Incidental Mutation 'R7441:Eif2ak4'
ID 576941
Institutional Source Beutler Lab
Gene Symbol Eif2ak4
Ensembl Gene ENSMUSG00000005102
Gene Name eukaryotic translation initiation factor 2 alpha kinase 4
Synonyms GCN2
MMRRC Submission 045517-MU
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # R7441 (G1)
Quality Score 225.009
Status Not validated
Chromosome 2
Chromosomal Location 118219099-118305715 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 118302377 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Threonine to Alanine at position 1555 (T1555A)
Ref Sequence ENSEMBL: ENSMUSP00000005233 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000005233] [ENSMUST00000009693] [ENSMUST00000102527] [ENSMUST00000110870] [ENSMUST00000110872] [ENSMUST00000110874]
AlphaFold no structure available at present
Predicted Effect probably benign
Transcript: ENSMUST00000005233
AA Change: T1555A

PolyPhen 2 Score 0.007 (Sensitivity: 0.96; Specificity: 0.75)
SMART Domains Protein: ENSMUSP00000005233
Gene: ENSMUSG00000005102
AA Change: T1555A

DomainStartEndE-ValueType
low complexity region 2 13 N/A INTRINSIC
RWD 25 137 3.42e-38 SMART
coiled coil region 146 205 N/A INTRINSIC
Pfam:Pkinase 323 538 4.6e-27 PFAM
Pfam:Pkinase_Tyr 326 535 5.5e-18 PFAM
Pfam:Pkinase 589 663 1.7e-11 PFAM
Pfam:Pkinase_Tyr 589 663 1.2e-5 PFAM
low complexity region 728 738 N/A INTRINSIC
Pfam:Pkinase 781 1000 2.6e-38 PFAM
Pfam:Pkinase_Tyr 786 998 1.8e-18 PFAM
Pfam:tRNA-synt_His 1054 1380 5.7e-18 PFAM
Pfam:HGTP_anticodon2 1392 1647 5.8e-17 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000009693
SMART Domains Protein: ENSMUSP00000009693
Gene: ENSMUSG00000009549

DomainStartEndE-ValueType
Pfam:SRP14 4 94 5.5e-31 PFAM
low complexity region 95 107 N/A INTRINSIC
Predicted Effect probably benign
Transcript: ENSMUST00000102527
AA Change: T1443A

PolyPhen 2 Score 0.005 (Sensitivity: 0.97; Specificity: 0.74)
SMART Domains Protein: ENSMUSP00000099586
Gene: ENSMUSG00000005102
AA Change: T1443A

DomainStartEndE-ValueType
coiled coil region 34 93 N/A INTRINSIC
Pfam:Pkinase 211 426 1.6e-22 PFAM
Pfam:Pkinase_Tyr 215 423 6.8e-18 PFAM
Pfam:Pkinase_Tyr 477 551 1.2e-5 PFAM
Pfam:Pkinase 477 552 3.9e-11 PFAM
low complexity region 616 626 N/A INTRINSIC
Pfam:Pkinase 647 888 9.4e-42 PFAM
Pfam:Pkinase_Tyr 672 886 1.4e-19 PFAM
Pfam:tRNA-synt_His 941 1268 4.8e-19 PFAM
Pfam:HGTP_anticodon2 1280 1535 1e-16 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000110870
AA Change: T1277A

PolyPhen 2 Score 0.007 (Sensitivity: 0.96; Specificity: 0.75)
SMART Domains Protein: ENSMUSP00000106494
Gene: ENSMUSG00000005102
AA Change: T1277A

DomainStartEndE-ValueType
Pfam:Pkinase 45 260 3.3e-22 PFAM
Pfam:Pkinase_Tyr 47 257 1.3e-17 PFAM
Pfam:Pkinase_Tyr 311 385 2.5e-5 PFAM
Pfam:Pkinase 311 386 8e-11 PFAM
low complexity region 450 460 N/A INTRINSIC
Pfam:Pkinase 481 722 1.9e-41 PFAM
Pfam:Pkinase_Tyr 506 720 2.8e-19 PFAM
Pfam:tRNA-synt_His 775 1102 8.7e-19 PFAM
Pfam:HGTP_anticodon2 1114 1369 1.9e-16 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000110872
AA Change: T1434A

PolyPhen 2 Score 0.007 (Sensitivity: 0.96; Specificity: 0.75)
SMART Domains Protein: ENSMUSP00000106496
Gene: ENSMUSG00000005102
AA Change: T1434A

DomainStartEndE-ValueType
coiled coil region 25 84 N/A INTRINSIC
Pfam:Pkinase 202 417 3.8e-22 PFAM
Pfam:Pkinase_Tyr 206 414 1.6e-17 PFAM
Pfam:Pkinase_Tyr 468 542 2.8e-5 PFAM
Pfam:Pkinase 468 543 9.1e-11 PFAM
low complexity region 607 617 N/A INTRINSIC
Pfam:Pkinase 638 879 2.2e-41 PFAM
Pfam:Pkinase_Tyr 663 877 3.3e-19 PFAM
Pfam:tRNA-synt_His 932 1259 1.1e-18 PFAM
Pfam:HGTP_anticodon2 1271 1526 2.2e-16 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000110874
AA Change: T1477A

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)
SMART Domains Protein: ENSMUSP00000106498
Gene: ENSMUSG00000005102
AA Change: T1477A

DomainStartEndE-ValueType
Pfam:RWD 8 56 6.4e-8 PFAM
coiled coil region 68 127 N/A INTRINSIC
Pfam:Pkinase 245 460 1.1e-22 PFAM
Pfam:Pkinase_Tyr 247 457 4.2e-18 PFAM
Pfam:Pkinase_Tyr 511 585 7.8e-6 PFAM
Pfam:Pkinase 511 586 2.5e-11 PFAM
low complexity region 650 660 N/A INTRINSIC
Pfam:Pkinase 681 922 6.2e-42 PFAM
Pfam:Pkinase_Tyr 706 920 9.3e-20 PFAM
Pfam:tRNA-synt_His 975 1302 3.8e-19 PFAM
Pfam:HGTP_anticodon2 1314 1569 5.4e-17 PFAM
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 100.0%
  • 10x: 99.7%
  • 20x: 99.0%
Validation Efficiency
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of a family of kinases that phosphorylate the alpha subunit of eukaryotic translation initiation factor-2 (EIF2), resulting in the downregulaton of protein synthesis. The encoded protein responds to amino acid deprivation by binding uncharged transfer RNAs. It may also be activated by glucose deprivation and viral infection. Mutations in this gene have been found in individuals suffering from autosomal recessive pulmonary venoocclusive-disease-2. [provided by RefSeq, Mar 2014]
PHENOTYPE: Homozygotes for a null allele have altered feeding behavior, synaptic plasticity and dendritic cell function. Homozygotes for another null allele show enhanced muscle loss and morbidity after amino acid deprivation. Homozygotes for an ENU-induced allele show higher susceptibility to viral infection. [provided by MGI curators]
Allele List at MGI

All alleles(8) : Targeted(3) Gene trapped(4) Chemically induced(1)
 

Other mutations in this stock
Total: 56 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
4921509C19Rik A C 2: 151,314,845 (GRCm39) S278A possibly damaging Het
Adamts20 T C 15: 94,251,554 (GRCm39) D411G probably damaging Het
Adgrl3 A G 5: 81,871,987 (GRCm39) I894V possibly damaging Het
Adprhl1 C T 8: 13,273,069 (GRCm39) V1230I probably benign Het
Agpat1 T A 17: 34,829,883 (GRCm39) Y77N probably damaging Het
Anpep A G 7: 79,477,392 (GRCm39) V725A possibly damaging Het
Apc T A 18: 34,445,126 (GRCm39) I674K probably damaging Het
Arhgef2 A G 3: 88,551,262 (GRCm39) R808G probably damaging Het
Asap1 A G 15: 64,002,105 (GRCm39) V402A probably damaging Het
Aspg T C 12: 112,091,255 (GRCm39) V479A possibly damaging Het
B3galnt2 G A 13: 14,169,070 (GRCm39) V368M probably benign Het
Bahcc1 T C 11: 120,177,132 (GRCm39) S2007P probably damaging Het
Cyfip2 A T 11: 46,087,254 (GRCm39) I1212N possibly damaging Het
Dnajc16 A T 4: 141,491,124 (GRCm39) D675E probably damaging Het
Dram2 T C 3: 106,462,503 (GRCm39) F4L probably damaging Het
Dsp A G 13: 38,379,425 (GRCm39) T2057A probably benign Het
Dync1h1 T G 12: 110,602,887 (GRCm39) L2176R probably damaging Het
Efhb A T 17: 53,708,549 (GRCm39) I707N possibly damaging Het
Erc1 G A 6: 119,801,912 (GRCm39) T35I possibly damaging Het
Esr2 C A 12: 76,188,168 (GRCm39) M363I probably benign Het
Etl4 A T 2: 20,749,000 (GRCm39) N446I possibly damaging Het
Evpl T A 11: 116,113,782 (GRCm39) K1303* probably null Het
Fam135b A T 15: 71,335,529 (GRCm39) V555E probably damaging Het
Fam186b A G 15: 99,177,970 (GRCm39) L452P probably benign Het
Fmn1 A T 2: 113,271,956 (GRCm39) Q108L unknown Het
Gcc2 A G 10: 58,092,723 (GRCm39) T48A probably benign Het
Gm6619 T G 6: 131,467,354 (GRCm39) I73S possibly damaging Het
Gm8267 T A 14: 44,960,397 (GRCm39) D116V probably damaging Het
Gtf3c3 G A 1: 54,459,607 (GRCm39) T385M probably benign Het
Iqgap2 C A 13: 95,764,584 (GRCm39) M1553I probably benign Het
Kcnk1 G T 8: 126,722,307 (GRCm39) G37C probably damaging Het
Kifc3 T C 8: 95,864,615 (GRCm39) M32V probably benign Het
Krt81 C A 15: 101,359,251 (GRCm39) K222N possibly damaging Het
Lrrc63 A G 14: 75,363,697 (GRCm39) S145P possibly damaging Het
Mybbp1a T A 11: 72,342,101 (GRCm39) V1279E probably benign Het
Niban3 A G 8: 72,052,808 (GRCm39) D94G probably benign Het
Or11g26 A T 14: 50,752,853 (GRCm39) Y64F probably damaging Het
Or8u9 T A 2: 86,001,354 (GRCm39) D269V probably damaging Het
Pierce1 TCTCTGGGGCAGGCTTAGCCTTGGGCTCCCCCGGCTCCGGCTCCTCTGGGGCAGGCTTAGCCTTGGGCTCCCCCGGCTCCGGCTCCTCTGGGGCGGGCTTAGCCTTGGGCTCCCCCGGCTCCGGCTCCTC TCTCTGGGGCAGGCTTAGCCTTGGGCTCCCCCGGCTCCGGCTCCTCTGGGGCGGGCTTAGCCTTGGGCTCCCCCGGCTCCGGCTCCTC 2: 28,356,122 (GRCm39) probably benign Het
Pramel12 A G 4: 143,145,410 (GRCm39) Y293C probably benign Het
Ptpn18 T C 1: 34,512,416 (GRCm39) V407A probably benign Het
Ptpn9 T A 9: 56,934,717 (GRCm39) Y160* probably null Het
Ptprj T C 2: 90,280,163 (GRCm39) K1045R possibly damaging Het
Rundc3a G T 11: 102,290,872 (GRCm39) probably null Het
Scn11a C T 9: 119,587,692 (GRCm39) V1351I probably benign Het
Slc26a9 A G 1: 131,690,556 (GRCm39) Y520C probably damaging Het
Spata20 G A 11: 94,374,867 (GRCm39) A245V probably benign Het
Steap3 A C 1: 120,169,248 (GRCm39) F350V probably benign Het
Swt1 A T 1: 151,286,815 (GRCm39) F226I probably benign Het
Taar7f A G 10: 23,925,885 (GRCm39) T160A possibly damaging Het
Timd5 G A 11: 46,419,382 (GRCm39) W66* probably null Het
Upf2 A T 2: 6,023,743 (GRCm39) I698F unknown Het
Vmn2r84 T C 10: 130,227,982 (GRCm39) T85A possibly damaging Het
Zfp426 T C 9: 20,382,147 (GRCm39) E280G possibly damaging Het
Zfp810 C A 9: 22,190,568 (GRCm39) E78* probably null Het
Zfp937 GTGATAAGGCATTTGCACAAAACAGTCATCTCCTAACACATAAAAGAACACAT G 2: 150,080,630 (GRCm39) probably null Het
Other mutations in Eif2ak4
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00233:Eif2ak4 APN 2 118,294,536 (GRCm39) missense probably damaging 1.00
IGL00806:Eif2ak4 APN 2 118,271,647 (GRCm39) missense probably benign 0.08
IGL01343:Eif2ak4 APN 2 118,252,570 (GRCm39) missense probably benign 0.00
IGL01796:Eif2ak4 APN 2 118,276,785 (GRCm39) missense probably benign 0.10
IGL02263:Eif2ak4 APN 2 118,292,259 (GRCm39) missense probably benign 0.00
IGL02391:Eif2ak4 APN 2 118,251,272 (GRCm39) missense probably benign 0.19
IGL02516:Eif2ak4 APN 2 118,266,735 (GRCm39) missense probably damaging 1.00
IGL02603:Eif2ak4 APN 2 118,280,807 (GRCm39) missense probably damaging 1.00
IGL02731:Eif2ak4 APN 2 118,219,295 (GRCm39) missense probably benign
IGL02928:Eif2ak4 APN 2 118,303,168 (GRCm39) critical splice donor site probably null
IGL02947:Eif2ak4 APN 2 118,261,514 (GRCm39) missense probably benign 0.00
IGL03191:Eif2ak4 APN 2 118,252,693 (GRCm39) missense probably damaging 1.00
IGL03202:Eif2ak4 APN 2 118,231,101 (GRCm39) missense probably damaging 1.00
IGL03235:Eif2ak4 APN 2 118,273,621 (GRCm39) missense probably damaging 1.00
IGL03375:Eif2ak4 APN 2 118,252,799 (GRCm39) missense probably benign 0.08
absurdum UTSW 2 118,251,291 (GRCm39) nonsense probably null
Ad UTSW 2 118,266,722 (GRCm39) missense probably damaging 1.00
atchoum UTSW 2 118,231,134 (GRCm39) splice site probably benign
reductio UTSW 2 118,266,639 (GRCm39) splice site probably null
PIT4520001:Eif2ak4 UTSW 2 118,292,808 (GRCm39) missense probably damaging 1.00
R0023:Eif2ak4 UTSW 2 118,293,202 (GRCm39) missense probably damaging 1.00
R0358:Eif2ak4 UTSW 2 118,294,410 (GRCm39) splice site probably null
R0482:Eif2ak4 UTSW 2 118,292,828 (GRCm39) missense probably damaging 1.00
R0505:Eif2ak4 UTSW 2 118,261,517 (GRCm39) missense probably benign 0.01
R0523:Eif2ak4 UTSW 2 118,272,577 (GRCm39) critical splice donor site probably null
R0578:Eif2ak4 UTSW 2 118,305,472 (GRCm39) splice site probably benign
R0615:Eif2ak4 UTSW 2 118,266,666 (GRCm39) missense probably damaging 1.00
R1300:Eif2ak4 UTSW 2 118,294,464 (GRCm39) missense possibly damaging 0.79
R1531:Eif2ak4 UTSW 2 118,273,691 (GRCm39) missense probably damaging 1.00
R1777:Eif2ak4 UTSW 2 118,261,320 (GRCm39) missense probably damaging 0.98
R1866:Eif2ak4 UTSW 2 118,303,142 (GRCm39) missense probably damaging 1.00
R1932:Eif2ak4 UTSW 2 118,278,967 (GRCm39) missense probably damaging 1.00
R1977:Eif2ak4 UTSW 2 118,292,238 (GRCm39) nonsense probably null
R2011:Eif2ak4 UTSW 2 118,261,428 (GRCm39) missense probably damaging 1.00
R2046:Eif2ak4 UTSW 2 118,281,889 (GRCm39) splice site probably benign
R2122:Eif2ak4 UTSW 2 118,286,274 (GRCm39) missense probably damaging 1.00
R2125:Eif2ak4 UTSW 2 118,252,604 (GRCm39) missense probably benign 0.02
R2126:Eif2ak4 UTSW 2 118,252,604 (GRCm39) missense probably benign 0.02
R2193:Eif2ak4 UTSW 2 118,252,747 (GRCm39) missense probably benign 0.12
R2259:Eif2ak4 UTSW 2 118,286,264 (GRCm39) missense probably damaging 0.97
R2513:Eif2ak4 UTSW 2 118,257,064 (GRCm39) missense probably damaging 1.00
R3798:Eif2ak4 UTSW 2 118,304,564 (GRCm39) missense probably damaging 1.00
R3898:Eif2ak4 UTSW 2 118,261,404 (GRCm39) missense probably damaging 1.00
R3900:Eif2ak4 UTSW 2 118,305,510 (GRCm39) missense probably damaging 1.00
R4375:Eif2ak4 UTSW 2 118,258,405 (GRCm39) missense probably damaging 1.00
R4423:Eif2ak4 UTSW 2 118,269,547 (GRCm39) missense probably benign 0.01
R4589:Eif2ak4 UTSW 2 118,247,819 (GRCm39) missense probably damaging 1.00
R4734:Eif2ak4 UTSW 2 118,252,568 (GRCm39) missense probably damaging 1.00
R5173:Eif2ak4 UTSW 2 118,238,841 (GRCm39) missense probably damaging 1.00
R5367:Eif2ak4 UTSW 2 118,266,639 (GRCm39) splice site probably null
R5471:Eif2ak4 UTSW 2 118,304,613 (GRCm39) missense probably benign 0.02
R5528:Eif2ak4 UTSW 2 118,258,419 (GRCm39) missense probably damaging 1.00
R5634:Eif2ak4 UTSW 2 118,292,792 (GRCm39) missense probably damaging 1.00
R5726:Eif2ak4 UTSW 2 118,273,613 (GRCm39) missense probably damaging 1.00
R5756:Eif2ak4 UTSW 2 118,293,221 (GRCm39) missense possibly damaging 0.95
R5779:Eif2ak4 UTSW 2 118,243,444 (GRCm39) missense possibly damaging 0.85
R5807:Eif2ak4 UTSW 2 118,219,332 (GRCm39) missense probably benign
R6045:Eif2ak4 UTSW 2 118,219,296 (GRCm39) nonsense probably null
R6187:Eif2ak4 UTSW 2 118,287,638 (GRCm39) missense probably damaging 0.98
R6193:Eif2ak4 UTSW 2 118,231,081 (GRCm39) start gained probably benign
R6468:Eif2ak4 UTSW 2 118,266,722 (GRCm39) missense probably damaging 1.00
R6555:Eif2ak4 UTSW 2 118,258,350 (GRCm39) missense probably damaging 0.96
R6616:Eif2ak4 UTSW 2 118,285,326 (GRCm39) nonsense probably null
R6737:Eif2ak4 UTSW 2 118,292,749 (GRCm39) frame shift probably null
R6956:Eif2ak4 UTSW 2 118,252,748 (GRCm39) missense probably damaging 0.96
R7075:Eif2ak4 UTSW 2 118,251,291 (GRCm39) nonsense probably null
R7109:Eif2ak4 UTSW 2 118,235,532 (GRCm39) missense probably damaging 1.00
R7228:Eif2ak4 UTSW 2 118,287,638 (GRCm39) missense probably damaging 0.98
R7555:Eif2ak4 UTSW 2 118,247,764 (GRCm39) missense possibly damaging 0.64
R7567:Eif2ak4 UTSW 2 118,280,795 (GRCm39) missense probably benign
R8004:Eif2ak4 UTSW 2 118,247,775 (GRCm39) missense possibly damaging 0.64
R8063:Eif2ak4 UTSW 2 118,241,382 (GRCm39) missense possibly damaging 0.94
R8092:Eif2ak4 UTSW 2 118,272,513 (GRCm39) missense probably damaging 1.00
R8195:Eif2ak4 UTSW 2 118,280,819 (GRCm39) missense possibly damaging 0.50
R8306:Eif2ak4 UTSW 2 118,287,656 (GRCm39) missense possibly damaging 0.68
R8470:Eif2ak4 UTSW 2 118,293,207 (GRCm39) missense probably damaging 0.98
R8671:Eif2ak4 UTSW 2 118,252,667 (GRCm39) missense possibly damaging 0.88
R8693:Eif2ak4 UTSW 2 118,262,718 (GRCm39) missense probably damaging 0.98
R8714:Eif2ak4 UTSW 2 118,292,765 (GRCm39) missense possibly damaging 0.89
R8744:Eif2ak4 UTSW 2 118,261,474 (GRCm39) nonsense probably null
R8813:Eif2ak4 UTSW 2 118,278,806 (GRCm39) missense probably damaging 1.00
R8917:Eif2ak4 UTSW 2 118,287,617 (GRCm39) missense probably damaging 1.00
R8924:Eif2ak4 UTSW 2 118,258,513 (GRCm39) missense probably damaging 1.00
R9177:Eif2ak4 UTSW 2 118,271,701 (GRCm39) critical splice donor site probably null
R9189:Eif2ak4 UTSW 2 118,258,393 (GRCm39) missense probably damaging 1.00
R9231:Eif2ak4 UTSW 2 118,271,662 (GRCm39) missense probably benign 0.00
R9268:Eif2ak4 UTSW 2 118,271,701 (GRCm39) critical splice donor site probably null
R9321:Eif2ak4 UTSW 2 118,292,798 (GRCm39) missense possibly damaging 0.93
R9512:Eif2ak4 UTSW 2 118,293,196 (GRCm39) missense probably damaging 1.00
R9569:Eif2ak4 UTSW 2 118,251,316 (GRCm39) missense probably benign 0.00
R9658:Eif2ak4 UTSW 2 118,269,511 (GRCm39) missense probably damaging 1.00
R9748:Eif2ak4 UTSW 2 118,247,730 (GRCm39) missense probably benign 0.01
R9757:Eif2ak4 UTSW 2 118,269,398 (GRCm39) missense probably benign 0.02
R9766:Eif2ak4 UTSW 2 118,261,313 (GRCm39) nonsense probably null
X0061:Eif2ak4 UTSW 2 118,298,657 (GRCm39) missense probably damaging 1.00
Predicted Primers PCR Primer
(F):5'- GCAAGAGTGTGCCATGATCC -3'
(R):5'- CATGAGGAACAGCCAGGTTG -3'

Sequencing Primer
(F):5'- CTGTAGTCACTCTGTAGACCAGG -3'
(R):5'- GGTTGATACCATATACAGCTGACAGC -3'
Posted On 2019-10-07