Mutagenetix > Incidental Mutation

Incidental Mutation 'R8753:Dlat'

663983

Institutional Source

Beutler Lab

Gene Symbol

Dlat

Ensembl Gene

ENSMUSG00000000168

Gene Name

dihydrolipoamide S-acetyltransferase

Synonyms

6332404G05Rik, PDC-E2

MMRRC Submission

068619-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R8753 (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: 99.7%
20x: 98.9%

Validation Efficiency

95% (59/62)

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: 62 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abca2	T	C	2: 25,332,706 (GRCm39)	Y1496H	probably damaging	Het
Acan	G	A	7: 78,748,516 (GRCm39)	E1096K	possibly damaging	Het
Adprhl1	T	C	8: 13,272,118 (GRCm39)	K1547E	possibly damaging	Het
Ampd2	C	A	3: 107,987,432 (GRCm39)	V134L	probably benign	Het
Arf4	T	A	14: 26,374,114 (GRCm39)		probably benign	Het
Boc	A	T	16: 44,320,775 (GRCm39)	M295K		Het
C2cd3	T	A	7: 100,049,024 (GRCm39)		probably null	Het
Calcrl	C	G	2: 84,178,659 (GRCm39)	G223A	probably benign	Het
Calcrl	C	A	2: 84,178,661 (GRCm39)	M222I	probably benign	Het
Ccdc88b	T	C	19: 6,833,213 (GRCm39)	E278G	probably damaging	Het
Ccz1	A	G	5: 143,925,050 (GRCm39)	C469R	probably benign	Het
Cdc40	C	T	10: 40,717,480 (GRCm39)	D404N	probably damaging	Het
Clpx	G	A	9: 65,223,958 (GRCm39)	G251S	probably damaging	Het
Col6a3	C	G	1: 90,695,328 (GRCm39)		probably benign	Het
Cpox	T	A	16: 58,498,391 (GRCm39)	M408K	probably damaging	Het
Crybb3	A	G	5: 113,226,247 (GRCm39)		probably null	Het
Cubn	A	T	2: 13,313,377 (GRCm39)	C3064*	probably null	Het
Cxcl3	CCTGCTGCTGCTGCTG	CCTGCTGCTGCTG	5: 90,934,071 (GRCm39)		probably benign	Het
Cyp4a31	A	T	4: 115,432,158 (GRCm39)	S432C	probably benign	Het
Ddias	A	T	7: 92,508,668 (GRCm39)	F416I	probably damaging	Het
Dnttip2	A	G	3: 122,074,398 (GRCm39)	T612A	probably damaging	Het
Fnip1	A	G	11: 54,400,867 (GRCm39)	T1089A	probably damaging	Het
Gm12117	A	T	11: 33,225,953 (GRCm39)	L128M	probably benign	Het
Gtf2h5	C	CA	17: 6,134,833 (GRCm39)		probably null	Het
Ibtk	T	C	9: 85,610,819 (GRCm39)	T285A	probably benign	Het
Ifi206	A	T	1: 173,301,223 (GRCm39)	N818K	unknown	Het
Itga10	T	G	3: 96,558,471 (GRCm39)	L305R	probably damaging	Het
Khnyn	T	C	14: 56,125,223 (GRCm39)	Y461H	possibly damaging	Het
Macroh2a2	T	C	10: 61,585,113 (GRCm39)	D177G	possibly damaging	Het
Mbtps1	T	C	8: 120,235,601 (GRCm39)	S1026G	possibly damaging	Het
Msantd4	A	G	9: 4,385,013 (GRCm39)	E246G	probably damaging	Het
N4bp1	T	C	8: 87,575,085 (GRCm39)	I737V	probably damaging	Het
Nav2	T	G	7: 49,102,320 (GRCm39)	S373A	probably benign	Het
Nbea	T	C	3: 55,534,329 (GRCm39)	Y2936C	probably damaging	Het
Nbeal1	A	T	1: 60,307,542 (GRCm39)	I1685F	probably damaging	Het
Nt5c3	C	G	6: 56,860,677 (GRCm39)	G293R	probably damaging	Het
Or4f14c	A	T	2: 111,940,802 (GRCm39)	V265E	probably benign	Het
Or52z1	T	A	7: 103,436,567 (GRCm39)	I306F	probably benign	Het
Pcnx2	A	T	8: 126,613,999 (GRCm39)	V484E	probably benign	Het
Pcsk5	C	T	19: 17,446,408 (GRCm39)	R1195Q	probably benign	Het
Perm1	TGCCTCTGAGCCTGACACGGCTTTGTCTACACCCGCCTCTGAGCCTGACACGGCTTTGTCTACACCCGCCTCTGAGCCTGACACGGCTTTGTCTACACCCGCCTCT	TGCCTCTGAGCCTGACACGGCTTTGTCTACACCCGCCTCTGAGCCTGACACGGCTTTGTCTACACCCGCCTCT	4: 156,302,525 (GRCm39)		probably benign	Het
Pitpnm3	A	G	11: 71,942,704 (GRCm39)	V861A	probably benign	Het
Pkd1	A	G	17: 24,793,176 (GRCm39)	Y1621C	probably damaging	Het
Polr3a	C	A	14: 24,513,702 (GRCm39)	E846*	probably null	Het
Polr3e	T	C	7: 120,539,540 (GRCm39)	V455A	possibly damaging	Het
Prr5l	C	T	2: 101,571,723 (GRCm39)	G118D	probably damaging	Het
Pygl	G	T	12: 70,242,400 (GRCm39)	N685K	probably damaging	Het
Rfx8	A	G	1: 39,757,600 (GRCm39)	V56A	probably damaging	Het
Sbf1	T	C	15: 89,179,662 (GRCm39)	D1341G	probably benign	Het
Selenon	T	C	4: 134,275,330 (GRCm39)	T123A	probably benign	Het
Slc23a1	T	G	18: 35,752,631 (GRCm39)	K549Q	probably benign	Het
Slc7a13	T	C	4: 19,841,443 (GRCm39)	F430S	probably damaging	Het
Smarcc2	G	A	10: 128,319,070 (GRCm39)	V707M	probably damaging	Het
St18	A	G	1: 6,916,015 (GRCm39)	S887G	probably damaging	Het
T2	T	C	17: 8,615,477 (GRCm39)		probably benign	Het
Tbc1d16	A	G	11: 119,101,492 (GRCm39)	L6P	probably damaging	Het
Tcf7l2	T	C	19: 55,920,195 (GRCm39)	L576P	possibly damaging	Het
Tnr	A	G	1: 159,677,936 (GRCm39)	D107G	probably benign	Het
Trpv1	G	T	11: 73,135,082 (GRCm39)	K426N	probably damaging	Het
Vmn1r15	A	T	6: 57,235,895 (GRCm39)	L254F	probably benign	Het
Vmn1r219	A	T	13: 23,347,191 (GRCm39)	I127F	probably damaging	Het
Zc3h14	A	T	12: 98,724,831 (GRCm39)	E164D	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
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
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
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'- GCCAGGAAAGTGCATAACATC -3'

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

Posted On

2021-03-08