Mutagenetix > Incidental Mutation

Incidental Mutation 'R3715:Dlat'

259856

Institutional Source

Beutler Lab

Gene Symbol

Dlat

Ensembl Gene

ENSMUSG00000000168

Gene Name

dihydrolipoamide S-acetyltransferase

Synonyms

6332404G05Rik, PDC-E2

MMRRC Submission

040708-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R3715 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

50545933-50571080 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 50549354 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Valine to Alanine at position 510 (V510A)

Ref Sequence

ENSEMBL: ENSMUSP00000034567 (fasta)

Gene Model

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

AlphaFold

Q8BMF4

Predicted Effect

probably damaging
Transcript: ENSMUST00000034567
AA Change: V510A

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

SMART Domains

Protein: ENSMUSP00000034567
Gene: ENSMUSG00000000168
AA Change: V510A

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

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000125919

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000126933

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000132455

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000142275

Meta Mutation Damage Score

0.7527

Coding Region Coverage

1x: 99.1%
3x: 98.5%
10x: 97.0%
20x: 94.2%

Validation Efficiency

98% (52/53)

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: 54 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2310079G19Rik	T	C	16: 88,424,081 (GRCm39)	M137V	probably benign	Het
9930111J21Rik1	T	C	11: 48,838,803 (GRCm39)	T595A	possibly damaging	Het
Aaas	T	C	15: 102,248,771 (GRCm39)	I236V	probably benign	Het
Abcd4	C	T	12: 84,658,533 (GRCm39)	M223I	probably benign	Het
Adamtsl1	T	A	4: 86,135,213 (GRCm39)	I246N	probably benign	Het
Ak9	A	G	10: 41,233,508 (GRCm39)	D582G	probably damaging	Het
Aqr	A	G	2: 113,949,150 (GRCm39)		probably benign	Het
Bmal2	A	G	6: 146,724,187 (GRCm39)	K360E	probably damaging	Het
Cacna2d3	T	C	14: 29,068,880 (GRCm39)	I282M	probably damaging	Het
Cers3	G	T	7: 66,435,823 (GRCm39)	A261S	probably benign	Het
Dexi	A	T	16: 10,360,553 (GRCm39)	M1K	probably null	Het
Eaf1	T	C	14: 31,224,402 (GRCm39)	I173T	possibly damaging	Het
Elavl3	G	T	9: 21,929,895 (GRCm39)	D336E	probably benign	Het
Epm2a	A	G	10: 11,219,420 (GRCm39)	Y69C	probably benign	Het
Fam168a	A	G	7: 100,473,432 (GRCm39)	N107S	probably damaging	Het
Fam43b	G	C	4: 138,122,409 (GRCm39)	R304G	probably benign	Het
Fras1	T	C	5: 96,793,829 (GRCm39)		probably null	Het
Fscn3	C	T	6: 28,428,091 (GRCm39)	T26I	possibly damaging	Het
Glt8d2	C	A	10: 82,488,571 (GRCm39)	A300S	probably benign	Het
Hcn4	G	A	9: 58,751,319 (GRCm39)	R315H	unknown	Het
Lipk	A	G	19: 34,017,829 (GRCm39)	N289S	probably damaging	Het
Lyg1	G	T	1: 37,989,759 (GRCm39)	R43S	probably damaging	Het
Marchf6	A	G	15: 31,465,405 (GRCm39)	L833P	probably benign	Het
Mc4r	T	A	18: 66,992,892 (GRCm39)	N74Y	probably damaging	Het
Med17	G	A	9: 15,175,062 (GRCm39)		probably benign	Het
Mink1	G	T	11: 70,499,776 (GRCm39)	R773L	possibly damaging	Het
Myo15a	A	T	11: 60,370,057 (GRCm39)	E939V	possibly damaging	Het
Ndst4	A	T	3: 125,355,154 (GRCm39)	H354L	possibly damaging	Het
Or2t26	T	C	11: 49,039,642 (GRCm39)	L186P	probably damaging	Het
Or4c15	A	G	2: 88,759,757 (GRCm39)	W301R	probably benign	Het
Or4p22	C	A	2: 88,317,787 (GRCm39)	T237N	probably damaging	Het
Otof	T	A	5: 30,534,215 (GRCm39)	K1397*	probably null	Het
Rangap1	C	A	15: 81,594,661 (GRCm39)	E389D	probably benign	Het
Rbfox2	A	G	15: 76,983,451 (GRCm39)	I270T	probably damaging	Het
Rnf217	G	T	10: 31,410,728 (GRCm39)	C322*	probably null	Het
Sbk1	A	G	7: 125,889,183 (GRCm39)	T50A	probably benign	Het
Shmt1	T	C	11: 60,688,402 (GRCm39)	T248A	probably damaging	Het
Smim29	G	A	17: 27,785,043 (GRCm39)		probably benign	Het
Sox30	C	T	11: 45,875,619 (GRCm39)	T457I	probably damaging	Het
Stox2	T	A	8: 47,866,187 (GRCm39)	I52F	possibly damaging	Het
Syncrip	A	T	9: 88,361,738 (GRCm39)		probably benign	Het
Tars3	G	A	7: 65,338,700 (GRCm39)		probably null	Het
Tdrd12	T	C	7: 35,204,405 (GRCm39)	E235G	probably benign	Het
Tmem82	A	T	4: 141,344,945 (GRCm39)		probably null	Het
Tro	T	C	X: 149,437,230 (GRCm39)	T476A	probably damaging	Het
Ttn	G	A	2: 76,561,363 (GRCm39)	P27302S	probably damaging	Het
Ttn	C	T	2: 76,571,610 (GRCm39)	V26428I	probably damaging	Het
Usp53	T	C	3: 122,742,968 (GRCm39)	E656G	probably benign	Het
Vmn2r100	A	G	17: 19,752,272 (GRCm39)	R772G	probably damaging	Het
Xkr5	T	C	8: 18,984,474 (GRCm39)	E190G	probably benign	Het
Zfp236	A	G	18: 82,651,095 (GRCm39)		probably benign	Het
Zfr2	T	G	10: 81,081,913 (GRCm39)	V493G	probably benign	Het
Zp2	A	T	7: 119,741,057 (GRCm39)	S156T	possibly damaging	Het
Zswim5	A	G	4: 116,819,755 (GRCm39)	T387A	probably benign	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
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
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'- TACAAGCCATACAGCCGAGG -3'
(R):5'- TCTTTTGGCAAGGCAGAGGATG -3'

Sequencing Primer
(F):5'- GAGGAACAGCACCCTACCTGG -3'
(R):5'- TCTGAGTGAGGATGCCAGATC -3'

Posted On

2015-01-23