Incidental Mutation 'B5639:Pdk2'
ID 549
Institutional Source Beutler Lab
Gene Symbol Pdk2
Ensembl Gene ENSMUSG00000038967
Gene Name pyruvate dehydrogenase kinase, isoenzyme 2
Synonyms
Accession Numbers

Genbank: NM_133667

Is this an essential gene? Non essential (E-score: 0.000) question?
Stock # B5639 of strain 3d
Quality Score
Status Validated
Chromosome 11
Chromosomal Location 95026258-95041354 bp(-) (GRCm38)
Type of Mutation missense
DNA Base Change (assembly) T to C at 95032498 bp (GRCm38)
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

DomainStartEndE-ValueType
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 question?
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
GeneRefVarChr/LocMutationPredicted EffectZygosity
Dnmt1 G A 9: 20,907,968 probably benign Het
Eno1 A G 4: 150,245,112 probably benign Het
Ercc8 G A 13: 108,160,723 G56R probably damaging Homo
Gm8773 C T 5: 5,574,060 probably benign Homo
Idh1 A G 1: 65,165,098 probably null Homo
Incenp G A 19: 9,893,818 T149I unknown Het
Olfr1155 G A 2: 87,943,598 S10F probably benign Het
Olfr181 A T 16: 58,926,526 I15K probably benign Homo
Prss56 T C 1: 87,187,170 L465P probably benign Homo
Slc10a3 G A X: 74,369,539 P416L probably damaging Homo
Syne2 C A 12: 75,929,790 T1243K probably benign Het
Vwf T C 6: 125,642,984 Y1542H probably damaging Homo
Zc3h13 G A 14: 75,316,039 R302Q probably damaging Het
Zfhx4 G T 3: 5,403,175 G2798W probably damaging Homo
Zfp667 A G 7: 6,290,545 T15A probably damaging Het
Other mutations in Pdk2
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00786:Pdk2 APN 11 95031935 missense probably benign
IGL01489:Pdk2 APN 11 95032022 critical splice acceptor site probably null
IGL01538:Pdk2 APN 11 95027285 missense probably damaging 1.00
IGL02057:Pdk2 APN 11 95028498 missense probably benign 0.00
IGL02439:Pdk2 APN 11 95039497 unclassified probably benign
IGL02539:Pdk2 APN 11 95032495 missense probably benign 0.05
IGL02551:Pdk2 APN 11 95028586 missense probably benign 0.01
R0063:Pdk2 UTSW 11 95032480 missense probably benign
R0063:Pdk2 UTSW 11 95032480 missense probably benign
R0864:Pdk2 UTSW 11 95027933 missense probably damaging 1.00
R1435:Pdk2 UTSW 11 95031895 missense probably damaging 1.00
R1704:Pdk2 UTSW 11 95028550 missense possibly damaging 0.75
R2114:Pdk2 UTSW 11 95027262 missense probably damaging 1.00
R2566:Pdk2 UTSW 11 95027202 splice site probably null
R3613:Pdk2 UTSW 11 95027246 missense probably benign 0.39
R4259:Pdk2 UTSW 11 95041144 missense probably benign 0.17
R5051:Pdk2 UTSW 11 95028772 missense probably benign 0.29
R5055:Pdk2 UTSW 11 95039416 missense probably benign 0.18
R5457:Pdk2 UTSW 11 95028582 missense probably damaging 0.98
R5512:Pdk2 UTSW 11 95039466 missense probably damaging 1.00
R5570:Pdk2 UTSW 11 95030000 missense probably damaging 0.98
R5687:Pdk2 UTSW 11 95029025 unclassified probably benign
R6328:Pdk2 UTSW 11 95039402 missense possibly damaging 0.72
R6675:Pdk2 UTSW 11 95028742 missense probably benign 0.00
R7658:Pdk2 UTSW 11 95028965 missense probably damaging 1.00
R8436:Pdk2 UTSW 11 95039433 missense probably damaging 1.00
R8809:Pdk2 UTSW 11 95032513 missense probably damaging 1.00
R9260:Pdk2 UTSW 11 95039434 missense probably damaging 1.00
Z1176:Pdk2 UTSW 11 95027918 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