Incidental Mutation 'R6850:Pdhx'
ID 535579
Institutional Source Beutler Lab
Gene Symbol Pdhx
Ensembl Gene ENSMUSG00000010914
Gene Name pyruvate dehydrogenase complex, component X
Synonyms Pdx1
MMRRC Submission 044954-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R6850 (G1)
Quality Score 225.009
Status Validated
Chromosome 2
Chromosomal Location 102851420-102903858 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to C at 102871445 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Histidine to Arginine at position 195 (H195R)
Ref Sequence ENSEMBL: ENSMUSP00000106814 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000011058] [ENSMUST00000111183] [ENSMUST00000132449]
AlphaFold Q8BKZ9
Predicted Effect possibly damaging
Transcript: ENSMUST00000011058
AA Change: H195R

PolyPhen 2 Score 0.790 (Sensitivity: 0.85; Specificity: 0.93)
SMART Domains Protein: ENSMUSP00000011058
Gene: ENSMUSG00000010914
AA Change: H195R

DomainStartEndE-ValueType
low complexity region 13 28 N/A INTRINSIC
Pfam:Biotin_lipoyl 57 131 1.3e-21 PFAM
low complexity region 148 172 N/A INTRINSIC
Pfam:E3_binding 182 217 5e-9 PFAM
low complexity region 233 249 N/A INTRINSIC
Pfam:2-oxoacid_dh 272 501 8.4e-74 PFAM
Predicted Effect probably damaging
Transcript: ENSMUST00000111183
AA Change: H195R

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000106814
Gene: ENSMUSG00000010914
AA Change: H195R

DomainStartEndE-ValueType
low complexity region 13 28 N/A INTRINSIC
Pfam:Biotin_lipoyl 57 131 1.8e-21 PFAM
low complexity region 148 172 N/A INTRINSIC
Pfam:E3_binding 180 216 6.9e-12 PFAM
Predicted Effect possibly damaging
Transcript: ENSMUST00000132449
AA Change: H130R

PolyPhen 2 Score 0.950 (Sensitivity: 0.79; Specificity: 0.95)
SMART Domains Protein: ENSMUSP00000119172
Gene: ENSMUSG00000010914
AA Change: H130R

DomainStartEndE-ValueType
Pfam:Biotin_lipoyl 5 66 1.3e-14 PFAM
low complexity region 83 107 N/A INTRINSIC
Pfam:E3_binding 115 153 6.1e-14 PFAM
low complexity region 168 184 N/A INTRINSIC
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 99.9%
  • 10x: 99.6%
  • 20x: 98.7%
Validation Efficiency 98% (54/55)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The pyruvate dehydrogenase (PDH) complex is located in the mitochondrial matrix and catalyzes the conversion of pyruvate to acetyl coenzyme A. The PDH complex thereby links glycolysis to Krebs cycle. The PDH complex contains three catalytic subunits, E1, E2, and E3, two regulatory subunits, E1 kinase and E1 phosphatase, and a non-catalytic subunit, E3 binding protein (E3BP). This gene encodes the E3 binding protein subunit; also known as component X of the pyruvate dehydrogenase complex. This protein tethers E3 dimers to the E2 core of the PDH complex. Defects in this gene are a cause of pyruvate dehydrogenase deficiency which results in neurological dysfunction and lactic acidosis in infancy and early childhood. This protein is also a minor antigen for antimitochondrial antibodies. These autoantibodies are present in nearly 95% of patients with the autoimmune liver disease primary biliary cirrhosis (PBC). In PBC, activated T lymphocytes attack and destroy epithelial cells in the bile duct where this protein is abnormally distributed and overexpressed. PBC eventually leads to cirrhosis and liver failure. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Oct 2009]
Allele List at MGI
Other mutations in this stock
Total: 54 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Adgb T C 10: 10,270,318 (GRCm39) M927V probably benign Het
Agr2 A G 12: 36,045,558 (GRCm39) I15V probably benign Het
Alpk1 A G 3: 127,523,012 (GRCm39) I10T possibly damaging Het
Art5 A G 7: 101,747,302 (GRCm39) V159A possibly damaging Het
Asz1 G A 6: 18,108,942 (GRCm39) R32W probably benign Het
Atp8b1 A C 18: 64,689,923 (GRCm39) M603R possibly damaging Het
Cacna1s G A 1: 136,020,432 (GRCm39) R823Q probably benign Het
Car9 A G 4: 43,507,321 (GRCm39) E3G probably damaging Het
Cpne3 A T 4: 19,535,231 (GRCm39) I267N possibly damaging Het
Cyp2c65 T A 19: 39,057,535 (GRCm39) F57I probably benign Het
D430041D05Rik T C 2: 104,031,604 (GRCm39) K980R probably damaging Het
Dnhd1 G T 7: 105,369,137 (GRCm39) G4303W possibly damaging Het
Dnmt3a A G 12: 3,947,600 (GRCm39) N485D probably benign Het
Dusp4 A T 8: 35,283,651 (GRCm39) K166* probably null Het
Ect2 T C 3: 27,193,034 (GRCm39) D344G probably damaging Het
Eif2b1 T C 5: 124,717,069 (GRCm39) D3G probably benign Het
Ermp1 A G 19: 29,594,041 (GRCm39) Y710H probably damaging Het
Gar1 T C 3: 129,623,038 (GRCm39) N117S probably damaging Het
H2-T10 A G 17: 36,430,152 (GRCm39) L263P probably damaging Het
Iqcn A T 8: 71,163,425 (GRCm39) N873Y probably damaging Het
Itga7 A T 10: 128,781,385 (GRCm39) I621F probably damaging Het
Kcna3 A T 3: 106,944,475 (GRCm39) D246V probably damaging Het
Kctd12 C T 14: 103,219,414 (GRCm39) G155S probably benign Het
Lrtm1 T C 14: 28,749,407 (GRCm39) V256A probably benign Het
Mcf2l T C 8: 13,059,476 (GRCm39) F629L possibly damaging Het
Mphosph9 A G 5: 124,399,019 (GRCm39) F999L probably damaging Het
Mtres1 ACTGCACCACCT ACT 10: 43,408,721 (GRCm39) probably benign Het
Obscn C T 11: 58,958,950 (GRCm39) V3643M possibly damaging Het
Obscn C T 11: 58,892,955 (GRCm39) A6764T possibly damaging Het
Or4c102 T A 2: 88,422,650 (GRCm39) C167* probably null Het
Or8g18 T C 9: 39,149,271 (GRCm39) I150V probably benign Het
Pdilt A T 7: 119,086,182 (GRCm39) V511E probably damaging Het
Prima1 C T 12: 103,163,594 (GRCm39) D126N probably benign Het
Prrc2c TTGCTGCTGCTGCTGCTGCTGCTGCTGC TTGCTGCTGCTGCTGCTGCTGCTGC 1: 162,536,630 (GRCm39) probably benign Het
Prune2 C A 19: 17,099,552 (GRCm39) D1685E probably benign Het
Ptgs2 A T 1: 149,981,291 (GRCm39) I525F probably damaging Het
Rab11fip2 A T 19: 59,925,441 (GRCm39) F259I possibly damaging Het
Ranbp3l C A 15: 9,058,808 (GRCm39) D216E probably damaging Het
Scn5a A T 9: 119,330,815 (GRCm39) L1240Q possibly damaging Het
Sohlh2 A T 3: 55,099,707 (GRCm39) T160S probably benign Het
Sorbs1 G C 19: 40,365,244 (GRCm39) R180G probably benign Het
Spata31h1 A C 10: 82,128,888 (GRCm39) M1374R possibly damaging Het
Tank A G 2: 61,480,346 (GRCm39) E294G probably benign Het
Tars1 T A 15: 11,392,885 (GRCm39) Y187F probably benign Het
Tas2r144 T A 6: 42,192,857 (GRCm39) M199K possibly damaging Het
Tdrd3 T C 14: 87,695,515 (GRCm39) probably benign Het
Tecta T A 9: 42,255,134 (GRCm39) D1683V probably benign Het
Tln2 A G 9: 67,165,817 (GRCm39) I2098T probably damaging Het
Tmie A G 9: 110,695,980 (GRCm39) I137T possibly damaging Het
Trim45 T A 3: 100,830,541 (GRCm39) L105* probably null Het
Trpv3 G A 11: 73,182,519 (GRCm39) G568S probably damaging Het
Wdr75 A G 1: 45,853,758 (GRCm39) T390A probably benign Het
Wdr97 A G 15: 76,241,996 (GRCm39) Y763C probably damaging Het
Zfp35 G A 18: 24,135,839 (GRCm39) R61H possibly damaging Het
Other mutations in Pdhx
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL02147:Pdhx APN 2 102,860,686 (GRCm39) unclassified probably benign
IGL02450:Pdhx APN 2 102,872,594 (GRCm39) missense probably benign 0.00
R0152:Pdhx UTSW 2 102,858,625 (GRCm39) missense probably benign 0.04
R0317:Pdhx UTSW 2 102,858,625 (GRCm39) missense probably benign 0.04
R2351:Pdhx UTSW 2 102,854,562 (GRCm39) nonsense probably null
R3937:Pdhx UTSW 2 102,852,564 (GRCm39) missense probably damaging 1.00
R3950:Pdhx UTSW 2 102,865,586 (GRCm39) missense probably damaging 0.99
R4546:Pdhx UTSW 2 102,903,742 (GRCm39) missense probably null 0.99
R4677:Pdhx UTSW 2 102,903,811 (GRCm39) splice site probably null
R4744:Pdhx UTSW 2 102,872,641 (GRCm39) missense probably benign 0.01
R4996:Pdhx UTSW 2 102,860,657 (GRCm39) missense probably damaging 1.00
R5000:Pdhx UTSW 2 102,871,385 (GRCm39) splice site probably null
R5076:Pdhx UTSW 2 102,871,422 (GRCm39) missense probably damaging 0.99
R5682:Pdhx UTSW 2 102,865,685 (GRCm39) missense probably benign 0.00
R6246:Pdhx UTSW 2 102,877,137 (GRCm39) missense probably damaging 1.00
R7141:Pdhx UTSW 2 102,903,659 (GRCm39) missense probably benign 0.21
R7219:Pdhx UTSW 2 102,858,760 (GRCm39) missense probably benign 0.01
R7460:Pdhx UTSW 2 102,877,124 (GRCm39) missense probably damaging 1.00
R7552:Pdhx UTSW 2 102,877,099 (GRCm39) missense probably benign 0.01
R8325:Pdhx UTSW 2 102,872,597 (GRCm39) missense probably benign 0.08
R9163:Pdhx UTSW 2 102,852,561 (GRCm39) missense probably damaging 1.00
Predicted Primers PCR Primer
(F):5'- GGATTACGCAAGCGCACATAC -3'
(R):5'- CTGAGACTCATTTTAGCTTCAGTG -3'

Sequencing Primer
(F):5'- GGGGCATATAATCTTCGCAAGTCC -3'
(R):5'- GCTTCAGTGTTAAGAATTCATTTTCC -3'
Posted On 2018-09-12