Mutagenetix > Incidental Mutation

Incidental Mutation 'R4662:Chek2'

352924

Institutional Source

Beutler Lab

Gene Symbol

Chek2

Ensembl Gene

ENSMUSG00000029521

Gene Name

checkpoint kinase 2

Synonyms

CHK2, Rad53

MMRRC Submission

042011-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R4662 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

110987845-111022011 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 111014908 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Valine to Aspartic acid at position 459 (V459D)

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: V459D

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

SMART Domains

Protein: ENSMUSP00000066679
Gene: ENSMUSG00000029521
AA Change: V459D

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

noncoding transcript
Transcript: ENSMUST00000196650

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: 99.2%
3x: 98.6%
10x: 97.2%
20x: 95.1%

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: 64 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4930590J08Rik	A	T	6: 91,891,939 (GRCm39)	Q67L	probably benign	Het
Adam34l	T	A	8: 44,080,116 (GRCm39)	Y36F	probably benign	Het
Adrb1	A	G	19: 56,711,206 (GRCm39)	T135A	probably damaging	Het
Ark2n	T	A	18: 77,762,186 (GRCm39)	Q42L	probably benign	Het
Asxl2	G	T	12: 3,477,193 (GRCm39)	W13L	probably damaging	Het
Atp4a	G	A	7: 30,419,650 (GRCm39)	R671Q	probably benign	Het
Brsk1	T	C	7: 4,710,298 (GRCm39)	S436P	possibly damaging	Het
Calb2	A	G	8: 110,894,709 (GRCm39)	F21L	probably benign	Het
Camk2a	T	C	18: 61,074,411 (GRCm39)	Y39H	probably damaging	Het
Cavin2	T	C	1: 51,340,510 (GRCm39)	S396P	probably benign	Het
Cfdp1	A	G	8: 112,557,577 (GRCm39)	F188S	probably benign	Het
Cldn8	G	A	16: 88,359,296 (GRCm39)	H210Y	probably benign	Het
Cobl	A	G	11: 12,203,672 (GRCm39)	V1003A	probably benign	Het
Ctsll3	A	G	13: 60,947,416 (GRCm39)	F257L	possibly damaging	Het
Dnajc13	A	C	9: 104,084,957 (GRCm39)	F819V	probably damaging	Het
Dram1	C	A	10: 88,161,246 (GRCm39)	V208L	probably damaging	Het
Dynlt1b	A	G	17: 6,699,279 (GRCm39)	T10A	probably benign	Het
Eml6	A	T	11: 29,727,390 (GRCm39)	V1244E	probably damaging	Het
Ethe1	G	A	7: 24,293,405 (GRCm39)	S17N	probably benign	Het
Foxi1	T	C	11: 34,157,578 (GRCm39)	D149G	probably damaging	Het
Fzd9	T	C	5: 135,278,475 (GRCm39)	E470G	probably damaging	Het
Ggnbp2	A	G	11: 84,753,072 (GRCm39)	F56L	probably damaging	Het
Hao1	G	A	2: 134,364,947 (GRCm39)	R227*	probably null	Het
Hyal1	G	A	9: 107,456,420 (GRCm39)	R369H	probably damaging	Het
Jam2	G	A	16: 84,609,840 (GRCm39)	V151M	probably damaging	Het
Kcna2	T	A	3: 107,012,733 (GRCm39)	I438N	probably benign	Het
Lrp1	A	T	10: 127,388,054 (GRCm39)	C3331*	probably null	Het
Mcm9	T	C	10: 53,424,623 (GRCm39)	I656V	probably benign	Het
Mroh9	C	T	1: 162,883,162 (GRCm39)	C439Y	probably damaging	Het
N4bp2l2	T	C	5: 150,574,160 (GRCm39)	D85G	probably damaging	Het
Nr1h2	A	G	7: 44,199,855 (GRCm39)	Y355H	probably damaging	Het
Nr5a2	T	C	1: 136,868,167 (GRCm39)	I322V	probably benign	Het
Nup153	A	C	13: 46,840,750 (GRCm39)	L273V	possibly damaging	Het
Obscn	A	G	11: 58,890,422 (GRCm39)	L7370P	unknown	Het
Or1a1	T	C	11: 74,086,542 (GRCm39)	I71T	probably damaging	Het
Or4b1	T	A	2: 89,980,222 (GRCm39)	I43F	probably damaging	Het
Or5k15	A	G	16: 58,710,287 (GRCm39)	C99R	probably damaging	Het
Prkdc	G	A	16: 15,551,916 (GRCm39)	D2041N	probably damaging	Het
Ptdss1	A	G	13: 67,081,675 (GRCm39)	D35G	possibly damaging	Het
Ptprs	G	T	17: 56,724,666 (GRCm39)	T1118K	probably damaging	Het
Pygb	C	T	2: 150,657,036 (GRCm39)	T329I	probably benign	Het
Rhoh	T	A	5: 66,050,157 (GRCm39)	D142E	probably benign	Het
Saraf	C	A	8: 34,635,616 (GRCm39)	A306E	probably damaging	Het
Scn1a	T	C	2: 66,181,332 (GRCm39)	I64V	probably benign	Het
Sec16a	A	G	2: 26,320,582 (GRCm39)	W1333R	probably damaging	Het
Shroom1	A	T	11: 53,357,289 (GRCm39)	T651S	possibly damaging	Het
Skint3	C	A	4: 112,134,863 (GRCm39)	Y345*	probably null	Het
Slc1a7	T	A	4: 107,864,751 (GRCm39)	N263K	probably damaging	Het
Sptbn2	C	T	19: 4,789,267 (GRCm39)	R1236C	probably damaging	Het
Tbx21	T	C	11: 96,992,393 (GRCm39)	N226S	probably benign	Het
Thada	A	G	17: 84,743,078 (GRCm39)	L782P	probably damaging	Het
Tle1	T	G	4: 72,055,335 (GRCm39)	I446L	possibly damaging	Het
Trgv1	T	A	13: 19,524,503 (GRCm39)	L76I	possibly damaging	Het
Triobp	A	G	15: 78,877,469 (GRCm39)	D1621G	probably damaging	Het
Trpm2	G	C	10: 77,773,972 (GRCm39)	A481G	probably benign	Het
Unc80	A	T	1: 66,685,595 (GRCm39)	M2240L	probably benign	Het
Usp9x	A	G	X: 12,989,747 (GRCm39)	R776G	possibly damaging	Homo
Vangl1	T	C	3: 102,074,238 (GRCm39)	T290A	probably benign	Het
Vmn1r233	T	A	17: 21,214,393 (GRCm39)	I186F	probably benign	Het
Vmn2r102	G	A	17: 19,901,424 (GRCm39)	C517Y	probably damaging	Het
Vrk2	G	A	11: 26,421,611 (GRCm39)	T449M	possibly damaging	Het
Zfp518a	A	G	19: 40,900,304 (GRCm39)	S78G	probably benign	Het
Zscan25	T	C	5: 145,223,120 (GRCm39)	S131P	unknown	Het
Zscan29	G	A	2: 120,997,096 (GRCm39)	T140I	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
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'- GAAGCCTGTGTATCCAATGCC -3'
(R):5'- AGCAGACCCTTGACTCTGTTATAC -3'

Sequencing Primer
(F):5'- GTGTATCCAATGCCACTGAGAATGC -3'
(R):5'- ACAAAACCTTTCATGTCTGGGC -3'

Posted On

2015-10-08