Mutagenetix > Incidental Mutations

Incidental Mutation 'R0558:Chek1'

45731

Institutional Source

Beutler Lab

Gene Symbol

Chek1

Ensembl Gene

ENSMUSG00000032113

Gene Name

checkpoint kinase 1

Synonyms

Chk1

MMRRC Submission

038750-MU

Accession Numbers

Is this an essential gene?

Essential (E-score: 1.000) question?

Stock #

R0558 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

36708482-36727065 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 36712115 bp

Zygosity

Heterozygous

Amino Acid Change

Asparagine to Isoleucine at position 421 (N421I)

Ref Sequence

ENSEMBL: ENSMUSP00000134388 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000034625] [ENSMUST00000172702] [ENSMUST00000173963]

Predicted Effect

possibly damaging
Transcript: ENSMUST00000034625
AA Change: N421I

PolyPhen 2 Score 0.716 (Sensitivity: 0.86; Specificity: 0.92)

SMART Domains

Protein: ENSMUSP00000034625
Gene: ENSMUSG00000032113
AA Change: N421I

Domain	Start	End	E-Value	Type
S_TKc	9	265	4.79e-85	SMART
low complexity region	280	291	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000172702
AA Change: N421I

PolyPhen 2 Score 0.716 (Sensitivity: 0.86; Specificity: 0.92)

SMART Domains

Protein: ENSMUSP00000134388
Gene: ENSMUSG00000032113
AA Change: N421I

Domain	Start	End	E-Value	Type
S_TKc	9	265	4.79e-85	SMART
low complexity region	280	291	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000173534
AA Change: N377I

PolyPhen 2 Score 0.716 (Sensitivity: 0.86; Specificity: 0.92)

SMART Domains

Protein: ENSMUSP00000134013
Gene: ENSMUSG00000032113
AA Change: N377I

Domain	Start	End	E-Value	Type
S_TKc	9	265	4.79e-85	SMART
low complexity region	280	291	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000173963

SMART Domains

Protein: ENSMUSP00000134029
Gene: ENSMUSG00000032113

Domain	Start	End	E-Value	Type
S_TKc	9	265	4.79e-85	SMART
low complexity region	280	291	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000174105

SMART Domains

Protein: ENSMUSP00000134398
Gene: ENSMUSG00000032113

Domain	Start	End	E-Value	Type
STYKc	1	99	4.6e-3	SMART
low complexity region	114	125	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000174794

Meta Mutation Damage Score

0.1643

Coding Region Coverage

1x: 99.2%
3x: 98.5%
10x: 96.7%
20x: 93.8%

Validation Efficiency

100% (80/80)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene belongs to the Ser/Thr protein kinase family. It is required for checkpoint mediated cell cycle arrest in response to DNA damage or the presence of unreplicated DNA. This protein acts to integrate signals from ATM and ATR, two cell cycle proteins involved in DNA damage responses, that also associate with chromatin in meiotic prophase I. Phosphorylation of CDC25A protein phosphatase by this protein is required for cells to delay cell cycle progression in response to double-strand DNA breaks. Several alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Oct 2011]
PHENOTYPE: Mice homozygous for disruptions in this gene display embryonic lethality between E2.5 and E7.5, impaired cell cycle checkpoint function, increase in blastocyst apoptosis and lack of inner cell mass proliferation. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 78 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
A930017K11Rik	T	C	17: 25,947,549	N338S	probably benign	Het
Abcc2	G	A	19: 43,800,724	G273R	probably benign	Het
Adamts10	T	C	17: 33,550,609	V935A	probably benign	Het
Anapc15-ps	T	C	10: 95,673,121	D90G	probably damaging	Het
Atic	T	A	1: 71,563,788	V107E	probably benign	Het
Atp4b	T	C	8: 13,393,523	T52A	possibly damaging	Het
Cacna1h	C	T	17: 25,381,550	A1606T	probably damaging	Het
Cacng6	T	A	7: 3,434,808	Y217*	probably null	Het
Cc2d2a	T	G	5: 43,724,387		probably benign	Het
Cd226	T	A	18: 89,207,214	H78Q	probably benign	Het
Cers3	A	G	7: 66,783,418	D161G	probably damaging	Het
Ces1f	T	C	8: 93,275,389	H37R	probably benign	Het
Cma2	T	C	14: 55,972,792	Y45H	probably damaging	Het
Cmas	C	A	6: 142,775,244	Y401*	probably null	Het
Cyp2j8	A	T	4: 96,444,634	S492T	probably benign	Het
Dnah12	T	C	14: 26,709,310	S358P	probably benign	Het
Dnajc13	T	C	9: 104,201,952		probably null	Het
Ep400	A	C	5: 110,685,067		probably benign	Het
Fam209	T	A	2: 172,472,838	N82K	probably benign	Het
Fam92a	T	C	4: 12,164,095	D248G	probably damaging	Het
G3bp2	A	T	5: 92,073,197	Y20N	probably damaging	Het
Gli2	T	C	1: 118,837,649	D924G	probably benign	Het
Gm10787	T	C	10: 77,022,016		noncoding transcript	Het
Gm11568	A	G	11: 99,858,046	R26G	unknown	Het
Gm4788	A	G	1: 139,739,492	V376A	probably damaging	Het
Hivep3	T	G	4: 120,096,566	L693R	probably damaging	Het
Hook1	A	G	4: 95,993,212		probably benign	Het
Ibtk	A	C	9: 85,737,538	D116E	probably damaging	Het
Insrr	C	T	3: 87,810,981	T927I	possibly damaging	Het
Irx1	T	G	13: 71,959,628	S312R	probably benign	Het
Itga11	T	C	9: 62,752,288	Y441H	probably benign	Het
Itsn1	A	G	16: 91,899,623	D38G	possibly damaging	Het
Kat6b	G	T	14: 21,669,421	E1280D	probably benign	Het
Kcnk10	T	A	12: 98,436,301	Y293F	possibly damaging	Het
Krt74	T	A	15: 101,760,963		noncoding transcript	Het
Lars	T	G	18: 42,214,837	I974L	probably benign	Het
Limch1	A	G	5: 66,969,155	D42G	probably damaging	Het
Mau2	G	C	8: 70,042,432	T85R	probably damaging	Het
Mkrn3	A	G	7: 62,418,864	I393T	probably benign	Het
Mpl	A	C	4: 118,444,020	S541R	probably damaging	Het
Nfrkb	T	C	9: 31,410,268	S754P	possibly damaging	Het
Olfr1170	A	G	2: 88,224,474	V186A	possibly damaging	Het
Olfr1233	A	G	2: 89,340,236	L22P	probably benign	Het
Olfr1350	T	C	7: 6,570,653	Y221H	possibly damaging	Het
Olfr1537	T	A	9: 39,238,200	T75S	probably damaging	Het
P2rx7	A	T	5: 122,673,798	I391F	possibly damaging	Het
Pbrm1	T	A	14: 31,085,059		probably null	Het
Pcdh8	T	C	14: 79,770,076	D349G	probably damaging	Het
Pias1	A	G	9: 62,882,009	S639P	possibly damaging	Het
Pkhd1l1	A	T	15: 44,484,424	I232F	probably damaging	Het
Plxnc1	C	T	10: 94,837,935	R995Q	probably damaging	Het
Pnliprp2	T	A	19: 58,774,087	S375T	probably benign	Het
Prkar1b	C	T	5: 139,020,092	V313M	probably benign	Het
Ptpn13	T	C	5: 103,529,717	S734P	probably damaging	Het
Rdh1	T	C	10: 127,759,941	W2R	possibly damaging	Het
Rsph10b	A	T	5: 143,949,338	I285L	probably benign	Het
Rubcnl	T	C	14: 75,047,547	F502S	probably damaging	Het
Ryr2	T	A	13: 11,638,443	I3693F	probably damaging	Het
Ryr2	T	C	13: 11,799,861	Y675C	probably damaging	Het
Scaper	T	C	9: 55,685,923	T477A	probably benign	Het
Scn2a	G	T	2: 65,711,925	V791L	probably benign	Het
Sdk1	A	T	5: 142,132,065	T1573S	probably damaging	Het
Sema3c	A	T	5: 17,714,415	H483L	probably benign	Het
Sema6c	T	C	3: 95,168,691	S219P	probably damaging	Het
Slc10a5	T	G	3: 10,335,117	E161A	probably damaging	Het
Slc22a23	C	T	13: 34,344,383	G139S	possibly damaging	Het
Slc34a3	C	T	2: 25,233,065		probably benign	Het
Slc38a9	A	T	13: 112,729,196		probably null	Het
Taok1	A	C	11: 77,559,844	S367R	possibly damaging	Het
Tlr6	G	A	5: 64,954,860	Q235*	probably null	Het
Top2a	A	G	11: 98,996,839	V1281A	probably benign	Het
Tpgs1	T	C	10: 79,675,782	Y253H	probably damaging	Het
Tubgcp3	T	C	8: 12,653,462	T288A	probably benign	Het
Ubr4	A	G	4: 139,426,902	E2140G	probably benign	Het
Uso1	A	G	5: 92,174,019	Q257R	probably benign	Het
Zfp106	A	G	2: 120,532,196	V48A	probably damaging	Het
Zfp174	T	A	16: 3,848,254	S128T	possibly damaging	Het
Zscan26	T	A	13: 21,445,055	D426V	probably benign	Het

Other mutations in Chek1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00659:Chek1	APN	9	36722599	splice site	probably null
IGL01061:Chek1	APN	9	36714519	missense	possibly damaging	0.70
IGL01322:Chek1	APN	9	36718421	nonsense	probably null
IGL01627:Chek1	APN	9	36723895	missense	probably damaging	1.00
IGL02379:Chek1	APN	9	36723946	missense	probably benign	0.03
IGL03160:Chek1	APN	9	36722645	missense	probably damaging	1.00
R1035:Chek1	UTSW	9	36716473	missense	probably damaging	1.00
R1466:Chek1	UTSW	9	36725857	missense	probably damaging	1.00
R1466:Chek1	UTSW	9	36725857	missense	probably damaging	1.00
R1606:Chek1	UTSW	9	36719524	missense	probably damaging	1.00
R1627:Chek1	UTSW	9	36714441	missense	probably benign
R2152:Chek1	UTSW	9	36723983	missense	probably damaging	1.00
R2153:Chek1	UTSW	9	36723983	missense	probably damaging	1.00
R2154:Chek1	UTSW	9	36723983	missense	probably damaging	1.00
R2270:Chek1	UTSW	9	36719686	missense	probably damaging	1.00
R4014:Chek1	UTSW	9	36722754	splice site	probably benign
R5285:Chek1	UTSW	9	36714452	missense	probably benign	0.00
R5458:Chek1	UTSW	9	36714429	missense	probably benign	0.30
R5547:Chek1	UTSW	9	36712104	missense	probably benign	0.02
R5819:Chek1	UTSW	9	36710405	missense	probably benign	0.01
R5853:Chek1	UTSW	9	36713687	missense	probably damaging	1.00
R6334:Chek1	UTSW	9	36714492	missense	possibly damaging	0.59
R6353:Chek1	UTSW	9	36723959	missense	probably benign	0.01
R7319:Chek1	UTSW	9	36722643	missense	probably damaging	1.00
R8235:Chek1	UTSW	9	36719574	missense	probably benign	0.00
R8380:Chek1	UTSW	9	36712112	missense	probably benign	0.41

Predicted Primers

PCR Primer
(F):5'- AGGGAGGTGGACCACTGAAAGTAAAAT -3'
(R):5'- CGAGCTGCTTAGAGCTACTTACCGA -3'

Sequencing Primer
(F):5'- GAAAGTCGGAAGTCAACCAGT -3'
(R):5'- ggagtgggagagagagtgg -3'

Posted On

2013-06-11