Incidental Mutation 'R8065:Dlat'
ID 619950
Institutional Source Beutler Lab
Gene Symbol Dlat
Ensembl Gene ENSMUSG00000000168
Gene Name dihydrolipoamide S-acetyltransferase
Synonyms 6332404G05Rik, PDC-E2
MMRRC Submission 067501-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R8065 (G1)
Quality Score 225.009
Status Validated
Chromosome 9
Chromosomal Location 50545933-50571080 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to T at 50569149 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Methionine to Lysine at position 218 (M218K)
Ref Sequence ENSEMBL: ENSMUSP00000034567 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000034566] [ENSMUST00000034567] [ENSMUST00000117646]
AlphaFold Q8BMF4
Predicted Effect probably benign
Transcript: ENSMUST00000034566
SMART Domains Protein: ENSMUSP00000034566
Gene: ENSMUSG00000032064

CH 22 151 5.48e-8 SMART
low complexity region 178 190 N/A INTRINSIC
low complexity region 237 254 N/A INTRINSIC
coiled coil region 306 338 N/A INTRINSIC
coiled coil region 359 492 N/A INTRINSIC
Pfam:DIX 627 706 1.1e-33 PFAM
Predicted Effect possibly damaging
Transcript: ENSMUST00000034567
AA Change: M218K

PolyPhen 2 Score 0.674 (Sensitivity: 0.86; Specificity: 0.92)
SMART Domains Protein: ENSMUSP00000034567
Gene: ENSMUSG00000000168
AA Change: M218K

Pfam:Biotin_lipoyl 91 164 4.3e-17 PFAM
low complexity region 183 210 N/A INTRINSIC
Pfam:Biotin_lipoyl 218 292 1.2e-17 PFAM
low complexity region 315 344 N/A INTRINSIC
Pfam:E3_binding 350 385 2.6e-18 PFAM
Pfam:2-oxoacid_dh 412 642 9.9e-82 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000117646
SMART Domains Protein: ENSMUSP00000112431
Gene: ENSMUSG00000032064

CH 22 125 1.25e-11 SMART
low complexity region 152 164 N/A INTRINSIC
low complexity region 211 228 N/A INTRINSIC
coiled coil region 280 312 N/A INTRINSIC
coiled coil region 333 466 N/A INTRINSIC
Pfam:DIX 600 682 5.1e-37 PFAM
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 100.0%
  • 10x: 99.7%
  • 20x: 99.1%
Validation Efficiency 100% (47/47)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes component E2 of the multi-enzyme pyruvate dehydrogenase complex (PDC). PDC resides in the inner mitochondrial membrane and catalyzes the conversion of pyruvate to acetyl coenzyme A. The protein product of this gene, dihydrolipoamide acetyltransferase, accepts acetyl groups formed by the oxidative decarboxylation of pyruvate and transfers them to coenzyme A. Dihydrolipoamide acetyltransferase is the 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 enventually leads to cirrhosis and liver failure. Mutations in this gene are also a cause of pyruvate dehydrogenase E2 deficiency which causes primary lactic acidosis in infancy and early childhood.[provided by RefSeq, Oct 2009]
Allele List at MGI
Other mutations in this stock
Total: 46 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Cap2 T C 13: 46,791,337 (GRCm39) V280A probably damaging Het
Cbx7 A T 15: 79,818,099 (GRCm39) V1D unknown Het
Chodl A T 16: 78,743,601 (GRCm39) L229F probably damaging Het
Depdc5 C A 5: 33,053,252 (GRCm39) N197K possibly damaging Het
Diaph3 A T 14: 87,274,931 (GRCm39) L175Q probably damaging Het
Dnai1 T A 4: 41,614,258 (GRCm39) D311E probably damaging Het
Dpp10 A G 1: 123,280,389 (GRCm39) S646P probably benign Het
Ebf1 G A 11: 44,511,374 (GRCm39) V90M probably benign Het
Efhd1 C T 1: 87,192,313 (GRCm39) P48S probably benign Het
Fbxl16 G A 17: 26,036,957 (GRCm39) V313I probably damaging Het
Flrt2 A G 12: 95,747,548 (GRCm39) T629A probably benign Het
Gpr87 T A 3: 59,087,308 (GRCm39) I66F probably damaging Het
Hmmr G A 11: 40,612,499 (GRCm39) S206F probably damaging Het
Hsd17b4 A T 18: 50,303,819 (GRCm39) I431F possibly damaging Het
Iba57 T C 11: 59,054,086 (GRCm39) probably benign Het
Ibtk A C 9: 85,602,916 (GRCm39) S696R probably benign Het
Igkv11-125 C A 6: 67,890,814 (GRCm39) T44N probably benign Het
Itih2 T A 2: 10,128,294 (GRCm39) I136F probably damaging Het
Itpr3 T A 17: 27,329,836 (GRCm39) D1543E probably benign Het
Ldlr T A 9: 21,649,241 (GRCm39) C339S probably damaging Het
Myh2 G A 11: 67,072,170 (GRCm39) E633K probably null Het
Myl10 G C 5: 136,726,825 (GRCm39) V70L probably benign Het
Mylk A T 16: 34,792,389 (GRCm39) E1570V probably benign Het
Myo15b G A 11: 115,778,769 (GRCm39) probably null Het
N4bp2 T A 5: 65,964,639 (GRCm39) L896H probably damaging Het
Naip2 A T 13: 100,325,730 (GRCm39) S59R probably damaging Het
Ndc1 T A 4: 107,247,595 (GRCm39) S468T probably benign Het
Ndst3 T C 3: 123,395,094 (GRCm39) N512S probably damaging Het
Or51b6 A G 7: 103,555,610 (GRCm39) probably benign Het
Or5w15 T A 2: 87,568,147 (GRCm39) I174F probably damaging Het
Plekhn1 T C 4: 156,312,697 (GRCm39) I54V possibly damaging Het
Polr3c T C 3: 96,622,968 (GRCm39) E350G probably null Het
Pskh1 T G 8: 106,656,487 (GRCm39) S388A possibly damaging Het
Pum1 T C 4: 130,478,836 (GRCm39) V486A possibly damaging Het
Rin2 T G 2: 145,702,977 (GRCm39) S558A probably damaging Het
Ripk4 A T 16: 97,564,737 (GRCm39) V58D probably damaging Het
Slc17a3 A G 13: 24,042,070 (GRCm39) R491G unknown Het
Smyd3 A G 1: 179,238,028 (GRCm39) M113T possibly damaging Het
Ssh2 A G 11: 77,332,811 (GRCm39) R431G probably damaging Het
Timm22 G A 11: 76,304,931 (GRCm39) D190N probably damaging Het
Ube2g1 G A 11: 72,568,591 (GRCm39) G103D probably benign Het
Zbtb5 A T 4: 44,994,972 (GRCm39) S137R probably benign Het
Zfp105 A G 9: 122,754,194 (GRCm39) T8A probably benign Het
Zfp286 A T 11: 62,644,345 (GRCm39) I192K unknown Het
Zfp942 T C 17: 22,149,391 (GRCm39) Y38C probably damaging Het
Zfpm1 T C 8: 123,062,323 (GRCm39) S461P probably benign Het
Other mutations in Dlat
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00570:Dlat APN 9 50,556,332 (GRCm39) splice site probably benign
IGL00870:Dlat APN 9 50,562,169 (GRCm39) missense probably damaging 1.00
R0440:Dlat UTSW 9 50,556,419 (GRCm39) splice site probably null
R0530:Dlat UTSW 9 50,548,869 (GRCm39) missense probably damaging 1.00
R0745:Dlat UTSW 9 50,565,008 (GRCm39) missense probably damaging 0.99
R1870:Dlat UTSW 9 50,548,874 (GRCm39) missense probably damaging 0.99
R3237:Dlat UTSW 9 50,549,331 (GRCm39) missense possibly damaging 0.81
R3696:Dlat UTSW 9 50,562,176 (GRCm39) missense possibly damaging 0.63
R3715:Dlat UTSW 9 50,549,354 (GRCm39) missense probably damaging 1.00
R3924:Dlat UTSW 9 50,569,490 (GRCm39) missense possibly damaging 0.55
R4016:Dlat UTSW 9 50,560,931 (GRCm39) critical splice donor site probably null
R4197:Dlat UTSW 9 50,547,826 (GRCm39) missense probably damaging 1.00
R4713:Dlat UTSW 9 50,555,781 (GRCm39) missense probably benign
R4789:Dlat UTSW 9 50,570,670 (GRCm39) missense probably benign
R5893:Dlat UTSW 9 50,555,439 (GRCm39) splice site probably benign
R6138:Dlat UTSW 9 50,556,417 (GRCm39) splice site probably null
R6778:Dlat UTSW 9 50,562,157 (GRCm39) missense probably damaging 1.00
R7010:Dlat UTSW 9 50,569,274 (GRCm39) missense probably damaging 1.00
R8677:Dlat UTSW 9 50,570,007 (GRCm39) missense probably damaging 0.99
R8724:Dlat UTSW 9 50,560,967 (GRCm39) missense probably damaging 1.00
R8725:Dlat UTSW 9 50,560,967 (GRCm39) missense probably damaging 1.00
R8742:Dlat UTSW 9 50,560,967 (GRCm39) missense probably damaging 1.00
R8745:Dlat UTSW 9 50,560,967 (GRCm39) missense probably damaging 1.00
R8753:Dlat UTSW 9 50,560,967 (GRCm39) missense probably damaging 1.00
R8754:Dlat UTSW 9 50,560,967 (GRCm39) missense probably damaging 1.00
R9111:Dlat UTSW 9 50,570,906 (GRCm39) unclassified probably benign
R9777:Dlat UTSW 9 50,562,208 (GRCm39) missense probably damaging 0.99
U15987:Dlat UTSW 9 50,556,417 (GRCm39) splice site probably null
Predicted Primers PCR Primer

Sequencing Primer
Posted On 2020-01-23