Incidental Mutation 'R1929:Shc1'
ID 215145
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 039947-MU
Accession Numbers
Essential gene? Probably essential (E-score: 0.969) question?
Stock # R1929 (G1)
Quality Score 225
Status Validated
Chromosome 3
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

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 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

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 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

DomainStartEndE-ValueType
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

DomainStartEndE-ValueType
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

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 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

DomainStartEndE-ValueType
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

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 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

DomainStartEndE-ValueType
low complexity region 6 17 N/A INTRINSIC
Pfam:PID 52 100 5.7e-13 PFAM
Meta Mutation Damage Score 0.7054 question?
Coding Region Coverage
  • 1x: 97.5%
  • 3x: 96.9%
  • 10x: 95.3%
  • 20x: 92.4%
Validation Efficiency 98% (107/109)
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: 103 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Adcy10 A T 1: 165,337,866 (GRCm39) E160V probably damaging Het
Amdhd2 T C 17: 24,376,860 (GRCm39) probably null Het
Angel1 A C 12: 86,749,093 (GRCm39) L656V probably damaging Het
Ankrd12 G A 17: 66,293,681 (GRCm39) S584L possibly damaging Het
Apbb2 T A 5: 66,464,958 (GRCm39) N679Y probably benign 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
Bnip3 T G 7: 138,496,359 (GRCm39) silent Het
Btc T C 5: 91,510,260 (GRCm39) Y111C probably damaging Het
Carnmt1 T C 19: 18,680,734 (GRCm39) L336P probably damaging Het
Ccdc83 C T 7: 89,873,285 (GRCm39) V357I probably damaging Het
Cd2bp2 T C 7: 126,793,050 (GRCm39) D324G probably benign Het
Cdc20b A G 13: 113,208,451 (GRCm39) T216A probably benign Het
Cdk17 T C 10: 93,064,540 (GRCm39) Y270H probably damaging Het
Cenpv T C 11: 62,416,059 (GRCm39) E230G probably benign Het
Chst11 T C 10: 83,027,004 (GRCm39) Y144H probably damaging Het
Cracr2a T A 6: 127,584,261 (GRCm39) F107I probably damaging Het
Cyfip1 G T 7: 55,549,705 (GRCm39) R624L probably null Het
Cyp27b1 T A 10: 126,884,181 (GRCm39) V11D probably damaging Het
Ddc T C 11: 11,785,764 (GRCm39) N308D 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
Dnah3 T A 7: 119,574,352 (GRCm39) I2136F probably benign Het
Dnah9 T C 11: 65,867,224 (GRCm39) S2785G probably benign Het
Dop1a T G 9: 86,376,471 (GRCm39) V235G probably damaging Het
Dtx3l A T 16: 35,754,059 (GRCm39) D182E possibly damaging Het
Efcab6 A G 15: 83,777,163 (GRCm39) probably benign Het
Elac2 T A 11: 64,870,015 (GRCm39) S27T 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
Fgd6 T C 10: 93,880,868 (GRCm39) V574A probably benign Het
Filip1 T C 9: 79,727,212 (GRCm39) E469G probably damaging Het
Fmo1 A T 1: 162,661,424 (GRCm39) D286E probably damaging Het
Fmo4 A T 1: 162,626,616 (GRCm39) I310N possibly damaging Het
Focad A G 4: 88,260,449 (GRCm39) N902D unknown Het
Focad A G 4: 88,315,416 (GRCm39) S1525G probably benign Het
Fras1 T C 5: 96,815,296 (GRCm39) W1338R probably benign Het
Fry A G 5: 150,324,389 (GRCm39) I1151V probably null Het
Garin5b T A 7: 4,761,186 (GRCm39) T509S probably benign Het
Gm10076 T G 14: 105,919,304 (GRCm39) noncoding transcript Het
Gm5698 T G 1: 31,017,042 (GRCm39) D3A probably damaging Het
Gngt2 C T 11: 95,735,972 (GRCm39) probably benign Het
Gsdma T C 11: 98,562,193 (GRCm39) probably null Het
Gtf2h3 A T 5: 124,740,262 (GRCm39) probably benign Het
Hkdc1 T C 10: 62,253,677 (GRCm39) T35A probably benign Het
Irs1 T C 1: 82,266,180 (GRCm39) S679G probably benign Het
Itpr1 T A 6: 108,470,716 (GRCm39) C2214S probably damaging Het
Kcnh8 GAGACCAACGAGCAGCTGATGCTTCAGA GAGA 17: 53,032,934 (GRCm39) 74 probably benign Het
Kcnk16 A G 14: 20,315,347 (GRCm39) V72A probably damaging Het
Lipa T A 19: 34,488,290 (GRCm39) R119* probably null Het
Matr3 T A 18: 35,721,378 (GRCm39) probably benign Het
Med13l T G 5: 118,866,898 (GRCm39) F651V probably benign Het
Mfsd11 T C 11: 116,764,740 (GRCm39) V388A probably benign Het
Mki67 C T 7: 135,299,794 (GRCm39) V1747I possibly damaging Het
Mms22l T C 4: 24,535,936 (GRCm39) probably benign Het
Msh5 A G 17: 35,263,366 (GRCm39) I154T probably benign Het
Myo5b G T 18: 74,866,996 (GRCm39) L1382F probably 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
Ntrk3 A C 7: 78,166,471 (GRCm39) probably null Het
Or1e1c T A 11: 73,266,427 (GRCm39) V287E probably damaging Het
Or4a15 A G 2: 89,193,353 (GRCm39) V140A probably benign Het
Or8b12i T A 9: 20,082,705 (GRCm39) H54L possibly damaging Het
P4ha1 A G 10: 59,206,859 (GRCm39) E523G probably damaging Het
Per3 T A 4: 151,103,342 (GRCm39) Y530F probably damaging Het
Pes1 C A 11: 3,919,524 (GRCm39) L66I probably damaging Het
Pigr G A 1: 130,774,399 (GRCm39) probably benign Het
Pkd1l1 A T 11: 8,786,197 (GRCm39) probably benign Het
Plch1 T A 3: 63,651,956 (GRCm39) K378N probably damaging Het
Plxnb1 T C 9: 108,931,776 (GRCm39) probably null Het
Pramel22 G A 4: 143,380,712 (GRCm39) T437I probably damaging Het
Prkdc A G 16: 15,472,681 (GRCm39) probably null Het
Prrc1 G T 18: 57,514,718 (GRCm39) D312Y probably damaging Het
Psma5-ps A G 10: 85,149,595 (GRCm39) noncoding transcript Het
Rab3gap2 T A 1: 185,015,739 (GRCm39) probably null Het
Rgs3 A G 4: 62,620,384 (GRCm39) I537V probably damaging Het
Rhobtb2 T G 14: 70,033,893 (GRCm39) D444A probably damaging Het
Rnf40 T C 7: 127,190,956 (GRCm39) S314P probably damaging Het
Rngtt T A 4: 33,500,302 (GRCm39) C565* probably null Het
Samd3 A G 10: 26,139,884 (GRCm39) probably benign Het
Sec61a2 A G 2: 5,878,547 (GRCm39) probably benign Het
Serpina3m G A 12: 104,355,581 (GRCm39) A83T probably damaging Het
Serpinb13 A T 1: 106,926,756 (GRCm39) I251L possibly damaging Het
Sez6 C T 11: 77,863,758 (GRCm39) T439I probably damaging Het
Slc26a2 A G 18: 61,331,650 (GRCm39) C594R possibly damaging Het
Specc1l C T 10: 75,081,438 (GRCm39) S278F probably damaging Het
Spg11 C T 2: 121,890,688 (GRCm39) V2044M probably damaging Het
Stx18 T A 5: 38,285,383 (GRCm39) probably null Het
Suclg2 T C 6: 95,566,075 (GRCm39) probably benign Het
Tlr4 A T 4: 66,757,681 (GRCm39) H158L probably damaging Het
Tmem131 A G 1: 36,851,352 (GRCm39) V966A possibly damaging Het
Tram1l1 T A 3: 124,115,635 (GRCm39) I265N probably damaging Het
Trim58 T A 11: 58,531,493 (GRCm39) F67Y possibly damaging Het
Ttc19 A G 11: 62,172,650 (GRCm39) Q74R probably benign Het
Usp7 T C 16: 8,516,333 (GRCm39) S649G probably benign Het
Vmn2r16 A G 5: 109,487,124 (GRCm39) Y115C possibly damaging Het
Zfp444 T C 7: 6,192,554 (GRCm39) C191R probably damaging Het
Zfp451 A G 1: 33,821,274 (GRCm39) F151L probably damaging Het
Zfp451 G A 1: 33,822,937 (GRCm39) P99S probably benign 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
Zfp804b A G 5: 6,819,748 (GRCm39) V1069A probably benign Het
Zfp938 C T 10: 82,061,381 (GRCm39) G413D probably damaging 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
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'- TAGCCATTGAAGCCCTAACC -3'
(R):5'- GGCATTCCAGCAAACTTCAGG -3'

Sequencing Primer
(F):5'- CGGTGTCATCAAATATTAAAGGCCC -3'
(R):5'- GCATTCCAGCAAACTTCAGGTTACTC -3'
Posted On 2014-07-14