Incidental Mutation 'R1980:Acly'
| ID |
222185 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Acly
|
| Ensembl Gene |
ENSMUSG00000020917 |
| Gene Name |
ATP citrate lyase |
| Synonyms |
A730098H14Rik |
| MMRRC Submission |
039992-MU
|
| Accession Numbers |
|
| Essential gene? |
Essential
(E-score: 1.000)
|
| Stock # |
R1980 (G1)
|
| Quality Score |
225 |
|
Status
|
Not validated
|
| Chromosome |
11 |
| Chromosomal Location |
100367179-100418826 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
A to C
at 100386702 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Isoleucine to Serine
at position 620
(I620S)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000103012
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000007131]
[ENSMUST00000107385]
[ENSMUST00000107389]
[ENSMUST00000165111]
|
| AlphaFold |
Q91V92 |
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000007131
AA Change: I610S
PolyPhen 2
Score 0.762 (Sensitivity: 0.85; Specificity: 0.92)
|
| SMART Domains |
Protein: ENSMUSP00000007131
Gene: ENSMUSG00000020917
AA Change: I610S
| 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 benign
Transcript: ENSMUST00000107385
|
| SMART Domains |
Protein: ENSMUSP00000103008
Gene: ENSMUSG00000020917
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:ATP-grasp_2
|
6 |
207 |
2.1e-6 |
PFAM |
|
SCOP:d1eucb1
|
255 |
417 |
1e-26 |
SMART |
|
low complexity region
|
441 |
457 |
N/A |
INTRINSIC |
|
low complexity region
|
465 |
475 |
N/A |
INTRINSIC |
|
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000107389
AA Change: I620S
PolyPhen 2
Score 0.870 (Sensitivity: 0.83; Specificity: 0.93)
|
| SMART Domains |
Protein: ENSMUSP00000103012
Gene: ENSMUSG00000020917
AA Change: I620S
| 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: ENSMUST00000154888
|
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000165111
AA Change: I610S
PolyPhen 2
Score 0.762 (Sensitivity: 0.85; Specificity: 0.92)
|
| SMART Domains |
Protein: ENSMUSP00000127632
Gene: ENSMUSG00000020917
AA Change: I610S
| 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 |
|
| Coding Region Coverage |
- 1x: 99.1%
- 3x: 98.4%
- 10x: 96.8%
- 20x: 94.1%
|
| Validation Efficiency |
|
| 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: 68 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Acot8 |
A |
G |
2: 164,636,964 (GRCm39) |
F262S |
probably damaging |
Het |
| Adgb |
C |
T |
10: 10,309,242 (GRCm39) |
V246I |
probably benign |
Het |
| Akap9 |
T |
A |
5: 4,022,771 (GRCm39) |
M1200K |
probably damaging |
Het |
| Alg11 |
T |
A |
8: 22,551,903 (GRCm39) |
F16I |
possibly damaging |
Het |
| Apol7c |
A |
G |
15: 77,410,244 (GRCm39) |
V234A |
probably benign |
Het |
| Arhgap19 |
T |
G |
19: 41,776,784 (GRCm39) |
I122L |
possibly damaging |
Het |
| Arhgef37 |
A |
G |
18: 61,641,767 (GRCm39) |
S201P |
probably damaging |
Het |
| Asgr1 |
A |
T |
11: 69,945,772 (GRCm39) |
D16V |
probably damaging |
Het |
| Camta2 |
A |
T |
11: 70,573,308 (GRCm39) |
C227S |
probably benign |
Het |
| Cd22 |
A |
T |
7: 30,572,658 (GRCm39) |
L317Q |
probably damaging |
Het |
| Cenpf |
A |
T |
1: 189,386,112 (GRCm39) |
I2056K |
probably benign |
Het |
| Cenpi |
T |
A |
X: 133,218,782 (GRCm39) |
F161L |
possibly damaging |
Het |
| Ciapin1 |
C |
T |
8: 95,559,161 (GRCm39) |
V43I |
probably benign |
Het |
| Cox5b-ps |
T |
G |
13: 21,685,294 (GRCm39) |
T99P |
possibly damaging |
Het |
| Dach1 |
A |
G |
14: 98,068,777 (GRCm39) |
L601P |
probably damaging |
Het |
| Ddx11 |
T |
A |
17: 66,455,734 (GRCm39) |
L711Q |
probably damaging |
Het |
| Dsg1a |
A |
T |
18: 20,471,707 (GRCm39) |
N653I |
probably damaging |
Het |
| Fezf2 |
G |
T |
14: 12,344,405 (GRCm38) |
P261T |
probably benign |
Het |
| Galnt5 |
T |
C |
2: 57,914,735 (GRCm39) |
|
probably null |
Het |
| Gemin5 |
A |
G |
11: 58,027,743 (GRCm39) |
L935P |
probably damaging |
Het |
| Gm9507 |
A |
T |
10: 77,647,519 (GRCm39) |
C53* |
probably null |
Het |
| Irgm2 |
A |
G |
11: 58,110,902 (GRCm39) |
I198V |
probably damaging |
Het |
| Kcnh8 |
GAGACCAACGAGCAGCTGATGCTTCAGA |
GAGA |
17: 53,032,934 (GRCm39) |
74 |
probably benign |
Het |
| Klf12 |
A |
C |
14: 100,387,162 (GRCm39) |
|
probably null |
Het |
| Lpp |
C |
T |
16: 24,480,451 (GRCm39) |
P73L |
probably damaging |
Het |
| Lrrc34 |
G |
A |
3: 30,696,890 (GRCm39) |
H127Y |
probably benign |
Het |
| Lyar |
T |
C |
5: 38,382,053 (GRCm39) |
S12P |
probably damaging |
Het |
| Maml3 |
A |
G |
3: 52,011,473 (GRCm39) |
I31T |
unknown |
Het |
| Mei1 |
A |
G |
15: 81,987,513 (GRCm39) |
N859S |
probably benign |
Het |
| Minar2 |
T |
A |
18: 59,208,739 (GRCm39) |
M129K |
probably damaging |
Het |
| Mysm1 |
A |
T |
4: 94,840,450 (GRCm39) |
N655K |
probably benign |
Het |
| Npnt |
T |
C |
3: 132,653,893 (GRCm39) |
I29M |
probably benign |
Het |
| Nrxn1 |
A |
G |
17: 91,395,746 (GRCm39) |
W137R |
probably benign |
Het |
| Numb |
C |
T |
12: 83,844,118 (GRCm39) |
|
probably null |
Het |
| Obsl1 |
A |
G |
1: 75,482,480 (GRCm39) |
F130S |
probably damaging |
Het |
| Or2h1 |
T |
G |
17: 37,404,295 (GRCm39) |
Q157P |
probably damaging |
Het |
| Or4k47 |
T |
A |
2: 111,451,586 (GRCm39) |
I278F |
probably benign |
Het |
| Pbx4 |
T |
C |
8: 70,322,776 (GRCm39) |
V294A |
probably benign |
Het |
| Pde4dip |
A |
C |
3: 97,664,312 (GRCm39) |
L524R |
possibly damaging |
Het |
| Plppr1 |
G |
A |
4: 49,337,655 (GRCm39) |
A319T |
probably benign |
Het |
| Ppid |
A |
T |
3: 79,500,925 (GRCm39) |
I32F |
probably damaging |
Het |
| Ppp4r3c1 |
A |
T |
X: 88,975,051 (GRCm39) |
V382E |
probably damaging |
Het |
| Prkcsh |
A |
G |
9: 21,924,164 (GRCm39) |
D458G |
probably damaging |
Het |
| Prr27 |
A |
G |
5: 87,991,261 (GRCm39) |
E291G |
probably benign |
Het |
| Psme4 |
A |
T |
11: 30,782,615 (GRCm39) |
K923N |
possibly damaging |
Het |
| Rab25 |
T |
C |
3: 88,450,765 (GRCm39) |
T45A |
probably damaging |
Het |
| Rapgef1 |
C |
T |
2: 29,612,239 (GRCm39) |
P630S |
probably benign |
Het |
| Rasa2 |
T |
C |
9: 96,452,821 (GRCm39) |
D355G |
probably damaging |
Het |
| Rel |
C |
T |
11: 23,692,761 (GRCm39) |
G424D |
probably benign |
Het |
| Rtn4 |
A |
T |
11: 29,658,634 (GRCm39) |
E929D |
probably benign |
Het |
| Samt3 |
A |
C |
X: 85,090,740 (GRCm39) |
M211L |
probably benign |
Het |
| Slk |
T |
G |
19: 47,600,428 (GRCm39) |
I151S |
probably damaging |
Het |
| Spin1 |
T |
A |
13: 51,298,506 (GRCm39) |
V175D |
probably damaging |
Het |
| Ssxb10 |
A |
G |
X: 8,197,258 (GRCm39) |
D77G |
probably benign |
Het |
| Ticam1 |
C |
T |
17: 56,578,555 (GRCm39) |
R180H |
probably damaging |
Het |
| Tmem151b |
G |
C |
17: 45,856,387 (GRCm39) |
P351R |
possibly damaging |
Het |
| Tmod1 |
A |
C |
4: 46,061,043 (GRCm39) |
Y10S |
probably damaging |
Het |
| Tns2 |
C |
T |
15: 102,017,369 (GRCm39) |
R281C |
probably damaging |
Het |
| Trpm1 |
T |
C |
7: 63,858,182 (GRCm39) |
Y225H |
possibly damaging |
Het |
| Ttc17 |
T |
C |
2: 94,157,049 (GRCm39) |
N411S |
probably benign |
Het |
| Tyro3 |
A |
G |
2: 119,639,298 (GRCm39) |
D335G |
probably benign |
Het |
| Unc79 |
C |
A |
12: 102,977,538 (GRCm39) |
Y180* |
probably null |
Het |
| Upp1 |
A |
T |
11: 9,084,872 (GRCm39) |
D197V |
possibly damaging |
Het |
| Vmn1r226 |
T |
A |
17: 20,908,308 (GRCm39) |
M180K |
possibly damaging |
Het |
| Vtn |
T |
A |
11: 78,392,724 (GRCm39) |
I434N |
probably damaging |
Het |
| Zfp329 |
T |
A |
7: 12,545,395 (GRCm39) |
N43I |
probably benign |
Het |
| Zfp819 |
A |
G |
7: 43,265,885 (GRCm39) |
T47A |
probably benign |
Het |
| Zyg11b |
G |
A |
4: 108,123,127 (GRCm39) |
T280I |
probably damaging |
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 |
|
R1115:Acly
|
UTSW |
11 |
100,370,081 (GRCm39) |
missense |
probably damaging |
0.99 |
|
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 |
|
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'- AACAGCTAGTCATTGTCCTCTG -3'
(R):5'- CTGAGAACACTGGGCTTAGGAG -3'
Sequencing Primer
(F):5'- CAAGGTCACTTAGGGCTTGCAG -3'
(R):5'- AGGAGGGCCTCAGTGTCTG -3'
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| Posted On |
2014-08-25 |
Incidental Mutation