	5: 21,604,719 (GRCm39)	D40Y	probably benign	Het
Ccdc83	C	T	7: 89,873,285 (GRCm39)	V357I	probably damaging	Het
Cdh22	A	T	2: 164,985,767 (GRCm39)		probably null	Het
Cdk5rap2	A	C	4: 70,184,915 (GRCm39)	S1178R	probably benign	Het
Cdkl3	T	C	11: 51,923,322 (GRCm39)	V45A	probably benign	Het
Chd7	A	G	4: 8,785,532 (GRCm39)	D612G	probably damaging	Het
Chst11	T	C	10: 83,027,004 (GRCm39)	Y144H	probably damaging	Het
Cops6	A	T	5: 138,159,403 (GRCm39)	N10I	probably benign	Het
Cyfip1	G	T	7: 55,549,705 (GRCm39)	R624L	probably null	Het
Cyp27a1	A	G	1: 74,775,846 (GRCm39)	N344D	probably damaging	Het
Des	T	G	1: 75,340,137 (GRCm39)	M348R	probably damaging	Het
Dis3l	T	A	9: 64,238,165 (GRCm39)	D109V	probably damaging	Het
Disp3	C	T	4: 148,356,059 (GRCm39)	R267Q	possibly damaging	Het
Dnah3	T	A	7: 119,574,352 (GRCm39)	I2136F	probably benign	Het
Dnah9	T	C	11: 66,003,188 (GRCm39)	D872G	probably benign	Het
Dnajb14	G	A	3: 137,591,141 (GRCm39)	G31S	probably benign	Het
Dop1a	T	G	9: 86,376,471 (GRCm39)	V235G	probably damaging	Het
Efcab6	T	A	15: 83,831,200 (GRCm39)	R571S	probably benign	Het
Emsy	T	G	7: 98,275,830 (GRCm39)	K352N	probably damaging	Het
Erbb4	T	C	1: 68,238,047 (GRCm39)	N814S	probably damaging	Het
Fgfbp1	T	A	5: 44,136,672 (GRCm39)	M207L	probably benign	Het
Filip1	T	C	9: 79,727,212 (GRCm39)	E469G	probably damaging	Het
Garem2	T	G	5: 30,321,972 (GRCm39)	L777R	probably damaging	Het
Garin5b	T	A	7: 4,761,186 (GRCm39)	T509S	probably benign	Het
Hkdc1	T	C	10: 62,253,677 (GRCm39)	T35A	probably benign	Het
Hps6	C	T	19: 45,994,121 (GRCm39)	A686V	possibly damaging	Het
Irs1	T	C	1: 82,266,180 (GRCm39)	S679G	probably benign	Het
Ism1	T	A	2: 139,599,293 (GRCm39)	I415N	probably damaging	Het
Kdm1b	TCATTGTCC	TCATTGTCCATTGTCC	13: 47,217,564 (GRCm39)		probably null	Het
Kpna1	G	A	16: 35,851,591 (GRCm39)	A392T	probably damaging	Het
Lipa	T	A	19: 34,488,290 (GRCm39)	R119*	probably null	Het
Lrrc37	T	C	11: 103,505,033 (GRCm39)	T2312A	possibly damaging	Het
Mocs1	A	T	17: 49,756,137 (GRCm39)	K198M	probably damaging	Het
Mrc2	G	A	11: 105,239,257 (GRCm39)		probably null	Het
Msh5	A	G	17: 35,263,366 (GRCm39)	I154T	probably benign	Het
Muc6	T	A	7: 141,217,423 (GRCm39)	T2417S	possibly damaging	Het
Ncbp2	T	C	16: 31,775,769 (GRCm39)	Y138H	probably damaging	Het
Ndufv1	C	A	19: 4,058,347 (GRCm39)	R359L	probably benign	Het
Neu3	G	C	7: 99,462,650 (GRCm39)	R358G	probably benign	Het
Ntrk3	A	C	7: 78,166,471 (GRCm39)		probably null	Het
Or1n1	G	A	2: 36,749,637 (GRCm39)	S241F	probably damaging	Het
Or8b12i	T	A	9: 20,082,705 (GRCm39)	H54L	possibly damaging	Het
Or8j3	A	G	2: 86,028,161 (GRCm39)	F312L	probably benign	Het
Pik3c2b	T	C	1: 133,031,166 (GRCm39)	S1491P	probably benign	Het
Plb1	G	T	5: 32,450,586 (GRCm39)	D376Y	probably damaging	Het
Plch1	T	A	3: 63,651,956 (GRCm39)	K378N	probably damaging	Het
Plekhm1	C	T	11: 103,277,948 (GRCm39)	E383K	probably benign	Het
Plxnb1	T	C	9: 108,931,776 (GRCm39)		probably null	Het
Prkdc	A	G	16: 15,472,681 (GRCm39)		probably null	Het
Prpf8	T	A	11: 75,386,189 (GRCm39)	V946E	probably damaging	Het
Psma5-ps	A	G	10: 85,149,595 (GRCm39)		noncoding transcript	Het
Ptprh	C	A	7: 4,606,132 (GRCm39)		probably benign	Het
Rngtt	T	A	4: 33,500,302 (GRCm39)	C565*	probably null	Het
Sacs	A	G	14: 61,442,109 (GRCm39)	H1385R	probably benign	Het
Sec24a	A	G	11: 51,607,277 (GRCm39)	S656P	possibly damaging	Het
Serpinb13	A	T	1: 106,926,756 (GRCm39)	I251L	possibly damaging	Het
Sin3b	T	A	8: 73,460,047 (GRCm39)	N211K	probably benign	Het
Slc22a2	A	T	17: 12,805,692 (GRCm39)	M148L	probably benign	Het
Slc3a1	G	A	17: 85,371,220 (GRCm39)	V591I	probably benign	Het
Slc47a2	A	T	11: 61,219,352 (GRCm39)		probably null	Het
Spag17	C	T	3: 100,014,113 (GRCm39)	P2129S	probably damaging	Het
Specc1l	C	T	10: 75,081,438 (GRCm39)	S278F	probably damaging	Het
Sphkap	T	A	1: 83,234,942 (GRCm39)	D1628V	probably damaging	Het
Themis3	C	T	17: 66,862,699 (GRCm39)	V420I	possibly damaging	Het
Ttc39d	A	G	17: 80,524,675 (GRCm39)	K445E	probably damaging	Het
U2surp	T	C	9: 95,373,473 (GRCm39)	E232G	possibly damaging	Het
Usp25	T	A	16: 76,873,317 (GRCm39)	F458L	probably damaging	Het
Usp7	T	C	16: 8,516,333 (GRCm39)	S649G	probably benign	Het
Vmn1r10	A	G	6: 57,091,088 (GRCm39)	T227A	probably damaging	Het
Zcchc12	C	T	X: 35,462,118 (GRCm39)	T345M	possibly damaging	Het
Zfp444	T	C	7: 6,192,554 (GRCm39)	C191R	probably damaging	Het
Zfp729b	A	T	13: 67,740,352 (GRCm39)	C648S	probably damaging	Het
Zfp799	A	G	17: 33,040,777 (GRCm39)	Y58H	probably damaging	Het
Zfp938	C	T	10: 82,061,381 (GRCm39)	G413D	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
R1497:Shc1	UTSW	3	89,335,752 (GRCm39)	makesense	probably null
R1929: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'- TAGCCATTGAAGCCCTAACC -3'
(R):5'- GGCATTCCAGCAAACTTCAGG -3'

Sequencing Primer
(F):5'- CGGTGTCATCAAATATTAAAGGCCC -3'
(R):5'- GCATTCCAGCAAACTTCAGGTTACTC -3'

Posted On

2014-10-16