Incidental Mutation 'R7285:Irs2'
ID 565939
Institutional Source Beutler Lab
Gene Symbol Irs2
Ensembl Gene ENSMUSG00000038894
Gene Name insulin receptor substrate 2
Synonyms Irs-2
MMRRC Submission 045393-MU
Accession Numbers
Essential gene? Possibly essential (E-score: 0.579) question?
Stock # R7285 (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 G at 11056797 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Leucine to Proline at position 545 (L545P)
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: L545P

PolyPhen 2 Score 0.994 (Sensitivity: 0.69; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000038514
Gene: ENSMUSG00000038894
AA Change: L545P

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 0.0658 question?
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 99.9%
  • 10x: 99.7%
  • 20x: 98.9%
Validation Efficiency 100% (58/58)
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: 57 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abca12 A T 1: 71,388,314 (GRCm39) C185* probably null Het
Abcc3 C T 11: 94,247,873 (GRCm39) A1207T probably benign Het
Adam1b T G 5: 121,639,056 (GRCm39) D663A probably damaging Het
Arhgap12 A T 18: 6,111,920 (GRCm39) L148Q probably damaging Het
Cdh4 A T 2: 179,439,258 (GRCm39) Q135L probably benign Het
Clca3b T C 3: 144,543,519 (GRCm39) I437V probably benign Het
Cldn15 A T 5: 137,001,327 (GRCm39) H124L probably benign Het
Cyp4a30b T C 4: 115,313,848 (GRCm39) M143T probably damaging Het
Dgcr2 A T 16: 17,662,944 (GRCm39) C353* probably null Het
Dhcr24 T A 4: 106,428,716 (GRCm39) probably null Het
Dock1 T G 7: 134,346,737 (GRCm39) L223R probably benign Het
Ece1 T A 4: 137,641,074 (GRCm39) probably null Het
Efcab5 A G 11: 77,028,170 (GRCm39) V387A probably benign Het
Efcab5 A G 11: 77,029,041 (GRCm39) F97L possibly damaging Het
Eme2 A T 17: 25,113,543 (GRCm39) probably null Het
Enpp1 G A 10: 24,536,059 (GRCm39) T447I probably benign Het
Fam222b T C 11: 78,034,007 (GRCm39) S17P probably benign Het
Fbln1 A G 15: 85,121,829 (GRCm39) I317V probably benign Het
Fn1 T C 1: 71,676,498 (GRCm39) K578E probably damaging Het
Fscb A T 12: 64,518,323 (GRCm39) S1048T unknown Het
Fsd1l T A 4: 53,682,200 (GRCm39) probably null Het
Hexa T A 9: 59,471,222 (GRCm39) I492K probably benign Het
Inpp5e G A 2: 26,287,870 (GRCm39) A642V probably benign Het
Ints11 C T 4: 155,970,568 (GRCm39) A241V probably damaging Het
Katnal2 G A 18: 77,081,271 (GRCm39) A409V probably benign Het
Kif13a C T 13: 46,905,931 (GRCm39) V671M possibly damaging Het
Lbx2 A G 6: 83,064,877 (GRCm39) K138R probably damaging Het
Lcor A G 19: 41,572,754 (GRCm39) K503R possibly damaging Het
Lpp G A 16: 24,796,029 (GRCm39) A558T probably damaging Het
Lypla1 T C 1: 4,911,321 (GRCm39) I202T probably benign Het
Magi3 G A 3: 103,941,430 (GRCm39) P842S probably benign Het
Meioc G A 11: 102,557,168 (GRCm39) V25M probably benign Het
Mthfr C T 4: 148,138,056 (GRCm39) T557I probably benign Het
Nbeal1 G C 1: 60,276,310 (GRCm39) V684L probably benign Het
Or2t44 T A 11: 58,677,310 (GRCm39) Y83* probably null Het
Or5d20-ps1 A T 2: 87,932,049 (GRCm39) I94N probably damaging Het
Osbpl10 A T 9: 115,052,771 (GRCm39) I440F probably damaging Het
Otx2 G A 14: 48,898,922 (GRCm39) A36V probably benign Het
Parg A G 14: 31,932,465 (GRCm39) Y435C probably damaging Het
Parvb A T 15: 84,166,985 (GRCm39) D100V possibly damaging Het
Prss27 A G 17: 24,264,665 (GRCm39) H276R probably benign Het
Prune1 T A 3: 95,162,357 (GRCm39) S439C probably damaging Het
Pudp C G 18: 50,701,287 (GRCm39) E149Q possibly damaging Het
Qng1 T C 13: 58,532,199 (GRCm39) Y119C probably damaging Het
Sin3a C A 9: 57,034,583 (GRCm39) T1252N possibly damaging Het
Sptbn2 A G 19: 4,787,471 (GRCm39) D927G probably benign Het
Stx18 C T 5: 38,262,251 (GRCm39) T89I possibly damaging Het
Ticrr T C 7: 79,310,610 (GRCm39) S175P possibly damaging Het
Tinag T C 9: 76,952,943 (GRCm39) T14A probably benign Het
Tmco3 G A 8: 13,369,605 (GRCm39) probably null Het
Trpm1 G T 7: 63,859,729 (GRCm39) E396* probably null Het
Txndc11 A G 16: 10,902,163 (GRCm39) Y684H probably damaging Het
Usp47 G A 7: 111,692,315 (GRCm39) E926K probably benign Het
Vmn1r233 A G 17: 21,214,221 (GRCm39) I243T probably damaging Het
Ythdf3 T A 3: 16,258,049 (GRCm39) probably null Het
Zfp12 A G 5: 143,230,444 (GRCm39) K289R probably damaging Het
Zfp950 T A 19: 61,107,550 (GRCm39) H511L probably benign 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
R7261:Irs2 UTSW 8 11,057,018 (GRCm39) missense possibly damaging 0.95
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 2019-06-26