Incidental Mutation 'R8700:Shc1'
| ID |
668982 |
| 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 |
068554-MU
|
| Accession Numbers |
|
| Essential gene? |
Probably essential
(E-score: 0.969)
|
| Stock # |
R8700 (G1)
|
| Quality Score |
225.009 |
|
Status
|
Validated
|
| Chromosome |
3 |
| Chromosomal Location |
89325858-89337336 bp(+) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
A to G
at 89334740 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Aspartic acid to Glycine
at position 533
(D533G)
|
| 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 |
possibly damaging
Transcript: ENSMUST00000039110
AA Change: D423G
PolyPhen 2
Score 0.921 (Sensitivity: 0.81; Specificity: 0.94)
|
| SMART Domains |
Protein: ENSMUSP00000035361
Gene: ENSMUSG00000042626
AA Change: D423G
| 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 |
possibly damaging
Transcript: ENSMUST00000094378
AA Change: D533G
PolyPhen 2
Score 0.921 (Sensitivity: 0.81; Specificity: 0.94)
|
| SMART Domains |
Protein: ENSMUSP00000091940
Gene: ENSMUSG00000042626
AA Change: D533G
| 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 |
possibly damaging
Transcript: ENSMUST00000107417
AA Change: D378G
PolyPhen 2
Score 0.921 (Sensitivity: 0.81; Specificity: 0.94)
|
| SMART Domains |
Protein: ENSMUSP00000103040
Gene: ENSMUSG00000042626
AA Change: D378G
| 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 |
possibly damaging
Transcript: ENSMUST00000191485
AA Change: D423G
PolyPhen 2
Score 0.921 (Sensitivity: 0.81; Specificity: 0.94)
|
| SMART Domains |
Protein: ENSMUSP00000140336
Gene: ENSMUSG00000042626
AA Change: D423G
| 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: 100.0%
- 3x: 99.9%
- 10x: 99.7%
- 20x: 98.8%
|
| Validation Efficiency |
98% (59/60) |
| 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: 59 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| 4933414I15Rik |
T |
A |
11: 50,833,344 (GRCm39) |
D86V |
unknown |
Het |
| Abtb2 |
C |
A |
2: 103,397,289 (GRCm39) |
T73K |
probably damaging |
Het |
| Akr1c14 |
T |
C |
13: 4,131,157 (GRCm39) |
|
probably benign |
Het |
| Anapc7 |
T |
A |
5: 122,560,669 (GRCm39) |
M10K |
probably damaging |
Het |
| Ano7 |
T |
G |
1: 93,316,329 (GRCm39) |
I204S |
probably damaging |
Het |
| Arhgef39 |
T |
A |
4: 43,496,715 (GRCm39) |
Q333L |
probably benign |
Het |
| Art5 |
T |
C |
7: 101,748,862 (GRCm39) |
|
probably benign |
Het |
| Asah1 |
T |
C |
8: 41,813,312 (GRCm39) |
T34A |
probably benign |
Het |
| Atp9b |
T |
C |
18: 80,796,361 (GRCm39) |
E894G |
|
Het |
| Atxn7l3 |
A |
T |
11: 102,184,747 (GRCm39) |
M126K |
possibly damaging |
Het |
| Cacna2d4 |
A |
G |
6: 119,258,654 (GRCm39) |
D580G |
probably damaging |
Het |
| Calcoco2 |
T |
A |
11: 95,994,330 (GRCm39) |
K74N |
probably benign |
Het |
| Ccdc163 |
T |
C |
4: 116,571,348 (GRCm39) |
|
probably null |
Het |
| Cep164 |
T |
C |
9: 45,686,667 (GRCm39) |
|
probably null |
Het |
| Chd7 |
T |
A |
4: 8,833,892 (GRCm39) |
N1215K |
probably damaging |
Het |
| Chsy3 |
T |
C |
18: 59,309,487 (GRCm39) |
Y247H |
probably damaging |
Het |
| Clec16a |
A |
G |
16: 10,506,422 (GRCm39) |
Y714C |
probably damaging |
Het |
| Col12a1 |
A |
G |
9: 79,527,371 (GRCm39) |
V2653A |
probably benign |
Het |
| Daam2 |
T |
A |
17: 49,803,180 (GRCm39) |
K77N |
probably damaging |
Het |
| Dhx35 |
T |
A |
2: 158,682,552 (GRCm39) |
M495K |
possibly damaging |
Het |
| Disp2 |
T |
A |
2: 118,620,340 (GRCm39) |
C357* |
probably null |
Het |
| Dnah6 |
T |
A |
6: 73,052,873 (GRCm39) |
|
probably benign |
Het |
| Dnah7a |
T |
G |
1: 53,535,088 (GRCm39) |
D2724A |
possibly damaging |
Het |
| Entpd5 |
A |
T |
12: 84,443,508 (GRCm39) |
D53E |
probably damaging |
Het |
| Fto |
T |
A |
8: 92,249,461 (GRCm39) |
I431N |
probably damaging |
Het |
| Gabrr2 |
T |
C |
4: 33,095,488 (GRCm39) |
I459T |
probably damaging |
Het |
| Gm5565 |
T |
A |
5: 146,097,236 (GRCm39) |
I29F |
probably damaging |
Het |
| Gm9195 |
C |
T |
14: 72,720,171 (GRCm39) |
G87R |
probably damaging |
Het |
| Grin2a |
T |
C |
16: 9,397,412 (GRCm39) |
S892G |
probably benign |
Het |
| Katnip |
A |
G |
7: 125,429,042 (GRCm39) |
|
probably benign |
Het |
| Mki67 |
T |
C |
7: 135,307,436 (GRCm39) |
N106S |
|
Het |
| Myo16 |
T |
C |
8: 10,463,172 (GRCm39) |
S580P |
unknown |
Het |
| Neo1 |
A |
G |
9: 58,825,913 (GRCm39) |
S672P |
probably benign |
Het |
| Nxph3 |
A |
T |
11: 95,401,706 (GRCm39) |
V236E |
probably damaging |
Het |
| Or10j7 |
G |
T |
1: 173,011,429 (GRCm39) |
P191T |
probably benign |
Het |
| Or7e171-ps1 |
A |
C |
9: 19,852,996 (GRCm39) |
L247V |
unknown |
Het |
| Pcdhb14 |
T |
C |
18: 37,582,652 (GRCm39) |
V586A |
probably damaging |
Het |
| Peg10 |
T |
TCCA |
6: 4,756,451 (GRCm39) |
|
probably benign |
Het |
| Pja2 |
C |
T |
17: 64,599,949 (GRCm39) |
D512N |
probably damaging |
Het |
| Ppfibp2 |
A |
G |
7: 107,345,602 (GRCm39) |
T875A |
possibly damaging |
Het |
| Ppp3cc |
C |
A |
14: 70,474,001 (GRCm39) |
C332F |
probably damaging |
Het |
| Pramel16 |
T |
A |
4: 143,675,701 (GRCm39) |
H375L |
possibly damaging |
Het |
| Psg18 |
A |
T |
7: 18,087,550 (GRCm39) |
V36D |
probably damaging |
Het |
| Ptprh |
A |
G |
7: 4,567,190 (GRCm39) |
S561P |
probably damaging |
Het |
| Rhbdf2 |
G |
A |
11: 116,498,230 (GRCm39) |
|
probably benign |
Het |
| Ripk2 |
T |
A |
4: 16,158,422 (GRCm39) |
N61I |
possibly damaging |
Het |
| Setdb2 |
T |
C |
14: 59,654,888 (GRCm39) |
Y318C |
probably damaging |
Het |
| Sirpb1a |
T |
C |
3: 15,476,419 (GRCm39) |
E193G |
probably damaging |
Het |
| Slc41a2 |
T |
C |
10: 83,152,097 (GRCm39) |
E126G |
probably damaging |
Het |
| Spata31h1 |
A |
T |
10: 82,127,859 (GRCm39) |
I1717N |
possibly damaging |
Het |
| Srms |
C |
A |
2: 180,848,521 (GRCm39) |
A413S |
probably damaging |
Het |
| Tob2 |
G |
T |
15: 81,735,802 (GRCm39) |
R56S |
probably damaging |
Het |
| Unc119 |
T |
C |
11: 78,238,137 (GRCm39) |
I105T |
probably benign |
Het |
| Unc13c |
T |
C |
9: 73,479,679 (GRCm39) |
I1742V |
probably benign |
Het |
| Vmn1r46 |
C |
T |
6: 89,953,325 (GRCm39) |
T58I |
probably benign |
Het |
| Vmn2r81 |
G |
T |
10: 79,129,517 (GRCm39) |
V803F |
probably damaging |
Het |
| Zfp365 |
T |
C |
10: 67,745,535 (GRCm39) |
K81R |
possibly damaging |
Het |
| Zfp974 |
G |
T |
7: 27,609,472 (GRCm39) |
T751K |
possibly damaging |
Het |
| Zfpl1 |
T |
C |
19: 6,132,464 (GRCm39) |
N149S |
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 |
|
|
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 |
|
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 |
|
| Predicted Primers |
PCR Primer
(F):5'- TAGAGCCCTTTGAAGATGCAC -3'
(R):5'- AGAACACAGCTCAGACTCGAGG -3'
Sequencing Primer
(F):5'- ATGTCCATGGCTGAGCAG -3'
(R):5'- CTCAGACTCGAGGACAGCAG -3'
|
| Posted On |
2021-04-30 |
Incidental Mutation