Incidental Mutation 'R6049:Irs2'
| ID |
483448 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Irs2
|
| Ensembl Gene |
ENSMUSG00000038894 |
| Gene Name |
insulin receptor substrate 2 |
| Synonyms |
Irs-2 |
| MMRRC Submission |
044217-MU
|
| Accession Numbers |
|
| Essential gene? |
Possibly essential
(E-score: 0.528)
|
| Stock # |
R6049 (G1)
|
| Quality Score |
118.008 |
|
Status
|
Validated
|
| Chromosome |
8 |
| Chromosomal Location |
11034681-11058458 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
A to C
at 11056805 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Aspartic acid to Glutamic Acid
at position 542
(D542E)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000038514
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000040514]
|
| AlphaFold |
P81122 |
| PDB Structure |
Crystal structure of the insulin receptor kinase in complex with IRS2 KRLB peptide [X-RAY DIFFRACTION]
Crystal structure of the insulin receptor kinase in complex with IRS2 KRLB peptide and ATP [X-RAY DIFFRACTION]
Crystal structure of the insulin receptor kinase in complex with IRS2 KRLB phosphopeptide [X-RAY DIFFRACTION]
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000040514
AA Change: D542E
PolyPhen 2
Score 0.009 (Sensitivity: 0.96; Specificity: 0.77)
|
| SMART Domains |
Protein: ENSMUSP00000038514
Gene: ENSMUSG00000038894
AA Change: D542E
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
2 |
18 |
N/A |
INTRINSIC |
|
low complexity region
|
19 |
28 |
N/A |
INTRINSIC |
|
PH
|
31 |
146 |
2.83e-13 |
SMART |
|
IRS
|
191 |
293 |
4.98e-38 |
SMART |
|
PTBI
|
191 |
293 |
2.24e-51 |
SMART |
|
low complexity region
|
301 |
309 |
N/A |
INTRINSIC |
|
low complexity region
|
364 |
377 |
N/A |
INTRINSIC |
|
low complexity region
|
435 |
473 |
N/A |
INTRINSIC |
|
low complexity region
|
478 |
490 |
N/A |
INTRINSIC |
|
low complexity region
|
688 |
710 |
N/A |
INTRINSIC |
|
low complexity region
|
721 |
730 |
N/A |
INTRINSIC |
|
low complexity region
|
834 |
846 |
N/A |
INTRINSIC |
|
low complexity region
|
923 |
959 |
N/A |
INTRINSIC |
|
low complexity region
|
976 |
984 |
N/A |
INTRINSIC |
|
low complexity region
|
997 |
1028 |
N/A |
INTRINSIC |
|
low complexity region
|
1137 |
1154 |
N/A |
INTRINSIC |
|
low complexity region
|
1191 |
1208 |
N/A |
INTRINSIC |
|
low complexity region
|
1274 |
1296 |
N/A |
INTRINSIC |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000180750
|
| Meta Mutation Damage Score |
0.0898 |
| Coding Region Coverage |
- 1x: 99.9%
- 3x: 99.6%
- 10x: 98.1%
- 20x: 94.3%
|
| Validation Efficiency |
98% (60/61) |
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes the insulin receptor substrate 2, a cytoplasmic signaling molecule that mediates effects of insulin, insulin-like growth factor 1, and other cytokines by acting as a molecular adaptor between diverse receptor tyrosine kinases and downstream effectors. The product of this gene is phosphorylated by the insulin receptor tyrosine kinase upon receptor stimulation, as well as by an interleukin 4 receptor-associated kinase in response to IL4 treatment. [provided by RefSeq, Jul 2008]
PHENOTYPE: Homozygous disruption of this gene results in type 2 diabetes due to insulin resistance and pancreatic beta cell dysfunction, causes defects in leptin action, energy balance, lipid homeostasis and vascular wound healing, and leads to female infertility due to hypothalamic and ovarian dysfunction. [provided by MGI curators]
|
| Allele List at MGI |
|
| Other mutations in this stock |
Total: 62 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| 4921539E11Rik |
G |
A |
4: 103,088,520 (GRCm39) |
H229Y |
probably benign |
Het |
| Aadacl2fm2 |
A |
C |
3: 59,659,570 (GRCm39) |
D341A |
probably damaging |
Het |
| Abcd2 |
A |
G |
15: 91,062,439 (GRCm39) |
F500L |
probably benign |
Het |
| Adgb |
A |
G |
10: 10,253,770 (GRCm39) |
L1190P |
probably damaging |
Het |
| Adgrv1 |
A |
G |
13: 81,545,473 (GRCm39) |
V5604A |
probably benign |
Het |
| Ank2 |
T |
A |
3: 126,736,669 (GRCm39) |
T3072S |
possibly damaging |
Het |
| Arhgap39 |
A |
G |
15: 76,611,601 (GRCm39) |
|
probably null |
Het |
| C6 |
T |
C |
15: 4,764,654 (GRCm39) |
C117R |
probably damaging |
Het |
| Cacna1a |
A |
G |
8: 85,365,475 (GRCm39) |
E2206G |
probably damaging |
Het |
| Cd2bp2 |
A |
T |
7: 126,793,007 (GRCm39) |
F338L |
probably damaging |
Het |
| Cemip2 |
A |
T |
19: 21,803,490 (GRCm39) |
Q841L |
probably benign |
Het |
| Cngb1 |
T |
C |
8: 95,997,470 (GRCm39) |
D575G |
probably damaging |
Het |
| Cplane2 |
T |
A |
4: 140,945,473 (GRCm39) |
V108D |
probably benign |
Het |
| Crat |
A |
G |
2: 30,293,553 (GRCm39) |
F63S |
probably damaging |
Het |
| Crybg3 |
T |
C |
16: 59,364,417 (GRCm39) |
T2402A |
probably benign |
Het |
| Ctsq |
A |
G |
13: 61,186,572 (GRCm39) |
|
probably null |
Het |
| Cux1 |
T |
C |
5: 136,361,564 (GRCm39) |
R248G |
probably damaging |
Het |
| D7Ertd443e |
T |
C |
7: 133,899,961 (GRCm39) |
H420R |
probably benign |
Het |
| Deup1 |
A |
G |
9: 15,472,552 (GRCm39) |
F587L |
possibly damaging |
Het |
| Dnah6 |
T |
C |
6: 73,063,149 (GRCm39) |
K2651R |
probably benign |
Het |
| Dnah7b |
A |
G |
1: 46,124,762 (GRCm39) |
I144V |
probably benign |
Het |
| Dnajc1 |
T |
C |
2: 18,236,511 (GRCm39) |
|
probably null |
Het |
| Fscb |
T |
C |
12: 64,521,094 (GRCm39) |
N124S |
possibly damaging |
Het |
| Gabbr2 |
A |
G |
4: 46,787,641 (GRCm39) |
Y341H |
probably damaging |
Het |
| Greb1 |
T |
A |
12: 16,731,395 (GRCm39) |
I1648F |
probably damaging |
Het |
| Hace1 |
A |
T |
10: 45,562,758 (GRCm39) |
N758Y |
probably damaging |
Het |
| Kat6a |
T |
A |
8: 23,429,053 (GRCm39) |
H1469Q |
possibly damaging |
Het |
| Kif15 |
G |
A |
9: 122,840,687 (GRCm39) |
R36K |
probably damaging |
Het |
| Krt42 |
C |
T |
11: 100,157,886 (GRCm39) |
V193M |
probably damaging |
Het |
| Limch1 |
A |
T |
5: 67,188,203 (GRCm39) |
E878V |
probably benign |
Het |
| Med18 |
G |
T |
4: 132,187,024 (GRCm39) |
D158E |
probably benign |
Het |
| Med6 |
T |
C |
12: 81,638,097 (GRCm39) |
N38S |
probably damaging |
Het |
| Mup13 |
T |
C |
4: 61,183,596 (GRCm39) |
T76A |
probably benign |
Het |
| Nlrp4b |
T |
A |
7: 10,448,640 (GRCm39) |
L281* |
probably null |
Het |
| Or5h23 |
A |
T |
16: 58,906,509 (GRCm39) |
C112* |
probably null |
Het |
| Or7g28 |
C |
A |
9: 19,272,640 (GRCm39) |
G4* |
probably null |
Het |
| Or9r3 |
A |
T |
10: 129,948,481 (GRCm39) |
H59Q |
probably benign |
Het |
| Pde4d |
A |
T |
13: 109,169,119 (GRCm39) |
R54* |
probably null |
Het |
| Pdpk1 |
A |
T |
17: 24,317,109 (GRCm39) |
Y251* |
probably null |
Het |
| Pdzk1 |
A |
G |
3: 96,758,979 (GRCm39) |
E128G |
probably benign |
Het |
| Phf12 |
A |
G |
11: 77,918,996 (GRCm39) |
|
probably null |
Het |
| Pnliprp2 |
A |
G |
19: 58,748,884 (GRCm39) |
E63G |
possibly damaging |
Het |
| Prkcd |
T |
C |
14: 30,329,254 (GRCm39) |
E62G |
possibly damaging |
Het |
| Prl7b1 |
G |
T |
13: 27,790,161 (GRCm39) |
D77E |
probably benign |
Het |
| Rbck1 |
G |
T |
2: 152,165,094 (GRCm39) |
C85* |
probably null |
Het |
| Rfx3 |
A |
T |
19: 27,779,795 (GRCm39) |
M481K |
probably damaging |
Het |
| Rmdn3 |
A |
G |
2: 118,983,906 (GRCm39) |
F159L |
probably damaging |
Het |
| Rpusd3 |
A |
C |
6: 113,394,802 (GRCm39) |
|
probably null |
Het |
| Ska1 |
T |
C |
18: 74,335,671 (GRCm39) |
T100A |
probably benign |
Het |
| Slc1a3 |
T |
C |
15: 8,675,177 (GRCm39) |
E276G |
probably damaging |
Het |
| Slc27a6 |
T |
A |
18: 58,731,732 (GRCm39) |
Y361N |
probably damaging |
Het |
| Smc1b |
A |
G |
15: 85,005,896 (GRCm39) |
L336S |
probably damaging |
Het |
| St7 |
A |
G |
6: 17,694,347 (GRCm39) |
D46G |
possibly damaging |
Het |
| Supt5 |
A |
G |
7: 28,014,622 (GRCm39) |
I1059T |
probably benign |
Het |
| Syne1 |
A |
T |
10: 5,297,926 (GRCm39) |
S1124T |
possibly damaging |
Het |
| Szt2 |
A |
G |
4: 118,260,185 (GRCm39) |
S54P |
probably damaging |
Het |
| Tanc2 |
G |
A |
11: 105,758,543 (GRCm39) |
R768Q |
probably damaging |
Het |
| Tbc1d7 |
A |
C |
13: 43,312,836 (GRCm39) |
M19R |
probably damaging |
Het |
| Tbpl2 |
T |
C |
2: 23,985,004 (GRCm39) |
N47D |
possibly damaging |
Het |
| Tgfbr3 |
C |
T |
5: 107,266,351 (GRCm39) |
A790T |
probably damaging |
Het |
| Tnr |
T |
C |
1: 159,740,324 (GRCm39) |
V1166A |
probably damaging |
Het |
| Ttn |
G |
A |
2: 76,676,654 (GRCm39) |
|
probably benign |
Het |
|
| Other mutations in Irs2 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL00963:Irs2
|
APN |
8 |
11,055,867 (GRCm39) |
missense |
probably benign |
0.00 |
|
IGL01328:Irs2
|
APN |
8 |
11,054,792 (GRCm39) |
missense |
probably damaging |
0.99 |
|
IGL01875:Irs2
|
APN |
8 |
11,056,221 (GRCm39) |
missense |
probably damaging |
0.98 |
|
IGL02444:Irs2
|
APN |
8 |
11,056,306 (GRCm39) |
missense |
probably benign |
0.03 |
|
IGL02448:Irs2
|
APN |
8 |
11,057,862 (GRCm39) |
missense |
probably benign |
0.21 |
|
IGL02945:Irs2
|
APN |
8 |
11,057,781 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL03068:Irs2
|
APN |
8 |
11,054,974 (GRCm39) |
missense |
probably damaging |
0.99 |
|
beefed
|
UTSW |
8 |
11,056,522 (GRCm39) |
nonsense |
probably null |
|
|
Dum_dum
|
UTSW |
8 |
11,037,012 (GRCm39) |
makesense |
probably null |
|
|
Lush
|
UTSW |
8 |
11,056,678 (GRCm39) |
nonsense |
probably null |
|
|
muscular
|
UTSW |
8 |
11,054,659 (GRCm39) |
nonsense |
probably null |
|
|
Plink
|
UTSW |
8 |
11,055,121 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R0062:Irs2
|
UTSW |
8 |
11,055,723 (GRCm39) |
missense |
possibly damaging |
0.65 |
|
R0062:Irs2
|
UTSW |
8 |
11,055,723 (GRCm39) |
missense |
possibly damaging |
0.65 |
|
R0107:Irs2
|
UTSW |
8 |
11,054,691 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0147:Irs2
|
UTSW |
8 |
11,057,568 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0501:Irs2
|
UTSW |
8 |
11,056,396 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0565:Irs2
|
UTSW |
8 |
11,054,592 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R2042:Irs2
|
UTSW |
8 |
11,057,580 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R2268:Irs2
|
UTSW |
8 |
11,057,586 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R2518:Irs2
|
UTSW |
8 |
11,055,352 (GRCm39) |
missense |
probably benign |
0.00 |
|
R2762:Irs2
|
UTSW |
8 |
11,056,408 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R3623:Irs2
|
UTSW |
8 |
11,057,643 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R3624:Irs2
|
UTSW |
8 |
11,057,643 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5022:Irs2
|
UTSW |
8 |
11,037,012 (GRCm39) |
makesense |
probably null |
|
|
R5270:Irs2
|
UTSW |
8 |
11,056,678 (GRCm39) |
nonsense |
probably null |
|
|
R5377:Irs2
|
UTSW |
8 |
11,055,277 (GRCm39) |
missense |
probably benign |
0.00 |
|
R5604:Irs2
|
UTSW |
8 |
11,055,007 (GRCm39) |
missense |
possibly damaging |
0.84 |
|
R6219:Irs2
|
UTSW |
8 |
11,055,121 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R6654:Irs2
|
UTSW |
8 |
11,056,486 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6726:Irs2
|
UTSW |
8 |
11,054,961 (GRCm39) |
missense |
possibly damaging |
0.86 |
|
R6813:Irs2
|
UTSW |
8 |
11,054,659 (GRCm39) |
nonsense |
probably null |
|
|
R6934:Irs2
|
UTSW |
8 |
11,054,697 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R7261:Irs2
|
UTSW |
8 |
11,057,018 (GRCm39) |
missense |
possibly damaging |
0.95 |
|
R7285:Irs2
|
UTSW |
8 |
11,056,797 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R7458:Irs2
|
UTSW |
8 |
11,057,739 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R7757:Irs2
|
UTSW |
8 |
11,056,522 (GRCm39) |
nonsense |
probably null |
|
|
R8347:Irs2
|
UTSW |
8 |
11,058,000 (GRCm39) |
missense |
possibly damaging |
0.82 |
|
R8348:Irs2
|
UTSW |
8 |
11,054,974 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R8377:Irs2
|
UTSW |
8 |
11,054,848 (GRCm39) |
nonsense |
probably null |
|
|
R8444:Irs2
|
UTSW |
8 |
11,056,683 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R8912:Irs2
|
UTSW |
8 |
11,056,655 (GRCm39) |
missense |
probably damaging |
0.96 |
|
R9229:Irs2
|
UTSW |
8 |
11,057,400 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9344:Irs2
|
UTSW |
8 |
11,057,289 (GRCm39) |
nonsense |
probably null |
|
|
R9405:Irs2
|
UTSW |
8 |
11,055,061 (GRCm39) |
missense |
possibly damaging |
0.95 |
|
R9484:Irs2
|
UTSW |
8 |
11,057,334 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R9736:Irs2
|
UTSW |
8 |
11,058,217 (GRCm39) |
missense |
probably damaging |
1.00 |
|
Z1176:Irs2
|
UTSW |
8 |
11,056,185 (GRCm39) |
missense |
probably damaging |
0.97 |
|
| Predicted Primers |
PCR Primer
(F):5'- GAAGGTGGCCCTCATGAGAG -3'
(R):5'- CGAGCAAAGTGACTCTGGCG -3'
Sequencing Primer
(F):5'- GCCCTCATGAGAGTGTATTCATCTAG -3'
(R):5'- ACAGCCGCTCCATGTCCATG -3'
|
| Posted On |
2017-07-14 |
Incidental Mutation