Mutagenetix > Incidental Mutation

Incidental Mutation 'R7748:Cdk4'

597023

Institutional Source

Beutler Lab

Gene Symbol

Cdk4

Ensembl Gene

ENSMUSG00000006728

Gene Name

cyclin-dependent kinase 4

Synonyms

Crk3, p34/cdk4

MMRRC Submission

045804-MU

Accession Numbers

Essential gene?

Probably essential (E-score: 0.915) question?

Stock #

R7748 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

127063534-127067920 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

C to T at 127064429 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Alanine to Valine at position 65 (A65V)

Ref Sequence

ENSEMBL: ENSMUSP00000006911 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000006911] [ENSMUST00000040307] [ENSMUST00000060991] [ENSMUST00000120226] [ENSMUST00000125682] [ENSMUST00000133115] [ENSMUST00000142558]

AlphaFold

P30285

Predicted Effect

possibly damaging
Transcript: ENSMUST00000006911
AA Change: A65V

PolyPhen 2 Score 0.779 (Sensitivity: 0.85; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000006911
Gene: ENSMUSG00000006728
AA Change: A65V

Domain	Start	End	E-Value	Type
S_TKc	6	295	9.2e-96	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000040307

SMART Domains

Protein: ENSMUSP00000041581
Gene: ENSMUSG00000040502

Domain	Start	End	E-Value	Type
low complexity region	20	45	N/A	INTRINSIC
low complexity region	50	60	N/A	INTRINSIC
low complexity region	76	105	N/A	INTRINSIC
RINGv	109	156	7.51e-18	SMART
transmembrane domain	183	205	N/A	INTRINSIC
Blast:AAA	211	238	2e-9	BLAST
low complexity region	267	284	N/A	INTRINSIC
low complexity region	291	302	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000060991

SMART Domains

Protein: ENSMUSP00000057751
Gene: ENSMUSG00000006736

Domain	Start	End	E-Value	Type
Pfam:Tetraspannin	8	200	1.2e-19	PFAM

Predicted Effect

possibly damaging
Transcript: ENSMUST00000120226
AA Change: A65V

PolyPhen 2 Score 0.948 (Sensitivity: 0.79; Specificity: 0.95)

SMART Domains

Protein: ENSMUSP00000112549
Gene: ENSMUSG00000006728
AA Change: A65V

Domain	Start	End	E-Value	Type
Pfam:Pkinase	6	103	6e-10	PFAM
low complexity region	121	138	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000125682
AA Change: A65V

PolyPhen 2 Score 0.779 (Sensitivity: 0.85; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000117234
Gene: ENSMUSG00000006728
AA Change: A65V

Domain	Start	End	E-Value	Type
S_TKc	6	261	5.19e-72	SMART

Predicted Effect

possibly damaging
Transcript: ENSMUST00000133115
AA Change: A65V

PolyPhen 2 Score 0.779 (Sensitivity: 0.85; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000122973
Gene: ENSMUSG00000006728
AA Change: A65V

Domain	Start	End	E-Value	Type
S_TKc	6	250	1.55e-70	SMART

Predicted Effect

possibly damaging
Transcript: ENSMUST00000142558
AA Change: A65V

PolyPhen 2 Score 0.792 (Sensitivity: 0.85; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000116190
Gene: ENSMUSG00000006728
AA Change: A65V

Domain	Start	End	E-Value	Type
Pfam:Pkinase	6	74	1.6e-8	PFAM

Coding Region Coverage

1x: 100.0%
3x: 100.0%
10x: 99.8%
20x: 99.2%

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 is a member of the Ser/Thr protein kinase family. This protein is highly similar to the gene products of S. cerevisiae cdc28 and S. pombe cdc2. It is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression. The activity of this kinase is restricted to the G1-S phase, which is controlled by the regulatory subunits D-type cyclins and CDK inhibitor p16(INK4a). This kinase was shown to be responsible for the phosphorylation of retinoblastoma gene product (Rb). Mutations in this gene as well as in its related proteins including D-type cyclins, p16(INK4a) and Rb were all found to be associated with tumorigenesis of a variety of cancers. Multiple polyadenylation sites of this gene have been reported. [provided by RefSeq, Jul 2008]
PHENOTYPE: Homozygous null mutants have small size, insulin-deficient diabetes, sterility in females; near-sterility in males and impaired prolactin secretion due to hypoplastic pituitary development. Locomotor and endocrine gland defects are seen with some alleles. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 111 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2310057M21Rik	T	A	7: 131,361,792 (GRCm38)	L103F	probably benign	Het
4932438A13Rik	A	G	3: 36,959,335 (GRCm38)		probably null	Het
5330417H12Rik	A	G	7: 107,624,558 (GRCm38)	L103P	unknown	Het
Actb	T	C	5: 142,904,695 (GRCm38)	I151V	probably benign	Het
Adcy6	T	A	15: 98,604,556 (GRCm38)	H59L	probably benign	Het
Adss	G	C	1: 177,772,202 (GRCm38)	S272*	probably null	Het
Aga	A	T	8: 53,511,805 (GRCm38)	M1L	possibly damaging	Het
Anxa5	G	A	3: 36,465,331 (GRCm38)	T3M	probably damaging	Het
Arhgap45	A	T	10: 80,016,932 (GRCm38)		probably benign	Het
Atp6v0a2	A	T	5: 124,716,496 (GRCm38)	H639L	probably benign	Het
BC005537	C	T	13: 24,803,399 (GRCm38)	R7W	possibly damaging	Het
Bcl2l2	C	T	14: 54,884,379 (GRCm38)		probably benign	Het
Bod1l	A	C	5: 41,832,340 (GRCm38)	S347A	probably damaging	Het
Calcoco1	T	C	15: 102,719,561 (GRCm38)	D46G	probably damaging	Het
Camk1	T	C	6: 113,340,328 (GRCm38)	E60G	probably damaging	Het
Capza1	A	T	3: 104,825,405 (GRCm38)		probably null	Het
Ccdc18	T	A	5: 108,149,041 (GRCm38)		probably null	Het
Cdh20	G	A	1: 104,941,299 (GRCm38)	A172T	probably damaging	Het
Cftr	T	C	6: 18,277,889 (GRCm38)		probably null	Het
Chd3	T	C	11: 69,355,633 (GRCm38)	M1092V	probably benign	Het
Chd6	A	T	2: 160,966,619 (GRCm38)	H1558Q	probably benign	Het
Chil1	A	G	1: 134,189,228 (GRCm38)	H318R	probably benign	Het
Cps1	A	G	1: 67,139,806 (GRCm38)	Y59C	probably damaging	Het
Cyb5r4	T	C	9: 87,032,381 (GRCm38)	V111A	probably damaging	Het
D430042O09Rik	A	T	7: 125,829,801 (GRCm38)	M558L	probably benign	Het
Ddx39b	G	A	17: 35,252,750 (GRCm38)	V291M	probably damaging	Het
Dhx57	A	G	17: 80,265,117 (GRCm38)	F709S	probably damaging	Het
Eef1b2	A	T	1: 63,177,865 (GRCm38)	K64N	probably damaging	Het
Fam135a	A	G	1: 24,028,969 (GRCm38)	S940P	probably benign	Het
Fam234b	T	A	6: 135,209,351 (GRCm38)	V119E	probably damaging	Het
Fbxo46	G	C	7: 19,136,533 (GRCm38)	C359S	probably damaging	Het
Fkbp14	C	A	6: 54,595,520 (GRCm38)		probably benign	Het
Fmn2	T	A	1: 174,666,649 (GRCm38)	V1243E	probably damaging	Het
Fsbp	C	A	4: 11,579,924 (GRCm38)	T64K	probably damaging	Het
Fscb	A	T	12: 64,474,407 (GRCm38)	M95K	probably benign	Het
Fyb	T	G	15: 6,638,826 (GRCm38)	V500G	probably damaging	Het
G2e3	A	G	12: 51,371,667 (GRCm38)	N615S	probably benign	Het
Gart	T	C	16: 91,630,652 (GRCm38)	D486G	possibly damaging	Het
Gas2l2	T	A	11: 83,422,398 (GRCm38)	D696V	probably benign	Het
Glmn	C	T	5: 107,562,244 (GRCm38)		probably null	Het
Gm47985	A	T	1: 151,182,974 (GRCm38)	D122V	probably damaging	Het
Gm49333	A	T	16: 20,633,084 (GRCm38)	D407V	probably damaging	Het
Gm7168	A	G	17: 13,948,652 (GRCm38)	K94E	probably benign	Het
Gm996	T	A	2: 25,578,959 (GRCm38)	E313D	possibly damaging	Het
Gnai2	T	C	9: 107,615,735 (GRCm38)	H323R		Het
Helz2	C	T	2: 181,234,531 (GRCm38)	R1390H	probably damaging	Het
Igf2bp1	T	C	11: 95,967,587 (GRCm38)	M453V	probably benign	Het
Ighv3-1	C	T	12: 113,964,650 (GRCm38)	V30M	probably damaging	Het
Inpp5a	A	T	7: 139,574,995 (GRCm38)	R343S	probably damaging	Het
Itga8	T	A	2: 12,230,239 (GRCm38)	I403F	possibly damaging	Het
Krt33a	C	T	11: 100,011,602 (GRCm38)	R404H	probably benign	Het
Krt34	T	A	11: 100,038,938 (GRCm38)	E244V	probably damaging	Het
Krt42	T	C	11: 100,266,966 (GRCm38)	E224G	probably damaging	Het
Krtap5-2	TCCACAGGAACTACAGCCTCCCTTGCAGCCCCCACAGGAACCACAGCCCCCACAGGAACTACA	TCCACAGGAACTACA	7: 142,175,108 (GRCm38)		probably benign	Het
Lama1	T	C	17: 67,750,590 (GRCm38)	L553P		Het
Lcn9	T	A	2: 25,824,914 (GRCm38)	*179K	probably null	Het
Lrrc2	T	G	9: 110,980,931 (GRCm38)	M345R	possibly damaging	Het
March11	T	C	15: 26,387,830 (GRCm38)	V257A	probably damaging	Het
Masp2	T	C	4: 148,605,706 (GRCm38)	I224T	probably benign	Het
Mpz	A	T	1: 171,159,940 (GRCm38)		probably null	Het
Mtr	C	T	13: 12,227,839 (GRCm38)	A442T	probably benign	Het
Muc5b	A	G	7: 141,847,805 (GRCm38)	K596R	unknown	Het
Myo15	T	G	11: 60,504,901 (GRCm38)	F1397C		Het
Ncor2	T	C	5: 125,109,967 (GRCm38)	I173V	unknown	Het
Ngly1	T	A	14: 16,290,820 (GRCm38)	I434K	possibly damaging	Het
Notch2	A	G	3: 98,138,484 (GRCm38)	H1655R	possibly damaging	Het
Notum	C	T	11: 120,654,801 (GRCm38)	A390T	probably damaging	Het
Olfr381	T	G	11: 73,486,168 (GRCm38)	I219L	probably benign	Het
Olfr519	T	C	7: 108,894,078 (GRCm38)	T115A	probably benign	Het
Pds5a	T	A	5: 65,619,666 (GRCm38)	I51F	possibly damaging	Het
Pdzd2	C	A	15: 12,385,786 (GRCm38)	R966L	possibly damaging	Het
Plk3	T	C	4: 117,131,728 (GRCm38)	Y278C	probably damaging	Het
Plxna1	T	A	6: 89,337,353 (GRCm38)		probably null	Het
Plxna1	C	G	6: 89,337,352 (GRCm38)		probably null	Het
Ppp4r4	G	A	12: 103,605,061 (GRCm38)		probably null	Het
Pramel6	T	A	2: 87,508,699 (GRCm38)	V81E	probably damaging	Het
Prdm2	T	C	4: 143,135,889 (GRCm38)	E277G	possibly damaging	Het
Prkg1	T	A	19: 30,993,091 (GRCm38)	I222F	possibly damaging	Het
Proser3	A	T	7: 30,540,072 (GRCm38)	S536T	possibly damaging	Het
Prrt4	C	A	6: 29,177,191 (GRCm38)	G193V	probably damaging	Het
Ptpn21	A	T	12: 98,688,772 (GRCm38)	H645Q	probably benign	Het
Ptprd	T	C	4: 76,099,504 (GRCm38)	I744V	probably null	Het
Rad54l2	A	G	9: 106,719,034 (GRCm38)	V235A	possibly damaging	Het
Repin1	G	T	6: 48,597,345 (GRCm38)	E403*	probably null	Het
Rgs22	C	T	15: 36,122,269 (GRCm38)		probably null	Het
Rtcb	A	T	10: 85,941,968 (GRCm38)	D447E	probably benign	Het
Rtn1	C	T	12: 72,216,926 (GRCm38)	V744I	possibly damaging	Het
Scfd1	T	G	12: 51,389,357 (GRCm38)	I96M	probably benign	Het
Serpina3b	T	C	12: 104,130,463 (GRCm38)	M1T	probably null	Het
Slc1a4	T	C	11: 20,332,252 (GRCm38)	Y74C	probably damaging	Het
Slc9b2	A	T	3: 135,326,179 (GRCm38)	I267F	possibly damaging	Het
Sorcs2	A	T	5: 36,229,175 (GRCm38)	M173K	possibly damaging	Het
Sparc	T	C	11: 55,398,600 (GRCm38)	I226V	probably benign	Het
Spata22	T	G	11: 73,336,254 (GRCm38)	I98S	probably null	Het
Spef2	C	T	15: 9,652,945 (GRCm38)	V917M	probably damaging	Het
Sspo	C	A	6: 48,449,465 (GRCm38)	C139*	probably null	Het
Tenm4	A	G	7: 96,894,702 (GRCm38)	D2012G	probably damaging	Het
Tgm5	G	A	2: 121,052,808 (GRCm38)	R351C	probably damaging	Het
Tmem145	G	A	7: 25,307,328 (GRCm38)	W82*	probably null	Het
Tmem159	A	T	7: 120,115,479 (GRCm38)	I64F	possibly damaging	Het
Topors	T	A	4: 40,262,654 (GRCm38)	D210V	probably damaging	Het
Tssk4	A	T	14: 55,651,112 (GRCm38)	H146L	probably damaging	Het
Unc93b1	T	A	19: 3,935,250 (GRCm38)	D19E	unknown	Het
Usp17lc	A	G	7: 103,418,481 (GRCm38)	T328A	probably damaging	Het
Utrn	A	G	10: 12,614,508 (GRCm38)	Y43H	probably benign	Het
Vmn1r25	T	A	6: 57,978,564 (GRCm38)	I247F	probably damaging	Het
Vmn2r78	A	T	7: 86,921,135 (GRCm38)	Q287L	probably benign	Het
Vps13c	T	A	9: 67,963,089 (GRCm38)	I3170N	probably benign	Het
Zfc3h1	T	A	10: 115,400,815 (GRCm38)	M398K	probably benign	Het
Zfp354c	TCACACTCGGCACA	TCACA	11: 50,815,240 (GRCm38)		probably benign	Het
Zfp773	T	C	7: 7,132,908 (GRCm38)	R230G	probably benign	Het

Other mutations in Cdk4

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00960:Cdk4	APN	10	127,064,297 (GRCm38)	missense	probably damaging	1.00
IGL01326:Cdk4	APN	10	127,064,623 (GRCm38)	missense	possibly damaging	0.95
R0140:Cdk4	UTSW	10	127,064,345 (GRCm38)	missense	probably damaging	1.00
R0799:Cdk4	UTSW	10	127,064,994 (GRCm38)	missense	probably damaging	0.98
R1437:Cdk4	UTSW	10	127,064,689 (GRCm38)	missense	probably damaging	1.00
R1575:Cdk4	UTSW	10	127,064,651 (GRCm38)	missense	probably damaging	1.00
R1656:Cdk4	UTSW	10	127,064,980 (GRCm38)	missense	probably benign	0.00
R1761:Cdk4	UTSW	10	127,064,677 (GRCm38)	unclassified	probably benign
R2567:Cdk4	UTSW	10	127,064,276 (GRCm38)	missense	probably benign	0.01
R4679:Cdk4	UTSW	10	127,064,911 (GRCm38)	missense	possibly damaging	0.93
R4790:Cdk4	UTSW	10	127,064,701 (GRCm38)	missense	probably damaging	1.00
R4897:Cdk4	UTSW	10	127,064,575 (GRCm38)	intron	probably benign
R4946:Cdk4	UTSW	10	127,064,890 (GRCm38)	splice site	probably null
R5755:Cdk4	UTSW	10	127,064,722 (GRCm38)	critical splice donor site	probably null
R6515:Cdk4	UTSW	10	127,066,183 (GRCm38)	missense	probably null	0.06
R6868:Cdk4	UTSW	10	127,065,001 (GRCm38)	missense	probably benign	0.43
R7488:Cdk4	UTSW	10	127,064,237 (GRCm38)	start codon destroyed	probably null	0.26
R8956:Cdk4	UTSW	10	127,064,677 (GRCm38)	unclassified	probably benign
R9082:Cdk4	UTSW	10	127,064,863 (GRCm38)	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- AGATCCCCTGCTTCGAGAATGG -3'
(R):5'- TCAGTTCGGGAAGTAGCACAG -3'

Sequencing Primer
(F):5'- AATGGCTGCCACTCGATATG -3'
(R):5'- TTCGGGAAGTAGCACAGACATCC -3'

Posted On

2019-11-26