Mutagenetix > Incidental Mutation

Incidental Mutation 'R1761:Cdk4'

192787

Institutional Source

Beutler Lab

Gene Symbol

Cdk4

Ensembl Gene

ENSMUSG00000006728

Gene Name

cyclin dependent kinase 4

Synonyms

Crk3, p34/cdk4

MMRRC Submission

039793-MU

Accession Numbers

Essential gene?

Probably essential (E-score: 0.925) question?

Stock #

R1761 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

126899404-126903157 bp(+) (GRCm39)

Type of Mutation

unclassified

DNA Base Change (assembly)

T to A at 126900546 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Ref Sequence

ENSEMBL: ENSMUSP00000041581 (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: L104Q

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

SMART Domains

Protein: ENSMUSP00000006911
Gene: ENSMUSG00000006728
AA Change: L104Q

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

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: L104Q

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

SMART Domains

Protein: ENSMUSP00000117234
Gene: ENSMUSG00000006728
AA Change: L104Q

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

Predicted Effect

probably damaging
Transcript: ENSMUST00000133115
AA Change: L104Q

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

SMART Domains

Protein: ENSMUSP00000122973
Gene: ENSMUSG00000006728
AA Change: L104Q

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

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000135179

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000145670

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000140254

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000220344

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000218488

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

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000217875

Coding Region Coverage

1x: 97.5%
3x: 96.9%
10x: 95.4%
20x: 92.9%

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: 68 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abi3bp	C	T	16: 56,488,672 (GRCm39)	H1268Y	possibly damaging	Het
Acan	T	A	7: 78,743,833 (GRCm39)	Y621*	probably null	Het
Aig1	T	C	10: 13,566,328 (GRCm39)	Y152C	probably damaging	Het
Arhgap33	C	T	7: 30,232,488 (GRCm39)		probably null	Het
Bcl6	G	T	16: 23,796,292 (GRCm39)	A45D	probably damaging	Het
Cbx5	T	C	15: 103,121,607 (GRCm39)	D10G	possibly damaging	Het
Ccdc191	A	G	16: 43,763,873 (GRCm39)	I445V	probably benign	Het
Chil6	A	G	3: 106,301,654 (GRCm39)	F149L	probably damaging	Het
Cntn5	T	C	9: 10,172,059 (GRCm39)	T42A	probably benign	Het
Cpn2	A	T	16: 30,079,014 (GRCm39)	I229N	probably damaging	Het
Cpne8	A	G	15: 90,532,821 (GRCm39)	V62A	probably damaging	Het
Cr2	A	G	1: 194,837,431 (GRCm39)		probably null	Het
Crnn	A	T	3: 93,055,958 (GRCm39)	H248L	probably benign	Het
Csn1s1	A	G	5: 87,826,894 (GRCm39)	S254G	probably benign	Het
Cubn	A	G	2: 13,494,128 (GRCm39)		probably null	Het
Dnah8	A	G	17: 30,998,890 (GRCm39)	N3525S	probably damaging	Het
Dpp3	A	G	19: 4,971,177 (GRCm39)	L220P	probably benign	Het
Fam110a	T	C	2: 151,812,125 (GRCm39)	E215G	probably benign	Het
Fam20a	A	T	11: 109,568,664 (GRCm39)	N287K	probably damaging	Het
Fat4	T	C	3: 38,941,638 (GRCm39)	V177A	possibly damaging	Het
Fzd8	C	T	18: 9,213,643 (GRCm39)	R242C	probably damaging	Het
Gimap5	A	T	6: 48,730,195 (GRCm39)	Q255L	probably damaging	Het
Gm4787	A	G	12: 81,423,950 (GRCm39)	L736S	probably benign	Het
Gmeb1	G	A	4: 131,962,198 (GRCm39)	Q154*	probably null	Het
Gpr156	T	C	16: 37,807,929 (GRCm39)	L192P	probably damaging	Het
Gpr179	A	C	11: 97,225,932 (GRCm39)	S2074R	probably benign	Het
Hddc2	G	T	10: 31,202,135 (GRCm39)	D161Y	probably damaging	Het
Hlcs	T	C	16: 94,068,866 (GRCm39)	D265G	probably benign	Het
Hspg2	A	T	4: 137,241,984 (GRCm39)	I573F	possibly damaging	Het
Il1b	T	C	2: 129,207,101 (GRCm39)	K220E	probably damaging	Het
Il5	T	C	11: 53,614,557 (GRCm39)	I66T	probably damaging	Het
Irf6	G	A	1: 192,851,609 (GRCm39)	R400H	probably damaging	Het
Klra1	A	T	6: 130,349,836 (GRCm39)	Y201N	probably damaging	Het
Lmf2	A	G	15: 89,236,916 (GRCm39)	V442A	possibly damaging	Het
Mcm2	T	C	6: 88,866,770 (GRCm39)	I412M	possibly damaging	Het
Mlkl	T	A	8: 112,060,355 (GRCm39)	L18F	possibly damaging	Het
Mug2	C	A	6: 122,051,664 (GRCm39)	H949N	probably benign	Het
Nf1	T	C	11: 79,275,091 (GRCm39)	F51L	probably damaging	Het
Or52j3	T	G	7: 102,836,325 (GRCm39)	C172W	probably damaging	Het
Or7d10	A	T	9: 19,832,445 (GRCm39)	*313C	probably null	Het
Or8k18	T	G	2: 86,085,383 (GRCm39)	Y218S	probably damaging	Het
P3h2	T	C	16: 25,803,800 (GRCm39)	E322G	probably damaging	Het
Pramel21	T	C	4: 143,342,438 (GRCm39)	Y182H	probably benign	Het
Psmg2	CTTCAGTT	CTTCAGTTCAGTT	18: 67,779,095 (GRCm39)		probably null	Het
Ptdss1	T	C	13: 67,104,476 (GRCm39)	V116A	possibly damaging	Het
Ranbp2	T	C	10: 58,321,563 (GRCm39)	V2620A	probably benign	Het
Robo2	A	G	16: 73,831,912 (GRCm39)	V256A	probably damaging	Het
Scg3	T	A	9: 75,584,040 (GRCm39)	I154F	probably damaging	Het
Scgn	A	T	13: 24,143,689 (GRCm39)	F225Y	probably damaging	Het
Sec61b	T	C	4: 47,480,137 (GRCm39)	C58R	possibly damaging	Het
Slc25a46	G	T	18: 31,740,315 (GRCm39)	Q96K	possibly damaging	Het
Spmip6	G	A	4: 41,507,223 (GRCm39)	P109L	probably damaging	Het
Sptb	A	G	12: 76,659,382 (GRCm39)	F1173L	probably damaging	Het
Srcap	T	A	7: 127,134,017 (GRCm39)	C893S	probably damaging	Het
Tet3	T	C	6: 83,380,641 (GRCm39)	E509G	probably damaging	Het
Timm10b	C	T	7: 105,332,915 (GRCm39)	R897*	probably null	Het
Tln2	C	T	9: 67,193,796 (GRCm39)	A1773T	probably benign	Het
Tom1	T	C	8: 75,778,179 (GRCm39)	V87A	probably benign	Het
Tti1	T	C	2: 157,849,617 (GRCm39)	I541V	probably benign	Het
Ttn	A	T	2: 76,641,587 (GRCm39)	L5176Q	possibly damaging	Het
Tubb1	A	G	2: 174,298,689 (GRCm39)	S124G	probably benign	Het
Vgll3	A	T	16: 65,636,614 (GRCm39)	D310V	probably damaging	Het
Vmac	A	G	17: 57,022,788 (GRCm39)	L74P	probably damaging	Het
Zbtb1	A	T	12: 76,432,595 (GRCm39)	K194*	probably null	Het
Zfp429	A	G	13: 67,544,195 (GRCm39)	M76T	probably benign	Het
Zfp808	T	A	13: 62,319,460 (GRCm39)	C230S	possibly damaging	Het
Zfp980	A	G	4: 145,428,612 (GRCm39)	Y447C	probably damaging	Het
Zfp985	A	G	4: 147,668,502 (GRCm39)	T457A	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
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
R4946:Cdk4	UTSW	10	126,900,759 (GRCm39)	splice site	probably null
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'- TGAGAGTTCCTAATGGAGGAGCAGC -3'
(R):5'- TTCAGGTCCCGGTGAACAATGCAG -3'

Sequencing Primer
(F):5'- GGCCTTTGAACATCCCAATG -3'
(R):5'- CGCTTAGAAACTGACGCATTAG -3'

Posted On

2014-05-23