Mutagenetix > Incidental Mutation

Incidental Mutation 'R6958:Eif2ak3'

541578

Institutional Source

Beutler Lab

Gene Symbol

Eif2ak3

Ensembl Gene

ENSMUSG00000031668

Gene Name

eukaryotic translation initiation factor 2 alpha kinase 3

Synonyms

PERK

MMRRC Submission

045009-MU

Accession Numbers

Essential gene?

Possibly essential (E-score: 0.680) question?

Stock #

R6958 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

70821499-70882229 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 70869667 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Cysteine to Serine at position 785 (C785S)

Ref Sequence

ENSEMBL: ENSMUSP00000034093 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000034093]

AlphaFold

no structure available at present

Predicted Effect

probably benign
Transcript: ENSMUST00000034093
AA Change: C785S

PolyPhen 2 Score 0.007 (Sensitivity: 0.96; Specificity: 0.75)

SMART Domains

Protein: ENSMUSP00000034093
Gene: ENSMUSG00000031668
AA Change: C785S

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

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.2%
20x: 96.9%

Validation Efficiency

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: 62 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2410004B18Rik	A	G	3: 145,649,558 (GRCm39)	D159G	probably benign	Het
Ahnak	A	G	19: 8,992,579 (GRCm39)	N4621S	possibly damaging	Het
Ankrd16	C	T	2: 11,784,604 (GRCm39)	A144V	probably damaging	Het
Bhmt1b	G	A	18: 87,775,046 (GRCm39)	E190K	probably benign	Het
Ccdc14	T	C	16: 34,511,176 (GRCm39)	V2A	probably damaging	Het
Ccdc187	C	T	2: 26,179,731 (GRCm39)	V243I	probably benign	Het
Cdk12	A	T	11: 98,132,525 (GRCm39)	I985F	unknown	Het
Cfap65	T	C	1: 74,971,058 (GRCm39)	T87A	possibly damaging	Het
Cilp2	G	A	8: 70,335,190 (GRCm39)	P603S	probably benign	Het
Cntnap5b	A	G	1: 100,202,197 (GRCm39)	E348G	probably benign	Het
Cpa6	C	T	1: 10,665,913 (GRCm39)	V42M	probably damaging	Het
Cpsf4	A	G	5: 145,112,402 (GRCm39)	I115V	probably benign	Het
Dnah11	G	T	12: 117,897,544 (GRCm39)	P3562Q	probably damaging	Het
Dnah9	A	G	11: 65,967,167 (GRCm39)	F1664L	probably damaging	Het
Dpysl3	T	C	18: 43,571,067 (GRCm39)	Q69R	probably benign	Het
Ebf3	T	C	7: 136,800,994 (GRCm39)	T455A	possibly damaging	Het
Elk4	T	A	1: 131,945,570 (GRCm39)	F149L	probably damaging	Het
Fgf14	A	G	14: 124,914,009 (GRCm39)	W41R	probably benign	Het
Fmnl1	T	A	11: 103,062,140 (GRCm39)	M1K	probably null	Het
Foxk2	A	T	11: 121,190,563 (GRCm39)	Q568L	probably benign	Het
Fryl	T	G	5: 73,231,272 (GRCm39)	I1602L	possibly damaging	Het
Gfm2	A	G	13: 97,282,744 (GRCm39)	I75V	probably damaging	Het
Gm3233	T	A	10: 77,595,369 (GRCm39)		probably benign	Het
Gnb1	G	T	4: 155,627,651 (GRCm39)		probably null	Het
Gphn	G	T	12: 78,727,073 (GRCm39)	V662L	possibly damaging	Het
Il3	A	C	11: 54,157,937 (GRCm39)	V47G	probably benign	Het
Iqgap3	A	G	3: 88,020,673 (GRCm39)	D401G	possibly damaging	Het
Kdm3b	T	A	18: 34,941,336 (GRCm39)	S276T	probably benign	Het
Krtap6-2	A	G	16: 89,216,698 (GRCm39)	S90P	unknown	Het
Lars1	C	T	18: 42,369,704 (GRCm39)	V394I	probably damaging	Het
Lrit1	G	C	14: 36,782,052 (GRCm39)	V242L	probably damaging	Het
Lrp10	A	G	14: 54,707,278 (GRCm39)		probably benign	Het
Ltn1	A	T	16: 87,194,679 (GRCm39)	C1407S	probably benign	Het
Lzts2	G	T	19: 45,012,582 (GRCm39)		probably benign	Het
Msantd2	A	G	9: 37,434,753 (GRCm39)	E331G	probably damaging	Het
Myo15a	G	A	11: 60,394,451 (GRCm39)	G1218S	probably benign	Het
Myom2	G	A	8: 15,167,741 (GRCm39)	A1109T	probably null	Het
Nhp2	A	G	11: 51,513,934 (GRCm39)	T118A	probably benign	Het
Nup155	A	G	15: 8,176,638 (GRCm39)	Y972C	probably damaging	Het
Nxpe2	A	T	9: 48,237,566 (GRCm39)	C230S	probably damaging	Het
Or12d13	T	C	17: 37,647,308 (GRCm39)	I272V	probably benign	Het
Or51g2	A	G	7: 102,623,091 (GRCm39)	L36P	possibly damaging	Het
Or5w8	T	C	2: 87,688,295 (GRCm39)	Y259H	probably damaging	Het
Pfkfb4	A	T	9: 108,839,615 (GRCm39)	N244I	probably damaging	Het
Pi4ka	C	T	16: 17,143,091 (GRCm39)	R24Q	probably damaging	Het
Pkd2l2	C	A	18: 34,542,543 (GRCm39)	Y8*	probably null	Het
Pramel20	A	T	4: 143,297,829 (GRCm39)	D83V	probably damaging	Het
Ptprb	T	A	10: 116,113,153 (GRCm39)	N44K	probably benign	Het
Sds	G	A	5: 120,619,537 (GRCm39)	V149M	probably damaging	Het
Slc22a30	A	G	19: 8,364,065 (GRCm39)	F204L	probably damaging	Het
Slc26a7	C	T	4: 14,506,442 (GRCm39)	A636T	probably benign	Het
Slc27a1	C	T	8: 72,038,083 (GRCm39)	A577V	possibly damaging	Het
Spata13	A	T	14: 60,989,300 (GRCm39)	T319S	possibly damaging	Het
Styxl2	T	A	1: 165,935,565 (GRCm39)	D211V	probably damaging	Het
Tdrd3	A	G	14: 87,694,532 (GRCm39)	D29G	probably damaging	Het
Tex15	A	T	8: 34,060,899 (GRCm39)	I110L	probably benign	Het
Treml2	A	G	17: 48,615,180 (GRCm39)	T222A	probably damaging	Het
Trpd52l3	A	T	19: 29,981,546 (GRCm39)	L100F	probably damaging	Het
Ttf2	C	T	3: 100,853,248 (GRCm39)	E975K	probably benign	Het
Vmn1r193	T	A	13: 22,404,144 (GRCm39)		probably benign	Het
Xpo1	A	G	11: 23,235,855 (GRCm39)	T648A	probably benign	Het
Zfp641	C	T	15: 98,190,832 (GRCm39)	V71I	possibly damaging	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
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
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'- AAAGAAGTCGGTCTTTCTCGGTG -3'
(R):5'- TCTGAAGAAGACCTGCTGCTG -3'

Sequencing Primer
(F):5'- ATTTCCTGTGGCCAGACAAG -3'
(R):5'- CTGGAGCACTTGAGATCAGTTAGC -3'

Posted On

2018-11-28