Mutagenetix > Incidental Mutation

Incidental Mutation 'R6755:Cdk8'

531003

Institutional Source

Beutler Lab

Gene Symbol

Cdk8

Ensembl Gene

ENSMUSG00000029635

Gene Name

cyclin dependent kinase 8

Synonyms

MMRRC Submission

044871-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R6755 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

146168040-146239684 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 146205126 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Histidine to Glutamine at position 102 (H102Q)

Ref Sequence

ENSEMBL: ENSMUSP00000125516 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000031640] [ENSMUST00000159467] [ENSMUST00000161181] [ENSMUST00000161652] [ENSMUST00000162494]

AlphaFold

Q8R3L8

Predicted Effect

probably damaging
Transcript: ENSMUST00000031640
AA Change: H102Q

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000031640
Gene: ENSMUSG00000029635
AA Change: H102Q

Domain	Start	End	E-Value	Type
S_TKc	21	335	1.89e-83	SMART
low complexity region	372	391	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000159467

SMART Domains

Protein: ENSMUSP00000124525
Gene: ENSMUSG00000029635

Domain	Start	End	E-Value	Type
Pfam:Pkinase_Tyr	22	104	2e-8	PFAM
Pfam:Pkinase	22	108	1.8e-12	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000161181
AA Change: H42Q

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

SMART Domains

Protein: ENSMUSP00000125668
Gene: ENSMUSG00000029635
AA Change: H42Q

Domain	Start	End	E-Value	Type
Pfam:Pkinase_Tyr	1	179	6e-16	PFAM
Pfam:Pkinase	1	270	1.6e-44	PFAM
low complexity region	307	326	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000161652
AA Change: H102Q

PolyPhen 2 Score 0.939 (Sensitivity: 0.80; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000124323
Gene: ENSMUSG00000029635
AA Change: H102Q

Domain	Start	End	E-Value	Type
Pfam:Pkinase_Tyr	22	215	2e-22	PFAM
Pfam:Pkinase	23	226	5.2e-42	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000162494
AA Change: H102Q

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

SMART Domains

Protein: ENSMUSP00000125516
Gene: ENSMUSG00000029635
AA Change: H102Q

Domain	Start	End	E-Value	Type
Pfam:Pkinase	22	153	5.9e-25	PFAM
Pfam:Pkinase_Tyr	22	156	1.5e-15	PFAM

Coding Region Coverage

1x: 99.9%
3x: 99.5%
10x: 97.6%
20x: 92.9%

Validation Efficiency

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the cyclin-dependent protein kinase (CDK) family. CDK family members are known to be important regulators of cell cycle progression. This kinase and its regulatory subunit, cyclin C, are components of the Mediator transcriptional regulatory complex, involved in both transcriptional activation and repression by phosphorylation of the carboxy-terminal domain of the largest subunit of RNA polymerase II. This kinase regulates transcription by targeting the cyclin-dependent kinase 7 subunits of the general transcription initiation factor IIH, thus providing a link between the Mediator complex and the basal transcription machinery. Multiple pseudogenes of this gene have been identified. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2016]
PHENOTYPE: Mice homozygous for a gene-trapped allele die prior to implantation exhibiting fragmented blastomeres and failure to undergo compaction. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 66 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2210408I21Rik	C	T	13: 77,475,994 (GRCm39)	T1101M	probably benign	Het
4930433I11Rik	T	C	7: 40,643,734 (GRCm39)	S468P	probably damaging	Het
Adam33	A	G	2: 130,895,069 (GRCm39)	V637A	probably damaging	Het
Adcy5	G	A	16: 35,124,004 (GRCm39)	V1228M	possibly damaging	Het
Ahi1	G	T	10: 20,893,812 (GRCm39)	V848F	probably damaging	Het
Akt3	A	T	1: 176,877,756 (GRCm39)	Y337*	probably null	Het
B4galt6	T	C	18: 20,822,386 (GRCm39)	E264G	probably benign	Het
Bpifb4	A	G	2: 153,799,658 (GRCm39)	T556A	probably damaging	Het
Bptf	A	T	11: 106,938,082 (GRCm39)	S64T	probably benign	Het
C3ar1	A	G	6: 122,826,817 (GRCm39)	S467P	probably benign	Het
Cables1	G	T	18: 12,072,882 (GRCm39)	S479I	probably null	Het
Cbl	T	C	9: 44,084,671 (GRCm39)	I155V	probably damaging	Het
Cdh16	T	C	8: 105,345,880 (GRCm39)	D297G	probably damaging	Het
Cpn2	A	T	16: 30,079,149 (GRCm39)	L184Q	probably damaging	Het
Ctso	T	A	3: 81,849,609 (GRCm39)	H109Q	probably benign	Het
Dnah8	G	A	17: 30,967,542 (GRCm39)	D2585N	probably benign	Het
Drc1	A	G	5: 30,512,490 (GRCm39)	E299G	probably damaging	Het
Elp6	A	G	9: 110,144,893 (GRCm39)	E150G	possibly damaging	Het
Fat3	C	T	9: 15,826,357 (GRCm39)	E4532K	possibly damaging	Het
Fbn2	A	G	18: 58,246,405 (GRCm39)	L499S	possibly damaging	Het
Fgf10	C	A	13: 118,925,821 (GRCm39)	A200D	probably damaging	Het
Fhad1	T	C	4: 141,691,915 (GRCm39)	E407G	probably damaging	Het
Hif1an	T	C	19: 44,556,891 (GRCm39)	V232A	probably damaging	Het
Ift172	T	A	5: 31,418,342 (GRCm39)	K1214*	probably null	Het
Il20ra	T	C	10: 19,626,542 (GRCm39)	Y189H	probably benign	Het
Isg20l2	T	A	3: 87,838,996 (GRCm39)	I69N	probably benign	Het
Kif11	A	G	19: 37,398,199 (GRCm39)	D675G	probably benign	Het
Klhdc7a	T	A	4: 139,693,786 (GRCm39)	D387V	possibly damaging	Het
Lrrc4	T	C	6: 28,831,292 (GRCm39)	N108D	probably damaging	Het
Ltbp2	T	A	12: 84,841,847 (GRCm39)	E944V	probably damaging	Het
Magi1	C	T	6: 93,685,158 (GRCm39)	S740N	probably damaging	Het
Med26	A	G	8: 73,249,677 (GRCm39)	I474T	probably damaging	Het
Mgst1	T	A	6: 138,124,770 (GRCm39)	M68K	probably damaging	Het
Myh7	G	A	14: 55,229,770 (GRCm39)	A91V	possibly damaging	Het
Nhlrc2	G	A	19: 56,580,216 (GRCm39)	V450I	probably benign	Het
Nup160	T	G	2: 90,530,800 (GRCm39)	F486C	probably damaging	Het
Nup50l	T	C	6: 96,141,953 (GRCm39)	T364A	probably benign	Het
Obscn	A	T	11: 58,994,152 (GRCm39)	Y1602N	probably damaging	Het
Or52ae9	T	A	7: 103,389,707 (GRCm39)	T247S	probably damaging	Het
Or5ak4	C	A	2: 85,162,142 (GRCm39)	M33I	probably benign	Het
Otogl	A	T	10: 107,689,164 (GRCm39)	Y955*	probably null	Het
Pi4ka	A	G	16: 17,194,846 (GRCm39)	L184P	possibly damaging	Het
Pianp	T	C	6: 124,976,347 (GRCm39)	V52A	probably benign	Het
Plekhh2	T	C	17: 84,899,013 (GRCm39)	Y997H	probably damaging	Het
Plekhm1	G	T	11: 103,278,069 (GRCm39)	S342R	possibly damaging	Het
Poglut2	C	T	1: 44,149,894 (GRCm39)		probably null	Het
Ppp4r4	T	A	12: 103,551,996 (GRCm39)	V81E	probably damaging	Het
Pramel52-ps	A	G	5: 94,529,268 (GRCm39)	T13A	probably benign	Het
Ptafr	A	G	4: 132,306,657 (GRCm39)	T16A	probably benign	Het
Ptpn23	A	T	9: 110,218,855 (GRCm39)	L445Q	probably damaging	Het
Rasa1	A	T	13: 85,374,717 (GRCm39)	F751L	possibly damaging	Het
Sap18	A	C	14: 58,039,474 (GRCm39)	D153A	probably damaging	Het
Slc38a11	C	T	2: 65,194,235 (GRCm39)	G10D	probably benign	Het
Snx32	T	C	19: 5,560,372 (GRCm39)	N10D	probably benign	Het
Sox6	T	C	7: 115,261,677 (GRCm39)	T180A	probably damaging	Het
Srrt	T	C	5: 137,301,192 (GRCm39)	K78R	probably damaging	Het
Syce3	T	C	15: 89,281,567 (GRCm39)	D24G	probably damaging	Het
Taok3	T	A	5: 117,344,732 (GRCm39)	I153N	probably damaging	Het
Tesk1	A	G	4: 43,445,991 (GRCm39)	Q308R	probably benign	Het
Tm7sf3	A	T	6: 146,511,471 (GRCm39)		probably null	Het
Tmbim6	T	C	15: 99,300,034 (GRCm39)	V50A	probably benign	Het
Tmem107	T	C	11: 68,961,837 (GRCm39)	V22A	probably damaging	Het
Ttc12	T	C	9: 49,364,646 (GRCm39)	I377V	probably benign	Het
Ufl1	T	A	4: 25,262,316 (GRCm39)	N310I	probably damaging	Het
Ush2a	C	A	1: 188,175,416 (GRCm39)	N1171K	possibly damaging	Het
Utrn	A	T	10: 12,574,831 (GRCm39)	V1032E	probably benign	Het

Other mutations in Cdk8

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01476:Cdk8	APN	5	146,231,973 (GRCm39)	splice site	probably null
R0506:Cdk8	UTSW	5	146,235,682 (GRCm39)	missense	probably damaging	1.00
R1132:Cdk8	UTSW	5	146,236,625 (GRCm39)	missense	probably benign	0.09
R1513:Cdk8	UTSW	5	146,233,188 (GRCm39)	missense	possibly damaging	0.93
R2231:Cdk8	UTSW	5	146,168,414 (GRCm39)	start gained	probably benign
R3692:Cdk8	UTSW	5	146,220,478 (GRCm39)	nonsense	probably null
R4157:Cdk8	UTSW	5	146,236,259 (GRCm39)	intron	probably benign
R4760:Cdk8	UTSW	5	146,229,476 (GRCm39)	missense	probably benign	0.15
R4804:Cdk8	UTSW	5	146,233,209 (GRCm39)	missense	probably damaging	1.00
R5119:Cdk8	UTSW	5	146,220,437 (GRCm39)	critical splice acceptor site	probably null
R6633:Cdk8	UTSW	5	146,235,656 (GRCm39)	nonsense	probably null
R7442:Cdk8	UTSW	5	146,229,579 (GRCm39)	critical splice donor site	probably null
R7936:Cdk8	UTSW	5	146,236,644 (GRCm39)	missense	possibly damaging	0.49
R8083:Cdk8	UTSW	5	146,205,100 (GRCm39)	missense	probably damaging	1.00
R8315:Cdk8	UTSW	5	146,205,061 (GRCm39)	missense	probably damaging	1.00
R9159:Cdk8	UTSW	5	146,168,549 (GRCm39)	missense	probably damaging	1.00
R9643:Cdk8	UTSW	5	146,235,664 (GRCm39)	missense	probably damaging	1.00
R9738:Cdk8	UTSW	5	146,236,539 (GRCm39)	missense	probably benign	0.08
Z1177:Cdk8	UTSW	5	146,238,447 (GRCm39)	missense	probably benign	0.00
Z1177:Cdk8	UTSW	5	146,236,606 (GRCm39)	missense	probably damaging	0.99
Z1177:Cdk8	UTSW	5	146,236,605 (GRCm39)	missense	probably damaging	0.96

Predicted Primers

PCR Primer
(F):5'- GGCCGTGGCATATCCTTGTATAC -3'
(R):5'- TCAAACACTTCTACTGCCTAGC -3'

Sequencing Primer
(F):5'- GTGCTACCACACCTAATTTGATG -3'
(R):5'- AACACTTCTACTGCCTAGCATTTTAG -3'

Posted On

2018-08-01