Mutagenetix > Incidental Mutation

Incidental Mutation 'R8898:Chek2'

678163

Institutional Source

Beutler Lab

Gene Symbol

Chek2

Ensembl Gene

ENSMUSG00000029521

Gene Name

checkpoint kinase 2

Synonyms

CHK2, Rad53

MMRRC Submission

068755-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R8898 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

110987845-111022011 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 111011175 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Lysine to Asparagine at position 324 (K324N)

Ref Sequence

ENSEMBL: ENSMUSP00000066679 (fasta)

Gene Model

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

AlphaFold

Q9Z265

Predicted Effect

probably benign
Transcript: ENSMUST00000066160
AA Change: K324N

PolyPhen 2 Score 0.003 (Sensitivity: 0.98; Specificity: 0.44)

SMART Domains

Protein: ENSMUSP00000066679
Gene: ENSMUSG00000029521
AA Change: K324N

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

Meta Mutation Damage Score

0.0873

Coding Region Coverage

1x: 100.0%
3x: 100.0%
10x: 99.8%
20x: 99.5%

Validation Efficiency

100% (64/64)

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: 65 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
3425401B19Rik	A	T	14: 32,383,001 (GRCm39)	L988*	probably null	Het
4930546C10Rik	A	G	18: 69,083,106 (GRCm39)	F36S	unknown	Het
Acan	C	A	7: 78,750,101 (GRCm39)	T1624K	possibly damaging	Het
Ambn	T	C	5: 88,613,051 (GRCm39)		probably null	Het
Ankrd24	T	C	10: 81,478,352 (GRCm39)	I437T	unknown	Het
Arl4d	C	T	11: 101,557,827 (GRCm39)	R118W	probably damaging	Het
Atg2a	A	G	19: 6,306,721 (GRCm39)		probably benign	Het
Bcan	T	C	3: 87,895,695 (GRCm39)	T814A	probably benign	Het
Brca2	T	A	5: 150,492,498 (GRCm39)	M3171K	possibly damaging	Het
Cd209a	T	A	8: 3,798,739 (GRCm39)	S23C	probably damaging	Het
Col12a1	C	T	9: 79,599,577 (GRCm39)	V859I	probably benign	Het
Cyp7b1	C	T	3: 18,150,788 (GRCm39)	R317H	probably benign	Het
Dmxl2	A	G	9: 54,308,941 (GRCm39)	S1937P	probably benign	Het
Epb41l1	T	G	2: 156,335,869 (GRCm39)	V11G	probably damaging	Het
Ephb6	C	T	6: 41,590,293 (GRCm39)	A15V	probably benign	Het
Fat3	G	A	9: 15,858,822 (GRCm39)	P3798L	probably benign	Het
Foxd1	T	A	13: 98,491,596 (GRCm39)	C157S	probably damaging	Het
Gja10	T	C	4: 32,601,058 (GRCm39)	Q442R	probably benign	Het
Gm17019	A	C	5: 15,081,798 (GRCm39)	M47R	possibly damaging	Het
Gpr179	C	A	11: 97,242,329 (GRCm39)	E172*	probably null	Het
Grhl1	G	A	12: 24,634,945 (GRCm39)		probably null	Het
Gtf2ird2	A	T	5: 134,226,106 (GRCm39)	E184V	probably benign	Het
Hace1	A	G	10: 45,576,766 (GRCm39)	I813V	probably benign	Het
Hk2	A	T	6: 82,715,379 (GRCm39)	L385Q	probably damaging	Het
Htt	C	T	5: 34,976,376 (GRCm39)	T726I	probably benign	Het
Itga8	T	C	2: 12,145,206 (GRCm39)	S916G	probably benign	Het
Jag1	A	T	2: 136,935,175 (GRCm39)	F396I	probably damaging	Het
Kif16b	A	G	2: 142,554,899 (GRCm39)	M633T	possibly damaging	Het
Klf5	T	A	14: 99,538,922 (GRCm39)	F112I	probably damaging	Het
Lama1	A	T	17: 68,128,610 (GRCm39)	Q2989L		Het
Lrrc28	C	A	7: 67,278,042 (GRCm39)		probably null	Het
Map4k5	T	C	12: 69,859,931 (GRCm39)	T739A	possibly damaging	Het
Mbd3l2	A	T	9: 18,355,914 (GRCm39)	R80*	probably null	Het
Mctp2	T	C	7: 71,752,904 (GRCm39)	E783G	probably damaging	Het
Mill2	A	T	7: 18,590,489 (GRCm39)	M190L	probably benign	Het
N4bp3	T	C	11: 51,535,256 (GRCm39)	N311S	probably benign	Het
Nanos2	A	T	7: 18,721,549 (GRCm39)	D7V	probably damaging	Het
Ndufs7	T	A	10: 80,089,619 (GRCm39)		probably null	Het
Nexn	T	C	3: 151,948,306 (GRCm39)	N483S	probably benign	Het
Nlrp1b	T	G	11: 71,073,288 (GRCm39)	E185A	probably damaging	Het
Nop2	C	A	6: 125,114,118 (GRCm39)	Q195K	probably benign	Het
Or4a15	A	G	2: 89,192,957 (GRCm39)	V272A	possibly damaging	Het
Or4n4	G	A	14: 50,518,952 (GRCm39)	P253S	probably damaging	Het
Pde12	G	A	14: 26,390,577 (GRCm39)	S44L	probably benign	Het
Pde1c	A	T	6: 56,114,371 (GRCm39)	V514E	probably damaging	Het
Pdzph1	A	T	17: 59,281,334 (GRCm39)	V316D	probably benign	Het
Prl3c1	A	T	13: 27,387,578 (GRCm39)	I208F	possibly damaging	Het
Raver2	G	A	4: 100,964,399 (GRCm39)		probably null	Het
Rpl13a-ps1	T	A	19: 50,018,747 (GRCm39)	H143L	probably benign	Het
Septin14	A	T	5: 129,760,642 (GRCm39)	I402K	possibly damaging	Het
Sla2	T	A	2: 156,717,885 (GRCm39)	Y129F	possibly damaging	Het
Smarca2	TGCAGCAGCAGCAGCAGCA	TGCAGCAGCAGCAGCA	19: 26,608,358 (GRCm39)		probably benign	Het
Sorl1	A	G	9: 41,911,567 (GRCm39)	S1448P	probably damaging	Het
Spast	G	A	17: 74,695,273 (GRCm39)	R604H	probably damaging	Het
Speg	G	A	1: 75,365,517 (GRCm39)	G633S	probably damaging	Het
Stxbp5l	ATTTT	ATTTTT	16: 37,036,414 (GRCm39)		probably null	Het
Syt11	T	C	3: 88,669,335 (GRCm39)	M186V	probably benign	Het
Tex26	C	A	5: 149,380,369 (GRCm39)	N133K	probably benign	Het
Tnfrsf17	T	C	16: 11,131,910 (GRCm39)	C32R	probably damaging	Het
Trem1	T	A	17: 48,544,374 (GRCm39)	V133E	probably damaging	Het
Trpm7	A	T	2: 126,664,661 (GRCm39)	M906K	possibly damaging	Het
Ugt2b35	T	A	5: 87,159,189 (GRCm39)	I461K	possibly damaging	Het
Vmn2r77	T	A	7: 86,444,430 (GRCm39)	C28S	probably damaging	Het
Zfp521	C	A	18: 13,979,137 (GRCm39)	L425F	probably damaging	Het
Zfp790	C	T	7: 29,522,525 (GRCm39)		probably benign	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
PIT4520001:Chek2	UTSW	5	111,011,195 (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
R8906:Chek2	UTSW	5	111,013,458 (GRCm39)	utr 3 prime	probably benign

Predicted Primers

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

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

Posted On

2021-08-02