Incidental Mutation 'R1115:Acly'
| ID |
97194 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Acly
|
| Ensembl Gene |
ENSMUSG00000020917 |
| Gene Name |
ATP citrate lyase |
| Synonyms |
A730098H14Rik |
| MMRRC Submission |
039188-MU
|
| Accession Numbers |
|
| Essential gene? |
Essential
(E-score: 1.000)
|
| Stock # |
R1115 (G1)
|
| Quality Score |
225 |
|
Status
|
Validated
|
| Chromosome |
11 |
| Chromosomal Location |
100367179-100418826 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
C to A
at 100370081 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Valine to Phenylalanine
at position 994
(V994F)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000103012
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000007131]
[ENSMUST00000107389]
[ENSMUST00000165111]
|
| AlphaFold |
Q91V92 |
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000007131
AA Change: V984F
PolyPhen 2
Score 0.982 (Sensitivity: 0.75; Specificity: 0.96)
|
| SMART Domains |
Protein: ENSMUSP00000007131
Gene: ENSMUSG00000020917
AA Change: V984F
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:ATP-grasp_2
|
6 |
207 |
2.4e-8 |
PFAM |
|
low complexity region
|
441 |
457 |
N/A |
INTRINSIC |
|
low complexity region
|
465 |
475 |
N/A |
INTRINSIC |
|
Pfam:CoA_binding
|
484 |
590 |
3.9e-14 |
PFAM |
|
Pfam:Ligase_CoA
|
650 |
775 |
1.2e-16 |
PFAM |
|
Pfam:Citrate_synt
|
868 |
1076 |
4.8e-22 |
PFAM |
|
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000107389
AA Change: V994F
PolyPhen 2
Score 0.994 (Sensitivity: 0.69; Specificity: 0.97)
|
| SMART Domains |
Protein: ENSMUSP00000103012
Gene: ENSMUSG00000020917
AA Change: V994F
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:Citrate_bind
|
244 |
421 |
1.7e-94 |
PFAM |
|
low complexity region
|
441 |
457 |
N/A |
INTRINSIC |
|
low complexity region
|
465 |
475 |
N/A |
INTRINSIC |
|
Pfam:CoA_binding
|
494 |
600 |
6.6e-15 |
PFAM |
|
Pfam:Ligase_CoA
|
660 |
785 |
2.1e-16 |
PFAM |
|
Pfam:Citrate_synt
|
879 |
1085 |
2e-21 |
PFAM |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000152969
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000154151
|
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000165111
AA Change: V984F
PolyPhen 2
Score 0.982 (Sensitivity: 0.75; Specificity: 0.96)
|
| SMART Domains |
Protein: ENSMUSP00000127632
Gene: ENSMUSG00000020917
AA Change: V984F
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:ATP-grasp_2
|
6 |
207 |
2.4e-8 |
PFAM |
|
low complexity region
|
441 |
457 |
N/A |
INTRINSIC |
|
low complexity region
|
465 |
475 |
N/A |
INTRINSIC |
|
Pfam:CoA_binding
|
484 |
590 |
3.9e-14 |
PFAM |
|
Pfam:Ligase_CoA
|
650 |
775 |
1.2e-16 |
PFAM |
|
Pfam:Citrate_synt
|
868 |
1076 |
4.8e-22 |
PFAM |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000195956
|
| Meta Mutation Damage Score |
0.8254 |
| Coding Region Coverage |
- 1x: 99.0%
- 3x: 98.2%
- 10x: 95.9%
- 20x: 91.8%
|
| Validation Efficiency |
100% (34/34) |
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] ATP citrate lyase is the primary enzyme responsible for the synthesis of cytosolic acetyl-CoA in many tissues. The enzyme is a tetramer (relative molecular weight approximately 440,000) of apparently identical subunits. It catalyzes the formation of acetyl-CoA and oxaloacetate from citrate and CoA with a concomitant hydrolysis of ATP to ADP and phosphate. The product, acetyl-CoA, serves several important biosynthetic pathways, including lipogenesis and cholesterogenesis. In nervous tissue, ATP citrate-lyase may be involved in the biosynthesis of acetylcholine. Multiple transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Dec 2014]
PHENOTYPE: Homozygous null mutation of this gene results in embryonic lethality. Heterozygous mutants display no obvious abnormalities. Mice homozygous for a transgenic gene disruption exhibit embryonic lethality at E7. [provided by MGI curators]
|
| Allele List at MGI |
All alleles(37) : Targeted(1) Gene trapped(35) Transgenic(1)
|
| Other mutations in this stock |
Total: 34 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Arfgap3 |
T |
C |
15: 83,214,741 (GRCm39) |
T182A |
probably benign |
Het |
| Bcl2l14 |
T |
C |
6: 134,409,102 (GRCm39) |
|
probably benign |
Het |
| Cabin1 |
T |
C |
10: 75,553,511 (GRCm39) |
M1183V |
possibly damaging |
Het |
| Ccr7 |
A |
T |
11: 99,036,103 (GRCm39) |
I273K |
possibly damaging |
Het |
| Cd40 |
A |
G |
2: 164,912,681 (GRCm39) |
M211V |
possibly damaging |
Het |
| Coro2b |
T |
G |
9: 62,338,609 (GRCm39) |
E208A |
probably damaging |
Het |
| Dennd5a |
A |
C |
7: 109,517,968 (GRCm39) |
M556R |
probably damaging |
Het |
| Efcab2 |
A |
T |
1: 178,265,062 (GRCm39) |
|
probably benign |
Het |
| Fastkd2 |
T |
C |
1: 63,787,114 (GRCm39) |
|
probably benign |
Het |
| Fbxw8 |
A |
C |
5: 118,215,636 (GRCm39) |
|
probably benign |
Het |
| Fhip1a |
T |
C |
3: 85,629,802 (GRCm39) |
E263G |
probably benign |
Het |
| Frem1 |
T |
C |
4: 82,939,007 (GRCm39) |
D25G |
probably benign |
Het |
| Gtf3c3 |
C |
T |
1: 54,456,937 (GRCm39) |
A488T |
probably damaging |
Het |
| Ift52 |
A |
G |
2: 162,871,702 (GRCm39) |
K178R |
probably benign |
Het |
| Kit |
T |
C |
5: 75,810,192 (GRCm39) |
|
probably benign |
Het |
| Map1a |
T |
C |
2: 121,137,859 (GRCm39) |
|
probably null |
Het |
| Mxra7 |
G |
T |
11: 116,701,696 (GRCm39) |
|
probably benign |
Het |
| Myt1 |
C |
A |
2: 181,453,024 (GRCm39) |
S7* |
probably null |
Het |
| Nphs1 |
C |
T |
7: 30,180,803 (GRCm39) |
|
probably benign |
Het |
| Or10h28 |
C |
T |
17: 33,487,940 (GRCm39) |
R81* |
probably null |
Het |
| Or1l8 |
C |
A |
2: 36,817,514 (GRCm39) |
G204V |
possibly damaging |
Het |
| Osgin2 |
A |
T |
4: 15,998,085 (GRCm39) |
D512E |
possibly damaging |
Het |
| Pde4b |
T |
A |
4: 102,399,352 (GRCm39) |
|
probably benign |
Het |
| Rasef |
G |
T |
4: 73,666,841 (GRCm39) |
T146K |
possibly damaging |
Het |
| Ren1 |
T |
A |
1: 133,284,256 (GRCm39) |
V207D |
probably damaging |
Het |
| S100a8 |
A |
G |
3: 90,577,180 (GRCm39) |
D59G |
probably damaging |
Het |
| Sdcbp |
G |
A |
4: 6,377,143 (GRCm39) |
|
probably null |
Het |
| Sdk2 |
C |
T |
11: 113,729,472 (GRCm39) |
|
silent |
Het |
| Slamf7 |
A |
T |
1: 171,466,751 (GRCm39) |
D151E |
probably benign |
Het |
| Slco1b2 |
A |
G |
6: 141,628,980 (GRCm39) |
M561V |
probably benign |
Het |
| Sned1 |
G |
A |
1: 93,209,376 (GRCm39) |
V830M |
possibly damaging |
Het |
| Stard9 |
T |
C |
2: 120,523,331 (GRCm39) |
I662T |
probably benign |
Het |
| Vwf |
T |
A |
6: 125,632,028 (GRCm39) |
V20D |
unknown |
Het |
| Znhit6 |
G |
T |
3: 145,300,440 (GRCm39) |
|
probably null |
Het |
|
| Other mutations in Acly |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL01336:Acly
|
APN |
11 |
100,386,736 (GRCm39) |
missense |
probably benign |
0.00 |
|
IGL01661:Acly
|
APN |
11 |
100,405,168 (GRCm39) |
splice site |
probably benign |
|
|
IGL02349:Acly
|
APN |
11 |
100,410,505 (GRCm39) |
missense |
probably benign |
0.01 |
|
IGL02792:Acly
|
APN |
11 |
100,369,236 (GRCm39) |
missense |
probably damaging |
0.97 |
|
IGL03026:Acly
|
APN |
11 |
100,410,516 (GRCm39) |
missense |
possibly damaging |
0.94 |
|
IGL03144:Acly
|
APN |
11 |
100,405,909 (GRCm39) |
missense |
possibly damaging |
0.84 |
|
IGL03230:Acly
|
APN |
11 |
100,384,885 (GRCm39) |
missense |
probably damaging |
0.99 |
|
IGL03266:Acly
|
APN |
11 |
100,374,578 (GRCm39) |
missense |
probably damaging |
1.00 |
|
Coyote
|
UTSW |
11 |
100,370,081 (GRCm39) |
missense |
probably damaging |
0.99 |
|
lupine
|
UTSW |
11 |
100,406,731 (GRCm39) |
missense |
probably damaging |
1.00 |
|
P0014:Acly
|
UTSW |
11 |
100,375,430 (GRCm39) |
missense |
probably benign |
0.03 |
|
R0195:Acly
|
UTSW |
11 |
100,403,800 (GRCm39) |
missense |
possibly damaging |
0.56 |
|
R0319:Acly
|
UTSW |
11 |
100,395,808 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0598:Acly
|
UTSW |
11 |
100,369,216 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1201:Acly
|
UTSW |
11 |
100,384,761 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1498:Acly
|
UTSW |
11 |
100,374,627 (GRCm39) |
missense |
probably benign |
0.27 |
|
R1593:Acly
|
UTSW |
11 |
100,372,581 (GRCm39) |
missense |
possibly damaging |
0.74 |
|
R1804:Acly
|
UTSW |
11 |
100,406,731 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1817:Acly
|
UTSW |
11 |
100,386,717 (GRCm39) |
missense |
probably benign |
0.00 |
|
R1980:Acly
|
UTSW |
11 |
100,386,702 (GRCm39) |
missense |
possibly damaging |
0.87 |
|
R1997:Acly
|
UTSW |
11 |
100,409,977 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R2125:Acly
|
UTSW |
11 |
100,414,322 (GRCm39) |
missense |
probably benign |
0.01 |
|
R3001:Acly
|
UTSW |
11 |
100,395,053 (GRCm39) |
missense |
possibly damaging |
0.91 |
|
R3002:Acly
|
UTSW |
11 |
100,395,053 (GRCm39) |
missense |
possibly damaging |
0.91 |
|
R3003:Acly
|
UTSW |
11 |
100,395,053 (GRCm39) |
missense |
possibly damaging |
0.91 |
|
R5194:Acly
|
UTSW |
11 |
100,414,372 (GRCm39) |
missense |
probably benign |
|
|
R5509:Acly
|
UTSW |
11 |
100,405,805 (GRCm39) |
missense |
probably damaging |
0.97 |
|
R5594:Acly
|
UTSW |
11 |
100,412,946 (GRCm39) |
splice site |
probably null |
|
|
R6077:Acly
|
UTSW |
11 |
100,410,583 (GRCm39) |
missense |
probably benign |
|
|
R6310:Acly
|
UTSW |
11 |
100,373,046 (GRCm39) |
missense |
possibly damaging |
0.92 |
|
R7099:Acly
|
UTSW |
11 |
100,383,117 (GRCm39) |
splice site |
probably null |
|
|
R7148:Acly
|
UTSW |
11 |
100,374,608 (GRCm39) |
missense |
possibly damaging |
0.49 |
|
R7149:Acly
|
UTSW |
11 |
100,375,451 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7349:Acly
|
UTSW |
11 |
100,412,817 (GRCm39) |
missense |
probably benign |
|
|
R7450:Acly
|
UTSW |
11 |
100,370,101 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7484:Acly
|
UTSW |
11 |
100,386,789 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7687:Acly
|
UTSW |
11 |
100,395,680 (GRCm39) |
critical splice donor site |
probably null |
|
|
R7728:Acly
|
UTSW |
11 |
100,410,513 (GRCm39) |
missense |
probably benign |
0.06 |
|
R7728:Acly
|
UTSW |
11 |
100,407,623 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7750:Acly
|
UTSW |
11 |
100,368,839 (GRCm39) |
critical splice donor site |
probably null |
|
|
R8042:Acly
|
UTSW |
11 |
100,405,151 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8221:Acly
|
UTSW |
11 |
100,410,576 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8407:Acly
|
UTSW |
11 |
100,384,897 (GRCm39) |
missense |
possibly damaging |
0.67 |
|
R8677:Acly
|
UTSW |
11 |
100,410,569 (GRCm39) |
missense |
probably damaging |
0.96 |
|
R8721:Acly
|
UTSW |
11 |
100,412,806 (GRCm39) |
critical splice donor site |
probably null |
|
|
R8861:Acly
|
UTSW |
11 |
100,375,424 (GRCm39) |
critical splice donor site |
probably null |
|
|
R8894:Acly
|
UTSW |
11 |
100,407,639 (GRCm39) |
missense |
probably benign |
0.21 |
|
R9171:Acly
|
UTSW |
11 |
100,407,657 (GRCm39) |
missense |
probably benign |
|
|
R9622:Acly
|
UTSW |
11 |
100,395,785 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9632:Acly
|
UTSW |
11 |
100,389,072 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9729:Acly
|
UTSW |
11 |
100,407,711 (GRCm39) |
missense |
probably benign |
0.00 |
|
R9784:Acly
|
UTSW |
11 |
100,389,112 (GRCm39) |
missense |
probably benign |
0.03 |
|
X0028:Acly
|
UTSW |
11 |
100,386,759 (GRCm39) |
missense |
probably damaging |
1.00 |
|
| Predicted Primers |
PCR Primer
(F):5'- GCCAGGCATTTGTCATAGTAACGGG -3'
(R):5'- TGAAAATCCTTCCAGCTCTCAGCG -3'
Sequencing Primer
(F):5'- agtgacttcaaagccagcc -3'
(R):5'- AGCTCTCAGCGTTATCCTTAG -3'
|
| Posted On |
2014-01-05 |
Incidental Mutation