Incidental Mutation 'R5194:Eif2ak3'
| ID |
399951 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Eif2ak3
|
| Ensembl Gene |
ENSMUSG00000031668 |
| Gene Name |
eukaryotic translation initiation factor 2 alpha kinase 3 |
| Synonyms |
PERK |
| MMRRC Submission |
042770-MU
|
| Accession Numbers |
|
| Essential gene? |
Possibly essential
(E-score: 0.650)
|
| Stock # |
R5194 (G1)
|
| Quality Score |
225 |
|
Status
|
Validated
|
| Chromosome |
6 |
| Chromosomal Location |
70821499-70882229 bp(+) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
T to C
at 70835462 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Serine to Proline
at position 130
(S130P)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000123759
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000034093]
[ENSMUST00000162950]
|
| AlphaFold |
no structure available at present |
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000034093
AA Change: S130P
PolyPhen 2
Score 0.524 (Sensitivity: 0.88; Specificity: 0.90)
|
| SMART Domains |
Protein: ENSMUSP00000034093
Gene: ENSMUSG00000031668
AA Change: S130P
| Domain | Start | End | E-Value | Type |
|---|
|
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: ENSMUST00000083816
|
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000162950
AA Change: S130P
PolyPhen 2
Score 0.827 (Sensitivity: 0.84; Specificity: 0.93)
|
| SMART Domains |
Protein: ENSMUSP00000123759
Gene: ENSMUSG00000031668
AA Change: S130P
| Domain | Start | End | E-Value | Type |
|---|
|
signal peptide
|
1 |
28 |
N/A |
INTRINSIC |
|
low complexity region
|
48 |
82 |
N/A |
INTRINSIC |
|
Blast:PQQ
|
93 |
124 |
8e-11 |
BLAST |
|
low complexity region
|
125 |
139 |
N/A |
INTRINSIC |
|
| Meta Mutation Damage Score |
0.0989 |
| Coding Region Coverage |
- 1x: 99.3%
- 3x: 98.7%
- 10x: 97.3%
- 20x: 95.5%
|
| Validation Efficiency |
98% (59/60) |
| 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: 55 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| 1700122O11Rik |
T |
C |
17: 48,348,059 (GRCm39) |
N82D |
probably benign |
Het |
| Aadacl4fm2 |
A |
G |
4: 144,281,652 (GRCm39) |
V380A |
probably benign |
Het |
| Acadm |
C |
T |
3: 153,638,755 (GRCm39) |
R206H |
possibly damaging |
Het |
| Acly |
T |
A |
11: 100,414,372 (GRCm39) |
Y18F |
probably benign |
Het |
| Acnat2 |
G |
T |
4: 49,380,452 (GRCm39) |
Q291K |
probably benign |
Het |
| Agtpbp1 |
T |
C |
13: 59,648,453 (GRCm39) |
I456V |
probably benign |
Het |
| Ankrd7 |
A |
G |
6: 18,868,076 (GRCm39) |
N114S |
possibly damaging |
Het |
| Arfgef1 |
A |
T |
1: 10,275,132 (GRCm39) |
L307I |
probably benign |
Het |
| Arhgef2 |
A |
T |
3: 88,542,956 (GRCm39) |
I383F |
probably damaging |
Het |
| Cbs |
C |
T |
17: 31,843,198 (GRCm39) |
|
probably null |
Het |
| Cep135 |
T |
C |
5: 76,763,624 (GRCm39) |
V538A |
probably benign |
Het |
| Dennd5a |
T |
C |
7: 109,532,936 (GRCm39) |
E254G |
probably damaging |
Het |
| Drc7 |
T |
C |
8: 95,788,345 (GRCm39) |
V236A |
probably benign |
Het |
| Dtna |
C |
T |
18: 23,723,302 (GRCm39) |
Q169* |
probably null |
Het |
| Egfem1 |
G |
A |
3: 29,411,345 (GRCm39) |
|
probably null |
Het |
| Ewsr1 |
T |
C |
11: 5,032,355 (GRCm39) |
N297S |
unknown |
Het |
| F13a1 |
T |
G |
13: 37,156,037 (GRCm39) |
D192A |
probably damaging |
Het |
| Fam120a |
A |
G |
13: 49,034,411 (GRCm39) |
V1067A |
probably benign |
Het |
| Gm17490 |
T |
C |
2: 11,631,062 (GRCm39) |
Y5C |
unknown |
Het |
| Gm57859 |
T |
C |
11: 113,579,654 (GRCm39) |
S350P |
possibly damaging |
Het |
| Gm8587 |
C |
T |
12: 88,056,556 (GRCm39) |
|
noncoding transcript |
Het |
| H2-Ab1 |
C |
T |
17: 34,488,352 (GRCm39) |
|
probably benign |
Het |
| Hoxd12 |
T |
C |
2: 74,505,447 (GRCm39) |
L6P |
probably damaging |
Het |
| Ifi204 |
C |
T |
1: 173,576,910 (GRCm39) |
D564N |
possibly damaging |
Het |
| Irak2 |
T |
C |
6: 113,667,751 (GRCm39) |
V444A |
probably benign |
Het |
| Lgr6 |
C |
T |
1: 134,921,748 (GRCm39) |
A199T |
probably damaging |
Het |
| Lrba |
A |
C |
3: 86,235,526 (GRCm39) |
N877H |
probably damaging |
Het |
| Mylk3 |
T |
C |
8: 86,079,495 (GRCm39) |
I388V |
probably benign |
Het |
| Myo9b |
C |
T |
8: 71,801,733 (GRCm39) |
A1286V |
probably benign |
Het |
| Myt1l |
A |
C |
12: 29,861,647 (GRCm39) |
D143A |
unknown |
Het |
| Ngfr |
T |
C |
11: 95,471,808 (GRCm39) |
N63S |
probably benign |
Het |
| Or2ag16 |
A |
T |
7: 106,352,426 (GRCm39) |
H56Q |
probably benign |
Het |
| Or4c3 |
T |
A |
2: 89,851,870 (GRCm39) |
Y180F |
probably damaging |
Het |
| Or51a7 |
A |
G |
7: 102,615,071 (GRCm39) |
I255V |
probably benign |
Het |
| Or6c70 |
C |
T |
10: 129,709,967 (GRCm39) |
V220I |
probably benign |
Het |
| Or6z6 |
A |
G |
7: 6,491,519 (GRCm39) |
L118P |
probably damaging |
Het |
| P2rx7 |
T |
C |
5: 122,811,858 (GRCm39) |
S390P |
probably benign |
Het |
| Pcdhga4 |
A |
C |
18: 37,820,794 (GRCm39) |
Q781P |
probably benign |
Het |
| Phip |
G |
A |
9: 82,790,915 (GRCm39) |
S677F |
probably benign |
Het |
| Ptpdc1 |
C |
A |
13: 48,740,265 (GRCm39) |
V389F |
possibly damaging |
Het |
| Rab2a |
T |
A |
4: 8,604,381 (GRCm39) |
I161N |
probably benign |
Het |
| Rnf113a2 |
T |
A |
12: 84,464,111 (GRCm39) |
M1K |
probably null |
Het |
| Schip1 |
T |
C |
3: 68,402,205 (GRCm39) |
V122A |
probably benign |
Het |
| Sdr16c5 |
C |
A |
4: 4,006,663 (GRCm39) |
A210S |
probably benign |
Het |
| Sh3bp1 |
A |
G |
15: 78,787,301 (GRCm39) |
K83E |
probably damaging |
Het |
| Sipa1l2 |
T |
C |
8: 126,166,012 (GRCm39) |
S1541G |
possibly damaging |
Het |
| Slc22a21 |
T |
C |
11: 53,870,673 (GRCm39) |
Y4C |
probably damaging |
Het |
| Smco1 |
C |
T |
16: 32,092,592 (GRCm39) |
H88Y |
probably damaging |
Het |
| Tll2 |
T |
C |
19: 41,084,336 (GRCm39) |
D697G |
probably damaging |
Het |
| Trim34a |
A |
G |
7: 103,910,200 (GRCm39) |
N334S |
possibly damaging |
Het |
| Ubqln1 |
A |
G |
13: 58,346,847 (GRCm39) |
I64T |
probably benign |
Het |
| Vstm2b |
T |
A |
7: 40,551,912 (GRCm39) |
|
probably null |
Het |
| Wdr17 |
A |
G |
8: 55,140,639 (GRCm39) |
F238L |
probably damaging |
Het |
| Wiz |
T |
C |
17: 32,596,822 (GRCm39) |
|
probably benign |
Het |
| Zfp407 |
T |
C |
18: 84,579,434 (GRCm39) |
S560G |
probably benign |
Het |
|
| Other mutations in Eif2ak3 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH 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 |
|
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'- ACCAAGTGTCTTTCAGTGATGAC -3'
(R):5'- TACAGCGGACACAGTTCCTC -3'
Sequencing Primer
(F):5'- CTTTCAGTGATGACATAAGTGCAAGG -3'
(R):5'- GATTAACACATTTAATGCCTGCAGCG -3'
|
| Posted On |
2016-07-06 |
Incidental Mutation