Incidental Mutation 'R2875:Eif2ak3'
ID 260506
Institutional Source Beutler Lab
Gene Symbol Eif2ak3
Ensembl Gene ENSMUSG00000031668
Gene Name eukaryotic translation initiation factor 2 alpha kinase 3
Synonyms PERK
MMRRC Submission 040463-MU
Accession Numbers
Essential gene? Possibly essential (E-score: 0.650) question?
Stock # R2875 (G1)
Quality Score 225
Status Not validated
Chromosome 6
Chromosomal Location 70821499-70882229 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to C at 70860623 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Serine to Proline at position 400 (S400P)
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: S400P

PolyPhen 2 Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)
SMART Domains Protein: ENSMUSP00000034093
Gene: ENSMUSG00000031668
AA Change: S400P

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
Coding Region Coverage
  • 1x: 99.2%
  • 3x: 98.6%
  • 10x: 97.4%
  • 20x: 95.3%
Validation Efficiency 100% (1/1)
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
Adam34l T A 8: 44,080,177 (GRCm39) K16* probably null Het
Adgb T G 10: 10,298,463 (GRCm39) T422P probably damaging Het
Adrm1 A G 2: 179,817,411 (GRCm39) T293A probably damaging Het
Baz1a A T 12: 54,969,904 (GRCm39) D585E probably damaging Het
Ccdc152 T C 15: 3,327,663 (GRCm39) N38S probably damaging Het
Cenpf A G 1: 189,390,841 (GRCm39) M997T probably benign Het
Dnah12 A G 14: 26,414,625 (GRCm39) I9V probably benign Het
Dnah12 A G 14: 26,598,907 (GRCm39) N995S probably benign Het
Dnah9 C A 11: 66,059,287 (GRCm39) G3C possibly damaging Het
Dock2 A G 11: 34,609,712 (GRCm39) S243P probably damaging Het
Eno1b A G 18: 48,180,851 (GRCm39) K343R possibly damaging Het
Grk6 A G 13: 55,600,117 (GRCm39) H271R probably damaging Het
H2-Ab1 A C 17: 34,482,286 (GRCm39) M1L probably benign Het
Irf8 C A 8: 121,481,202 (GRCm39) P262Q probably damaging Het
Kcnc3 G T 7: 44,240,961 (GRCm39) G218* probably null Het
Krt9 C A 11: 100,080,031 (GRCm39) G454* probably null Het
Mgrn1 C T 16: 4,725,280 (GRCm39) T47I possibly damaging Het
Ndst1 A T 18: 60,823,119 (GRCm39) F816I probably damaging Het
Or11g26 T A 14: 50,753,269 (GRCm39) W203R probably benign Het
Or5h25 A T 16: 58,930,165 (GRCm39) D269E probably benign Het
Phf12 C A 11: 77,900,573 (GRCm39) T223N probably damaging Het
Rad1 T C 15: 10,490,417 (GRCm39) V128A probably benign Het
Rad54l C T 4: 115,959,050 (GRCm39) R382Q probably benign Het
Rhbdd1 A G 1: 82,346,090 (GRCm39) D215G probably benign Het
Sdc4 T C 2: 164,273,211 (GRCm39) D33G possibly damaging Het
Smarca4 A T 9: 21,553,876 (GRCm39) K387N possibly damaging Het
St3gal5 A G 6: 72,124,114 (GRCm39) M214V possibly damaging Het
Stk25 T C 1: 93,556,973 (GRCm39) D15G possibly damaging Het
Timm21 T C 18: 84,969,217 (GRCm39) D69G probably benign Het
Ttll4 A G 1: 74,725,597 (GRCm39) probably null Het
Ttn T A 2: 76,589,438 (GRCm39) N21272I probably damaging Het
Uchl3 A G 14: 101,905,996 (GRCm39) H153R probably benign Het
Zbed6 C T 1: 133,584,598 (GRCm39) C913Y probably damaging Het
Zcwpw1 T C 5: 137,808,304 (GRCm39) S251P probably damaging Het
Zeb1 GGA GGAAGA 18: 5,772,859 (GRCm39) probably benign Het
Zscan29 T C 2: 120,994,581 (GRCm39) Y468C 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
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'- TTTGAGCATCTTCCCTGGAAAG -3'
(R):5'- GCCTGGCTTATTCTGTTTTAAATGC -3'

Sequencing Primer
(F):5'- CTTCCCTGGAAAGAGCTATGTAGC -3'
(R):5'- ACTCATTGTGCAGACTAGGC -3'
Posted On 2015-01-23