Incidental Mutation 'R6934:Irs2'
ID 540203
Institutional Source Beutler Lab
Gene Symbol Irs2
Ensembl Gene ENSMUSG00000038894
Gene Name insulin receptor substrate 2
Synonyms Irs-2
MMRRC Submission 045049-MU
Accession Numbers
Essential gene? Possibly essential (E-score: 0.579) question?
Stock # R6934 (G1)
Quality Score 223.009
Status Not validated
Chromosome 8
Chromosomal Location 11034681-11058458 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to T at 11054697 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Isoleucine to Asparagine at position 1245 (I1245N)
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: I1245N

PolyPhen 2 Score 0.994 (Sensitivity: 0.69; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000038514
Gene: ENSMUSG00000038894
AA Change: I1245N

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
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 99.9%
  • 10x: 99.3%
  • 20x: 97.9%
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: 43 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
1700018B08Rik T A 8: 122,266,712 (GRCm39) Y58F probably benign Het
Asap2 T C 12: 21,218,251 (GRCm39) V58A probably damaging Het
Bccip A G 7: 133,322,520 (GRCm39) M289V probably benign Het
Bhmt2 A T 13: 93,798,819 (GRCm39) I334N probably benign Het
Copa T A 1: 171,938,253 (GRCm39) I513N possibly damaging Het
Cspg4b T C 13: 113,505,800 (GRCm39) S2310P probably benign Het
Ctif G A 18: 75,568,431 (GRCm39) T569M probably benign Het
Dennd1a A T 2: 37,691,225 (GRCm39) M231K possibly damaging Het
Dnah3 A G 7: 119,653,824 (GRCm39) probably null Het
Fat3 T C 9: 16,288,252 (GRCm39) I424V probably damaging Het
Foxred2 G T 15: 77,836,530 (GRCm39) C328* probably null Het
Gemin5 A T 11: 58,038,738 (GRCm39) H590Q probably damaging Het
Gm5475 T C 15: 100,325,007 (GRCm39) probably benign Het
Gmip A G 8: 70,273,576 (GRCm39) T956A probably benign Het
Hmbox1 A T 14: 65,134,281 (GRCm39) D106E probably benign Het
Kcnk1 A G 8: 126,752,129 (GRCm39) Y245C probably damaging Het
Krtap4-9 A T 11: 99,676,708 (GRCm39) R210* probably null Het
Lama1 A G 17: 68,081,538 (GRCm39) D1325G probably benign Het
Lyz3 C T 10: 117,074,413 (GRCm39) D25N probably benign Het
Mep1a A T 17: 43,793,121 (GRCm39) V361E probably damaging Het
Mrgprx2 A G 7: 48,131,813 (GRCm39) I92T possibly damaging Het
Nup214 A T 2: 31,872,683 (GRCm39) R242* probably null Het
Nynrin T G 14: 56,101,335 (GRCm39) S335A probably benign Het
Or13a24 T G 7: 140,154,564 (GRCm39) L166R probably damaging Het
Or5p60 A G 7: 107,724,026 (GRCm39) V148A probably benign Het
Or8b1c T G 9: 38,384,472 (GRCm39) I143S probably benign Het
Orc2 T C 1: 58,539,523 (GRCm39) K39E probably benign Het
Ppl C T 16: 4,912,373 (GRCm39) G736D probably benign Het
Ppp2r1a A G 17: 21,181,895 (GRCm39) E471G possibly damaging Het
Prrc2c G A 1: 162,548,074 (GRCm39) P161S probably benign Het
Rnf213 A G 11: 119,310,893 (GRCm39) I804V probably benign Het
Saal1 A G 7: 46,352,088 (GRCm39) C144R probably benign Het
Slc29a4 G A 5: 142,698,713 (GRCm39) V125I probably benign Het
Smarcc2 A G 10: 128,305,541 (GRCm39) T322A probably benign Het
Srgap2 A T 1: 131,244,969 (GRCm39) M591K possibly damaging Het
Stard9 A G 2: 120,528,176 (GRCm39) I1478V probably benign Het
Tet2 A G 3: 133,188,998 (GRCm39) probably null Het
Tmem150c C T 5: 100,243,465 (GRCm39) probably null Het
Tmem39b T A 4: 129,572,366 (GRCm39) H412L possibly damaging Het
Tox A C 4: 6,697,635 (GRCm39) H389Q probably damaging Het
Trank1 T C 9: 111,202,158 (GRCm39) I1595T probably damaging Het
Vmn2r-ps117 T G 17: 19,044,967 (GRCm39) Y461* probably null Het
Vps13a T C 19: 16,653,558 (GRCm39) H1941R probably 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
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
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
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'- GACAGGAAGTCGATGCTTGC -3'
(R):5'- TGTCTCACTCAGGAAAAGCAG -3'

Sequencing Primer
(F):5'- CAGGAAGTCGATGCTTGCATAGG -3'
(R):5'- TGAAGGCAGCAGTACCCTG -3'
Posted On 2018-11-06