Incidental Mutation 'R7221:Pdp1'
ID 561804
Institutional Source Beutler Lab
Gene Symbol Pdp1
Ensembl Gene ENSMUSG00000049225
Gene Name pyruvate dehydrogenase phosphatase catalytic subunit 1
Synonyms LOC381511, Ppm2c
MMRRC Submission 045293-MU
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # R7221 (G1)
Quality Score 225.009
Status Validated
Chromosome 4
Chromosomal Location 11958183-11966450 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to C at 11961004 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Threonine to Alanine at position 455 (T455A)
Ref Sequence ENSEMBL: ENSMUSP00000103936 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000056050] [ENSMUST00000095144] [ENSMUST00000108297] [ENSMUST00000108299] [ENSMUST00000108301] [ENSMUST00000108302]
AlphaFold Q3UV70
Predicted Effect probably damaging
Transcript: ENSMUST00000056050
AA Change: T396A

PolyPhen 2 Score 0.989 (Sensitivity: 0.72; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000050521
Gene: ENSMUSG00000049225
AA Change: T396A

DomainStartEndE-ValueType
PP2Cc 99 523 3.36e-97 SMART
PP2C_SIG 177 525 2.77e0 SMART
Predicted Effect probably damaging
Transcript: ENSMUST00000095144
AA Change: T421A

PolyPhen 2 Score 0.961 (Sensitivity: 0.78; Specificity: 0.95)
SMART Domains Protein: ENSMUSP00000092766
Gene: ENSMUSG00000049225
AA Change: T421A

DomainStartEndE-ValueType
PP2Cc 124 548 3.36e-97 SMART
PP2C_SIG 202 550 2.77e0 SMART
Predicted Effect probably damaging
Transcript: ENSMUST00000108297
AA Change: T396A

PolyPhen 2 Score 0.989 (Sensitivity: 0.72; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000103932
Gene: ENSMUSG00000049225
AA Change: T396A

DomainStartEndE-ValueType
PP2Cc 99 523 3.36e-97 SMART
PP2C_SIG 177 525 2.77e0 SMART
Predicted Effect probably damaging
Transcript: ENSMUST00000108299
AA Change: T421A

PolyPhen 2 Score 0.961 (Sensitivity: 0.78; Specificity: 0.95)
SMART Domains Protein: ENSMUSP00000103934
Gene: ENSMUSG00000049225
AA Change: T421A

DomainStartEndE-ValueType
PP2Cc 124 548 3.36e-97 SMART
PP2C_SIG 202 550 2.77e0 SMART
Predicted Effect probably damaging
Transcript: ENSMUST00000108301
AA Change: T455A

PolyPhen 2 Score 0.989 (Sensitivity: 0.72; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000103936
Gene: ENSMUSG00000049225
AA Change: T455A

DomainStartEndE-ValueType
low complexity region 11 18 N/A INTRINSIC
PP2Cc 158 582 3.36e-97 SMART
PP2C_SIG 236 584 2.77e0 SMART
Predicted Effect probably damaging
Transcript: ENSMUST00000108302
AA Change: T436A

PolyPhen 2 Score 0.981 (Sensitivity: 0.75; Specificity: 0.96)
SMART Domains Protein: ENSMUSP00000103937
Gene: ENSMUSG00000049225
AA Change: T436A

DomainStartEndE-ValueType
PP2Cc 139 563 3.36e-97 SMART
PP2C_SIG 217 565 2.77e0 SMART
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 99.9%
  • 10x: 99.7%
  • 20x: 98.9%
Validation Efficiency 100% (77/77)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] Pyruvate dehydrogenase (E1) is one of the three components (E1, E2, and E3) of the large pyruvate dehydrogenase complex. Pyruvate dehydrogenase kinases catalyze phosphorylation of serine residues of E1 to inactivate the E1 component and inhibit the complex. Pyruvate dehydrogenase phosphatases catalyze the dephosphorylation and activation of the E1 component to reverse the effects of pyruvate dehydrogenase kinases. Pyruvate dehydrogenase phosphatase is a heterodimer consisting of catalytic and regulatory subunits. Two catalytic subunits have been reported; one is predominantly expressed in skeletal muscle and another one is is much more abundant in the liver. The catalytic subunit, encoded by this gene, is the former, and belongs to the protein phosphatase 2C (PP2C) superfamily. Along with the pyruvate dehydrogenase complex and pyruvate dehydrogenase kinases, this enzyme is located in the mitochondrial matrix. Mutation in this gene causes pyruvate dehydrogenase phosphatase deficiency. Multiple alternatively spliced transcript variants encoding different isoforms have been identified.[provided by RefSeq, Jun 2009]
Allele List at MGI
Other mutations in this stock
Total: 78 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Aadacl2fm1 A G 3: 59,836,354 (GRCm39) probably benign Het
Abr A C 11: 76,313,987 (GRCm39) M720R probably benign Het
Acad10 G A 5: 121,768,273 (GRCm39) T761M probably damaging Het
Agxt G T 1: 93,065,623 (GRCm39) G164V possibly damaging Het
Ankar C T 1: 72,689,390 (GRCm39) G1247D probably damaging Het
Bptf A C 11: 106,945,658 (GRCm39) L2527R probably damaging Het
Brinp2 T C 1: 158,094,117 (GRCm39) H195R possibly damaging Het
Cacna2d4 G T 6: 119,213,624 (GRCm39) R14S probably benign Het
Cep126 A T 9: 8,100,988 (GRCm39) C515* probably null Het
Chia1 A T 3: 106,039,236 (GRCm39) N442I probably damaging Het
Clasp2 A G 9: 113,681,825 (GRCm39) D327G probably damaging Het
Cnbd2 T C 2: 156,215,581 (GRCm39) F519L probably benign Het
Cntrl T A 2: 35,041,869 (GRCm39) F1214I possibly damaging Het
Cul9 A T 17: 46,839,491 (GRCm39) M829K probably damaging Het
Cyp4b1 T C 4: 115,493,175 (GRCm39) Q223R possibly damaging Het
Defb37 A T 8: 19,040,988 (GRCm39) M1K probably null Het
Dnah7c A T 1: 46,494,937 (GRCm39) Q55L possibly damaging Het
Efcab3 A G 11: 104,791,432 (GRCm39) N2882S probably benign Het
Eif2b4 A T 5: 31,345,131 (GRCm39) D463E possibly damaging Het
Elapor1 T G 3: 108,382,317 (GRCm39) D232A possibly damaging Het
Elovl1 C T 4: 118,288,811 (GRCm39) H167Y probably damaging Het
Emb T A 13: 117,404,013 (GRCm39) L255Q probably damaging Het
Eogt T C 6: 97,089,685 (GRCm39) Y465C probably damaging Het
Erc2 A G 14: 27,375,115 (GRCm39) H111R probably damaging Het
Fam234b T C 6: 135,205,529 (GRCm39) F498S probably damaging Het
Fgfr3 GAGGCTGGCAGCGTGTACGCAGGC GAGGC 5: 33,890,092 (GRCm39) probably null Het
Flrt3 T A 2: 140,503,090 (GRCm39) E179D probably damaging Het
Fndc3a T C 14: 72,793,597 (GRCm39) R993G probably benign Het
Gm14325 T C 2: 177,476,403 (GRCm39) T14A probably damaging Het
Gm5464 T A 14: 67,106,681 (GRCm39) V106D unknown Het
Gpatch11 T A 17: 79,149,546 (GRCm39) I182N possibly damaging Het
Grm6 A G 11: 50,753,870 (GRCm39) R725G probably damaging Het
Hap1 A T 11: 100,239,655 (GRCm39) M588K probably benign Het
Icam2 A G 11: 106,273,268 (GRCm39) F15L probably benign Het
Ints8 A G 4: 11,225,613 (GRCm39) M648T probably benign Het
Ipo11 A T 13: 107,029,065 (GRCm39) L296Q probably damaging Het
Kirrel1 G A 3: 86,993,704 (GRCm39) Q518* probably null Het
Krt18 G T 15: 101,937,967 (GRCm39) D155Y possibly damaging Het
Lctl A T 9: 64,026,217 (GRCm39) K91* probably null Het
Marf1 C A 16: 13,960,349 (GRCm39) R565L probably damaging Het
Med13 A T 11: 86,178,921 (GRCm39) D1458E probably benign Het
Mroh8 T A 2: 157,071,837 (GRCm39) Y556F probably benign Het
Muc16 C T 9: 18,553,495 (GRCm39) G4266D probably benign Het
Nsrp1 A T 11: 76,939,249 (GRCm39) F182I probably damaging Het
Obox3 A T 7: 15,359,983 (GRCm39) Y229N probably benign Het
Or11h7 A T 14: 50,891,528 (GRCm39) Y278F probably damaging Het
Or2b2 T C 13: 21,887,272 (GRCm39) S34P probably damaging Het
Or2b4 A G 17: 38,116,452 (GRCm39) K139E probably benign Het
Or4a74 T C 2: 89,440,272 (GRCm39) Y58C probably damaging Het
Or4c108 A G 2: 88,803,497 (GRCm39) V246A probably damaging Het
Or4p22 T A 2: 88,317,973 (GRCm39) V299D probably damaging Het
Or8d1 A G 9: 38,766,538 (GRCm39) Y60C probably damaging Het
Pabpc2 T A 18: 39,906,963 (GRCm39) V76D possibly damaging Het
Parp9 T C 16: 35,774,071 (GRCm39) W348R probably benign Het
Phactr2 A C 10: 13,122,783 (GRCm39) D446E possibly damaging Het
Pi4kb T C 3: 94,901,500 (GRCm39) L389P probably damaging Het
Pla2g4f C T 2: 120,131,476 (GRCm39) R749H probably benign Het
Plec A G 15: 76,059,974 (GRCm39) V3321A probably damaging Het
Plod2 T C 9: 92,466,580 (GRCm39) V180A probably damaging Het
Plppr5 A G 3: 117,414,618 (GRCm39) I80V probably damaging Het
Potefam3d T G 8: 69,975,316 (GRCm39) D50A probably benign Het
Rubcn T C 16: 32,687,293 (GRCm39) probably null Het
Sacs T C 14: 61,446,255 (GRCm39) V2767A probably damaging Het
Selenbp2 C G 3: 94,611,133 (GRCm39) Y414* probably null Het
Slc45a4 A T 15: 73,458,259 (GRCm39) M430K probably benign Het
Smg1 A G 7: 117,782,020 (GRCm39) L1145P possibly damaging Het
Spns2 A G 11: 72,347,742 (GRCm39) V316A probably benign Het
Srl T A 16: 4,300,811 (GRCm39) E753D probably damaging Het
Thada T C 17: 84,771,794 (GRCm39) T23A possibly damaging Het
Tmem231 T C 8: 112,660,308 (GRCm39) T31A probably benign Het
Tpr C T 1: 150,321,929 (GRCm39) T2321M possibly damaging Het
Ttn T A 2: 76,772,195 (GRCm39) N2615I unknown Het
Vmn1r41 A G 6: 89,724,034 (GRCm39) I192V probably benign Het
Vmn2r83 A T 10: 79,316,001 (GRCm39) T466S probably benign Het
Vnn1 A G 10: 23,770,952 (GRCm39) D60G probably benign Het
Wiz G A 17: 32,578,139 (GRCm39) P449S probably benign Het
Zic1 A G 9: 91,246,785 (GRCm39) S96P probably damaging Het
Zw10 T A 9: 48,981,012 (GRCm39) S471T probably benign Het
Other mutations in Pdp1
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL02243:Pdp1 APN 4 11,961,873 (GRCm39) missense probably benign 0.20
IGL02643:Pdp1 APN 4 11,962,062 (GRCm39) missense probably benign
R1931:Pdp1 UTSW 4 11,962,074 (GRCm39) missense probably benign 0.01
R2162:Pdp1 UTSW 4 11,961,123 (GRCm39) missense probably damaging 0.98
R2418:Pdp1 UTSW 4 11,961,838 (GRCm39) missense probably damaging 0.98
R3843:Pdp1 UTSW 4 11,961,961 (GRCm39) missense probably benign 0.00
R5699:Pdp1 UTSW 4 11,960,907 (GRCm39) missense possibly damaging 0.79
R6479:Pdp1 UTSW 4 11,961,327 (GRCm39) missense probably damaging 1.00
R7263:Pdp1 UTSW 4 11,960,821 (GRCm39) missense possibly damaging 0.82
R8483:Pdp1 UTSW 4 11,961,982 (GRCm39) missense probably benign
R9184:Pdp1 UTSW 4 11,962,143 (GRCm39) missense possibly damaging 0.80
R9712:Pdp1 UTSW 4 11,961,607 (GRCm39) missense probably benign 0.41
Z1177:Pdp1 UTSW 4 11,961,639 (GRCm39) missense possibly damaging 0.67
Predicted Primers PCR Primer
(F):5'- TGTCCCAGAGTCACCTTGTACC -3'
(R):5'- CGTCTGAAACTGGAACACCC -3'

Sequencing Primer
(F):5'- TGTACCCACCAACTGCTATTG -3'
(R):5'- GCCAAGAGCGTGGTAAAGC -3'
Posted On 2019-06-26