Incidental Mutation 'R7261:Irs2'
ID 564621
Institutional Source Beutler Lab
Gene Symbol Irs2
Ensembl Gene ENSMUSG00000038894
Gene Name insulin receptor substrate 2
Synonyms Irs-2
MMRRC Submission 045387-MU
Accession Numbers
Essential gene? Possibly essential (E-score: 0.579) question?
Stock # R7261 (G1)
Quality Score 225.009
Status Validated
Chromosome 8
Chromosomal Location 11034681-11058458 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to T at 11057018 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Histidine to Glutamine at position 471 (H471Q)
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 possibly damaging
Transcript: ENSMUST00000040514
AA Change: H471Q

PolyPhen 2 Score 0.948 (Sensitivity: 0.79; Specificity: 0.95)
SMART Domains Protein: ENSMUSP00000038514
Gene: ENSMUSG00000038894
AA Change: H471Q

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
Meta Mutation Damage Score 0.1712 question?
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 99.9%
  • 10x: 99.6%
  • 20x: 98.5%
Validation Efficiency 99% (84/85)
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: 82 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Acaca T C 11: 84,259,526 (GRCm39) F1954L probably damaging Het
Acmsd T G 1: 127,687,561 (GRCm39) I281R probably damaging Het
Adamts2 A T 11: 50,677,424 (GRCm39) M742L possibly damaging Het
Adgrf4 G A 17: 42,978,326 (GRCm39) T339I probably benign Het
Aff1 T C 5: 103,976,245 (GRCm39) S448P probably damaging Het
Agbl2 A T 2: 90,619,288 (GRCm39) S38C possibly damaging Het
Akap7 C T 10: 25,147,416 (GRCm39) D105N possibly damaging Het
Arhgap21 A G 2: 20,885,177 (GRCm39) F677L probably benign Het
Atf6b G T 17: 34,869,792 (GRCm39) V271F probably damaging Het
B3gnt5 A G 16: 19,588,123 (GRCm39) Y114C probably damaging Het
Casp7 T A 19: 56,424,765 (GRCm39) D161E probably benign Het
Catsper4 TTCTC TTC 4: 133,954,423 (GRCm39) probably null Het
Ccdc162 T C 10: 41,437,136 (GRCm39) T1758A probably benign Het
Cfap74 C A 4: 155,549,831 (GRCm39) P155T unknown Het
Champ1 A G 8: 13,928,517 (GRCm39) D225G possibly damaging Het
Chrng A T 1: 87,134,962 (GRCm39) probably null Het
Cnksr1 T C 4: 133,963,084 (GRCm39) probably null Het
Col15a1 G A 4: 47,269,088 (GRCm39) G582D probably benign Het
Cwc25 A G 11: 97,648,585 (GRCm39) V81A possibly damaging Het
Ddhd1 A G 14: 45,894,688 (GRCm39) Y261H probably damaging Het
Defa29 A G 8: 21,816,818 (GRCm39) probably null Het
Diaph3 A C 14: 87,202,893 (GRCm39) C666G probably benign Het
Dlx2 A G 2: 71,375,019 (GRCm39) Y282H probably damaging Het
Dsc3 A T 18: 20,113,814 (GRCm39) Y369* probably null Het
Dtwd1 A G 2: 126,000,424 (GRCm39) N120S probably benign Het
Dysf G A 6: 84,169,992 (GRCm39) S1761N probably damaging Het
Enthd1 A T 15: 80,444,416 (GRCm39) N46K probably damaging Het
Epha7 T A 4: 28,813,418 (GRCm39) I12N probably benign Het
Fam171a2 T A 11: 102,328,900 (GRCm39) N620Y probably damaging Het
Garin4 T C 1: 190,896,308 (GRCm39) S112G unknown Het
Gfpt2 A T 11: 49,714,078 (GRCm39) E278D possibly damaging Het
Gm3285 A G 10: 77,698,244 (GRCm39) Q131R unknown Het
Gpcpd1 A C 2: 132,410,619 (GRCm39) C23G probably damaging Het
Gtpbp4 A T 13: 9,037,954 (GRCm39) H228Q probably benign Het
Hdac7 A G 15: 97,704,415 (GRCm39) V500A probably benign Het
Hykk T G 9: 54,828,010 (GRCm39) M83R possibly damaging Het
Idi1 A G 13: 8,936,931 (GRCm39) I101V probably benign Het
Itsn1 T C 16: 91,702,194 (GRCm39) V12A probably benign Het
Jak2 A G 19: 29,288,385 (GRCm39) I1079V possibly damaging Het
Kcnt2 G A 1: 140,282,255 (GRCm39) R80H possibly damaging Het
Lamb2 T C 9: 108,358,496 (GRCm39) Y178H probably damaging Het
Lgr5 A T 10: 115,423,370 (GRCm39) L10Q possibly damaging Het
Lnx1 G T 5: 74,838,175 (GRCm39) S29* probably null Het
Lpcat3 T A 6: 124,675,050 (GRCm39) F57I probably benign Het
Manf T C 9: 106,769,088 (GRCm39) T4A probably benign Het
Map2k3 G A 11: 60,836,393 (GRCm39) probably null Het
Myh14 G A 7: 44,273,761 (GRCm39) Q1329* probably null Het
Myocd T C 11: 65,078,422 (GRCm39) S458G probably damaging Het
Ncor2 T C 5: 125,187,143 (GRCm39) probably null Het
Ndufs8 A T 19: 3,961,606 (GRCm39) N23K probably benign Het
Nkx6-1 T C 5: 101,812,006 (GRCm39) K32R unknown Het
Nlrp3 T G 11: 59,439,272 (GRCm39) V283G possibly damaging Het
Nme3 A G 17: 25,116,037 (GRCm39) probably null Het
Or1o3 A G 17: 37,574,076 (GRCm39) F160L probably benign Het
Or8g23 C T 9: 38,971,504 (GRCm39) V153M possibly damaging Het
Parvg T C 15: 84,215,297 (GRCm39) probably null Het
Peg10 T A 6: 4,756,591 (GRCm39) M389K unknown Het
Phf23 G T 11: 69,890,091 (GRCm39) C340F possibly damaging Het
Piwil2 A G 14: 70,611,860 (GRCm39) Y929H probably damaging Het
Prss39 A G 1: 34,539,369 (GRCm39) D203G probably damaging Het
Prss54 G T 8: 96,286,367 (GRCm39) D235E probably benign Het
Prtg T A 9: 72,815,117 (GRCm39) M1015K possibly damaging Het
Rbbp8 T C 18: 11,838,799 (GRCm39) I160T probably damaging Het
Rxylt1 A T 10: 121,924,822 (GRCm39) D293E probably benign Het
Scn10a C A 9: 119,438,790 (GRCm39) C1692F probably damaging Het
Scn11a C T 9: 119,648,899 (GRCm39) D55N probably damaging Het
Secisbp2 G T 13: 51,836,498 (GRCm39) V768F probably damaging Het
Skic3 A G 13: 76,261,698 (GRCm39) T138A probably benign Het
Spag16 T C 1: 70,338,780 (GRCm39) I426T possibly damaging Het
Sspo G A 6: 48,427,011 (GRCm39) V250M possibly damaging Het
Strbp A T 2: 37,531,149 (GRCm39) probably null Het
Sv2c C T 13: 96,224,809 (GRCm39) V167M probably damaging Het
Tdpoz1 G A 3: 93,577,794 (GRCm39) S330L not run Het
Tigd2 T A 6: 59,188,052 (GRCm39) D306E probably benign Het
Trrap C T 5: 144,782,287 (GRCm39) P3278S possibly damaging Het
Vdac1 A T 11: 52,265,761 (GRCm39) K28N probably damaging Het
Vmn1r84 A T 7: 12,096,069 (GRCm39) M208K probably damaging Het
Vmn2r77 A T 7: 86,460,518 (GRCm39) K615* probably null Het
Vps11 A G 9: 44,265,800 (GRCm39) L493P probably damaging Het
Zbtb21 T C 16: 97,754,179 (GRCm39) I35V possibly damaging Het
Zbtb26 A T 2: 37,326,667 (GRCm39) M123K possibly damaging Het
Zfp236 A T 18: 82,627,470 (GRCm39) D1576E 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
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
R6934:Irs2 UTSW 8 11,054,697 (GRCm39) missense probably damaging 0.99
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'- TGTACCCATAGAGTTCGCCC -3'
(R):5'- CAAAGAGCTCTTCGAGTTCCGG -3'

Sequencing Primer
(F):5'- ATAGAGTTCGCCCCCACTG -3'
(R):5'- AGCCAAGTGCACTTCGTG -3'
Posted On 2019-06-26