Incidental Mutation 'R8284:Shc1'
ID 638362
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 067707-MU
Accession Numbers
Essential gene? Probably essential (E-score: 0.969) question?
Stock # R8284 (G1)
Quality Score 225.009
Status Validated
Chromosome 3
Chromosomal Location 89325858-89337336 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to G at 89329215 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Serine to Alanine at position 20 (S20A)
Ref Sequence ENSEMBL: ENSMUSP00000091940 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000029679] [ENSMUST00000039110] [ENSMUST00000094378] [ENSMUST00000107417] [ENSMUST00000107422] [ENSMUST00000125036] [ENSMUST00000128238] [ENSMUST00000137793] [ENSMUST00000154791] [ENSMUST00000183484] [ENSMUST00000191485]
AlphaFold P98083
Predicted Effect probably benign
Transcript: ENSMUST00000029679
SMART Domains Protein: ENSMUSP00000029679
Gene: ENSMUSG00000028044

DomainStartEndE-ValueType
CKS 5 74 4.1e-48 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000039110
SMART Domains Protein: ENSMUSP00000035361
Gene: ENSMUSG00000042626

DomainStartEndE-ValueType
low complexity region 6 17 N/A INTRINSIC
PTB 47 211 2.15e-31 SMART
SH2 372 451 1.71e-26 SMART
Predicted Effect possibly damaging
Transcript: ENSMUST00000094378
AA Change: S20A

PolyPhen 2 Score 0.705 (Sensitivity: 0.86; Specificity: 0.92)
SMART Domains Protein: ENSMUSP00000091940
Gene: ENSMUSG00000042626
AA Change: S20A

DomainStartEndE-ValueType
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: ENSMUST00000107417
SMART Domains Protein: ENSMUSP00000103040
Gene: ENSMUSG00000042626

DomainStartEndE-ValueType
PTB 2 166 2.15e-31 SMART
SH2 327 406 1.71e-26 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000107422
SMART Domains Protein: ENSMUSP00000103045
Gene: ENSMUSG00000028044

DomainStartEndE-ValueType
CKS 1 52 3.88e-26 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000125036
SMART Domains Protein: ENSMUSP00000115509
Gene: ENSMUSG00000042626

DomainStartEndE-ValueType
PTB 1 155 1.5e-21 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000128238
SMART Domains Protein: ENSMUSP00000119293
Gene: ENSMUSG00000042626

DomainStartEndE-ValueType
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

DomainStartEndE-ValueType
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

DomainStartEndE-ValueType
low complexity region 6 17 N/A INTRINSIC
Pfam:PID 52 100 5.7e-13 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000183484
SMART Domains Protein: ENSMUSP00000138900
Gene: ENSMUSG00000028044

DomainStartEndE-ValueType
Pfam:CKS 5 36 2.4e-8 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000191485
SMART Domains Protein: ENSMUSP00000140336
Gene: ENSMUSG00000042626

DomainStartEndE-ValueType
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: 99.6%
  • 20x: 98.6%
Validation Efficiency 100% (54/54)
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: 55 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Adamts14 T C 10: 61,034,438 (GRCm39) Y1147C possibly damaging Het
Adgrf5 T A 17: 43,766,161 (GRCm39) S1328T unknown Het
Aff4 A G 11: 53,295,379 (GRCm39) K860E probably damaging Het
Aox1 A C 1: 58,115,250 (GRCm39) H745P probably damaging Het
Bpifc T C 10: 85,836,413 (GRCm39) T31A probably benign Het
C3 C A 17: 57,530,938 (GRCm39) V388L probably benign Het
Celsr3 G T 9: 108,723,612 (GRCm39) M2874I probably damaging Het
Cnga4 T A 7: 105,057,239 (GRCm39) D550E probably benign Het
Dhx8 A G 11: 101,648,455 (GRCm39) T918A probably damaging Het
Dnah14 A C 1: 181,601,376 (GRCm39) E3670A probably benign Het
Fbxo31 T C 8: 122,287,181 (GRCm39) I131V probably benign Het
Ftcd T C 10: 76,413,893 (GRCm39) V99A probably benign Het
Gucy2e A G 11: 69,123,177 (GRCm39) V471A probably benign Het
H60b T A 10: 22,162,971 (GRCm39) L182Q probably benign Het
Hbp1 G A 12: 31,987,625 (GRCm39) H188Y probably damaging Het
Itga4 C T 2: 79,151,783 (GRCm39) T862I probably benign Het
Kcnmb4 T A 10: 116,254,158 (GRCm39) K206N probably damaging Het
Klra4 A G 6: 130,042,243 (GRCm39) F8S possibly damaging Het
Mrpl2 C A 17: 46,958,435 (GRCm39) Y72* probably null Het
Nars2 C A 7: 96,600,845 (GRCm39) probably benign Het
Nup214 T C 2: 31,886,458 (GRCm39) S607P possibly damaging Het
Oas1d C T 5: 121,057,221 (GRCm39) R276* probably null Het
Or12d13 C T 17: 37,647,587 (GRCm39) V179I probably benign Het
Or1l8 T A 2: 36,818,018 (GRCm39) Y36F probably damaging Het
Or2t1 T A 14: 14,329,011 (GRCm38) L300Q possibly damaging Het
Or2y1b A G 11: 49,209,002 (GRCm39) T210A probably benign Het
Pex13 A G 11: 23,605,685 (GRCm39) S182P possibly damaging Het
Piwil4 G T 9: 14,638,774 (GRCm39) N297K probably benign Het
Plxna4 T C 6: 32,129,789 (GRCm39) T1845A probably benign Het
Pml T C 9: 58,136,643 (GRCm39) N579D probably benign Het
Ppl A G 16: 4,950,201 (GRCm39) S3P probably damaging Het
Pramel16 G T 4: 143,676,695 (GRCm39) D136E possibly damaging Het
Prss54 G A 8: 96,285,994 (GRCm39) Q360* probably null Het
Ralgps2 A G 1: 156,655,718 (GRCm39) I402T probably benign Het
Rnf213 T A 11: 119,318,909 (GRCm39) D1123E Het
Sdha A T 13: 74,479,416 (GRCm39) probably null Het
Senp8 G A 9: 59,644,814 (GRCm39) T114I Het
Setx C T 2: 29,035,348 (GRCm39) T611I possibly damaging Het
Slc15a1 T C 14: 121,727,275 (GRCm39) I98V probably benign Het
Snrk A G 9: 121,989,538 (GRCm39) E294G probably damaging Het
Sox18 G A 2: 181,312,751 (GRCm39) P127S probably damaging Het
Spta1 A G 1: 174,007,387 (GRCm39) T206A probably benign Het
Tcfl5 A G 2: 180,280,330 (GRCm39) S358P probably benign Het
Tecta T A 9: 42,289,325 (GRCm39) L413F possibly damaging Het
Tlk1 T C 2: 70,544,365 (GRCm39) T757A probably benign Het
Tmem232 T A 17: 65,709,990 (GRCm39) I433F probably damaging Het
Top1mt T A 15: 75,539,712 (GRCm39) K300* probably null Het
Trbv20 C T 6: 41,165,782 (GRCm39) A69V probably damaging Het
Trim12a A T 7: 103,955,282 (GRCm39) L147Q probably damaging Het
Tuba8 G A 6: 121,199,736 (GRCm39) S140N probably damaging Het
Vcan A T 13: 89,852,454 (GRCm39) N835K possibly damaging Het
Xrcc1 G A 7: 24,271,703 (GRCm39) R562H probably damaging Het
Yipf7 C T 5: 69,674,539 (GRCm39) G202D probably benign Het
Ythdc1 T G 5: 86,964,325 (GRCm39) S45A probably benign Het
Zfp1002 T C 2: 150,097,276 (GRCm39) probably benign Het
Other mutations in Shc1
AlleleSourceChrCoordTypePredicted EffectPPH 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
R8700:Shc1 UTSW 3 89,334,740 (GRCm39) missense possibly damaging 0.92
Predicted Primers PCR Primer
(F):5'- ATCTGTTATCACCGGGCTGC -3'
(R):5'- TCAGCTTGTTCATGTCCTGGAG -3'

Sequencing Primer
(F):5'- TGCCGAGGTCAGACTAGG -3'
(R):5'- CAAGAGGCCTGAGTCCCGAAG -3'
Posted On 2020-07-28