Incidental Mutation 'R4789:Dlat'
ID 367325
Institutional Source Beutler Lab
Gene Symbol Dlat
Ensembl Gene ENSMUSG00000000168
Gene Name dihydrolipoamide S-acetyltransferase
Synonyms 6332404G05Rik, PDC-E2
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R4789 (G1)
Quality Score 201
Status Not validated
Chromosome 9
Chromosomal Location 50545933-50571080 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to T at 50570670 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Cysteine to Serine at position 33 (C33S)
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

DomainStartEndE-ValueType
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 probably benign
Transcript: ENSMUST00000034567
AA Change: C33S

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
SMART Domains Protein: ENSMUSP00000034567
Gene: ENSMUSG00000000168
AA Change: C33S

DomainStartEndE-ValueType
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

DomainStartEndE-ValueType
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
Predicted Effect noncoding transcript
Transcript: ENSMUST00000141919
Coding Region Coverage
  • 1x: 98.8%
  • 3x: 98.4%
  • 10x: 96.9%
  • 20x: 94.4%
Validation Efficiency
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: 70 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
1110004F10Rik C A 7: 115,692,757 (GRCm39) D20E probably benign Het
Abcb9 T A 5: 124,216,853 (GRCm39) M455L probably benign Het
Add2 G A 6: 86,095,752 (GRCm39) V475M probably benign Het
Apoh T A 11: 108,300,064 (GRCm39) Y238N probably damaging Het
Arpp21 A G 9: 111,896,360 (GRCm39) S681P probably benign Het
Atp1a3 A C 7: 24,698,389 (GRCm39) F149C probably damaging Het
B9d1 A G 11: 61,397,186 (GRCm39) D27G probably benign Het
Bfar T A 16: 13,503,001 (GRCm39) M1K probably null Het
Bok T C 1: 93,616,963 (GRCm39) V103A probably damaging Het
Brca1 A C 11: 101,414,758 (GRCm39) H1125Q probably benign Het
Card9 T A 2: 26,247,632 (GRCm39) M218L probably damaging Het
Cers1 T C 8: 70,776,018 (GRCm39) V303A probably damaging Het
Col6a5 T C 9: 105,814,534 (GRCm39) I493V unknown Het
Coro7 T C 16: 4,446,085 (GRCm39) Y880C probably damaging Het
Cyp2b19 T C 7: 26,463,801 (GRCm39) Y318H probably benign Het
Dennd3 T A 15: 73,394,131 (GRCm39) L52Q probably damaging Het
Dmxl2 T A 9: 54,287,099 (GRCm39) Q2646L probably benign Het
Dnah3 T C 7: 119,610,295 (GRCm39) N1703D probably damaging Het
Dock10 T A 1: 80,518,998 (GRCm39) H1241L probably damaging Het
Fbxl17 T G 17: 63,794,910 (GRCm39) I391L probably benign Het
Fdxacb1 A G 9: 50,681,418 (GRCm39) D113G possibly damaging Het
Flii A G 11: 60,605,919 (GRCm39) S1185P probably benign Het
Gm14496 A T 2: 181,637,577 (GRCm39) Q217L possibly damaging Het
Heatr9 A T 11: 83,410,018 (GRCm39) D74E probably benign Het
Heca C A 10: 17,783,895 (GRCm39) E91* probably null Het
Ikzf4 T G 10: 128,468,575 (GRCm39) T635P probably benign Het
Kif17 C T 4: 138,008,688 (GRCm39) P382S probably damaging Het
Kmt5b T C 19: 3,865,330 (GRCm39) V775A probably benign Het
Mapk8ip2 T A 15: 89,343,241 (GRCm39) F661Y probably damaging Het
Mapkap1 A G 2: 34,423,859 (GRCm39) E111G possibly damaging Het
Med9 T A 11: 59,839,266 (GRCm39) N58K probably benign Het
Mid2 T A X: 139,578,981 (GRCm39) Y61N probably damaging Het
Mief1 T A 15: 80,132,080 (GRCm39) Y50* probably null Het
Mios T C 6: 8,235,429 (GRCm39) M859T probably benign Het
Muc5ac G T 7: 141,352,619 (GRCm39) C702F possibly damaging Het
Nkiras1 T C 14: 18,276,935 (GRCm38) probably benign Het
Or11i1 A C 3: 106,729,608 (GRCm39) I89R possibly damaging Het
Or11i1 T A 3: 106,729,624 (GRCm39) M84L possibly damaging Het
Or56a3b T G 7: 104,771,520 (GRCm39) H285Q probably null Het
Or5ae2 T A 7: 84,506,509 (GRCm39) C311S probably benign Het
Pcsk5 C T 19: 17,410,963 (GRCm39) V1810M probably benign Het
Pex1 T C 5: 3,680,270 (GRCm39) V964A probably damaging Het
Pgm2l1 A T 7: 99,916,794 (GRCm39) M471L probably benign Het
Pkd1l2 T C 8: 117,738,314 (GRCm39) T2182A probably damaging Het
Plscr1l1 G A 9: 92,233,084 (GRCm39) C69Y probably damaging Het
Polr1b T A 2: 128,951,257 (GRCm39) I290K probably benign Het
Prkg1 T A 19: 31,563,045 (GRCm39) M119L probably damaging Het
Rbl1 A G 2: 157,019,275 (GRCm39) V490A probably benign Het
Shtn1 G C 19: 59,039,305 (GRCm39) R45G probably damaging Het
Slc10a6 T A 5: 103,776,848 (GRCm39) Y84F probably benign Het
Slc25a23 T C 17: 57,366,597 (GRCm39) D26G probably damaging Het
Slc41a2 T C 10: 83,152,320 (GRCm39) K52E probably damaging Het
Slc4a5 T C 6: 83,247,951 (GRCm39) F501L probably benign Het
Slfn5 T A 11: 82,847,226 (GRCm39) M37K probably benign Het
Sptbn1 A C 11: 30,067,759 (GRCm39) F1818L probably benign Het
Taf3 T C 2: 9,956,770 (GRCm39) T466A probably damaging Het
Thbs2 C T 17: 14,891,750 (GRCm39) G929D probably damaging Het
Tmc3 A T 7: 83,271,746 (GRCm39) D995V probably damaging Het
Tmem262 T C 19: 6,130,452 (GRCm39) F59L possibly damaging Het
Triobp A G 15: 78,875,228 (GRCm39) D137G probably damaging Het
Tspear T C 10: 77,702,199 (GRCm39) F211L possibly damaging Het
Ttn A T 2: 76,728,670 (GRCm39) probably benign Het
Ugt2b5 T A 5: 87,287,550 (GRCm39) M206L probably benign Het
Ush1g A T 11: 115,209,466 (GRCm39) S243T probably damaging Het
Usp19 A T 9: 108,370,433 (GRCm39) T86S possibly damaging Het
Wdhd1 A G 14: 47,506,149 (GRCm39) V255A probably benign Het
Wdr11 G A 7: 129,220,394 (GRCm39) W594* probably null Het
Wnk3 T A X: 149,993,933 (GRCm39) Y331* probably null Het
Zfp429 A T 13: 67,538,523 (GRCm39) I307K probably benign Het
Zkscan14 T A 5: 145,132,444 (GRCm39) K362N probably damaging 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
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
R8065:Dlat UTSW 9 50,569,149 (GRCm39) missense possibly damaging 0.67
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
(F):5'- TCACTCACCTTCTGATGCGG -3'
(R):5'- AGCCGCTTTTACGACACTGC -3'

Sequencing Primer
(F):5'- ACCTTCTGATGCGGAGGGAG -3'
(R):5'- TTTACGACACTGCGCGAC -3'
Posted On 2015-12-29