Incidental Mutation 'R1648:Eif2ak3'
ID 174016
Institutional Source Beutler Lab
Gene Symbol Eif2ak3
Ensembl Gene ENSMUSG00000031668
Gene Name eukaryotic translation initiation factor 2 alpha kinase 3
Synonyms PERK
MMRRC Submission 039684-MU
Accession Numbers
Essential gene? Possibly essential (E-score: 0.650) question?
Stock # R1648 (G1)
Quality Score 225
Status Validated
Chromosome 6
Chromosomal Location 70821499-70882229 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to A at 70860615 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Valine to Aspartic acid at position 397 (V397D)
Ref Sequence ENSEMBL: ENSMUSP00000034093 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000034093]
AlphaFold no structure available at present
Predicted Effect possibly damaging
Transcript: ENSMUST00000034093
AA Change: V397D

PolyPhen 2 Score 0.524 (Sensitivity: 0.88; Specificity: 0.90)
SMART Domains Protein: ENSMUSP00000034093
Gene: ENSMUSG00000031668
AA Change: V397D

DomainStartEndE-ValueType
signal peptide 1 28 N/A INTRINSIC
low complexity region 48 82 N/A INTRINSIC
low complexity region 125 139 N/A INTRINSIC
low complexity region 221 230 N/A INTRINSIC
low complexity region 470 481 N/A INTRINSIC
Pfam:Pkinase_Tyr 589 662 1.6e-6 PFAM
Pfam:Pkinase 589 673 3.2e-12 PFAM
Pfam:Pkinase 839 1075 1.9e-38 PFAM
Pfam:Pkinase_Tyr 859 1073 5.8e-25 PFAM
Predicted Effect noncoding transcript
Transcript: ENSMUST00000159401
Predicted Effect noncoding transcript
Transcript: ENSMUST00000199580
Meta Mutation Damage Score 0.1274 question?
Coding Region Coverage
  • 1x: 99.1%
  • 3x: 98.2%
  • 10x: 95.9%
  • 20x: 91.4%
Validation Efficiency 95% (73/77)
MGI Phenotype FUNCTION: The protein encoded by this gene phosphorylates the alpha subunit of eukaryotic translation-initiation factor 2, leading to its inactivation, and thus to a rapid reduction of translational initiation and repression of global protein synthesis. This protein is thought to modulate mitochondrial function. It is a type I membrane protein located in the endoplasmic reticulum (ER), where it is induced by ER stress caused by malfolded proteins. Mutations in a similar gene in human are associated with Wolcott-Rallison syndrome. [provided by RefSeq, Sep 2015]
PHENOTYPE: Homozygous mutant mice develop exocrine pancreatic insufficiency and progressive diabetes mellitus. They are growth retarded, hyperglycemic, exhibit increased cell death in the pancreas, have decreased numbers of pancreatic beta cells and about half diebefore weaning. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 71 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
1110002E22Rik A G 3: 137,775,181 (GRCm39) N1457D probably benign Het
Adgb A G 10: 10,271,115 (GRCm39) F817L probably damaging Het
Akap6 A T 12: 53,188,789 (GRCm39) K2068* probably null Het
Alms1 T C 6: 85,655,384 (GRCm39) L3310P probably damaging Het
Ankrd27 T A 7: 35,303,278 (GRCm39) D219E probably benign Het
Atp10a T C 7: 58,434,575 (GRCm39) V283A probably damaging Het
Atp11a C T 8: 12,897,495 (GRCm39) S270L probably damaging Het
Casp3 T C 8: 47,091,109 (GRCm39) S254P probably benign Het
Cep104 G A 4: 154,063,553 (GRCm39) probably null Het
Cep170b C T 12: 112,702,806 (GRCm39) T423I probably damaging Het
Cfap58 A G 19: 47,943,844 (GRCm39) E348G probably benign Het
Chd6 A G 2: 160,883,978 (GRCm39) L89S probably damaging Het
Cyp2a22 T C 7: 26,631,793 (GRCm39) S488G probably damaging Het
D130040H23Rik C A 8: 69,755,633 (GRCm39) H363Q probably benign Het
Dcaf7 T A 11: 105,942,628 (GRCm39) F192I probably damaging Het
Ddx20 T C 3: 105,586,504 (GRCm39) I614V probably benign Het
Ehbp1 G A 11: 22,046,000 (GRCm39) T558I probably damaging Het
Eif2b5 T C 16: 20,321,335 (GRCm39) V296A possibly damaging Het
Esr1 A G 10: 4,951,260 (GRCm39) E546G possibly damaging Het
Fras1 T A 5: 96,874,472 (GRCm39) probably null Het
G930045G22Rik T C 6: 50,823,698 (GRCm39) noncoding transcript Het
Gemin5 A T 11: 58,038,805 (GRCm39) L568* probably null Het
Gm22697+Rbm27 AGGTCCAGGCCCAGGCCCTGGTCCTGGCCCTGGCCCTGGTCCCGGCCCAGGCCC AGGTCCCGGCCCAGGCCC 18: 42,434,948 (GRCm39) probably benign Het
Gpr155 T C 2: 73,194,508 (GRCm39) probably null Het
Has1 A G 17: 18,070,247 (GRCm39) Y225H probably damaging Het
Hk3 A G 13: 55,162,274 (GRCm39) F110S probably damaging Het
Iars1 A G 13: 49,876,478 (GRCm39) K848E possibly damaging Het
Kif17 A G 4: 137,997,206 (GRCm39) Y43C probably damaging Het
Kif20b A T 19: 34,914,190 (GRCm39) T355S possibly damaging Het
Kif21a T C 15: 90,878,570 (GRCm39) T237A probably damaging Het
Klc1 T C 12: 111,743,321 (GRCm39) L216P probably damaging Het
Krt7 A C 15: 101,310,448 (GRCm39) S32R probably damaging Het
Lama3 A G 18: 12,665,256 (GRCm39) D2330G possibly damaging Het
Limch1 T A 5: 67,156,599 (GRCm39) S511R probably damaging Het
Luzp2 T A 7: 54,914,018 (GRCm39) probably null Het
Macc1 T C 12: 119,410,156 (GRCm39) M308T probably benign Het
Mroh9 T G 1: 162,873,625 (GRCm39) E510A probably damaging Het
Myo1h G T 5: 114,474,336 (GRCm39) L458F probably damaging Het
Neto1 A T 18: 86,518,179 (GRCm39) Y528F probably damaging Het
Nlrp9b T A 7: 19,760,469 (GRCm39) C187S possibly damaging Het
Nup160 T C 2: 90,540,432 (GRCm39) Y854H probably damaging Het
Odc1 T C 12: 17,598,538 (GRCm39) probably benign Het
Or10a3n A G 7: 108,492,972 (GRCm39) I214T probably damaging Het
Or51a10 A G 7: 103,699,376 (GRCm39) Y62H probably damaging Het
Or5an10 T A 19: 12,276,023 (GRCm39) I158L probably benign Het
Plcb2 A T 2: 118,554,261 (GRCm39) M64K possibly damaging Het
Plcxd3 A T 15: 4,405,291 (GRCm39) I33F probably benign Het
Postn A G 3: 54,283,522 (GRCm39) T534A probably damaging Het
Prkd2 T A 7: 16,591,732 (GRCm39) F588I possibly damaging Het
Prrg4 C A 2: 104,663,088 (GRCm39) A173S probably benign Het
Rinl C T 7: 28,497,057 (GRCm39) A519V probably damaging Het
Rpgrip1l A C 8: 91,979,517 (GRCm39) V975G probably damaging Het
Rps6ka4 C A 19: 6,816,730 (GRCm39) V118L probably benign Het
Rtkn T C 6: 83,112,975 (GRCm39) S16P probably damaging Het
Sbspon C A 1: 15,953,983 (GRCm39) R99L probably damaging Het
Sdf4 G A 4: 156,083,886 (GRCm39) A119T probably damaging Het
Sgpp1 T A 12: 75,762,990 (GRCm39) H397L possibly damaging Het
Shc2 T A 10: 79,461,945 (GRCm39) M367L probably benign Het
Slc26a5 T A 5: 22,018,974 (GRCm39) K590* probably null Het
Slc39a12 T C 2: 14,456,803 (GRCm39) V597A probably benign Het
Smcp A T 3: 92,491,788 (GRCm39) C20S unknown Het
Tdrd6 A C 17: 43,938,000 (GRCm39) V1016G possibly damaging Het
Tmem132c T A 5: 127,540,120 (GRCm39) probably benign Het
Tmem170b A T 13: 41,759,738 (GRCm39) Q16L probably null Het
Tmem30a A G 9: 79,700,311 (GRCm39) F61S probably damaging Het
Tnfsf13b T C 8: 10,081,534 (GRCm39) M232T probably damaging Het
Trip11 T A 12: 101,850,651 (GRCm39) K853* probably null Het
Tusc3 C A 8: 39,513,721 (GRCm39) S64* probably null Het
Vmn2r111 A T 17: 22,788,042 (GRCm39) D436E probably benign Het
Zfp607a T C 7: 27,578,493 (GRCm39) V521A probably benign Het
Zfp704 A T 3: 9,536,099 (GRCm39) S140R probably damaging Het
Other mutations in Eif2ak3
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL01386:Eif2ak3 APN 6 70,869,710 (GRCm39) missense probably damaging 1.00
IGL02069:Eif2ak3 APN 6 70,873,949 (GRCm39) missense probably damaging 1.00
IGL02197:Eif2ak3 APN 6 70,878,441 (GRCm39) missense probably benign 0.37
IGL03150:Eif2ak3 APN 6 70,869,420 (GRCm39) missense possibly damaging 0.68
R0024:Eif2ak3 UTSW 6 70,869,340 (GRCm39) missense probably benign 0.01
R0130:Eif2ak3 UTSW 6 70,858,716 (GRCm39) splice site probably benign
R0394:Eif2ak3 UTSW 6 70,862,202 (GRCm39) missense probably benign 0.03
R0699:Eif2ak3 UTSW 6 70,869,514 (GRCm39) missense probably benign 0.16
R1708:Eif2ak3 UTSW 6 70,864,790 (GRCm39) missense probably damaging 0.99
R1953:Eif2ak3 UTSW 6 70,869,538 (GRCm39) missense probably benign 0.03
R2062:Eif2ak3 UTSW 6 70,881,181 (GRCm39) missense probably benign 0.02
R2875:Eif2ak3 UTSW 6 70,860,623 (GRCm39) missense probably damaging 1.00
R4260:Eif2ak3 UTSW 6 70,866,497 (GRCm39) missense probably damaging 0.98
R4357:Eif2ak3 UTSW 6 70,861,859 (GRCm39) missense probably damaging 0.98
R4786:Eif2ak3 UTSW 6 70,869,602 (GRCm39) missense possibly damaging 0.95
R4801:Eif2ak3 UTSW 6 70,864,877 (GRCm39) missense probably benign 0.01
R4802:Eif2ak3 UTSW 6 70,864,877 (GRCm39) missense probably benign 0.01
R5194:Eif2ak3 UTSW 6 70,835,462 (GRCm39) missense possibly damaging 0.83
R5260:Eif2ak3 UTSW 6 70,870,113 (GRCm39) missense probably damaging 1.00
R5710:Eif2ak3 UTSW 6 70,860,717 (GRCm39) missense probably damaging 1.00
R5724:Eif2ak3 UTSW 6 70,853,824 (GRCm39) missense probably benign 0.19
R6089:Eif2ak3 UTSW 6 70,873,918 (GRCm39) missense possibly damaging 0.87
R6656:Eif2ak3 UTSW 6 70,860,699 (GRCm39) missense probably damaging 1.00
R6940:Eif2ak3 UTSW 6 70,869,386 (GRCm39) missense possibly damaging 0.82
R6949:Eif2ak3 UTSW 6 70,855,829 (GRCm39) missense probably damaging 0.99
R6958:Eif2ak3 UTSW 6 70,869,667 (GRCm39) missense probably benign 0.01
R7168:Eif2ak3 UTSW 6 70,858,610 (GRCm39) missense probably benign
R7627:Eif2ak3 UTSW 6 70,869,919 (GRCm39) missense probably benign 0.01
R8322:Eif2ak3 UTSW 6 70,855,903 (GRCm39) missense probably damaging 1.00
R8693:Eif2ak3 UTSW 6 70,858,535 (GRCm39) missense possibly damaging 0.94
R8729:Eif2ak3 UTSW 6 70,821,864 (GRCm39) missense probably benign 0.00
R8924:Eif2ak3 UTSW 6 70,870,003 (GRCm39) missense probably damaging 1.00
R9127:Eif2ak3 UTSW 6 70,860,704 (GRCm39) missense probably damaging 1.00
R9156:Eif2ak3 UTSW 6 70,860,614 (GRCm39) missense probably damaging 1.00
R9171:Eif2ak3 UTSW 6 70,835,419 (GRCm39) missense probably damaging 1.00
R9608:Eif2ak3 UTSW 6 70,841,511 (GRCm39) nonsense probably null
Predicted Primers PCR Primer
(F):5'- GAAAAGGTGCTATTATTCAGTTCGGGGA -3'
(R):5'- ATGGCCTGGCTTATTCTGTTTTAAATGC -3'

Sequencing Primer
(F):5'- CTATTATTCAGTTCGGGGAACATTG -3'
(R):5'- acctcctgcttccacattc -3'
Posted On 2014-04-24