Mutagenetix > Incidental Mutation

Incidental Mutation 'R6089:Eif2ak3'

484653

Institutional Source

Beutler Lab

Gene Symbol

Eif2ak3

Ensembl Gene

ENSMUSG00000031668

Gene Name

eukaryotic translation initiation factor 2 alpha kinase 3

Synonyms

PERK

MMRRC Submission

044246-MU

Accession Numbers

Essential gene?

Possibly essential (E-score: 0.650) question?

Stock #

R6089 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

70821499-70882229 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 70873918 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Threonine to Serine at position 944 (T944S)

Ref Sequence

ENSEMBL: ENSMUSP00000034093 (fasta)

Gene Model

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

AlphaFold

no structure available at present

Predicted Effect

possibly damaging
Transcript: ENSMUST00000034093
AA Change: T944S

PolyPhen 2 Score 0.874 (Sensitivity: 0.83; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000034093
Gene: ENSMUSG00000031668
AA Change: T944S

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: ENSMUST00000159401

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000161316

Coding Region Coverage

1x: 99.9%
3x: 99.6%
10x: 97.8%
20x: 93.3%

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: 64 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Actr3	A	G	1: 125,335,132 (GRCm39)	V95A	probably damaging	Het
Ankrd40	A	T	11: 94,224,751 (GRCm39)	K53N	probably damaging	Het
Ash1l	C	T	3: 88,960,450 (GRCm39)	Q2338*	probably null	Het
Astn2	A	G	4: 65,712,810 (GRCm39)	F610S	probably damaging	Het
Baz2a	TCTCCTC	TCTC	10: 127,950,511 (GRCm39)		probably benign	Het
Btbd8	C	T	5: 107,654,895 (GRCm39)	A386V	probably damaging	Het
Calm4	A	T	13: 3,887,874 (GRCm39)		probably benign	Het
Card10	T	C	15: 78,686,614 (GRCm39)	T68A	probably benign	Het
Cars2	A	G	8: 11,580,301 (GRCm39)	M245T	probably damaging	Het
Cat	C	A	2: 103,303,296 (GRCm39)	L160F	probably null	Het
Cers5	G	T	15: 99,638,883 (GRCm39)	T144K	probably benign	Het
Cyp3a13	T	A	5: 137,908,215 (GRCm39)	L211F	probably benign	Het
Defb4	A	T	8: 19,251,321 (GRCm39)	R63*	probably null	Het
Dnah14	G	T	1: 181,577,719 (GRCm39)	W3012L	probably damaging	Het
Dusp18	A	G	11: 3,847,555 (GRCm39)	T182A	probably benign	Het
Dzip1l	C	A	9: 99,524,737 (GRCm39)	T286K	possibly damaging	Het
Fbn1	A	T	2: 125,163,145 (GRCm39)	I2119N	possibly damaging	Het
Gabbr2	A	G	4: 46,846,448 (GRCm39)	S154P	probably damaging	Het
Gm15440	A	T	13: 51,845,437 (GRCm39)	H107Q	unknown	Het
Grm2	G	A	9: 106,531,090 (GRCm39)	P133L	probably damaging	Het
Gsdme	A	G	6: 50,228,285 (GRCm39)	V61A	probably damaging	Het
Gtpbp1	A	G	15: 79,591,198 (GRCm39)	T23A	probably benign	Het
Helz	A	T	11: 107,485,963 (GRCm39)		probably null	Het
Herc1	A	C	9: 66,352,814 (GRCm39)	H2100P	probably damaging	Het
Hjurp	GT	GTT	1: 88,194,246 (GRCm39)		probably null	Het
Ifngr1	T	C	10: 19,482,048 (GRCm39)	S213P	probably benign	Het
Itgb7	T	C	15: 102,125,721 (GRCm39)	D636G	probably benign	Het
Mre11a	G	A	9: 14,730,760 (GRCm39)	D491N	probably benign	Het
Muc16	A	G	9: 18,554,548 (GRCm39)	L3915P	unknown	Het
Myh1	T	A	11: 67,092,993 (GRCm39)		probably null	Het
Myh1	T	G	11: 67,111,613 (GRCm39)		probably null	Het
Myh7b	C	T	2: 155,464,409 (GRCm39)	T608M	probably damaging	Het
Myof	T	C	19: 37,955,508 (GRCm39)	K23E	probably benign	Het
Nacad	A	G	11: 6,551,331 (GRCm39)	V620A	probably benign	Het
Pbrm1	T	C	14: 30,809,542 (GRCm39)	Y1121H	probably damaging	Het
Pcdha9	T	C	18: 37,131,551 (GRCm39)	F207L	probably benign	Het
Pcdhb10	T	C	18: 37,546,679 (GRCm39)	V585A	possibly damaging	Het
Pigg	A	T	5: 108,489,788 (GRCm39)	M798L	probably benign	Het
Poc5	G	T	13: 96,533,179 (GRCm39)	M102I	probably damaging	Het
Ppp2r3d	T	A	9: 101,088,835 (GRCm39)	Q496L	probably benign	Het
Ptprf	A	G	4: 118,068,281 (GRCm39)	Y1752H	probably damaging	Het
Ptpru	G	C	4: 131,499,941 (GRCm39)	S1244R	possibly damaging	Het
Rnf213	A	G	11: 119,307,385 (GRCm39)	K682E	probably benign	Het
Rtp3	T	C	9: 110,816,041 (GRCm39)	D170G	probably benign	Het
Sall4	T	C	2: 168,597,406 (GRCm39)	D478G	possibly damaging	Het
Scai	A	T	2: 38,973,566 (GRCm39)	Y58*	probably null	Het
Simc1	G	A	13: 54,676,303 (GRCm39)	V1007M	probably benign	Het
Tcf20	G	T	15: 82,737,409 (GRCm39)	D1347E	probably benign	Het
Tdo2	T	C	3: 81,870,035 (GRCm39)	Y279C	probably damaging	Het
Trdn	C	T	10: 33,340,571 (GRCm39)	P602S	probably benign	Het
Txndc5	A	T	13: 38,707,392 (GRCm39)	M1K	probably null	Het
Ubr2	A	C	17: 47,293,218 (GRCm39)	M356R	possibly damaging	Het
Uqcrc2	A	T	7: 120,253,232 (GRCm39)	D332V	probably damaging	Het
Usp48	T	C	4: 137,333,129 (GRCm39)	F108L	probably damaging	Het
Vill	A	G	9: 118,886,867 (GRCm39)	N4S	probably benign	Het
Vmn1r11	T	C	6: 57,114,645 (GRCm39)	V103A	possibly damaging	Het
Vmn2r98	A	G	17: 19,286,336 (GRCm39)	D278G	probably benign	Het
Vps35l	T	G	7: 118,345,658 (GRCm39)	S59A	possibly damaging	Het
Wfdc15a	A	T	2: 164,041,586 (GRCm39)	L79*	probably null	Het
Xxylt1	C	T	16: 30,899,799 (GRCm39)	V119M	probably damaging	Het
Zfp26	G	T	9: 20,348,989 (GRCm39)	A525D	probably damaging	Het
Zgrf1	G	A	3: 127,389,642 (GRCm39)	G396D	probably damaging	Het
Zkscan16	A	G	4: 58,948,889 (GRCm39)	D148G	possibly damaging	Het
Zscan26	G	T	13: 21,632,499 (GRCm39)	S77R	probably 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
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'- TCAGGTGGTCTCGAATATGCAC -3'
(R):5'- CACTGCCTAACTATCTAAAGTCGG -3'

Sequencing Primer
(F):5'- AGGTGGTCTCGAATATGCACTTCTC -3'
(R):5'- TCGGAAAGACTCACCTGCTCTG -3'

Posted On

2017-08-16