Mutagenetix > Incidental Mutation

Incidental Mutation 'PIT4382001:Shc1'

554667

Institutional Source

Beutler Lab

Gene Symbol

Shc1

Ensembl Gene

ENSMUSG00000042626

Gene Name

src homology 2 domain-containing transforming protein C1

Synonyms

ShcA, p66shc, p66

Accession Numbers

Essential gene?

Probably essential (E-score: 0.969) question?

Stock #

PIT4382001 (G1)

Quality Score

180.009

Status

Not validated

Chromosome

Chromosomal Location

89325858-89337336 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

C to A at 89334715 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Glutamine to Lysine at position 525 (Q525K)

Ref Sequence

ENSEMBL: ENSMUSP00000091940 (fasta)

Gene Model

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

AlphaFold

P98083

Predicted Effect

probably benign
Transcript: ENSMUST00000039110
AA Change: Q415K

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

SMART Domains

Protein: ENSMUSP00000035361
Gene: ENSMUSG00000042626
AA Change: Q415K

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 benign
Transcript: ENSMUST00000094378
AA Change: Q525K

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

SMART Domains

Protein: ENSMUSP00000091940
Gene: ENSMUSG00000042626
AA Change: Q525K

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 benign
Transcript: ENSMUST00000107417
AA Change: Q370K

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

SMART Domains

Protein: ENSMUSP00000103040
Gene: ENSMUSG00000042626
AA Change: Q370K

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

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: 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

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: ENSMUST00000191485
AA Change: Q415K

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

SMART Domains

Protein: ENSMUSP00000140336
Gene: ENSMUSG00000042626
AA Change: Q415K

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

Coding Region Coverage

1x: 92.9%
3x: 90.5%
10x: 84.6%
20x: 72.3%

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: 68 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
9430038I01Rik	G	T	7: 136,978,711 (GRCm39)	H144N	unknown	Het
Acsm4	C	T	7: 119,297,798 (GRCm39)	T145M	probably damaging	Het
Adam10	T	C	9: 70,673,363 (GRCm39)	L498P	probably damaging	Het
Adgrl2	A	G	3: 148,522,934 (GRCm39)	L430P		Het
Alk	T	C	17: 72,256,916 (GRCm39)	M648V	probably benign	Het
Arhgap35	T	C	7: 16,297,794 (GRCm39)	R424G	possibly damaging	Het
Baiap2l1	T	C	5: 144,215,480 (GRCm39)	K342E	possibly damaging	Het
Ccdc54	C	T	16: 50,411,219 (GRCm39)	V16M	probably damaging	Het
Chil3	T	G	3: 106,055,975 (GRCm39)	D366A	probably damaging	Het
Chuk	A	G	19: 44,087,046 (GRCm39)	V151A	probably damaging	Het
Cpd	T	G	11: 76,688,614 (GRCm39)	H886P	probably benign	Het
Cped1	T	A	6: 22,222,449 (GRCm39)	C736*	probably null	Het
Creb3l3	T	C	10: 80,920,746 (GRCm39)	E428G	probably benign	Het
Csad	G	A	15: 102,097,085 (GRCm39)	L7F	probably benign	Het
Dnah1	C	T	14: 31,006,412 (GRCm39)	D2255N	probably damaging	Het
Dnajb12	T	C	10: 59,728,508 (GRCm39)	Y159H	probably damaging	Het
Dpysl4	T	A	7: 138,669,494 (GRCm39)	Y57*	probably null	Het
F2rl1	T	G	13: 95,650,154 (GRCm39)	N243H	probably benign	Het
Fhl4	T	C	10: 84,934,293 (GRCm39)	K163E	possibly damaging	Het
Flot2	T	C	11: 77,944,193 (GRCm39)	S46P	possibly damaging	Het
Fsip2	C	A	2: 82,821,196 (GRCm39)	T5643K	possibly damaging	Het
Golga4	T	A	9: 118,382,521 (GRCm39)	Y542N	possibly damaging	Het
Il17re	A	G	6: 113,446,038 (GRCm39)	T426A	probably benign	Het
Kdm2a	T	A	19: 4,393,201 (GRCm39)	M385L	probably benign	Het
Kdm3b	T	C	18: 34,942,140 (GRCm39)	S744P	probably damaging	Het
Krtap20-1	T	A	16: 88,881,048 (GRCm39)	Y26*	probably null	Het
Lama2	T	C	10: 27,080,901 (GRCm39)	D974G	probably damaging	Het
Ldc1	A	T	4: 130,112,954 (GRCm39)	N147K	possibly damaging	Het
Lipo5	A	T	19: 33,443,339 (GRCm39)	L159Q	probably null	Het
LTO1	T	A	7: 144,470,181 (GRCm39)	Y37N	probably damaging	Het
Mau2	C	T	8: 70,483,302 (GRCm39)	E187K	possibly damaging	Het
Mrpl9	T	C	3: 94,355,136 (GRCm39)	L236P	probably benign	Het
Mta1	A	G	12: 113,096,870 (GRCm39)	T564A	probably benign	Het
Mylk	C	T	16: 34,696,012 (GRCm39)	S249L	probably damaging	Het
Ncor1	G	T	11: 62,235,489 (GRCm39)	T331K	probably damaging	Het
Nsun3	T	A	16: 62,606,228 (GRCm39)	K15N	probably damaging	Het
Nsun5	A	G	5: 135,400,355 (GRCm39)	Y132C	probably benign	Het
Obsl1	T	A	1: 75,464,607 (GRCm39)	T1605S	probably benign	Het
Or10a3n	A	G	7: 108,493,309 (GRCm39)	Y107H	probably damaging	Het
Or51f1	A	G	7: 102,505,809 (GRCm39)	Y227H	probably damaging	Het
Or51t4	A	T	7: 102,598,656 (GRCm39)	Y328F	probably benign	Het
Or5b109	T	C	19: 13,212,259 (GRCm39)	I215T	probably damaging	Het
P2rx1	A	G	11: 72,900,026 (GRCm39)	N148D	probably benign	Het
Pogz	T	A	3: 94,787,107 (GRCm39)	S1232T	probably damaging	Het
Polr3b	C	A	10: 84,520,049 (GRCm39)	T655N	probably damaging	Het
Prss34	T	C	17: 25,517,882 (GRCm39)		probably null	Het
Rhpn2	A	G	7: 35,090,178 (GRCm39)		probably null	Het
Runx1	T	A	16: 92,410,648 (GRCm39)	D256V	probably damaging	Het
Slc10a5	T	C	3: 10,400,507 (GRCm39)	D51G	probably benign	Het
Slc6a3	A	T	13: 73,719,642 (GRCm39)	N557I	probably benign	Het
Slmap	C	T	14: 26,254,586 (GRCm39)	R32H	probably damaging	Het
Spata31d1c	T	C	13: 65,183,985 (GRCm39)	I509T	probably benign	Het
Spata31e4	A	T	13: 50,855,007 (GRCm39)	E215V	probably damaging	Het
Srr	C	A	11: 74,801,134 (GRCm39)	V138F	probably benign	Het
Tas2r118	G	A	6: 23,969,785 (GRCm39)	T92I	possibly damaging	Het
Tcaf2	A	T	6: 42,601,300 (GRCm39)	*920K	probably null	Het
Tenm2	T	A	11: 35,954,729 (GRCm39)	Y1141F	probably damaging	Het
Thoc6	T	C	17: 23,887,841 (GRCm39)	N322S	probably benign	Het
Tlcd2	A	G	11: 75,359,417 (GRCm39)	I70V	probably benign	Het
Tmem214	A	G	5: 31,028,795 (GRCm39)	D128G	possibly damaging	Het
Trav13d-4	T	C	14: 53,995,238 (GRCm39)	V64A	probably benign	Het
Tyro3	T	C	2: 119,632,845 (GRCm39)	W122R	probably damaging	Het
Ugcg	A	G	4: 59,213,246 (GRCm39)	D144G	possibly damaging	Het
Uimc1	T	C	13: 55,178,828 (GRCm39)	D627G	probably benign	Het
Utp6	T	C	11: 79,853,099 (GRCm39)	I13V	probably benign	Het
Vmn2r99	A	G	17: 19,614,605 (GRCm39)	K775R	probably damaging	Het
Wdfy3	CG	C	5: 102,030,827 (GRCm39)		probably null	Het
Zw10	C	T	9: 48,982,944 (GRCm39)	T525I	probably benign	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
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
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'- AGAGCCCTTTGAAGATGCAC -3'
(R):5'- GAACACAGCTCAGACTCGAG -3'

Sequencing Primer
(F):5'- TCCATGTCCATGGCTGAG -3'
(R):5'- CAGCTCAGACTCGAGGACAG -3'

Posted On

2019-06-07