Mutagenetix > Incidental Mutation

Incidental Mutation 'R1466:Chek1'

166062

Institutional Source

Beutler Lab

Gene Symbol

Chek1

Ensembl Gene

ENSMUSG00000032113

Gene Name

checkpoint kinase 1

Synonyms

Chk1

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R1466 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

36708482-36727065 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

G to T at 36725857 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Alanine to Glutamic Acid at position 2 (A2E)

Ref Sequence

ENSEMBL: ENSMUSP00000134029 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000034625] [ENSMUST00000120381] [ENSMUST00000172702] [ENSMUST00000172742] [ENSMUST00000173963]

AlphaFold

O35280

Predicted Effect

possibly damaging
Transcript: ENSMUST00000034625
AA Change: A2E

PolyPhen 2 Score 0.917 (Sensitivity: 0.81; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000034625
Gene: ENSMUSG00000032113
AA Change: A2E

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: ENSMUST00000120381

SMART Domains

Protein: ENSMUSP00000113116
Gene: ENSMUSG00000032116

Domain	Start	End	E-Value	Type
Pfam:STT3	17	484	2e-163	PFAM
Pfam:PMT_2	97	257	9.3e-10	PFAM

Predicted Effect

possibly damaging
Transcript: ENSMUST00000172702
AA Change: A2E

PolyPhen 2 Score 0.917 (Sensitivity: 0.81; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000134388
Gene: ENSMUSG00000032113
AA Change: A2E

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: ENSMUST00000172742
AA Change: A2E

PolyPhen 2 Score 0.876 (Sensitivity: 0.83; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000133589
Gene: ENSMUSG00000032113
AA Change: A2E

Domain	Start	End	E-Value	Type
Pfam:Pkinase	9	73	9.9e-13	PFAM
Pfam:Pkinase_Tyr	9	74	8.5e-9	PFAM

Predicted Effect

possibly damaging
Transcript: ENSMUST00000173534
AA Change: A2E

PolyPhen 2 Score 0.917 (Sensitivity: 0.81; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000134013
Gene: ENSMUSG00000032113
AA Change: A2E

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: ENSMUST00000173796

Predicted Effect

probably damaging
Transcript: ENSMUST00000173963
AA Change: A2E

PolyPhen 2 Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000134029
Gene: ENSMUSG00000032113
AA Change: A2E

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: ENSMUST00000173977

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

Coding Region Coverage

1x: 99.4%
3x: 97.9%
10x: 90.8%
20x: 71.5%

Validation Efficiency

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: 108 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abhd15	C	T	11: 77,515,410	A71V	probably damaging	Het
Adamts12	T	C	15: 11,311,359	F1234S	probably benign	Het
Ahnak	A	G	19: 9,015,875	D4841G	probably damaging	Het
Akap13	T	C	7: 75,729,049	S2095P	possibly damaging	Het
Ampd2	T	C	3: 108,080,337		probably null	Het
Arhgef17	G	T	7: 100,929,659	P694Q	possibly damaging	Het
Arrdc1	T	C	2: 24,925,795	I398V	probably benign	Het
Ash1l	T	C	3: 89,052,065	Y2250H	probably damaging	Het
Aspg	A	G	12: 112,121,852	N385D	probably benign	Het
Atxn3	G	A	12: 101,926,499	R319C	possibly damaging	Het
BC005561	T	A	5: 104,518,257	I215N	probably damaging	Het
Brca2	G	A	5: 150,552,258	A2478T	probably damaging	Het
C1s1	C	T	6: 124,531,131	C633Y	probably damaging	Het
C8g	C	T	2: 25,500,216	A6T	probably benign	Het
Cbl	A	T	9: 44,154,244	V706E	probably benign	Het
Cfhr1	C	T	1: 139,557,574	E45K	probably benign	Het
Chd7	G	A	4: 8,840,561		probably null	Het
Cntnap1	C	A	11: 101,180,360	F366L	probably damaging	Het
Corin	C	T	5: 72,302,790		probably null	Het
Crb2	T	C	2: 37,783,388	Y99H	probably damaging	Het
Ctdspl2	G	A	2: 122,003,929	R332K	probably benign	Het
Cym	G	A	3: 107,213,458	T277I	probably damaging	Het
Cyp2d11	C	T	15: 82,391,735	C215Y	probably benign	Het
Dido1	G	A	2: 180,662,328	P1261L	probably damaging	Het
Dnah10	T	A	5: 124,763,096	Y1265N	probably benign	Het
Dtx3l	G	A	16: 35,932,728	L503F	probably damaging	Het
Efhb	A	G	17: 53,437,178	F462L	probably damaging	Het
Enpep	T	A	3: 129,319,448	T203S	probably damaging	Het
Fat3	A	C	9: 16,375,482	V915G	probably damaging	Het
Fbln7	A	G	2: 128,877,429	T49A	probably benign	Het
Fcho1	C	T	8: 71,712,560	A418T	probably benign	Het
Fgf14	T	A	14: 124,676,539	K60M	probably benign	Het
Galnt4	A	G	10: 99,108,709	R99G	probably benign	Het
Gimap4	C	A	6: 48,691,282	Q196K	probably benign	Het
Glcci1	C	T	6: 8,537,964	T6I	probably damaging	Het
Gm10110	A	T	14: 89,898,075		noncoding transcript	Het
Gm4884	A	G	7: 41,043,128	K174E	probably damaging	Het
Gm6583	C	T	5: 112,354,764	G358D	probably benign	Het
Grip2	A	T	6: 91,788,443	D19E	probably damaging	Het
Grk4	T	C	5: 34,694,750	S113P	probably benign	Het
Hectd3	G	A	4: 116,996,566	E220K	probably damaging	Het
Helz2	G	A	2: 181,236,297	P903S	probably damaging	Het
Hydin	T	A	8: 110,532,953	V2519E	possibly damaging	Het
Ints11	G	A	4: 155,888,110		probably null	Het
Kif1a	A	G	1: 93,054,929	W718R	possibly damaging	Het
Kif1b	A	T	4: 149,223,252	Y839N	probably damaging	Het
Kif20b	T	A	19: 34,950,599	V1047D	probably benign	Het
Klhl23	T	C	2: 69,833,888	I527T	probably damaging	Het
Klra10	T	A	6: 130,279,315	R125S	probably damaging	Het
Klra10	T	C	6: 130,279,431	N87D	probably damaging	Het
Lars	G	A	18: 42,210,050	R1101C	probably damaging	Het
Lcn4	G	A	2: 26,668,576	P166L	probably damaging	Het
Letmd1	T	A	15: 100,472,542		probably null	Het
Map4k2	G	T	19: 6,341,917	W87L	probably damaging	Het
Mccc1	A	G	3: 35,974,286	V457A	probably benign	Het
Mdn1	T	A	4: 32,730,788	S2886T	probably benign	Het
Mroh2b	G	T	15: 4,925,684	D720Y	probably damaging	Het
Mrpl24	T	A	3: 87,921,928	Y21*	probably null	Het
Mrps35	C	T	6: 147,055,984	T169M	probably damaging	Het
Mtcl1	T	A	17: 66,380,435	D492V	probably damaging	Het
Muc2	A	G	7: 141,748,974	Y457C	probably damaging	Het
Muc4	G	A	16: 32,753,595	G1157D	probably benign	Het
Myg1	T	A	15: 102,337,390	L275Q	probably damaging	Het
Naga	T	A	15: 82,334,788	M237L	probably null	Het
Oc90	T	A	15: 65,897,720	Y96F	probably damaging	Het
Olfr1029	T	A	2: 85,975,995	F251I	probably damaging	Het
Olfr103	A	T	17: 37,336,956	L92H	probably benign	Het
Olfr1253	C	T	2: 89,752,267	C187Y	probably damaging	Het
Olfr46	A	G	7: 140,610,969	I268V	probably benign	Het
Olfr522	A	G	7: 140,162,203	V249A	probably damaging	Het
Orc4	A	T	2: 48,909,494	C324S	possibly damaging	Het
Pcdh10	T	G	3: 45,379,974	L241R	probably damaging	Het
Pdzrn4	T	C	15: 92,770,537	S857P	probably benign	Het
Plec	C	T	15: 76,185,908	E1000K	possibly damaging	Het
Plvap	A	T	8: 71,508,481	V149D	probably benign	Het
Ppef1	C	A	X: 160,625,674		probably null	Het
Prkaa1	C	A	15: 5,178,798	P507T	probably benign	Het
Ptch1	A	G	13: 63,524,969	Y804H	probably benign	Het
R3hdm2	A	G	10: 127,476,690	I434V	probably benign	Het
Rfx5	T	A	3: 94,956,303	Y88N	probably damaging	Het
Rnase2b	A	T	14: 51,162,839	K126*	probably null	Het
Rpl3l	A	G	17: 24,730,871	I15V	probably benign	Het
Saal1	G	T	7: 46,702,545		probably null	Het
Sbpl	A	C	17: 23,953,254	D230E	unknown	Het
Scn10a	T	C	9: 119,666,490	Y322C	probably damaging	Het
Sec16a	A	T	2: 26,431,157	Y1308N	probably damaging	Het
Sis	A	T	3: 72,932,060	D824E	possibly damaging	Het
Slc25a36	A	G	9: 97,080,355	F194L	probably damaging	Het
Slc27a4	T	A	2: 29,811,190	V331E	probably damaging	Het
Slc7a11	G	T	3: 50,381,073		probably null	Het
Slco4c1	A	T	1: 96,841,172	S322T	probably damaging	Het
Smarcc2	A	T	10: 128,474,245	T376S	probably damaging	Het
Srebf1	C	T	11: 60,200,702	R999H	probably benign	Het
St3gal3	A	C	4: 118,107,662	M1R	probably null	Het
Syp	A	T	X: 7,648,705		probably benign	Het
Tas1r2	A	G	4: 139,669,411	D687G	probably damaging	Het
Tekt4	A	T	17: 25,472,074	Q118L	probably benign	Het
Tph2	T	C	10: 115,079,695	N480S	probably benign	Het
Tsc2	A	T	17: 24,608,973	M839K	probably damaging	Het
Ttc22	T	C	4: 106,622,780	F77S	probably damaging	Het
Uaca	C	T	9: 60,854,321	A205V	possibly damaging	Het
Uhmk1	A	T	1: 170,208,653		probably null	Het
Usp17lc	A	G	7: 103,418,941	H481R	possibly damaging	Het
Vwa3a	A	G	7: 120,768,165	Y181C	probably damaging	Het
Wfikkn2	G	A	11: 94,238,895	T140I	probably damaging	Het
Zfp704	G	T	3: 9,447,348	T288N	possibly damaging	Het
Zfp93	T	C	7: 24,276,096	V502A	probably damaging	Het
Zzef1	C	T	11: 72,924,679	P2942S	probably damaging	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
R0558:Chek1	UTSW	9	36712115	missense	possibly damaging	0.72
R1035:Chek1	UTSW	9	36716473	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
R8532:Chek1	UTSW	9	36719692	missense	probably benign	0.31
R8693:Chek1	UTSW	9	36713844	missense	probably benign
R8762:Chek1	UTSW	9	36718340	missense	probably benign	0.02
R8787:Chek1	UTSW	9	36713737	nonsense	probably null
R9511:Chek1	UTSW	9	36713451	missense	probably benign	0.06
R9520:Chek1	UTSW	9	36713825	missense	probably benign	0.04

Predicted Primers

PCR Primer
(F):5'- GGCCTAATGATCCCTCCAAACCTTC -3'
(R):5'- CCGAAAGCTCTTGTCTTGCAACCC -3'

Sequencing Primer
(F):5'- accagctcctgcaagttgtc -3'
(R):5'- CTCAGTTTTGCATAAAGGCGGAC -3'

Posted On

2014-03-28