Incidental Mutation 'R0501:Irs2'
ID 47127
Institutional Source Beutler Lab
Gene Symbol Irs2
Ensembl Gene ENSMUSG00000038894
Gene Name insulin receptor substrate 2
Synonyms Irs-2
MMRRC Submission 038696-MU
Accession Numbers
Essential gene? Possibly essential (E-score: 0.579) question?
Stock # R0501 (G1)
Quality Score 225
Status Not validated
Chromosome 8
Chromosomal Location 11034681-11058458 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) C to T at 11056396 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Valine to Methionine at position 679 (V679M)
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 damaging
Transcript: ENSMUST00000040514
AA Change: V679M

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000038514
Gene: ENSMUSG00000038894
AA Change: V679M

DomainStartEndE-ValueType
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
Coding Region Coverage
  • 1x: 99.7%
  • 3x: 98.9%
  • 10x: 97.0%
  • 20x: 94.2%
Validation Efficiency
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: 84 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
1700030K09Rik T C 8: 73,209,216 (GRCm39) S415P probably benign Het
Adam19 C T 11: 46,013,957 (GRCm39) P316S probably damaging Het
Adamts2 A G 11: 50,558,972 (GRCm39) D229G probably benign Het
Adcy10 C T 1: 165,337,959 (GRCm39) P191L probably damaging Het
Adgrv1 T C 13: 81,707,269 (GRCm39) Y1379C probably damaging Het
Akap9 T C 5: 4,020,685 (GRCm39) L1132P probably damaging Het
Aoah A G 13: 21,189,243 (GRCm39) T489A probably benign Het
Apc2 T C 10: 80,150,958 (GRCm39) L1975P probably damaging Het
Bpifa5 A T 2: 154,005,616 (GRCm39) D66V probably benign Het
C230029F24Rik T C 1: 49,374,629 (GRCm39) noncoding transcript Het
Cacna1h A T 17: 25,607,641 (GRCm39) V892E probably damaging Het
Car4 G A 11: 84,854,268 (GRCm39) V72I probably benign Het
Cfap91 C G 16: 38,155,997 (GRCm39) M75I probably damaging Het
Chst3 A G 10: 60,022,049 (GRCm39) L266P probably damaging Het
Ckap2l G A 2: 129,127,411 (GRCm39) R256W possibly damaging Het
Cntn4 A T 6: 106,595,296 (GRCm39) D471V probably damaging Het
Cntrob G A 11: 69,213,694 (GRCm39) S32F probably damaging Het
Cpne7 T A 8: 123,852,994 (GRCm39) N200K possibly damaging Het
Creb3l3 C A 10: 80,922,416 (GRCm39) M271I probably benign Het
Csmd1 T A 8: 17,077,339 (GRCm39) Q106L probably damaging Het
D7Ertd443e G A 7: 133,896,701 (GRCm39) T563I probably damaging Het
Dmac1 T G 4: 75,196,413 (GRCm39) N26H unknown Het
Dop1b T C 16: 93,549,750 (GRCm39) F230L probably benign Het
Dpp6 T A 5: 27,930,604 (GRCm39) I812N probably damaging Het
Fabp12 T C 3: 10,315,203 (GRCm39) D48G probably benign Het
Fbn1 G A 2: 125,143,669 (GRCm39) T2820M probably benign Het
Fcho1 C T 8: 72,165,204 (GRCm39) A418T probably benign Het
Fcho2 A T 13: 98,901,023 (GRCm39) S277R possibly damaging Het
Fmo2 A G 1: 162,704,497 (GRCm39) S470P probably benign Het
Gm17541 T G 12: 4,739,730 (GRCm39) probably benign Het
Gm4353 A T 7: 115,682,706 (GRCm39) Y292N probably benign Het
Igkv4-71 A T 6: 69,220,290 (GRCm39) I69N probably damaging Het
Insrr G T 3: 87,717,991 (GRCm39) A871S probably benign Het
Itpr3 T A 17: 27,326,263 (GRCm39) H1344Q probably benign Het
Kcnma1 T C 14: 23,361,784 (GRCm39) M1074V possibly damaging Het
Kif1a G A 1: 92,983,967 (GRCm39) R602W probably damaging Het
Kif21b A T 1: 136,090,837 (GRCm39) D1215V probably benign Het
Mapk13 G A 17: 28,995,327 (GRCm39) V183M probably damaging Het
Mbp C T 18: 82,593,322 (GRCm39) S100F probably damaging Het
Mcm6 A G 1: 128,283,373 (GRCm39) I44T probably benign Het
Ncor1 T A 11: 62,264,148 (GRCm39) D418V possibly damaging Het
Nid2 T A 14: 19,839,736 (GRCm39) probably null Het
Nolc1 T C 19: 46,067,359 (GRCm39) V80A probably damaging Het
Or10a5 A T 7: 106,635,439 (GRCm39) T26S probably benign Het
Or10ak14 C A 4: 118,611,027 (GRCm39) C238F probably benign Het
Or12e9 A T 2: 87,201,896 (GRCm39) R7W probably damaging Het
Or13e8 A C 4: 43,697,079 (GRCm39) C31W probably damaging Het
Or1j1 A T 2: 36,702,492 (GRCm39) L204* probably null Het
Or2ag1 A T 7: 106,313,810 (GRCm39) M26K probably benign Het
Or2ag18 G A 7: 106,405,018 (GRCm39) S217F probably damaging Het
Or4a68 T C 2: 89,270,060 (GRCm39) T188A probably benign Het
Or4e1 T A 14: 52,701,383 (GRCm39) M1L possibly damaging Het
Or5d14 A T 2: 87,880,815 (GRCm39) I51N probably damaging Het
Or5m12 A G 2: 85,735,348 (GRCm39) F17L probably damaging Het
Or7g35 T A 9: 19,495,914 (GRCm39) I27N probably damaging Het
Pcgf3 T A 5: 108,622,978 (GRCm39) C38S probably damaging Het
Pdia4 A T 6: 47,777,936 (GRCm39) V352E probably damaging Het
Pik3c2a C A 7: 115,953,290 (GRCm39) V1202L probably damaging Het
Rbm15 G T 3: 107,239,846 (GRCm39) A184E possibly damaging Het
Rsph3a T A 17: 8,197,952 (GRCm39) L442* probably null Het
Scg2 G C 1: 79,413,320 (GRCm39) L468V probably damaging Het
Sdk1 A T 5: 141,923,473 (GRCm39) I365L probably benign Het
Setdb1 A G 3: 95,246,140 (GRCm39) V595A probably benign Het
Skic3 A C 13: 76,295,925 (GRCm39) M1063L probably benign Het
Slc22a22 T A 15: 57,113,046 (GRCm39) T398S probably benign Het
Stk11 C A 10: 79,962,119 (GRCm39) P217Q probably damaging Het
Tes G A 6: 17,097,557 (GRCm39) D222N probably benign Het
Tmem132e T A 11: 82,325,894 (GRCm39) I206N possibly damaging Het
Tmem214 G T 5: 31,029,876 (GRCm39) R251L probably damaging Het
Tmem253 T A 14: 52,256,036 (GRCm39) I105N probably damaging Het
Toe1 A G 4: 116,664,682 (GRCm39) V12A probably benign Het
Top1 C A 2: 160,556,079 (GRCm39) H513N probably damaging Het
Tph1 G T 7: 46,299,412 (GRCm39) Y376* probably null Het
Trim45 T A 3: 100,830,535 (GRCm39) L103Q probably damaging Het
Ttn T A 2: 76,774,518 (GRCm39) probably null Het
Twnk T C 19: 44,996,185 (GRCm39) V206A probably damaging Het
Ube2z A G 11: 95,941,114 (GRCm39) S343P probably damaging Het
Vmn2r8 T C 5: 108,951,049 (GRCm39) D132G probably benign Het
Wdr20rt A T 12: 65,272,581 (GRCm39) T15S probably benign Het
Wdr59 C T 8: 112,185,579 (GRCm39) R841Q possibly damaging Het
Wdtc1 A G 4: 133,036,151 (GRCm39) F130L possibly damaging Het
Wnk1 C T 6: 119,939,764 (GRCm39) R43Q probably damaging Het
Ythdf3 T C 3: 16,259,236 (GRCm39) L461P probably damaging Het
Zcchc2 T G 1: 105,943,821 (GRCm39) F462C possibly damaging Het
Other mutations in Irs2
AlleleSourceChrCoordTypePredicted EffectPPH 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
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
R6049:Irs2 UTSW 8 11,056,805 (GRCm39) missense probably benign 0.01
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'- TCCATAGACAGCTTGGAGCCACAC -3'
(R):5'- GGACTTATTCCCTAACCACGCCTG -3'

Sequencing Primer
(F):5'- TTGGAGCCACACCACATTC -3'
(R):5'- ATGAGGGCCACCTTCTCTG -3'
Posted On 2013-06-12