Incidental Mutation 'R1804:Acly'
ID |
203400 |
Institutional Source |
Beutler Lab
|
Gene Symbol |
Acly
|
Ensembl Gene |
ENSMUSG00000020917 |
Gene Name |
ATP citrate lyase |
Synonyms |
A730098H14Rik |
MMRRC Submission |
039834-MU
|
Accession Numbers |
|
Essential gene? |
Essential
(E-score: 1.000)
|
Stock # |
R1804 (G1)
|
Quality Score |
184 |
Status
|
Validated
|
Chromosome |
11 |
Chromosomal Location |
100367179-100418826 bp(-) (GRCm39) |
Type of Mutation |
missense |
DNA Base Change (assembly) |
T to C
at 100406731 bp (GRCm39)
|
Zygosity |
Heterozygous |
Amino Acid Change |
Tyrosine to Cysteine
at position 288
(Y288C)
|
Ref Sequence |
ENSEMBL: ENSMUSP00000127632
(fasta)
|
Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000007131]
[ENSMUST00000107385]
[ENSMUST00000107389]
[ENSMUST00000165111]
|
AlphaFold |
Q91V92 |
Predicted Effect |
probably damaging
Transcript: ENSMUST00000007131
AA Change: Y288C
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
SMART Domains |
Protein: ENSMUSP00000007131 Gene: ENSMUSG00000020917 AA Change: Y288C
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: ENSMUST00000107385
AA Change: Y288C
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
SMART Domains |
Protein: ENSMUSP00000103008 Gene: ENSMUSG00000020917 AA Change: Y288C
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 |
probably damaging
Transcript: ENSMUST00000107389
AA Change: Y288C
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
SMART Domains |
Protein: ENSMUSP00000103012 Gene: ENSMUSG00000020917 AA Change: Y288C
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 |
probably damaging
Transcript: ENSMUST00000165111
AA Change: Y288C
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
SMART Domains |
Protein: ENSMUSP00000127632 Gene: ENSMUSG00000020917 AA Change: Y288C
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 |
|
Meta Mutation Damage Score |
0.9487 |
Coding Region Coverage |
- 1x: 97.4%
- 3x: 96.7%
- 10x: 94.5%
- 20x: 89.8%
|
Validation Efficiency |
96% (77/80) |
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: 70 list
Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
1700056E22Rik |
A |
G |
1: 183,765,400 (GRCm39) |
Y220H |
probably benign |
Het |
4930579C12Rik |
T |
C |
9: 89,034,113 (GRCm39) |
|
noncoding transcript |
Het |
Abcc8 |
T |
C |
7: 45,769,903 (GRCm39) |
S871G |
probably benign |
Het |
Adgrb1 |
T |
A |
15: 74,401,389 (GRCm39) |
D128E |
probably damaging |
Het |
Alms1 |
C |
T |
6: 85,598,257 (GRCm39) |
Q1497* |
probably null |
Het |
Bltp2 |
A |
G |
11: 78,164,295 (GRCm39) |
H1165R |
probably damaging |
Het |
Cacna1c |
G |
A |
6: 118,664,007 (GRCm39) |
T688M |
probably damaging |
Het |
Ccdc7a |
A |
T |
8: 129,715,247 (GRCm39) |
L279* |
probably null |
Het |
Cep135 |
A |
G |
5: 76,784,779 (GRCm39) |
E958G |
probably benign |
Het |
Clec4n |
G |
T |
6: 123,206,981 (GRCm39) |
V2L |
possibly damaging |
Het |
Col28a1 |
C |
T |
6: 8,164,612 (GRCm39) |
|
probably null |
Het |
Dcaf5 |
A |
G |
12: 80,386,603 (GRCm39) |
S508P |
probably benign |
Het |
Dlgap2 |
C |
A |
8: 14,777,809 (GRCm39) |
N351K |
possibly damaging |
Het |
Dnah8 |
T |
A |
17: 30,927,381 (GRCm39) |
Y1346N |
probably benign |
Het |
Dqx1 |
T |
C |
6: 83,037,303 (GRCm39) |
V322A |
probably damaging |
Het |
Ebf3 |
A |
C |
7: 136,802,250 (GRCm39) |
L412V |
possibly damaging |
Het |
Epha5 |
T |
C |
5: 84,479,674 (GRCm39) |
N110S |
probably benign |
Het |
Fcgbp |
T |
C |
7: 27,785,564 (GRCm39) |
C334R |
probably benign |
Het |
Glp1r |
T |
A |
17: 31,149,687 (GRCm39) |
|
probably null |
Het |
Gm4952 |
G |
T |
19: 12,595,784 (GRCm39) |
R58L |
probably damaging |
Het |
Gm7579 |
G |
A |
7: 141,765,675 (GRCm39) |
C27Y |
unknown |
Het |
Golm1 |
T |
A |
13: 59,790,203 (GRCm39) |
|
probably null |
Het |
Gucy2g |
T |
A |
19: 55,198,741 (GRCm39) |
I801F |
probably benign |
Het |
H2-D1 |
T |
C |
17: 35,482,528 (GRCm39) |
Y83H |
probably damaging |
Het |
Homez |
A |
T |
14: 55,094,598 (GRCm39) |
I19N |
probably damaging |
Het |
Hoxa5 |
T |
C |
6: 52,179,628 (GRCm39) |
K249R |
probably damaging |
Het |
Hsd17b4 |
A |
T |
18: 50,311,051 (GRCm39) |
N550Y |
probably damaging |
Het |
Ipo4 |
A |
T |
14: 55,866,913 (GRCm39) |
N668K |
probably damaging |
Het |
Kcnh8 |
GAGACCAACGAGCAGCTGATGCTTCAGA |
GAGA |
17: 53,032,934 (GRCm39) |
74 |
probably benign |
Het |
Klb |
A |
G |
5: 65,537,196 (GRCm39) |
D842G |
probably damaging |
Het |
Minar1 |
T |
A |
9: 89,485,152 (GRCm39) |
M82L |
possibly damaging |
Het |
Mmp21 |
G |
T |
7: 133,280,611 (GRCm39) |
P120T |
probably benign |
Het |
Mroh7 |
T |
A |
4: 106,551,589 (GRCm39) |
I918F |
possibly damaging |
Het |
Muc5b |
A |
G |
7: 141,417,517 (GRCm39) |
T3488A |
possibly damaging |
Het |
Npc1 |
C |
T |
18: 12,356,145 (GRCm39) |
C42Y |
probably damaging |
Het |
Ogdh |
A |
G |
11: 6,288,565 (GRCm39) |
Y214C |
probably damaging |
Het |
Or2q1 |
G |
A |
6: 42,795,155 (GRCm39) |
C250Y |
possibly damaging |
Het |
Or4k15c |
A |
T |
14: 50,321,359 (GRCm39) |
W260R |
probably damaging |
Het |
Or4k35 |
T |
C |
2: 111,100,275 (GRCm39) |
M146V |
probably benign |
Het |
Or5al1 |
G |
T |
2: 85,990,417 (GRCm39) |
T99N |
probably benign |
Het |
Or8d23 |
A |
G |
9: 38,841,946 (GRCm39) |
T160A |
possibly damaging |
Het |
Phtf1 |
A |
G |
3: 103,894,883 (GRCm39) |
|
probably benign |
Het |
Plb1 |
A |
G |
5: 32,511,041 (GRCm39) |
N1302S |
possibly damaging |
Het |
Prex2 |
A |
G |
1: 11,202,566 (GRCm39) |
K492E |
probably damaging |
Het |
Prkaa1 |
A |
G |
15: 5,208,259 (GRCm39) |
D509G |
probably benign |
Het |
Rims2 |
C |
T |
15: 39,300,439 (GRCm39) |
Q57* |
probably null |
Het |
Rnf40 |
T |
C |
7: 127,195,120 (GRCm39) |
V411A |
possibly damaging |
Het |
Rraga |
A |
G |
4: 86,494,681 (GRCm39) |
I176V |
probably damaging |
Het |
Rrm2 |
T |
C |
12: 24,758,611 (GRCm39) |
I51T |
probably benign |
Het |
Serpina3a |
T |
A |
12: 104,084,675 (GRCm39) |
|
probably benign |
Het |
Skint7 |
T |
C |
4: 111,839,209 (GRCm39) |
W168R |
probably damaging |
Het |
Slc27a4 |
A |
G |
2: 29,701,279 (GRCm39) |
M357V |
probably benign |
Het |
Slc4a3 |
A |
G |
1: 75,528,361 (GRCm39) |
H452R |
probably damaging |
Het |
Smc1b |
A |
T |
15: 85,011,991 (GRCm39) |
I127K |
possibly damaging |
Het |
Snap91 |
T |
A |
9: 86,665,470 (GRCm39) |
M383L |
probably benign |
Het |
Taf6l |
A |
T |
19: 8,750,998 (GRCm39) |
L52Q |
probably damaging |
Het |
Tas1r3 |
G |
A |
4: 155,944,927 (GRCm39) |
R765C |
probably damaging |
Het |
Tas2r124 |
A |
G |
6: 132,732,488 (GRCm39) |
I266V |
probably benign |
Het |
Tesk2 |
T |
C |
4: 116,657,818 (GRCm39) |
|
probably benign |
Het |
Tmem131l |
T |
G |
3: 83,817,786 (GRCm39) |
Q1237P |
possibly damaging |
Het |
Tmem67 |
A |
G |
4: 12,045,789 (GRCm39) |
|
probably null |
Het |
Tnfaip8 |
T |
A |
18: 50,223,728 (GRCm39) |
C179S |
probably damaging |
Het |
Ush2a |
G |
A |
1: 188,365,926 (GRCm39) |
|
probably null |
Het |
Vps13b |
A |
T |
15: 35,917,283 (GRCm39) |
E3709V |
probably damaging |
Het |
Wdr7 |
A |
T |
18: 63,998,511 (GRCm39) |
S1153C |
probably damaging |
Het |
Zc2hc1b |
A |
C |
10: 13,047,012 (GRCm39) |
|
probably benign |
Het |
Zfp438 |
A |
G |
18: 5,213,689 (GRCm39) |
I423T |
probably damaging |
Het |
Zfp592 |
C |
A |
7: 80,673,443 (GRCm39) |
P136T |
probably damaging |
Het |
Zfp783 |
T |
A |
6: 47,922,819 (GRCm39) |
|
noncoding transcript |
Het |
Zfp804b |
A |
T |
5: 6,821,756 (GRCm39) |
S400T |
possibly 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 |
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'- CTACGTGAGATTACAGAAGATGCTG -3'
(R):5'- TGCCCTCAGATAAAGAGCTGTG -3'
Sequencing Primer
(F):5'- ACAGAAGATGCTGTGCCC -3'
(R):5'- AAGAGCTGTGGTCTTGGGTTTG -3'
|
Posted On |
2014-06-23 |