Incidental Mutation 'R6656:Eif2ak3'
ID 526618
Institutional Source Beutler Lab
Gene Symbol Eif2ak3
Ensembl Gene ENSMUSG00000031668
Gene Name eukaryotic translation initiation factor 2 alpha kinase 3
Synonyms PERK
MMRRC Submission 044777-MU
Accession Numbers
Essential gene? Possibly essential (E-score: 0.650) question?
Stock # R6656 (G1)
Quality Score 225.009
Status Validated
Chromosome 6
Chromosomal Location 70821499-70882229 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to A at 70860699 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Isoleucine to Asparagine at position 425 (I425N)
Ref Sequence ENSEMBL: ENSMUSP00000034093 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000034093]
AlphaFold no structure available at present
Predicted Effect probably damaging
Transcript: ENSMUST00000034093
AA Change: I425N

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000034093
Gene: ENSMUSG00000031668
AA Change: I425N

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 0.1691 question?
Coding Region Coverage
  • 1x: 99.9%
  • 3x: 99.7%
  • 10x: 98.4%
  • 20x: 95.8%
Validation Efficiency 97% (35/36)
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: 36 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Ahctf1 T C 1: 179,581,078 (GRCm39) N1708S probably benign Het
Ahnak2 C T 12: 112,748,991 (GRCm39) M285I probably benign Het
Angptl1 A T 1: 156,684,806 (GRCm39) D325V probably damaging Het
Anln A T 9: 22,262,298 (GRCm39) V931E probably damaging Het
Ascc3 C T 10: 50,526,021 (GRCm39) R578* probably null Het
B3galnt2 C T 13: 14,150,161 (GRCm39) A168V probably benign Het
Bhlhe40 TG TGG 6: 108,641,818 (GRCm39) 254 probably null Het
Cd22 T C 7: 30,577,182 (GRCm39) I42V probably benign Het
Cyp2b19 C T 7: 26,466,280 (GRCm39) T361I probably benign Het
D930048N14Rik C A 11: 51,544,576 (GRCm39) probably benign Het
Ehf T C 2: 103,113,928 (GRCm39) N23S probably damaging Het
Fbxo4 C T 15: 4,005,305 (GRCm39) V192M probably damaging Het
Gm21190 T C 5: 15,730,849 (GRCm39) Q169R possibly damaging Het
Gngt1 A G 6: 3,994,246 (GRCm39) D8G possibly damaging Het
Ift140 T C 17: 25,251,147 (GRCm39) L31P probably damaging Het
Keg1 C T 19: 12,686,994 (GRCm39) Q8* probably null Het
Lama3 T A 18: 12,682,283 (GRCm39) M1083K possibly damaging Het
Lrp1b A T 2: 40,527,876 (GRCm39) Y68* probably null Het
Lyz3 A G 10: 117,071,534 (GRCm39) V115A probably benign Het
Mctp1 A T 13: 77,178,055 (GRCm39) K947N probably damaging Het
Muc5ac A G 7: 141,357,065 (GRCm39) Y1113C probably damaging Het
Myb C T 10: 21,028,844 (GRCm39) V85M probably damaging Het
Npas2 T G 1: 39,401,029 (GRCm39) S798A unknown Het
Or13a21 G T 7: 139,999,517 (GRCm39) H56Q probably damaging Het
Orc2 A G 1: 58,532,818 (GRCm39) probably null Het
Parpbp T C 10: 87,946,175 (GRCm39) T415A probably benign Het
Pcdha3 T C 18: 37,080,875 (GRCm39) V539A probably benign Het
Piwil4 T C 9: 14,621,230 (GRCm39) E601G probably damaging Het
Pramel51 A T 12: 88,142,763 (GRCm39) L285Q possibly damaging Het
Ptpn3 T A 4: 57,205,905 (GRCm39) I696F probably damaging Het
Sec63 C T 10: 42,692,379 (GRCm39) Q617* probably null Het
Sgip1 C A 4: 102,762,765 (GRCm39) probably benign Het
Sirpd T C 3: 15,385,558 (GRCm39) T115A probably damaging Het
Tktl2 T C 8: 66,965,381 (GRCm39) V313A probably benign Het
Tmem63b C A 17: 45,978,634 (GRCm39) R325L probably benign Het
Ttn C T 2: 76,539,700 (GRCm39) G34429R 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
R1648:Eif2ak3 UTSW 6 70,860,615 (GRCm39) missense possibly damaging 0.52
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
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'- AGAACTCCATCATGTGACTGAC -3'
(R):5'- CCATGGCCTGGCTTATTCTG -3'

Sequencing Primer
(F):5'- ACTGACATGTTTTTGACCATGTG -3'
(R):5'- ACTCATTGTGCAGACTAGGC -3'
Posted On 2018-07-23