Mutagenetix > Incidental Mutation

Incidental Mutation 'R0615:Eif2ak4'

54993

Institutional Source

Beutler Lab

Gene Symbol

Eif2ak4

Ensembl Gene

ENSMUSG00000005102

Gene Name

eukaryotic translation initiation factor 2 alpha kinase 4

Synonyms

GCN2

MMRRC Submission

038804-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R0615 (G1)

Quality Score

102

Status

Validated

Chromosome

Chromosomal Location

118219099-118305715 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

C to T at 118266666 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Threonine to Methionine at position 729 (T729M)

Ref Sequence

ENSEMBL: ENSMUSP00000106498 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000005233] [ENSMUST00000102527] [ENSMUST00000110869] [ENSMUST00000110870] [ENSMUST00000110872] [ENSMUST00000110874]

AlphaFold

no structure available at present

Predicted Effect

probably damaging
Transcript: ENSMUST00000005233
AA Change: T807M

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000005233
Gene: ENSMUSG00000005102
AA Change: T807M

Domain	Start	End	E-Value	Type
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 damaging
Transcript: ENSMUST00000102527
AA Change: T695M

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000099586
Gene: ENSMUSG00000005102
AA Change: T695M

Domain	Start	End	E-Value	Type
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: ENSMUST00000110869

SMART Domains

Protein: ENSMUSP00000106493
Gene: ENSMUSG00000005102

Domain	Start	End	E-Value	Type
Pfam:Pkinase	15	199	2.3e-32	PFAM
Pfam:Pkinase_Tyr	16	198	3.1e-13	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000110870
AA Change: T529M

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000106494
Gene: ENSMUSG00000005102
AA Change: T529M

Domain	Start	End	E-Value	Type
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 damaging
Transcript: ENSMUST00000110872
AA Change: T686M

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000106496
Gene: ENSMUSG00000005102
AA Change: T686M

Domain	Start	End	E-Value	Type
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 damaging
Transcript: ENSMUST00000110874
AA Change: T729M

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000106498
Gene: ENSMUSG00000005102
AA Change: T729M

Domain	Start	End	E-Value	Type
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

Meta Mutation Damage Score

0.6467

Coding Region Coverage

1x: 99.4%
3x: 98.9%
10x: 97.4%
20x: 94.8%

Validation Efficiency

100% (57/57)

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: 52 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4933411K16Rik	T	C	19: 42,040,962 (GRCm39)	I31T	possibly damaging	Het
Abca13	A	G	11: 9,206,197 (GRCm39)	I166V	probably damaging	Het
Acaa2	G	T	18: 74,931,517 (GRCm39)	V238L	probably benign	Het
Ahsg	A	T	16: 22,717,805 (GRCm39)	I296F	possibly damaging	Het
Aspm	T	A	1: 139,415,027 (GRCm39)	V1436D	probably damaging	Het
Ate1	A	T	7: 130,115,563 (GRCm39)		probably benign	Het
Atosa	T	A	9: 74,911,570 (GRCm39)	Y14N	probably damaging	Het
Atp1a4	A	T	1: 172,059,627 (GRCm39)		probably benign	Het
Aurkc	A	T	7: 7,005,402 (GRCm39)	I223L	possibly damaging	Het
Bckdha	G	T	7: 25,341,210 (GRCm39)	D50E	probably benign	Het
Brf2	C	T	8: 27,614,059 (GRCm39)	E376K	probably benign	Het
Cdk9	C	A	2: 32,599,813 (GRCm39)	L141F	possibly damaging	Het
Cgn	A	C	3: 94,678,024 (GRCm39)		probably benign	Het
Clcn1	G	A	6: 42,282,509 (GRCm39)	V526I	probably damaging	Het
Cnot2	A	G	10: 116,334,141 (GRCm39)	V343A	possibly damaging	Het
Commd2	A	T	3: 57,554,116 (GRCm39)	V195D	possibly damaging	Het
Cubn	C	T	2: 13,365,063 (GRCm39)		probably null	Het
Elac1	A	T	18: 73,871,954 (GRCm39)	V347E	probably damaging	Het
Fam209	T	C	2: 172,316,053 (GRCm39)	S143P	probably benign	Het
Fam20c	G	A	5: 138,793,241 (GRCm39)	R454Q	probably damaging	Het
Faxc	C	T	4: 21,958,608 (GRCm39)	S255L	probably benign	Het
Fem1al	C	A	11: 29,774,515 (GRCm39)	R314L	probably damaging	Het
Foxj1	T	C	11: 116,224,908 (GRCm39)	D153G	possibly damaging	Het
Gm6605	C	A	7: 38,147,699 (GRCm39)		noncoding transcript	Het
Lmo7	T	A	14: 102,114,295 (GRCm39)	Y12*	probably null	Het
Matn3	T	G	12: 9,013,594 (GRCm39)	C425W	probably damaging	Het
Mmd2	A	T	5: 142,550,668 (GRCm39)	M190K	probably benign	Het
Morn2	A	T	17: 80,603,026 (GRCm39)	T102S	probably damaging	Het
Nr3c2	A	C	8: 77,912,518 (GRCm39)	T710P	probably benign	Het
Nrros	C	A	16: 31,962,903 (GRCm39)	L343F	probably damaging	Het
Ntrk2	C	T	13: 59,276,000 (GRCm39)	Q767*	probably null	Het
Or2h2c	G	C	17: 37,422,347 (GRCm39)	L176V	probably benign	Het
Or4k47	C	T	2: 111,452,264 (GRCm39)	D52N	possibly damaging	Het
Plekhf2	C	T	4: 10,991,330 (GRCm39)	R4H	probably benign	Het
Ppox	A	G	1: 171,105,387 (GRCm39)		probably benign	Het
Qprt	T	A	7: 126,708,248 (GRCm39)	D61V	probably damaging	Het
Reln	A	G	5: 22,215,148 (GRCm39)	V1101A	probably benign	Het
Sbno1	T	C	5: 124,548,202 (GRCm39)	N124D	probably damaging	Het
Scx	C	T	15: 76,342,295 (GRCm39)	P165L	probably benign	Het
Sema6d	T	C	2: 124,496,055 (GRCm39)		probably benign	Het
Serf2	T	C	2: 121,281,336 (GRCm39)	F92L	probably benign	Het
Synpo2	A	T	3: 122,910,936 (GRCm39)	N236K	probably damaging	Het
Tbc1d32	C	A	10: 56,100,736 (GRCm39)	D81Y	probably benign	Het
Terf2	G	A	8: 107,809,622 (GRCm39)	T232I	possibly damaging	Het
Tpd52l2	A	G	2: 181,143,744 (GRCm39)	E50G	probably damaging	Het
Tprn	A	G	2: 25,154,210 (GRCm39)	E504G	probably damaging	Het
Tufm	G	T	7: 126,086,654 (GRCm39)	R12L	probably benign	Het
Vmn2r8	A	G	5: 108,947,195 (GRCm39)	F519S	probably damaging	Het
Vwa8	T	C	14: 79,145,590 (GRCm39)	V89A	probably benign	Het
Wnt3	T	C	11: 103,703,207 (GRCm39)	I230T	possibly damaging	Het
Zan	A	T	5: 137,466,693 (GRCm39)	F388Y	probably damaging	Het
Zfp474	C	T	18: 52,771,421 (GRCm39)	L25F	probably benign	Het

Other mutations in Eif2ak4

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH 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
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
R7441:Eif2ak4	UTSW	2	118,302,377 (GRCm39)	missense	probably benign	0.01
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'- TGCAAGTGGTCCTGGCTCAATC -3'
(R):5'- GGGGAGTGTATCCCTAATTCCCACAAC -3'

Sequencing Primer
(F):5'- GTAATGTGCTCTATCATTGAGCC -3'
(R):5'- TAATTCCCACAACACATGCAC -3'

Posted On

2013-07-11