Mutagenetix > Incidental Mutation

Incidental Mutation 'R8742:Dlat'

663296

Institutional Source

Beutler Lab

Gene Symbol

Dlat

Ensembl Gene

ENSMUSG00000000168

Gene Name

dihydrolipoamide S-acetyltransferase

Synonyms

6332404G05Rik, PDC-E2

MMRRC Submission

068587-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R8742 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

50545933-50571080 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

G to T at 50560967 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Alanine to Glutamic Acid at position 360 (A360E)

Ref Sequence

ENSEMBL: ENSMUSP00000034567 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000034567]

AlphaFold

Q8BMF4

Predicted Effect

probably damaging
Transcript: ENSMUST00000034567
AA Change: A360E

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000034567
Gene: ENSMUSG00000000168
AA Change: A360E

Domain	Start	End	E-Value	Type
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

Meta Mutation Damage Score

0.9511

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.3%
20x: 97.0%

Validation Efficiency

100% (55/55)

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: 58 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adgrb3	T	C	1: 25,265,835 (GRCm39)	I893V	probably benign	Het
Adhfe1	A	G	1: 9,630,401 (GRCm39)	I317V	probably benign	Het
Adnp2	A	G	18: 80,171,556 (GRCm39)	V951A	probably damaging	Het
Ankrd35	T	A	3: 96,586,502 (GRCm39)	H59Q	probably damaging	Het
Atg16l1	C	T	1: 87,694,620 (GRCm39)	T161I	probably damaging	Het
Axl	A	G	7: 25,463,861 (GRCm39)	V591A	probably damaging	Het
Cdc40	C	T	10: 40,717,480 (GRCm39)	D404N	probably damaging	Het
Cdcp3	A	G	7: 130,783,741 (GRCm39)	I45V	unknown	Het
Ceacam13	T	A	7: 17,743,934 (GRCm39)	S14T	probably damaging	Het
Cfh	A	T	1: 140,029,390 (GRCm39)	F986L	probably damaging	Het
Cfh	G	T	1: 140,064,469 (GRCm39)	T393K	probably damaging	Het
Clic1	A	G	17: 35,274,356 (GRCm39)	N179S	probably benign	Het
Col6a3	C	G	1: 90,695,328 (GRCm39)		probably benign	Het
Dst	T	A	1: 34,251,425 (GRCm39)	D2159E	probably benign	Het
Epn3	T	G	11: 94,386,921 (GRCm39)	T150P	probably damaging	Het
Fgr	T	C	4: 132,724,828 (GRCm39)	Y310H	probably damaging	Het
Filip1l	A	G	16: 57,391,593 (GRCm39)	Y727C	probably damaging	Het
Fis1	G	T	5: 136,982,365 (GRCm39)		probably benign	Het
G530012D18Rik	C	G	1: 85,504,935 (GRCm39)	D113E	unknown	Het
Gdf10	A	T	14: 33,654,426 (GRCm39)	H311L	probably benign	Het
Gphn	C	T	12: 78,659,766 (GRCm39)	R423C	probably damaging	Het
Gpr132	T	C	12: 112,819,517 (GRCm39)		probably benign	Het
Herc2	C	A	7: 55,744,143 (GRCm39)	T406K	probably benign	Het
Hpf1	T	C	8: 61,346,748 (GRCm39)	V21A	probably benign	Het
Ifitm6	A	G	7: 140,596,008 (GRCm39)	I75T	probably benign	Het
Itgax	A	T	7: 127,743,795 (GRCm39)	H852L	probably benign	Het
Klhl3	T	C	13: 58,159,021 (GRCm39)	Y546C	probably damaging	Het
Lbr	A	G	1: 181,644,571 (GRCm39)	L578P	possibly damaging	Het
Ltbp1	A	G	17: 75,617,217 (GRCm39)	Y734C	probably damaging	Het
Mapre2	C	A	18: 24,016,688 (GRCm39)	H281N	probably benign	Het
Mcm4	T	C	16: 15,443,430 (GRCm39)	D831G	possibly damaging	Het
Mlf1	G	A	3: 67,305,119 (GRCm39)	A207T	probably damaging	Het
Mslnl	A	T	17: 25,964,047 (GRCm39)	I459F	probably damaging	Het
Mtnr1a	A	G	8: 45,540,720 (GRCm39)	D227G	probably benign	Het
Ncapg	T	A	5: 45,851,216 (GRCm39)	L803Q	probably damaging	Het
Nr3c2	T	G	8: 77,635,210 (GRCm39)	S104A	probably damaging	Het
Or4k52	A	G	2: 111,610,910 (GRCm39)	I82V	probably benign	Het
Pard3	C	T	8: 128,050,592 (GRCm39)	A218V	possibly damaging	Het
Poteg	A	T	8: 27,984,957 (GRCm39)	N439Y	possibly damaging	Het
Pramel34	T	A	5: 93,785,935 (GRCm39)	D115V	probably damaging	Het
Ret	A	T	6: 118,155,484 (GRCm39)	L404Q	probably damaging	Het
Ripk4	A	T	16: 97,556,272 (GRCm39)	V157D	probably damaging	Het
Rsf1	CGGCGGCGGCGGCGGCGGCGGC	CGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC	7: 97,229,121 (GRCm39)		probably benign	Het
Serinc1	A	T	10: 57,395,895 (GRCm39)	N298K	probably benign	Het
Sh3pxd2a	G	A	19: 47,275,073 (GRCm39)	S230L	probably benign	Het
Shb	G	C	4: 45,458,319 (GRCm39)	R282G	probably benign	Het
Skint11	T	C	4: 114,051,922 (GRCm39)	I90T	probably damaging	Het
Slc36a4	A	G	9: 15,632,039 (GRCm39)	T72A	probably damaging	Het
Slc38a9	T	A	13: 112,865,818 (GRCm39)	I505K	probably damaging	Het
Sprr3	C	T	3: 92,364,307 (GRCm39)	R179H	possibly damaging	Het
Syne1	A	T	10: 5,058,661 (GRCm39)	I7284N	probably benign	Het
Timeless	A	T	10: 128,083,107 (GRCm39)	T648S	probably benign	Het
Trim44	A	G	2: 102,230,521 (GRCm39)	M170T	possibly damaging	Het
Trpm7	A	G	2: 126,667,469 (GRCm39)	F815L	probably damaging	Het
Uimc1	A	G	13: 55,240,971 (GRCm39)	L39S	possibly damaging	Het
Vmn2r13	T	C	5: 109,304,263 (GRCm39)	T723A	probably benign	Het
Vps11	A	G	9: 44,267,070 (GRCm39)		probably benign	Het
Zp3r	A	T	1: 130,511,230 (GRCm39)	C383S	probably damaging	Het

Other mutations in Dlat

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH 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
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
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'- AGAACACGGTGATGCTTGCC -3'
(R):5'- AGCCAGGAAAGTGCATAACATC -3'

Sequencing Primer
(F):5'- CTTCCGTGAAGGCAGCAAG -3'
(R):5'- CTTTTTTCCCAAAGGTGGC -3'

Posted On

2021-03-08