Mutagenetix > Incidental Mutation

Incidental Mutation 'B5639:Pdk2'

549

Institutional Source

Beutler Lab

Gene Symbol

Pdk2

Ensembl Gene

ENSMUSG00000038967

Gene Name

pyruvate dehydrogenase kinase, isoenzyme 2

Synonyms

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

B5639 of strain 3d

Quality Score

Status

Validated

Chromosome

Chromosomal Location

94917084-94932180 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 94923324 bp (GRCm39)

Zygosity

Homozygous

Amino Acid Change

Aspartic acid to Glycine at position 100 (D100G)

Ref Sequence

ENSEMBL: ENSMUSP00000041447 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000038431]

AlphaFold

Q9JK42

Predicted Effect

possibly damaging
Transcript: ENSMUST00000038431
AA Change: D100G

PolyPhen 2 Score 0.570 (Sensitivity: 0.88; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000041447
Gene: ENSMUSG00000038967
AA Change: D100G

Domain	Start	End	E-Value	Type
Pfam:BCDHK_Adom3	30	192	3.8e-52	PFAM
HATPase_c	240	364	9.32e-14	SMART

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000126730

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000129262

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000138855

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000141712

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000155857

Meta Mutation Damage Score

0.1005

Coding Region Coverage

1x: 89.7%
3x: 78.3%

Het Detection Efficiency

55.9%

Validation Efficiency

83% (206/248)

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 pyruvate dehydrogenase kinase family. The encoded protein phosphorylates pyruvate dehydrogenase, down-regulating the activity of the mitochondrial pyruvate dehydrogenase complex. Overexpression of this gene may play a role in both cancer and diabetes. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]
PHENOTYPE: Mice homozygous for a knock-out allele exhibit decreased muscle contractile force. [provided by MGI curators]

Allele List at MGI

none

Other mutations in this stock

Total: 15 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Dnmt1	G	A	9: 20,819,264 (GRCm39)		probably benign	Het
Eno1	A	G	4: 150,329,569 (GRCm39)		probably benign	Het
Ercc8	G	A	13: 108,297,257 (GRCm39)	G56R	probably damaging	Homo
Fam237b	C	T	5: 5,624,060 (GRCm39)		probably benign	Homo
Idh1	A	G	1: 65,204,257 (GRCm39)		probably null	Homo
Incenp	G	A	19: 9,871,182 (GRCm39)	T149I	unknown	Het
Or5d16	G	A	2: 87,773,942 (GRCm39)	S10F	probably benign	Het
Or5k17	A	T	16: 58,746,889 (GRCm39)	I15K	probably benign	Homo
Prss56	T	C	1: 87,114,892 (GRCm39)	L465P	probably benign	Homo
Slc10a3	G	A	X: 73,413,145 (GRCm39)	P416L	probably damaging	Homo
Syne2	C	A	12: 75,976,564 (GRCm39)	T1243K	probably benign	Het
Vwf	T	C	6: 125,619,947 (GRCm39)	Y1542H	probably damaging	Homo
Zc3h13	G	A	14: 75,553,479 (GRCm39)	R302Q	probably damaging	Het
Zfhx4	G	T	3: 5,468,235 (GRCm39)	G2798W	probably damaging	Homo
Zfp667	A	G	7: 6,293,544 (GRCm39)	T15A	probably damaging	Het

Other mutations in Pdk2

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00786:Pdk2	APN	11	94,922,761 (GRCm39)	missense	probably benign
IGL01489:Pdk2	APN	11	94,922,848 (GRCm39)	critical splice acceptor site	probably null
IGL01538:Pdk2	APN	11	94,918,111 (GRCm39)	missense	probably damaging	1.00
IGL02057:Pdk2	APN	11	94,919,324 (GRCm39)	missense	probably benign	0.00
IGL02439:Pdk2	APN	11	94,930,323 (GRCm39)	unclassified	probably benign
IGL02539:Pdk2	APN	11	94,923,321 (GRCm39)	missense	probably benign	0.05
IGL02551:Pdk2	APN	11	94,919,412 (GRCm39)	missense	probably benign	0.01
R0063:Pdk2	UTSW	11	94,923,306 (GRCm39)	missense	probably benign
R0063:Pdk2	UTSW	11	94,923,306 (GRCm39)	missense	probably benign
R0864:Pdk2	UTSW	11	94,918,759 (GRCm39)	missense	probably damaging	1.00
R1435:Pdk2	UTSW	11	94,922,721 (GRCm39)	missense	probably damaging	1.00
R1704:Pdk2	UTSW	11	94,919,376 (GRCm39)	missense	possibly damaging	0.75
R2114:Pdk2	UTSW	11	94,918,088 (GRCm39)	missense	probably damaging	1.00
R2566:Pdk2	UTSW	11	94,918,028 (GRCm39)	splice site	probably null
R3613:Pdk2	UTSW	11	94,918,072 (GRCm39)	missense	probably benign	0.39
R4259:Pdk2	UTSW	11	94,931,970 (GRCm39)	missense	probably benign	0.17
R5051:Pdk2	UTSW	11	94,919,598 (GRCm39)	missense	probably benign	0.29
R5055:Pdk2	UTSW	11	94,930,242 (GRCm39)	missense	probably benign	0.18
R5457:Pdk2	UTSW	11	94,919,408 (GRCm39)	missense	probably damaging	0.98
R5512:Pdk2	UTSW	11	94,930,292 (GRCm39)	missense	probably damaging	1.00
R5570:Pdk2	UTSW	11	94,920,826 (GRCm39)	missense	probably damaging	0.98
R5687:Pdk2	UTSW	11	94,919,851 (GRCm39)	unclassified	probably benign
R6328:Pdk2	UTSW	11	94,930,228 (GRCm39)	missense	possibly damaging	0.72
R6675:Pdk2	UTSW	11	94,919,568 (GRCm39)	missense	probably benign	0.00
R7658:Pdk2	UTSW	11	94,919,791 (GRCm39)	missense	probably damaging	1.00
R8436:Pdk2	UTSW	11	94,930,259 (GRCm39)	missense	probably damaging	1.00
R8809:Pdk2	UTSW	11	94,923,339 (GRCm39)	missense	probably damaging	1.00
R9260:Pdk2	UTSW	11	94,930,260 (GRCm39)	missense	probably damaging	1.00
Z1176:Pdk2	UTSW	11	94,918,744 (GRCm39)	missense	probably damaging	0.97

Nature of Mutation

DNA sequencing using the SOLiD technique identified an A to G transition at position 414 of the Pdk2 transcript, in exon 3 of 11 total exons (NM_0133667). Multiple transcripts are annotated in the Vega and Ensembl databases. The mutation causes an aspartic acid to glycine change at amino acid 100 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (see trace files for B5639).

Protein Function and Prediction

The 407 amino acid Pdk2 protein is one of four isozymes of pyruvate dehydrogenase kinase (PDK). Pyruvate dehydrogenase functions in a mitochondrial multienzyme complex to catalyze the oxidative decarboxylation of pyruvate to acetyl-CoA, a reaction that links glycolysis and the Krebs cycle. PDK inhibits the pyruvate dehydrogenase complex by phosphorylation of the E1 alpha subunit, thus contributing to the regulation of glucose metabolism (see Pdk1, Uniprot Q8BFP9).

The mutation is predicted to be benign by the PolyPhen-2 program.

Posted On

2010-11-23