Mutagenetix > Incidental Mutation

Incidental Mutation 'R4786:Eif2ak3'

367081

Institutional Source

Beutler Lab

Gene Symbol

Eif2ak3

Ensembl Gene

ENSMUSG00000031668

Gene Name

eukaryotic translation initiation factor 2 alpha kinase 3

Synonyms

PERK

MMRRC Submission

041995-MU

Accession Numbers

Essential gene?

Possibly essential (E-score: 0.650) question?

Stock #

R4786 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

70821499-70882229 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

C to T at 70869602 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Threonine to Methionine at position 763 (T763M)

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: T763M

PolyPhen 2 Score 0.953 (Sensitivity: 0.79; Specificity: 0.95)

SMART Domains

Protein: ENSMUSP00000034093
Gene: ENSMUSG00000031668
AA Change: T763M

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: 99.2%
3x: 98.6%
10x: 97.0%
20x: 94.7%

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: 86 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2700097O09Rik	A	T	12: 55,106,321 (GRCm39)	I134N	possibly damaging	Het
Acvr1c	T	C	2: 58,170,366 (GRCm39)	Y414C	probably damaging	Het
Adam32	A	C	8: 25,353,509 (GRCm39)	S693R	probably damaging	Het
Aldh2	A	T	5: 121,710,887 (GRCm39)	F314Y	probably benign	Het
Anks1	A	G	17: 28,271,704 (GRCm39)	D874G	possibly damaging	Het
Ap4b1	T	A	3: 103,726,120 (GRCm39)	V372E	probably benign	Het
Aqp12	G	A	1: 92,934,177 (GRCm39)	C18Y	probably damaging	Het
Arap1	T	A	7: 101,034,212 (GRCm39)	I218N	possibly damaging	Het
Arhgap42	C	A	9: 9,238,703 (GRCm39)	E28*	probably null	Het
Asb5	G	A	8: 55,038,874 (GRCm39)	E247K	probably benign	Het
Atg9b	T	C	5: 24,591,087 (GRCm39)	D781G	possibly damaging	Het
Atxn10	A	G	15: 85,271,344 (GRCm39)	H294R	probably benign	Het
Bod1l	G	T	5: 41,976,781 (GRCm39)	T1511K	probably benign	Het
Btnl2	A	T	17: 34,582,322 (GRCm39)	N296I	probably damaging	Het
Camta1	A	T	4: 151,374,496 (GRCm39)	L168H	probably damaging	Het
Cant1	A	T	11: 118,299,665 (GRCm39)	V265E	possibly damaging	Het
Ccdc157	T	C	11: 4,101,861 (GRCm39)	D20G	probably damaging	Het
Cd209c	T	G	8: 3,995,698 (GRCm39)	T35P	possibly damaging	Het
Cdc20b	G	A	13: 113,215,268 (GRCm39)	V279M	probably damaging	Het
Cdh18	T	A	15: 23,410,873 (GRCm39)	W453R	probably null	Het
Cdh24	A	G	14: 54,875,007 (GRCm39)	S333P	possibly damaging	Het
Ceacam11	T	C	7: 17,706,239 (GRCm39)		probably null	Het
Ciz1	C	T	2: 32,267,539 (GRCm39)	P150L	probably damaging	Het
Crip3	C	A	17: 46,741,968 (GRCm39)	Q152K	possibly damaging	Het
Dars2	G	A	1: 160,888,330 (GRCm39)	R197W	probably damaging	Het
Dctn4	A	G	18: 60,688,267 (GRCm39)	D394G	probably damaging	Het
Dido1	T	C	2: 180,312,664 (GRCm39)	Y1077C	possibly damaging	Het
Dnhd1	A	G	7: 105,323,651 (GRCm39)	T641A	probably benign	Het
Egln3	A	T	12: 54,232,367 (GRCm39)	I146N	probably damaging	Het
Etfbkmt	A	T	6: 149,048,744 (GRCm39)	M1L	probably benign	Het
Fam171a1	A	T	2: 3,226,615 (GRCm39)	I583F	probably damaging	Het
Fbxo38	A	C	18: 62,662,745 (GRCm39)	L249W	probably damaging	Het
Fxyd5	T	C	7: 30,740,907 (GRCm39)		probably benign	Het
Gabrr3	C	A	16: 59,250,463 (GRCm39)	T154K	probably benign	Het
Gm7233	C	A	14: 43,038,347 (GRCm39)	D90E	probably benign	Het
Gm8186	A	G	17: 26,318,014 (GRCm39)	V61A	probably benign	Het
Gnao1	A	G	8: 94,670,931 (GRCm39)	I137V	probably benign	Het
Gnptab	A	G	10: 88,272,044 (GRCm39)	M945V	probably damaging	Het
Gpsm1	G	A	2: 26,212,493 (GRCm39)	A78T	probably benign	Het
Gtf2b	T	C	3: 142,487,230 (GRCm39)	L222P	probably damaging	Het
Hnrnpf	A	G	6: 117,900,857 (GRCm39)	Y47C	probably damaging	Het
Itga6	A	G	2: 71,669,034 (GRCm39)	N608S	possibly damaging	Het
Kdm2b	T	C	5: 123,018,917 (GRCm39)		probably null	Het
Krit1	T	A	5: 3,862,467 (GRCm39)	H207Q	possibly damaging	Het
Ky	A	G	9: 102,419,186 (GRCm39)	N398D	probably benign	Het
Lama1	T	A	17: 68,080,854 (GRCm39)	V1294E	possibly damaging	Het
Lef1	C	T	3: 130,905,173 (GRCm39)	T18I	probably damaging	Het
Lrp2	T	C	2: 69,368,300 (GRCm39)	N178S	probably damaging	Het
Lrrc36	A	G	8: 106,181,910 (GRCm39)	T525A	probably benign	Het
Map3k8	A	T	18: 4,340,647 (GRCm39)	C222*	probably null	Het
Mapre2	G	C	18: 24,011,016 (GRCm39)	S199T	probably benign	Het
Mcm3ap	A	G	10: 76,324,300 (GRCm39)	N911S	probably benign	Het
Mroh4	G	T	15: 74,482,083 (GRCm39)	H722Q	probably benign	Het
Muc21	A	T	17: 35,930,221 (GRCm39)		probably benign	Het
Myo5b	A	C	18: 74,828,451 (GRCm39)	Y701S	probably benign	Het
Myt1l	G	T	12: 29,861,457 (GRCm39)	V80L	unknown	Het
Ncoa7	C	A	10: 30,531,638 (GRCm39)	V24L	probably benign	Het
Nlrp10	A	T	7: 108,524,445 (GRCm39)	V345D	probably damaging	Het
Nmral1	C	A	16: 4,534,288 (GRCm39)	G51V	probably damaging	Het
Npc1	A	G	18: 12,332,554 (GRCm39)	I797T	probably benign	Het
Or4x6	A	T	2: 89,949,351 (GRCm39)	I197N	possibly damaging	Het
Or8g22	T	A	9: 38,958,783 (GRCm39)	R22*	probably null	Het
Or8g34	A	T	9: 39,373,137 (GRCm39)	I134L	probably benign	Het
Pclo	A	T	5: 14,773,281 (GRCm39)	I4419F	unknown	Het
Phf3	C	A	1: 30,855,638 (GRCm39)	E983*	probably null	Het
Pitpnm2	A	T	5: 124,259,806 (GRCm39)	Y1149*	probably null	Het
Sdc3	A	T	4: 130,550,079 (GRCm39)	T430S	probably damaging	Het
Sema3f	A	G	9: 107,559,881 (GRCm39)	V671A	probably benign	Het
Sigirr	T	G	7: 140,671,346 (GRCm39)	S379R	probably benign	Het
Slc25a23	T	A	17: 57,354,326 (GRCm39)	N360I	possibly damaging	Het
Slco6c1	A	T	1: 97,015,720 (GRCm39)	M357K	probably benign	Het
Sox14	C	A	9: 99,757,018 (GRCm39)	M240I	probably benign	Het
Stradb	A	T	1: 59,030,367 (GRCm39)		probably benign	Het
Szt2	A	T	4: 118,256,259 (GRCm39)	M200K	probably benign	Het
Tef	T	C	15: 81,699,453 (GRCm39)	S85P	probably benign	Het
Thada	T	A	17: 84,766,283 (GRCm39)	H41L	possibly damaging	Het
Tinagl1	A	G	4: 130,067,724 (GRCm39)	F90S	probably benign	Het
Tnfaip1	G	A	11: 78,421,045 (GRCm39)	T5I	possibly damaging	Het
Tnfrsf23	A	T	7: 143,233,801 (GRCm39)	V59D	probably damaging	Het
Tnpo3	A	G	6: 29,578,541 (GRCm39)	V311A	probably benign	Het
Trak1	T	A	9: 121,301,560 (GRCm39)	M772K	probably benign	Het
Ubash3a	A	G	17: 31,436,938 (GRCm39)	D185G	probably benign	Het
Vmn2r120	T	C	17: 57,829,048 (GRCm39)	T516A	probably benign	Het
Wdr4	A	C	17: 31,728,785 (GRCm39)	L130R	probably damaging	Het
Zfp12	T	C	5: 143,231,257 (GRCm39)	I528T	probably damaging	Het
Zfp607a	T	C	7: 27,578,838 (GRCm39)	L636P	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
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'- AAGTCATAGCTCCTTCTCCTGAAAG -3'
(R):5'- GCTGGAGCACTTGAGATCAG -3'

Sequencing Primer
(F):5'- TTCTCCTGAAAGAAGTCGGTC -3'
(R):5'- AATGGTTGCCATCATGCAGC -3'

Posted On

2015-12-29