Incidental Mutation 'R0530:Dlat'
| ID |
49111 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Dlat
|
| Ensembl Gene |
ENSMUSG00000000168 |
| Gene Name |
dihydrolipoamide S-acetyltransferase |
| Synonyms |
6332404G05Rik, PDC-E2 |
| MMRRC Submission |
038722-MU
|
| Accession Numbers |
|
| Essential gene? |
Essential
(E-score: 1.000)
|
| Stock # |
R0530 (G1)
|
| Quality Score |
178 |
|
Status
|
Validated
|
| Chromosome |
9 |
| Chromosomal Location |
50545933-50571080 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
G to T
at 50548869 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Asparagine to Lysine
at position 562
(N562K)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000034567
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000034567]
|
| AlphaFold |
Q8BMF4 |
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000034567
AA Change: N562K
PolyPhen 2
Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
|
| SMART Domains |
Protein: ENSMUSP00000034567
Gene: ENSMUSG00000000168
AA Change: N562K
| 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 |
0.6467 |
| Coding Region Coverage |
- 1x: 99.6%
- 3x: 98.7%
- 10x: 96.6%
- 20x: 93.1%
|
| Validation Efficiency |
96% (51/53) |
| 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: 50 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Abcg3 |
A |
G |
5: 105,083,920 (GRCm39) |
W617R |
probably damaging |
Het |
| Adam34l |
A |
T |
8: 44,079,568 (GRCm39) |
C219S |
probably benign |
Het |
| Cep83 |
A |
T |
10: 94,555,450 (GRCm39) |
|
probably benign |
Het |
| Ces1e |
G |
A |
8: 93,946,149 (GRCm39) |
|
probably benign |
Het |
| Ckap2 |
A |
G |
8: 22,665,988 (GRCm39) |
|
probably benign |
Het |
| Clip1 |
C |
A |
5: 123,778,594 (GRCm39) |
R443L |
probably damaging |
Het |
| Clmp |
A |
G |
9: 40,672,302 (GRCm39) |
D44G |
probably benign |
Het |
| Cntnap2 |
G |
A |
6: 46,506,839 (GRCm39) |
Q304* |
probably null |
Het |
| Cst7 |
A |
T |
2: 150,412,435 (GRCm39) |
|
probably benign |
Het |
| Dclk3 |
A |
T |
9: 111,311,789 (GRCm39) |
Y677F |
probably damaging |
Het |
| Elmod1 |
A |
T |
9: 53,833,260 (GRCm39) |
Y182N |
probably damaging |
Het |
| Fzd10 |
T |
C |
5: 128,679,077 (GRCm39) |
F266L |
probably damaging |
Het |
| Gm8258 |
A |
G |
5: 104,923,952 (GRCm39) |
|
noncoding transcript |
Het |
| Gm9742 |
T |
A |
13: 8,080,041 (GRCm39) |
|
noncoding transcript |
Het |
| Hdlbp |
T |
C |
1: 93,358,039 (GRCm39) |
|
probably benign |
Het |
| Itga8 |
A |
G |
2: 12,196,627 (GRCm39) |
S597P |
probably damaging |
Het |
| Kndc1 |
A |
T |
7: 139,481,153 (GRCm39) |
I80F |
probably damaging |
Het |
| Ktn1 |
A |
G |
14: 47,970,700 (GRCm39) |
N1192S |
probably benign |
Het |
| Ldha |
G |
A |
7: 46,503,417 (GRCm39) |
V270M |
probably damaging |
Het |
| Lyst |
T |
C |
13: 13,931,891 (GRCm39) |
|
probably benign |
Het |
| Map3k9 |
A |
T |
12: 81,769,256 (GRCm39) |
F954I |
probably benign |
Het |
| Mroh2b |
A |
G |
15: 4,963,877 (GRCm39) |
N823S |
probably damaging |
Het |
| Mycbp2 |
A |
T |
14: 103,419,895 (GRCm39) |
N2480K |
probably damaging |
Het |
| Nat1 |
A |
G |
8: 67,943,977 (GRCm39) |
K121E |
probably benign |
Het |
| Neurl1b |
T |
A |
17: 26,660,519 (GRCm39) |
|
probably null |
Het |
| Nnt |
C |
A |
13: 119,531,257 (GRCm39) |
L163F |
probably damaging |
Het |
| Or10v5 |
A |
G |
19: 11,805,556 (GRCm39) |
V278A |
probably benign |
Het |
| Otog |
A |
G |
7: 45,947,668 (GRCm39) |
T2274A |
probably damaging |
Het |
| Pde4b |
G |
A |
4: 102,459,848 (GRCm39) |
R561Q |
probably damaging |
Het |
| Pitpnm2 |
A |
G |
5: 124,269,264 (GRCm39) |
F453L |
probably damaging |
Het |
| Pms1 |
T |
C |
1: 53,235,972 (GRCm39) |
|
probably null |
Het |
| Pot1a |
A |
G |
6: 25,771,540 (GRCm39) |
V227A |
possibly damaging |
Het |
| Prdx6b |
A |
G |
2: 80,123,659 (GRCm39) |
N156S |
probably damaging |
Het |
| Ptpn9 |
A |
G |
9: 56,968,417 (GRCm39) |
S586G |
probably benign |
Het |
| Serpina6 |
A |
T |
12: 103,618,053 (GRCm39) |
N253K |
probably damaging |
Het |
| Slc12a2 |
T |
A |
18: 58,052,608 (GRCm39) |
V809D |
possibly damaging |
Het |
| Slc2a8 |
C |
T |
2: 32,863,696 (GRCm39) |
A449T |
probably benign |
Het |
| Slc6a6 |
A |
G |
6: 91,701,939 (GRCm39) |
I116V |
probably null |
Het |
| Synj2 |
T |
A |
17: 6,058,380 (GRCm39) |
S58R |
possibly damaging |
Het |
| Tafa3 |
T |
C |
3: 104,679,487 (GRCm39) |
|
probably benign |
Het |
| Tktl2 |
T |
C |
8: 66,965,831 (GRCm39) |
V463A |
probably damaging |
Het |
| Uchl5 |
T |
C |
1: 143,670,082 (GRCm39) |
V105A |
possibly damaging |
Het |
| Usp9y |
T |
C |
Y: 1,333,600 (GRCm39) |
|
probably benign |
Het |
| Vmn1r200 |
T |
C |
13: 22,579,667 (GRCm39) |
S148P |
probably damaging |
Het |
| Vmn2r50 |
A |
T |
7: 9,781,644 (GRCm39) |
M367K |
possibly damaging |
Het |
| Vps13a |
T |
C |
19: 16,632,570 (GRCm39) |
|
probably benign |
Het |
| Wdr26 |
A |
T |
1: 181,013,635 (GRCm39) |
|
probably null |
Het |
| Wdr87-ps |
A |
G |
7: 29,229,545 (GRCm39) |
|
noncoding transcript |
Het |
| Ythdc2 |
T |
A |
18: 44,983,465 (GRCm39) |
M544K |
probably damaging |
Het |
| Zpld2 |
A |
G |
4: 133,930,221 (GRCm39) |
I28T |
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 |
|
|
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 |
|
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'- GCATTTACTGATGCCACTAAAAGCCAC -3'
(R):5'- TTTAGCCTCCAAAGCGAGAGAGGG -3'
Sequencing Primer
(F):5'- GCCACATGTAAAATCTGTAATGACAC -3'
(R):5'- TCATAATTGCATGGGAAAGCC -3'
|
| Posted On |
2013-06-12 |
Incidental Mutation