Mutagenetix > Incidental Mutation

Incidental Mutation 'R4946:Cdk4'

383432

Institutional Source

Beutler Lab

Gene Symbol

Cdk4

Ensembl Gene

ENSMUSG00000006728

Gene Name

cyclin dependent kinase 4

Synonyms

Crk3, p34/cdk4

MMRRC Submission

042543-MU

Accession Numbers

Essential gene?

Probably essential (E-score: 0.925) question?

Stock #

R4946 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

126899404-126903157 bp(+) (GRCm39)

Type of Mutation

splice site (2390 bp from exon)

DNA Base Change (assembly)

T to C at 126900759 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Ref Sequence

ENSEMBL: ENSMUSP00000057751 (fasta)

Gene Model

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

AlphaFold

P30285

Predicted Effect

probably damaging
Transcript: ENSMUST00000006911
AA Change: V137A

PolyPhen 2 Score 0.985 (Sensitivity: 0.74; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000006911
Gene: ENSMUSG00000006728
AA Change: V137A

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 null
Transcript: ENSMUST00000060991

SMART Domains

Protein: ENSMUSP00000057751
Gene: ENSMUSG00000006736

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

Predicted Effect

probably benign
Transcript: ENSMUST00000120226

SMART Domains

Protein: ENSMUSP00000112549
Gene: ENSMUSG00000006728

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

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000123456

Predicted Effect

probably damaging
Transcript: ENSMUST00000125682
AA Change: V137A

PolyPhen 2 Score 0.985 (Sensitivity: 0.74; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000117234
Gene: ENSMUSG00000006728
AA Change: V137A

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

Predicted Effect

possibly damaging
Transcript: ENSMUST00000133115
AA Change: V137A

PolyPhen 2 Score 0.895 (Sensitivity: 0.82; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000122973
Gene: ENSMUSG00000006728
AA Change: V137A

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

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000140254

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000145670

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000135179

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000218488

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000220344

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000217875

Predicted Effect

probably benign
Transcript: ENSMUST00000142558

SMART Domains

Protein: ENSMUSP00000116190
Gene: ENSMUSG00000006728

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

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000218603

Coding Region Coverage

1x: 99.0%
3x: 98.2%
10x: 96.0%
20x: 91.3%

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: 78 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abca8a	T	C	11: 109,977,300 (GRCm39)	D98G	probably damaging	Het
Adgre1	G	A	17: 57,750,918 (GRCm39)	V531I	probably benign	Het
Aldoart2	A	G	12: 55,612,801 (GRCm39)	Q242R	probably benign	Het
Ank2	A	T	3: 126,735,589 (GRCm39)		probably benign	Het
Ank3	C	T	10: 69,733,947 (GRCm39)	A737V	probably damaging	Het
Ankle2	A	G	5: 110,401,704 (GRCm39)	I789V	probably benign	Het
Ankrd13c	T	C	3: 157,711,410 (GRCm39)	V510A	probably damaging	Het
Arid1b	T	A	17: 5,393,118 (GRCm39)	M2216K	probably damaging	Het
Arrdc1	A	G	2: 24,815,860 (GRCm39)	V380A	probably benign	Het
B3galt1	C	A	2: 67,948,913 (GRCm39)	N209K	possibly damaging	Het
Cd300c2	A	T	11: 114,887,731 (GRCm39)	C224S	probably benign	Het
Cdk5rap1	T	C	2: 154,210,794 (GRCm39)	T115A	possibly damaging	Het
Clvs1	A	T	4: 9,281,831 (GRCm39)	R92*	probably null	Het
Cnga1	A	G	5: 72,762,107 (GRCm39)	V469A	probably damaging	Het
Ctns	A	G	11: 73,087,479 (GRCm39)	F16L	probably benign	Het
Dlg5	A	T	14: 24,204,429 (GRCm39)	C1299S	probably damaging	Het
Dnah3	T	A	7: 119,530,783 (GRCm39)	Y3690F	probably damaging	Het
Dnah5	A	G	15: 28,326,703 (GRCm39)	M1971V	probably damaging	Het
Dnah5	G	A	15: 28,388,050 (GRCm39)	V3170M	probably damaging	Het
Dpp8	T	C	9: 64,963,200 (GRCm39)	Y485H	probably benign	Het
Dsc2	T	C	18: 20,183,214 (GRCm39)	D68G	probably damaging	Het
Eeig2	A	G	3: 108,887,544 (GRCm39)	V240A	probably benign	Het
Elavl1	A	T	8: 4,351,752 (GRCm39)	D121E	probably benign	Het
Ermap	A	G	4: 119,040,505 (GRCm39)	V311A	probably damaging	Het
Fbxw11	C	T	11: 32,689,226 (GRCm39)	R437C	probably damaging	Het
Gas2l3	T	C	10: 89,249,634 (GRCm39)	M495V	probably benign	Het
Hacd1	C	T	2: 14,049,948 (GRCm39)		probably null	Het
Itgav	A	G	2: 83,619,327 (GRCm39)	R596G	probably benign	Het
Kars1	T	C	8: 112,728,352 (GRCm39)	H215R	possibly damaging	Het
Kif26a	G	A	12: 112,144,228 (GRCm39)	R1494H	probably damaging	Het
Klf12	G	A	14: 100,260,393 (GRCm39)	S112L	possibly damaging	Het
Krt77	T	C	15: 101,777,998 (GRCm39)	Y19C	unknown	Het
Lrrc4c	A	G	2: 97,460,834 (GRCm39)	T487A	probably benign	Het
Lrrn1	A	G	6: 107,545,851 (GRCm39)	M550V	probably benign	Het
Lsr	C	A	7: 30,657,634 (GRCm39)	R442L	probably benign	Het
Lysmd2	A	C	9: 75,542,728 (GRCm39)	T112P	probably damaging	Het
Mctp2	A	T	7: 71,909,017 (GRCm39)	S99T	probably benign	Het
Mettl4	A	G	17: 95,047,960 (GRCm39)	V227A	probably benign	Het
Mill2	T	A	7: 18,590,608 (GRCm39)		probably null	Het
Mpp3	T	C	11: 101,895,848 (GRCm39)	N476D	probably benign	Het
Mtmr6	C	T	14: 60,517,638 (GRCm39)	P83L	possibly damaging	Het
Myh3	T	C	11: 66,984,364 (GRCm39)	I1067T	probably benign	Het
Myh9	C	A	15: 77,657,540 (GRCm39)	Q1068H	probably damaging	Het
Narf	T	A	11: 121,141,179 (GRCm39)	H304Q	possibly damaging	Het
Nfatc2ip	G	T	7: 125,995,784 (GRCm39)	P35Q	possibly damaging	Het
Npas3	C	A	12: 54,112,618 (GRCm39)	P426Q	probably damaging	Het
Or10aa3	T	G	1: 173,878,400 (GRCm39)	S154A	possibly damaging	Het
Or4e1	G	A	14: 52,700,740 (GRCm39)	T242I	probably damaging	Het
Or4f4b	T	C	2: 111,314,311 (GRCm39)	Y207H	possibly damaging	Het
Or51i1	T	A	7: 103,671,219 (GRCm39)	Q102L	probably damaging	Het
Or5p5	A	G	7: 107,414,589 (GRCm39)	H266R	possibly damaging	Het
Pcdh10	A	T	3: 45,333,917 (GRCm39)	E77V	probably damaging	Het
Pcnt	C	T	10: 76,192,019 (GRCm39)	R2764Q	probably damaging	Het
Pgbd5	T	C	8: 125,097,324 (GRCm39)	D493G	possibly damaging	Het
Piezo2	G	T	18: 63,290,333 (GRCm39)	T142N	probably benign	Het
Plcb1	A	G	2: 135,187,015 (GRCm39)	I761V	probably benign	Het
Plekhg4	T	G	8: 106,108,628 (GRCm39)	D1196E	probably null	Het
Pparg	A	G	6: 115,427,989 (GRCm39)	K159E	probably damaging	Het
Psmb1	A	T	17: 15,718,478 (GRCm39)	M16K	probably benign	Het
Ptprq	T	C	10: 107,361,595 (GRCm39)	I2139V	probably benign	Het
Ralgapb	T	A	2: 158,282,887 (GRCm39)	S239T	probably damaging	Het
Serpina11	A	G	12: 103,950,923 (GRCm39)	V266A	probably damaging	Het
Sf3a2	C	G	10: 80,639,947 (GRCm39)		probably benign	Het
Smim18	T	C	8: 34,232,587 (GRCm39)	T11A	possibly damaging	Het
Snx6	G	A	12: 54,817,528 (GRCm39)	T7I	probably damaging	Het
Srcin1	T	A	11: 97,442,768 (GRCm39)	D75V	probably damaging	Het
Srsf12	T	A	4: 33,231,174 (GRCm39)	S223T	probably damaging	Het
Taf4b	G	T	18: 14,946,599 (GRCm39)	C474F	probably damaging	Het
Tango6	T	A	8: 107,444,722 (GRCm39)	C542*	probably null	Het
Tbc1d24	A	G	17: 24,427,510 (GRCm39)	S151P	possibly damaging	Het
Tssk6	T	C	8: 70,355,714 (GRCm39)	S253P	probably benign	Het
Ttc39c	G	A	18: 12,857,999 (GRCm39)	W300*	probably null	Het
Ttc6	T	A	12: 57,689,926 (GRCm39)	W539R	probably benign	Het
Ttn	T	C	2: 76,582,770 (GRCm39)	T22708A	probably damaging	Het
Ttn	C	A	2: 76,749,053 (GRCm39)	E3999*	probably null	Het
Vill	T	G	9: 118,897,508 (GRCm39)	L261R	probably damaging	Het
Vmn1r20	T	C	6: 57,409,159 (GRCm39)	S162P	probably damaging	Het
Zfp516	T	C	18: 82,974,219 (GRCm39)	I139T	probably benign	Het

Other mutations in Cdk4

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00960:Cdk4	APN	10	126,900,166 (GRCm39)	missense	probably damaging	1.00
IGL01326:Cdk4	APN	10	126,900,492 (GRCm39)	missense	possibly damaging	0.95
R0140:Cdk4	UTSW	10	126,900,214 (GRCm39)	missense	probably damaging	1.00
R0799:Cdk4	UTSW	10	126,900,863 (GRCm39)	missense	probably damaging	0.98
R1437:Cdk4	UTSW	10	126,900,558 (GRCm39)	missense	probably damaging	1.00
R1575:Cdk4	UTSW	10	126,900,520 (GRCm39)	missense	probably damaging	1.00
R1656:Cdk4	UTSW	10	126,900,849 (GRCm39)	missense	probably benign	0.00
R1761:Cdk4	UTSW	10	126,900,546 (GRCm39)	unclassified	probably benign
R2567:Cdk4	UTSW	10	126,900,145 (GRCm39)	missense	probably benign	0.01
R4679:Cdk4	UTSW	10	126,900,780 (GRCm39)	missense	possibly damaging	0.93
R4790:Cdk4	UTSW	10	126,900,570 (GRCm39)	missense	probably damaging	1.00
R4897:Cdk4	UTSW	10	126,900,444 (GRCm39)	intron	probably benign
R5755:Cdk4	UTSW	10	126,900,591 (GRCm39)	critical splice donor site	probably null
R6515:Cdk4	UTSW	10	126,902,052 (GRCm39)	missense	probably null	0.06
R6868:Cdk4	UTSW	10	126,900,870 (GRCm39)	missense	probably benign	0.43
R7488:Cdk4	UTSW	10	126,900,106 (GRCm39)	start codon destroyed	probably null	0.26
R7748:Cdk4	UTSW	10	126,900,298 (GRCm39)	missense	possibly damaging	0.78
R8956:Cdk4	UTSW	10	126,900,546 (GRCm39)	unclassified	probably benign
R9082:Cdk4	UTSW	10	126,900,732 (GRCm39)	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- TGCCGGTTGAGACCATTAAGG -3'
(R):5'- GCCTGGCTCTGAAAACTTCATG -3'

Sequencing Primer
(F):5'- CCATTAAGGTGAGTAGGGGTG -3'
(R):5'- GACTCCTCAGTTGCTATGGGAAAC -3'

Posted On

2016-04-27