Mutagenetix > Incidental Mutation

Incidental Mutation 'R7522:Gak'

582709

Institutional Source

Beutler Lab

Gene Symbol

Gak

Ensembl Gene

ENSMUSG00000062234

Gene Name

cyclin G associated kinase

Synonyms

D130045N16Rik

MMRRC Submission

045594-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R7522 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

108717277-108777621 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 108739065 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Asparagine at position 665 (I665N)

Ref Sequence

ENSEMBL: ENSMUSP00000036705 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000046603] [ENSMUST00000135225] [ENSMUST00000139303] [ENSMUST00000145467] [ENSMUST00000199048]

AlphaFold

no structure available at present

Predicted Effect

possibly damaging
Transcript: ENSMUST00000046603
AA Change: I665N

PolyPhen 2 Score 0.948 (Sensitivity: 0.79; Specificity: 0.95)

SMART Domains

Protein: ENSMUSP00000036705
Gene: ENSMUSG00000062234
AA Change: I665N

Domain	Start	End	E-Value	Type
low complexity region	11	22	N/A	INTRINSIC
Pfam:Pkinase	40	313	1.6e-49	PFAM
Pfam:Pkinase_Tyr	40	313	3e-30	PFAM
PTEN_C2	568	707	1.43e-44	SMART
low complexity region	819	833	N/A	INTRINSIC
low complexity region	932	945	N/A	INTRINSIC
low complexity region	1084	1092	N/A	INTRINSIC
low complexity region	1094	1110	N/A	INTRINSIC
DnaJ	1240	1301	2.3e-4	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000135225

SMART Domains

Protein: ENSMUSP00000118008
Gene: ENSMUSG00000062234

Domain	Start	End	E-Value	Type
low complexity region	11	22	N/A	INTRINSIC
Pfam:Pkinase	40	128	7.9e-11	PFAM
Pfam:Pkinase_Tyr	40	128	1.2e-6	PFAM

Predicted Effect

possibly damaging
Transcript: ENSMUST00000139303
AA Change: I138N

PolyPhen 2 Score 0.819 (Sensitivity: 0.84; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000116862
Gene: ENSMUSG00000062234
AA Change: I138N

Domain	Start	End	E-Value	Type
PTEN_C2	41	164	4.73e-27	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000145467

SMART Domains

Protein: ENSMUSP00000118713
Gene: ENSMUSG00000062234

Domain	Start	End	E-Value	Type
low complexity region	11	22	N/A	INTRINSIC
Pfam:Pkinase	40	128	7.9e-11	PFAM
Pfam:Pkinase_Tyr	40	128	1.2e-6	PFAM

Predicted Effect

SMART Domains

Protein: ENSMUSP00000115184
Gene: ENSMUSG00000062234
AA Change: I16N

Domain	Start	End	E-Value	Type
Pfam:PTEN_C2	4	59	9.5e-14	PFAM
low complexity region	122	136	N/A	INTRINSIC
low complexity region	235	248	N/A	INTRINSIC
low complexity region	387	395	N/A	INTRINSIC
low complexity region	397	413	N/A	INTRINSIC
DnaJ	543	604	2.3e-4	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000199048

SMART Domains

Protein: ENSMUSP00000142931
Gene: ENSMUSG00000062234

Domain	Start	End	E-Value	Type
low complexity region	11	22	N/A	INTRINSIC
PDB:4O38\|B	23	69	3e-10	PDB
SCOP:d1koba_	41	69	3e-5	SMART

Predicted Effect

Meta Mutation Damage Score

0.8520

Coding Region Coverage

1x: 100.0%
3x: 100.0%
10x: 99.8%
20x: 99.3%

Validation Efficiency

97% (75/77)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] In all eukaryotes, the cell cycle is governed by cyclin-dependent protein kinases (CDKs), whose activities are regulated by cyclins and CDK inhibitors in a diverse array of mechanisms that involve the control of phosphorylation and dephosphorylation of Ser, Thr or Tyr residues. Cyclins are molecules that possess a consensus domain called the 'cyclin box.' In mammalian cells, 9 cyclin species have been identified, and they are referred to as cyclins A through I. Cyclin G is a direct transcriptional target of the p53 tumor suppressor gene product and thus functions downstream of p53. GAK is an association partner of cyclin G and CDK5. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]
PHENOTYPE: Mice homozygous for a deletion of the kinase domain display neonatal lethality with abnormal lung alveolar morphology and development. Mice homozygous for a knock-out allele exhibit lethality during early development. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 76 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
A030014E15Rik	G	T	1: 82,902,949 (GRCm39)	C82F	unknown	Het
Adam21	G	C	12: 81,605,722 (GRCm39)	T680R	possibly damaging	Het
Adgrf4	A	C	17: 42,980,675 (GRCm39)	Y137D	probably benign	Het
Ago3	T	C	4: 126,257,600 (GRCm39)	K477R	probably benign	Het
Ahnak	T	A	19: 8,979,686 (GRCm39)	D323E	probably benign	Het
Amph	A	G	13: 19,270,715 (GRCm39)	D108G	probably damaging	Het
Ankrd10	A	T	8: 11,682,910 (GRCm39)	C106S	probably damaging	Het
Bmp5	A	T	9: 75,683,384 (GRCm39)	T4S	probably benign	Het
Brix1	G	A	15: 10,476,676 (GRCm39)	R267C	probably damaging	Het
Calcrl	G	A	2: 84,203,708 (GRCm39)	S24L	probably benign	Het
Ccdc40	T	G	11: 119,123,047 (GRCm39)	I213R	possibly damaging	Het
Cd300lg	A	G	11: 101,945,028 (GRCm39)	I413V	probably benign	Het
Cdh3	G	A	8: 107,268,005 (GRCm39)	D347N	probably damaging	Het
Clcn3	T	C	8: 61,394,446 (GRCm39)	T55A	probably benign	Het
Cnga4	A	G	7: 105,055,195 (GRCm39)	T260A	probably damaging	Het
Cpne8	G	T	15: 90,486,022 (GRCm39)	P147Q	probably benign	Het
Cpsf6	A	G	10: 117,203,734 (GRCm39)	Y74H	unknown	Het
Cryl1	A	T	14: 57,513,428 (GRCm39)	S264R	probably benign	Het
Cyp39a1	C	T	17: 43,978,370 (GRCm39)		probably benign	Het
Cyp4f39	T	C	17: 32,705,946 (GRCm39)	S346P	probably damaging	Het
Cyria	A	G	12: 12,408,057 (GRCm39)	T28A	possibly damaging	Het
Ddhd1	G	A	14: 45,895,104 (GRCm39)	A122V	possibly damaging	Het
Dnmt1	C	A	9: 20,831,498 (GRCm39)	C662F	probably damaging	Het
E2f6	G	A	12: 16,872,125 (GRCm39)	G190S	probably benign	Het
Esp34	A	T	17: 38,870,432 (GRCm39)	I109F	possibly damaging	Het
Espl1	A	T	15: 102,213,486 (GRCm39)	D604V	probably damaging	Het
Exo1	T	C	1: 175,728,870 (GRCm39)	C645R	probably benign	Het
Fah	A	G	7: 84,246,282 (GRCm39)	V189A	probably benign	Het
Fam184b	A	C	5: 45,688,093 (GRCm39)	Y939D	probably damaging	Het
Fchsd2	T	A	7: 100,908,829 (GRCm39)	L410*	probably null	Het
Galnt9	A	G	5: 110,743,705 (GRCm39)		probably null	Het
Gcg	T	C	2: 62,306,103 (GRCm39)	R165G	probably benign	Het
Hexd	T	C	11: 121,108,923 (GRCm39)	V214A	possibly damaging	Het
Hoxb3	A	T	11: 96,235,507 (GRCm39)	S145C	probably damaging	Het
Il18	A	G	9: 50,486,640 (GRCm39)	Y23C	probably damaging	Het
Itgav	A	T	2: 83,632,373 (GRCm39)	I954F	probably benign	Het
Kcna4	A	G	2: 107,126,600 (GRCm39)	R445G	probably damaging	Het
Kyat3	T	A	3: 142,440,305 (GRCm39)	L343Q	probably damaging	Het
Lgals4	A	T	7: 28,537,117 (GRCm39)	D139V	possibly damaging	Het
Lrp3	C	T	7: 34,903,755 (GRCm39)	G197D	probably damaging	Het
Lyst	T	A	13: 13,821,668 (GRCm39)	C1347*	probably null	Het
Man2a2	G	C	7: 80,018,613 (GRCm39)	A82G	probably benign	Het
Map3k4	T	C	17: 12,480,219 (GRCm39)	Q661R	probably benign	Het
Marcks	A	C	10: 37,012,577 (GRCm39)	F153V	unknown	Het
Mocs1	T	C	17: 49,742,292 (GRCm39)		probably null	Het
Naa60	A	G	16: 3,719,768 (GRCm39)	T232A	probably benign	Het
Oosp1	A	T	19: 11,666,065 (GRCm39)	I75N	probably benign	Het
Opn3	A	G	1: 175,493,189 (GRCm39)	V125A	probably benign	Het
Or2ag18	A	G	7: 106,404,994 (GRCm39)	V225A	probably damaging	Het
Or2f1	T	A	6: 42,721,568 (GRCm39)	I199N	probably damaging	Het
Or4c102	A	G	2: 88,423,005 (GRCm39)	T286A	possibly damaging	Het
Or7g27	T	A	9: 19,250,294 (GRCm39)	C179*	probably null	Het
Palb2	T	C	7: 121,712,501 (GRCm39)	T947A	probably damaging	Het
Pde5a	C	T	3: 122,634,648 (GRCm39)	R730*	probably null	Het
Plcl1	T	C	1: 55,735,523 (GRCm39)	I288T	probably benign	Het
Plxnb2	A	G	15: 89,045,977 (GRCm39)	I966T	probably benign	Het
Prkcz	T	C	4: 155,355,742 (GRCm39)	E400G	probably damaging	Het
Prpf8	A	G	11: 75,400,102 (GRCm39)	D2332G	possibly damaging	Het
Ptgds	T	G	2: 25,357,920 (GRCm39)	T154P	probably benign	Het
Rel	T	C	11: 23,720,676 (GRCm39)		probably null	Het
Rxylt1	A	G	10: 121,917,344 (GRCm39)	W390R	probably damaging	Het
Serpinb1c	T	A	13: 33,066,200 (GRCm39)	K248N	probably benign	Het
Shkbp1	A	C	7: 27,046,583 (GRCm39)	W394G	possibly damaging	Het
Slc47a2	A	G	11: 61,193,076 (GRCm39)	V559A	probably benign	Het
Sox6	A	T	7: 115,400,813 (GRCm39)	F10I	probably damaging	Het
Stkld1	T	C	2: 26,837,259 (GRCm39)	V303A	probably benign	Het
Styk1	T	A	6: 131,289,803 (GRCm39)		probably null	Het
Tet1	T	C	10: 62,654,762 (GRCm39)	T1574A	possibly damaging	Het
Tkt	A	T	14: 30,290,180 (GRCm39)	I270F	possibly damaging	Het
Trak1	A	G	9: 121,271,777 (GRCm39)	E166G	probably damaging	Het
Tsc2	A	T	17: 24,849,939 (GRCm39)	I58N	probably damaging	Het
Uhmk1	T	A	1: 170,042,809 (GRCm39)	M1L	probably benign	Het
Usp50	T	C	2: 126,625,146 (GRCm39)	Y21C	probably damaging	Het
Vmn1r180	C	G	7: 23,652,685 (GRCm39)	P283A	probably damaging	Het
Vmn1r83	A	G	7: 12,055,505 (GRCm39)	M184T	possibly damaging	Het
Vmn2r109	A	G	17: 20,774,665 (GRCm39)	I230T	probably benign	Het

Other mutations in Gak

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00694:Gak	APN	5	108,761,500 (GRCm39)	makesense	probably null
IGL00768:Gak	APN	5	108,724,520 (GRCm39)	missense	probably benign
IGL01128:Gak	APN	5	108,740,236 (GRCm39)	missense	probably damaging	0.97
IGL01557:Gak	APN	5	108,732,203 (GRCm39)	missense	probably damaging	1.00
IGL02559:Gak	APN	5	108,732,098 (GRCm39)	missense	probably null	0.07
PIT4449001:Gak	UTSW	5	108,728,791 (GRCm39)	missense	probably benign	0.00
R0030:Gak	UTSW	5	108,761,413 (GRCm39)	nonsense	probably null
R1403:Gak	UTSW	5	108,739,011 (GRCm39)	missense	probably damaging	1.00
R1403:Gak	UTSW	5	108,739,011 (GRCm39)	missense	probably damaging	1.00
R1530:Gak	UTSW	5	108,772,059 (GRCm39)	missense	probably damaging	0.97
R1646:Gak	UTSW	5	108,750,720 (GRCm39)	missense	probably damaging	1.00
R1699:Gak	UTSW	5	108,752,243 (GRCm39)	nonsense	probably null
R1702:Gak	UTSW	5	108,754,242 (GRCm39)	splice site	probably null
R1732:Gak	UTSW	5	108,724,448 (GRCm39)	missense	probably benign	0.28
R1738:Gak	UTSW	5	108,764,842 (GRCm39)	missense	probably damaging	1.00
R1772:Gak	UTSW	5	108,754,758 (GRCm39)	missense	probably damaging	1.00
R1792:Gak	UTSW	5	108,733,397 (GRCm39)	nonsense	probably null
R2068:Gak	UTSW	5	108,718,091 (GRCm39)	missense	probably benign
R2137:Gak	UTSW	5	108,754,743 (GRCm39)	splice site	probably null
R2138:Gak	UTSW	5	108,754,743 (GRCm39)	splice site	probably null
R2139:Gak	UTSW	5	108,754,743 (GRCm39)	splice site	probably null
R2904:Gak	UTSW	5	108,772,080 (GRCm39)	missense	possibly damaging	0.70
R3080:Gak	UTSW	5	108,761,468 (GRCm39)	missense	possibly damaging	0.90
R3773:Gak	UTSW	5	108,730,538 (GRCm39)	missense	probably benign	0.00
R4523:Gak	UTSW	5	108,724,432 (GRCm39)	missense	probably benign	0.22
R4665:Gak	UTSW	5	108,730,826 (GRCm39)	missense	probably benign
R4703:Gak	UTSW	5	108,717,743 (GRCm39)	missense	probably damaging	0.99
R4890:Gak	UTSW	5	108,728,742 (GRCm39)	unclassified	probably benign
R4951:Gak	UTSW	5	108,730,584 (GRCm39)	missense	probably benign
R4971:Gak	UTSW	5	108,744,672 (GRCm39)	missense	probably damaging	1.00
R5328:Gak	UTSW	5	108,764,867 (GRCm39)	missense	possibly damaging	0.94
R5436:Gak	UTSW	5	108,740,218 (GRCm39)	missense	possibly damaging	0.94
R5496:Gak	UTSW	5	108,724,483 (GRCm39)	missense	probably benign	0.00
R6207:Gak	UTSW	5	108,772,895 (GRCm39)	critical splice donor site	probably null
R6359:Gak	UTSW	5	108,719,766 (GRCm39)	missense	probably damaging	1.00
R6468:Gak	UTSW	5	108,771,202 (GRCm39)	nonsense	probably null
R6682:Gak	UTSW	5	108,746,742 (GRCm39)	missense	probably damaging	1.00
R6915:Gak	UTSW	5	108,750,816 (GRCm39)	missense	probably benign	0.20
R7403:Gak	UTSW	5	108,761,401 (GRCm39)	missense	probably benign	0.00
R7458:Gak	UTSW	5	108,730,940 (GRCm39)	missense	probably benign	0.00
R7650:Gak	UTSW	5	108,732,161 (GRCm39)	missense	probably benign	0.00
R7737:Gak	UTSW	5	108,764,874 (GRCm39)	missense	probably benign	0.15
R8437:Gak	UTSW	5	108,757,272 (GRCm39)	missense	probably benign	0.30
R8739:Gak	UTSW	5	108,739,604 (GRCm39)	missense	possibly damaging	0.65
R8954:Gak	UTSW	5	108,777,518 (GRCm39)	start gained	probably benign
X0064:Gak	UTSW	5	108,761,399 (GRCm39)	nonsense	probably null
Z1177:Gak	UTSW	5	108,733,218 (GRCm39)	frame shift	probably null

Predicted Primers

PCR Primer
(F):5'- ATCAGCATCACGTGGTAGGTC -3'
(R):5'- GGCATCTTCTCTACTCACACCAAG -3'

Sequencing Primer
(F):5'- GCATCACGTGGTAGGTCTCTCAC -3'
(R):5'- GCCCAGCTTCCAGATAGTGTC -3'

Posted On

2019-10-17