Incidental Mutation 'IGL01608:Shc1'
ID 91868
Institutional Source Australian Phenomics Network (link to record)
Gene Symbol Shc1
Ensembl Gene ENSMUSG00000042626
Gene Name src homology 2 domain-containing transforming protein C1
Synonyms ShcA, p66shc, p66
Accession Numbers
Is this an essential gene? Probably essential (E-score: 0.969) question?
Stock # IGL01608
Quality Score
Status
Chromosome 3
Chromosomal Location 89418443-89430027 bp(+) (GRCm38)
Type of Mutation missense
DNA Base Change (assembly) C to A at 89424849 bp (GRCm38)
Zygosity Heterozygous
Amino Acid Change Glutamine to Lysine at position 204 (Q204K)
Ref Sequence ENSEMBL: ENSMUSP00000140336 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000039110] [ENSMUST00000094378] [ENSMUST00000107417] [ENSMUST00000125036] [ENSMUST00000128238] [ENSMUST00000137793] [ENSMUST00000154791] [ENSMUST00000191485]
AlphaFold P98083
Predicted Effect probably damaging
Transcript: ENSMUST00000039110
AA Change: Q204K

PolyPhen 2 Score 0.959 (Sensitivity: 0.78; Specificity: 0.95)
SMART Domains Protein: ENSMUSP00000035361
Gene: ENSMUSG00000042626
AA Change: Q204K

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: Q314K

PolyPhen 2 Score 0.959 (Sensitivity: 0.78; Specificity: 0.95)
SMART Domains Protein: ENSMUSP00000091940
Gene: ENSMUSG00000042626
AA Change: Q314K

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: Q159K

PolyPhen 2 Score 0.959 (Sensitivity: 0.78; Specificity: 0.95)
SMART Domains Protein: ENSMUSP00000103040
Gene: ENSMUSG00000042626
AA Change: Q159K

DomainStartEndE-ValueType
PTB 2 166 2.15e-31 SMART
SH2 327 406 1.71e-26 SMART
Predicted Effect possibly damaging
Transcript: ENSMUST00000125036
AA Change: Q148K

PolyPhen 2 Score 0.954 (Sensitivity: 0.79; Specificity: 0.95)
SMART Domains Protein: ENSMUSP00000115509
Gene: ENSMUSG00000042626
AA Change: Q148K

DomainStartEndE-ValueType
PTB 1 155 1.5e-21 SMART
Predicted Effect probably damaging
Transcript: ENSMUST00000128238
AA Change: Q186K

PolyPhen 2 Score 0.959 (Sensitivity: 0.78; Specificity: 0.95)
SMART Domains Protein: ENSMUSP00000119293
Gene: ENSMUSG00000042626
AA Change: Q186K

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: Q204K

PolyPhen 2 Score 0.959 (Sensitivity: 0.78; Specificity: 0.95)
SMART Domains Protein: ENSMUSP00000117190
Gene: ENSMUSG00000042626
AA Change: Q204K

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 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 damaging
Transcript: ENSMUST00000191485
AA Change: Q204K

PolyPhen 2 Score 0.959 (Sensitivity: 0.78; Specificity: 0.95)
SMART Domains Protein: ENSMUSP00000140336
Gene: ENSMUSG00000042626
AA Change: Q204K

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
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: 60 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
4732456N10Rik A G 15: 101,562,629 I66T probably benign Het
Abca1 A T 4: 53,038,158 L2068Q probably damaging Het
Abca12 G T 1: 71,259,442 D2340E probably damaging Het
Adcy5 A G 16: 35,272,165 Y632C probably damaging Het
Adgrb3 A G 1: 25,553,774 S311P probably damaging Het
Adh4 C T 3: 138,429,027 probably benign Het
AF529169 T C 9: 89,596,498 T832A probably benign Het
Atf2 G T 2: 73,819,078 H396Q probably damaging Het
Atp8a1 G A 5: 67,813,136 R74* probably null Het
Brpf3 T C 17: 28,821,517 S971P probably benign Het
Btn1a1 T C 13: 23,461,608 E197G probably benign Het
Ccdc136 C T 6: 29,406,114 A87V possibly damaging Het
Celf4 A G 18: 25,497,503 L376P probably damaging Het
Chrm3 G A 13: 9,878,598 A134V possibly damaging Het
Col19a1 G A 1: 24,282,545 R961C probably damaging Het
Cr2 A G 1: 195,155,220 V1190A possibly damaging Het
Dopey1 T A 9: 86,507,561 S515T probably benign Het
Eprs T A 1: 185,385,114 probably benign Het
Fbn2 G T 18: 58,053,704 Y1708* probably null Het
Glt1d1 A G 5: 127,664,682 N148S possibly damaging Het
Gm20425 T A 9: 103,191,094 I44F probably damaging Het
Gpr22 T A 12: 31,708,780 K411* probably null Het
Ipo11 A G 13: 106,834,494 probably benign Het
Klri1 T A 6: 129,698,167 N210I possibly damaging Het
Kmt2c C T 5: 25,354,811 V950M probably damaging Het
Knop1 T C 7: 118,845,796 K315R probably benign Het
Lrrc32 T A 7: 98,499,357 V448D probably benign Het
Met T C 6: 17,558,730 V1119A probably damaging Het
Mipep T A 14: 60,802,230 I236N possibly damaging Het
Mrpl45 A G 11: 97,316,921 T81A probably benign Het
Mtbp G T 15: 55,557,689 E24* probably null Het
Muc5b C T 7: 141,846,437 T476I unknown Het
Mup6 C T 4: 60,006,021 T163I probably benign Het
Myo1g T A 11: 6,516,780 I278F possibly damaging Het
Myo9a A T 9: 59,870,836 K1292* probably null Het
Nbeal1 T A 1: 60,242,535 probably benign Het
Nck1 C A 9: 100,497,387 R270S probably benign Het
Neb T C 2: 52,170,536 E6035G probably damaging Het
Nlrp4f A C 13: 65,195,543 L96* probably null Het
Olfr1250 A T 2: 89,656,491 probably benign Het
Olfr141 A C 2: 86,806,425 Y191* probably null Het
Olfr606 A T 7: 103,451,804 I156F probably benign Het
Olfr738 A T 14: 50,414,453 H303L probably benign Het
Padi2 A G 4: 140,932,230 E282G probably damaging Het
Pcdhb4 A G 18: 37,308,750 D371G probably damaging Het
Pcdhb8 A G 18: 37,356,925 D552G probably damaging Het
Peli3 A G 19: 4,932,827 I270T probably damaging Het
Phf20 A G 2: 156,276,596 M407V probably benign Het
Ppm1h C T 10: 122,941,280 R103* probably null Het
Rangap1 C T 15: 81,709,504 V457M probably benign Het
Scube2 A G 7: 109,843,254 V257A probably benign Het
Slc6a4 T A 11: 77,027,135 Y568N probably damaging Het
Srgap3 A G 6: 112,946,478 F7L probably benign Het
St6galnac4 T A 2: 32,594,086 C99S probably damaging Het
Strc T C 2: 121,375,594 D779G probably benign Het
Supt6 A T 11: 78,225,483 Y685N probably damaging Het
Traf3ip3 T C 1: 193,187,110 T256A probably benign Het
Vmn1r74 A T 7: 11,847,633 I287F probably damaging Het
Zmym2 C A 14: 56,948,015 Q1035K possibly damaging Het
Zswim3 G A 2: 164,821,520 R640H probably damaging Het
Other mutations in Shc1
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00990:Shc1 APN 3 89424229 missense probably damaging 0.99
IGL02710:Shc1 APN 3 89424610 splice site probably null
PIT4382001:Shc1 UTSW 3 89427408 missense probably benign 0.00
R0323:Shc1 UTSW 3 89423713 missense probably damaging 0.98
R0445:Shc1 UTSW 3 89426537 missense probably damaging 1.00
R0827:Shc1 UTSW 3 89426783 splice site probably null
R0833:Shc1 UTSW 3 89422969 missense probably damaging 1.00
R0836:Shc1 UTSW 3 89422969 missense probably damaging 1.00
R1155:Shc1 UTSW 3 89424819 missense probably benign 0.30
R1497:Shc1 UTSW 3 89428445 makesense probably null
R1929:Shc1 UTSW 3 89423542 missense probably damaging 1.00
R2271:Shc1 UTSW 3 89423542 missense probably damaging 1.00
R4402:Shc1 UTSW 3 89426678 missense probably benign
R4965:Shc1 UTSW 3 89426996 missense probably damaging 0.98
R5898:Shc1 UTSW 3 89426967 nonsense probably null
R6198:Shc1 UTSW 3 89422107 missense probably benign
R6604:Shc1 UTSW 3 89421879 missense probably damaging 1.00
R6673:Shc1 UTSW 3 89421962 missense possibly damaging 0.93
R6705:Shc1 UTSW 3 89422959 nonsense probably null
R7379:Shc1 UTSW 3 89426822 missense probably benign 0.00
R8041:Shc1 UTSW 3 89422953 missense probably damaging 1.00
R8284:Shc1 UTSW 3 89421908 missense possibly damaging 0.70
R8700:Shc1 UTSW 3 89427433 missense possibly damaging 0.92
Posted On 2013-12-09