Mutagenetix > Incidental Mutation

Incidental Mutation 'PIT4520001:Chek2'

555170

Institutional Source

Beutler Lab

Gene Symbol

Chek2

Ensembl Gene

ENSMUSG00000029521

Gene Name

checkpoint kinase 2

Synonyms

CHK2, Rad53

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

PIT4520001 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

110987845-111022011 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 111011195 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Tyrosine to Cysteine at position 331 (Y331C)

Ref Sequence

ENSEMBL: ENSMUSP00000066679 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000066160] [ENSMUST00000199937]

AlphaFold

Q9Z265

Predicted Effect

probably damaging
Transcript: ENSMUST00000066160
AA Change: Y331C

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

SMART Domains

Protein: ENSMUSP00000066679
Gene: ENSMUSG00000029521
AA Change: Y331C

Domain	Start	End	E-Value	Type
low complexity region	2	37	N/A	INTRINSIC
low complexity region	41	72	N/A	INTRINSIC
FHA	116	179	5.14e-3	SMART
S_TKc	224	490	7.35e-104	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000199937

SMART Domains

Protein: ENSMUSP00000143558
Gene: ENSMUSG00000029521

Domain	Start	End	E-Value	Type
low complexity region	2	37	N/A	INTRINSIC
low complexity region	41	72	N/A	INTRINSIC
FHA	116	179	2.6e-5	SMART

Coding Region Coverage

1x: 93.5%
3x: 91.1%
10x: 86.1%
20x: 75.5%

Validation Efficiency

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] In response to DNA damage and replication blocks, cell cycle progression is halted through the control of critical cell cycle regulators. The protein encoded by this gene is a cell cycle checkpoint regulator and putative tumor suppressor. It contains a forkhead-associated protein interaction domain essential for activation in response to DNA damage and is rapidly phosphorylated in response to replication blocks and DNA damage. When activated, the encoded protein is known to inhibit CDC25C phosphatase, preventing entry into mitosis, and has been shown to stabilize the tumor suppressor protein p53, leading to cell cycle arrest in G1. In addition, this protein interacts with and phosphorylates BRCA1, allowing BRCA1 to restore survival after DNA damage. Mutations in this gene have been linked with Li-Fraumeni syndrome, a highly penetrant familial cancer phenotype usually associated with inherited mutations in TP53. Also, mutations in this gene are thought to confer a predisposition to sarcomas, breast cancer, and brain tumors. This nuclear protein is a member of the CDS1 subfamily of serine/threonine protein kinases. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]
PHENOTYPE: Homozygous mutation of this gene does not increase tumor incidence. Cells from the thymus, central nervous system (CNS), hair follicles, and skin are resistant to ionizing radiation- and gamma irradiation-induced apoptosis. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 59 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adcy1	A	G	11: 7,117,133 (GRCm39)	N1000S	probably damaging	Het
Adgrb1	A	G	15: 74,413,508 (GRCm39)	D564G	probably damaging	Het
Ankmy2	A	G	12: 36,207,390 (GRCm39)	E12G	probably benign	Het
Arid1a	C	T	4: 133,409,227 (GRCm39)	S1375N	unknown	Het
Atp1a2	G	A	1: 172,106,941 (GRCm39)	A793V	probably benign	Het
Atp8b1	T	C	18: 64,701,251 (GRCm39)	Y369C	probably benign	Het
Catsperg2	A	G	7: 29,409,586 (GRCm39)	Y536H	possibly damaging	Het
Ccdc178	A	G	18: 22,200,470 (GRCm39)	Y445H	probably damaging	Het
Cep170	G	T	1: 176,607,765 (GRCm39)	N230K	unknown	Het
Cftr	A	G	6: 18,277,842 (GRCm39)	I977V	probably benign	Het
Chst13	A	T	6: 90,286,167 (GRCm39)	I265K	probably benign	Het
Coil	T	C	11: 88,872,437 (GRCm39)	M266T	probably benign	Het
Col16a1	T	A	4: 129,945,456 (GRCm39)	C28S	unknown	Het
Col3a1	T	C	1: 45,374,943 (GRCm39)		probably null	Het
Csmd1	C	T	8: 15,956,023 (GRCm39)	V3395M	probably benign	Het
Cyp51	A	G	5: 4,151,200 (GRCm39)	V143A	probably damaging	Het
Eif2ak1	C	T	5: 143,836,027 (GRCm39)	Q573*	probably null	Het
Eif2ak4	T	A	2: 118,292,808 (GRCm39)	I1344N	probably damaging	Het
Fhip1a	G	A	3: 85,579,779 (GRCm39)	Q809*	probably null	Het
Gen1	A	G	12: 11,291,509 (GRCm39)	V825A	probably benign	Het
Gm28042	A	T	2: 119,870,148 (GRCm39)	K696*	probably null	Het
Gm4952	A	G	19: 12,602,048 (GRCm39)	Y152C	probably benign	Het
Hdac3	G	A	18: 38,074,817 (GRCm39)	T308I	probably damaging	Het
Hpx	T	C	7: 105,241,341 (GRCm39)	T357A	probably benign	Het
Hscb	A	T	5: 110,983,851 (GRCm39)	Y139N	probably damaging	Het
Kcnk9	T	A	15: 72,384,332 (GRCm39)	H282L	probably benign	Het
Kdm2b	G	A	5: 123,079,110 (GRCm39)	T287M	probably damaging	Het
Kif19a	C	T	11: 114,672,034 (GRCm39)	T207M	probably damaging	Het
Kmt2c	A	C	5: 25,520,664 (GRCm39)	N1815K	probably benign	Het
Ktn1	C	T	14: 47,923,774 (GRCm39)	T511M	probably damaging	Het
Lrp1	C	G	10: 127,443,843 (GRCm39)	Q141H	possibly damaging	Het
Lrrc43	T	C	5: 123,630,530 (GRCm39)	V131A	possibly damaging	Het
Man1b1	T	A	2: 25,233,282 (GRCm39)	H218Q	probably damaging	Het
Mapk8ip2	T	A	15: 89,344,900 (GRCm39)	C766S	probably damaging	Het
Mfn1	A	G	3: 32,615,695 (GRCm39)	N353D	probably benign	Het
Mtcl1	A	T	17: 66,692,907 (GRCm39)	L474Q	possibly damaging	Het
Mtr	T	A	13: 12,212,871 (GRCm39)	R915*	probably null	Het
Myh6	C	A	14: 55,187,581 (GRCm39)	V1263L	probably benign	Het
Nt5m	C	A	11: 59,765,415 (GRCm39)	L148M	probably benign	Het
Or4a67	A	G	2: 88,597,921 (GRCm39)	V246A	possibly damaging	Het
Or51t4	A	T	7: 102,597,921 (GRCm39)	D83V	probably damaging	Het
Or8k21	T	C	2: 86,145,142 (GRCm39)	I163V	possibly damaging	Het
Pbrm1	T	A	14: 30,789,818 (GRCm39)	F811I	probably damaging	Het
Pcnt	A	G	10: 76,256,069 (GRCm39)	S724P	probably damaging	Het
Pfdn5	C	A	15: 102,237,158 (GRCm39)	D98E	probably benign	Het
Ptprs	G	A	17: 56,721,980 (GRCm39)	P1715S	probably damaging	Het
Rtkn2	T	A	10: 67,823,291 (GRCm39)	L65Q	probably damaging	Het
Scn2a	G	A	2: 65,518,763 (GRCm39)	R379H	probably damaging	Het
Scn5a	G	T	9: 119,363,636 (GRCm39)	D501E	possibly damaging	Het
Spn	C	A	7: 126,735,611 (GRCm39)	G299W	probably damaging	Het
St6galnac1	T	C	11: 116,660,175 (GRCm39)	N46S	probably benign	Het
Stx19	A	G	16: 62,642,871 (GRCm39)	D229G	probably benign	Het
Tmc6	A	T	11: 117,663,556 (GRCm39)	M552K	possibly damaging	Het
Tnpo3	G	C	6: 29,555,221 (GRCm39)	D787E	possibly damaging	Het
Tyw5	T	C	1: 57,427,674 (GRCm39)	Y310C	probably damaging	Het
Vmn2r15	A	G	5: 109,434,871 (GRCm39)	F611S	probably damaging	Het
Vmn2r49	C	T	7: 9,722,988 (GRCm39)	M95I	probably benign	Het
Wfdc8	A	G	2: 164,445,223 (GRCm39)	S131P	probably benign	Het
Zfp407	A	T	18: 84,450,545 (GRCm39)	M1597K	probably damaging	Het

Other mutations in Chek2

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01025:Chek2	APN	5	110,996,536 (GRCm39)	missense	probably damaging	1.00
IGL01830:Chek2	APN	5	111,021,374 (GRCm39)	missense	probably benign
IGL01943:Chek2	APN	5	110,989,093 (GRCm39)	unclassified	probably benign
IGL02319:Chek2	APN	5	111,014,877 (GRCm39)	missense	possibly damaging	0.88
IGL03147:Chek2	UTSW	5	110,996,536 (GRCm39)	missense	probably damaging	1.00
R1484:Chek2	UTSW	5	110,996,553 (GRCm39)	missense	probably damaging	1.00
R1486:Chek2	UTSW	5	110,989,093 (GRCm39)	unclassified	probably benign
R1732:Chek2	UTSW	5	111,019,968 (GRCm39)	missense	probably benign	0.26
R2041:Chek2	UTSW	5	110,996,530 (GRCm39)	missense	probably damaging	1.00
R2071:Chek2	UTSW	5	110,989,112 (GRCm39)	unclassified	probably benign
R2873:Chek2	UTSW	5	111,011,202 (GRCm39)	nonsense	probably null
R2935:Chek2	UTSW	5	111,015,886 (GRCm39)	missense	probably damaging	1.00
R3899:Chek2	UTSW	5	111,013,479 (GRCm39)	splice site	probably benign
R4662:Chek2	UTSW	5	111,014,908 (GRCm39)	missense	probably damaging	1.00
R4748:Chek2	UTSW	5	111,003,705 (GRCm39)	splice site	probably null
R5358:Chek2	UTSW	5	110,989,148 (GRCm39)	unclassified	probably benign
R5582:Chek2	UTSW	5	111,015,901 (GRCm39)	missense	probably damaging	0.96
R5594:Chek2	UTSW	5	111,003,700 (GRCm39)	critical splice donor site	probably null
R6526:Chek2	UTSW	5	110,996,556 (GRCm39)	missense	probably damaging	1.00
R6972:Chek2	UTSW	5	111,003,705 (GRCm39)	splice site	probably null
R7232:Chek2	UTSW	5	111,008,781 (GRCm39)	missense	probably damaging	1.00
R7338:Chek2	UTSW	5	111,021,380 (GRCm39)	missense	probably benign
R7395:Chek2	UTSW	5	111,019,974 (GRCm39)	critical splice donor site	probably null
R7714:Chek2	UTSW	5	110,989,319 (GRCm39)	missense	probably benign	0.10
R7743:Chek2	UTSW	5	110,987,916 (GRCm39)	critical splice donor site	probably null
R8290:Chek2	UTSW	5	111,008,766 (GRCm39)	missense	possibly damaging	0.70
R8297:Chek2	UTSW	5	110,996,302 (GRCm39)	missense	probably damaging	1.00
R8719:Chek2	UTSW	5	111,014,908 (GRCm39)	missense	probably damaging	0.98
R8898:Chek2	UTSW	5	111,011,175 (GRCm39)	missense	probably benign	0.00
R8906:Chek2	UTSW	5	111,013,458 (GRCm39)	utr 3 prime	probably benign

Predicted Primers

PCR Primer
(F):5'- ACAAGTGCTCATCTGCTCAC -3'
(R):5'- AACTGGTCAGCCTTGCTTTC -3'

Sequencing Primer
(F):5'- ATTGGTGCTGTGCATCAG -3'
(R):5'- TCATTGCCACAAGGATCAGG -3'

Posted On

2019-06-07