Mutagenetix > Incidental Mutation

Incidental Mutation 'R7338:Chek2'

569640

Institutional Source

Beutler Lab

Gene Symbol

Chek2

Ensembl Gene

ENSMUSG00000029521

Gene Name

checkpoint kinase 2

Synonyms

CHK2, Rad53

MMRRC Submission

045428-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R7338 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

110987845-111022011 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 111021380 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Valine to Glutamic Acid at position 530 (V530E)

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: V530E

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

SMART Domains

Protein: ENSMUSP00000066679
Gene: ENSMUSG00000029521
AA Change: V530E

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: 100.0%
3x: 100.0%
10x: 99.7%
20x: 99.1%

Validation Efficiency

98% (54/55)

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: 56 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abca3	T	C	17: 24,595,717 (GRCm39)	S357P	possibly damaging	Het
Arhgap28	T	C	17: 68,203,106 (GRCm39)	R166G	probably damaging	Het
Bcan	T	A	3: 87,901,550 (GRCm39)	E384V	probably damaging	Het
Bcl9l	A	G	9: 44,420,005 (GRCm39)	N1137S	probably benign	Het
Caprin1	A	G	2: 103,609,768 (GRCm39)	L170S	probably benign	Het
Card6	C	T	15: 5,129,354 (GRCm39)	E681K	probably benign	Het
Catsperb	G	A	12: 101,447,243 (GRCm39)	V248I	probably benign	Het
Ccnj	T	A	19: 40,825,477 (GRCm39)	H62Q	probably damaging	Het
Cd180	A	C	13: 102,842,936 (GRCm39)	I661L	probably benign	Het
Cdk11b	A	G	4: 155,732,008 (GRCm39)	R473G	unknown	Het
Cep126	T	C	9: 8,099,799 (GRCm39)	T912A	possibly damaging	Het
Chga	G	T	12: 102,529,100 (GRCm39)	S359I	probably damaging	Het
Cnrip1	T	C	11: 17,004,657 (GRCm39)	V69A	probably damaging	Het
Cyp2a5	A	T	7: 26,542,372 (GRCm39)	Q458L	probably damaging	Het
Cyp2j11	T	A	4: 96,195,524 (GRCm39)	T391S	possibly damaging	Het
Dhx16	T	C	17: 36,199,036 (GRCm39)	L794P	probably damaging	Het
Dscaml1	A	G	9: 45,585,802 (GRCm39)	T580A	probably benign	Het
Elmo1	A	T	13: 20,464,982 (GRCm39)	I184L	probably benign	Het
Gabra1	C	T	11: 42,073,121 (GRCm39)	G51S	unknown	Het
Gabrr3	C	A	16: 59,268,439 (GRCm39)	L351I	possibly damaging	Het
Gbp7	A	T	3: 142,243,786 (GRCm39)	N111I	probably damaging	Het
Gjd2	C	T	2: 113,841,583 (GRCm39)	R298H	probably damaging	Het
Gm5930	T	C	14: 44,573,914 (GRCm39)	Y141C	probably damaging	Het
Grin3a	G	T	4: 49,771,238 (GRCm39)	N511K	probably benign	Het
Hdac7	T	C	15: 97,707,903 (GRCm39)	D122G	probably benign	Het
Ifi204	G	A	1: 173,587,703 (GRCm39)	T152I	possibly damaging	Het
Lrrc9	C	T	12: 72,510,305 (GRCm39)		probably null	Het
Med21	T	A	6: 146,544,082 (GRCm39)		probably benign	Het
Mmp19	A	T	10: 128,634,952 (GRCm39)	T523S	probably benign	Het
Nav3	G	A	10: 109,605,073 (GRCm39)	T1000I	probably benign	Het
Nherf2	T	A	17: 24,869,182 (GRCm39)		probably benign	Het
Nin	T	C	12: 70,090,838 (GRCm39)	D859G		Het
Nip7	T	G	8: 107,783,916 (GRCm39)	L52R	possibly damaging	Het
Or10d1c	A	G	9: 38,893,816 (GRCm39)	Y175H	probably damaging	Het
Or5al5	A	T	2: 85,961,726 (GRCm39)	F94I	probably damaging	Het
Or6b13	A	T	7: 139,782,446 (GRCm39)	V79E	probably benign	Het
Otop1	T	A	5: 38,457,547 (GRCm39)	Y435*	probably null	Het
Pak4	A	G	7: 28,264,381 (GRCm39)	S174P	probably benign	Het
Pcsk7	G	A	9: 45,837,287 (GRCm39)	R537Q	probably benign	Het
Podxl	G	A	6: 31,505,941 (GRCm39)	S34F	unknown	Het
Prr36	G	A	8: 4,266,212 (GRCm39)	R113C	probably damaging	Het
Ptk7	T	C	17: 46,890,525 (GRCm39)	I436V	probably benign	Het
Slc13a5	C	T	11: 72,157,310 (GRCm39)	V28I	probably benign	Het
Slco6d1	A	T	1: 98,349,097 (GRCm39)	D56V	probably benign	Het
Spg11	G	A	2: 121,885,858 (GRCm39)	R2317W	probably damaging	Het
Stom	T	A	2: 35,213,760 (GRCm39)		probably null	Het
Svs5	T	C	2: 164,174,728 (GRCm39)	L8P	possibly damaging	Het
Tmem141	C	A	2: 25,511,626 (GRCm39)	V39F	probably damaging	Het
Tmprss6	A	G	15: 78,344,019 (GRCm39)	L181P	probably damaging	Het
Tnni3	A	G	7: 4,524,379 (GRCm39)	S40P	probably benign	Het
Tubgcp4	A	G	2: 121,024,465 (GRCm39)	I548V	probably benign	Het
Twf2	A	G	9: 106,081,138 (GRCm39)		probably benign	Het
Wnt5b	C	A	6: 119,425,092 (GRCm39)		probably null	Het
Wrap73	A	G	4: 154,237,043 (GRCm39)	D210G	probably benign	Het
Yipf4	T	G	17: 74,796,771 (GRCm39)	S21A	probably benign	Het
Zscan20	A	G	4: 128,481,943 (GRCm39)	M573T	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
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'- GTTAGAAATCGCCAGGGAGC -3'
(R):5'- TCGTGTATCTGTGATGGAAAAGC -3'

Sequencing Primer
(F):5'- GGAGCATGGATAAGCATCTTGATTCC -3'
(R):5'- GCTGGCCTTGAACTCAGAAATCTG -3'

Posted On

2019-09-13