Incidental Mutation 'R0195:Acly'
ID |
23382 |
Institutional Source |
Beutler Lab
|
Gene Symbol |
Acly
|
Ensembl Gene |
ENSMUSG00000020917 |
Gene Name |
ATP citrate lyase |
Synonyms |
A730098H14Rik |
MMRRC Submission |
038454-MU
|
Accession Numbers |
|
Essential gene? |
Essential
(E-score: 1.000)
|
Stock # |
R0195 (G1)
|
Quality Score |
225 |
Status
|
Validated
|
Chromosome |
11 |
Chromosomal Location |
100367179-100418826 bp(-) (GRCm39) |
Type of Mutation |
missense |
DNA Base Change (assembly) |
C to G
at 100403800 bp (GRCm39)
|
Zygosity |
Heterozygous |
Amino Acid Change |
Arginine to Proline
at position 362
(R362P)
|
Ref Sequence |
ENSEMBL: ENSMUSP00000103008
(fasta)
|
Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000007131]
[ENSMUST00000107385]
[ENSMUST00000107389]
[ENSMUST00000165111]
|
AlphaFold |
Q91V92 |
Predicted Effect |
probably benign
Transcript: ENSMUST00000007131
AA Change: R362P
PolyPhen 2
Score 0.264 (Sensitivity: 0.91; Specificity: 0.88)
|
SMART Domains |
Protein: ENSMUSP00000007131 Gene: ENSMUSG00000020917 AA Change: R362P
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 |
possibly damaging
Transcript: ENSMUST00000107385
AA Change: R362P
PolyPhen 2
Score 0.565 (Sensitivity: 0.88; Specificity: 0.91)
|
SMART Domains |
Protein: ENSMUSP00000103008 Gene: ENSMUSG00000020917 AA Change: R362P
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 benign
Transcript: ENSMUST00000107389
AA Change: R362P
PolyPhen 2
Score 0.059 (Sensitivity: 0.94; Specificity: 0.84)
|
SMART Domains |
Protein: ENSMUSP00000103012 Gene: ENSMUSG00000020917 AA Change: R362P
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 benign
Transcript: ENSMUST00000165111
AA Change: R362P
PolyPhen 2
Score 0.264 (Sensitivity: 0.91; Specificity: 0.88)
|
SMART Domains |
Protein: ENSMUSP00000127632 Gene: ENSMUSG00000020917 AA Change: R362P
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 |
0.1750 |
Coding Region Coverage |
- 1x: 99.0%
- 3x: 98.1%
- 10x: 95.6%
- 20x: 89.4%
|
Validation Efficiency |
98% (156/160) |
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: 74 list
Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
Adam24 |
T |
A |
8: 41,134,805 (GRCm39) |
W758R |
probably benign |
Het |
Adam26b |
G |
T |
8: 43,973,307 (GRCm39) |
T565K |
probably damaging |
Het |
Adam7 |
T |
G |
14: 68,765,076 (GRCm39) |
|
probably benign |
Het |
Adamts19 |
A |
G |
18: 59,102,942 (GRCm39) |
|
probably benign |
Het |
Add1 |
A |
G |
5: 34,767,990 (GRCm39) |
|
probably benign |
Het |
Ago1 |
A |
G |
4: 126,357,484 (GRCm39) |
C64R |
probably benign |
Het |
Ankrd12 |
C |
T |
17: 66,356,943 (GRCm39) |
|
probably null |
Het |
Arhgef33 |
A |
G |
17: 80,688,863 (GRCm39) |
K820E |
probably damaging |
Het |
Arl9 |
T |
C |
5: 77,154,341 (GRCm39) |
V8A |
probably damaging |
Het |
Aspm |
T |
C |
1: 139,406,873 (GRCm39) |
L1920P |
probably damaging |
Het |
Atad2 |
A |
G |
15: 57,963,350 (GRCm39) |
|
probably benign |
Het |
Atp2b2 |
A |
T |
6: 113,770,835 (GRCm39) |
V358E |
probably benign |
Het |
C3ar1 |
A |
C |
6: 122,828,114 (GRCm39) |
C34W |
possibly damaging |
Het |
C6 |
G |
A |
15: 4,792,953 (GRCm39) |
V353M |
probably benign |
Het |
Capn7 |
T |
C |
14: 31,087,538 (GRCm39) |
I593T |
probably damaging |
Het |
Casc3 |
T |
A |
11: 98,712,319 (GRCm39) |
D119E |
probably damaging |
Het |
Ccna1 |
T |
A |
3: 54,961,785 (GRCm39) |
E45V |
probably damaging |
Het |
Cdc37 |
A |
G |
9: 21,053,576 (GRCm39) |
V180A |
probably benign |
Het |
Cdh23 |
A |
G |
10: 60,152,838 (GRCm39) |
I2393T |
probably damaging |
Het |
Cnbd1 |
T |
C |
4: 18,906,988 (GRCm39) |
|
probably benign |
Het |
Cngb3 |
A |
T |
4: 19,280,975 (GRCm39) |
M15L |
probably benign |
Het |
Crygn |
A |
G |
5: 24,961,036 (GRCm39) |
M90T |
possibly damaging |
Het |
Cse1l |
T |
A |
2: 166,782,008 (GRCm39) |
S661R |
probably benign |
Het |
D830013O20Rik |
C |
T |
12: 73,411,095 (GRCm39) |
|
noncoding transcript |
Het |
Ddx24 |
C |
T |
12: 103,385,220 (GRCm39) |
|
probably null |
Het |
Dnah3 |
A |
T |
7: 119,676,998 (GRCm39) |
|
probably null |
Het |
Dnah9 |
C |
T |
11: 65,786,731 (GRCm39) |
G3634E |
probably benign |
Het |
Dnttip2 |
A |
T |
3: 122,069,810 (GRCm39) |
T342S |
probably benign |
Het |
Evx2 |
G |
T |
2: 74,489,388 (GRCm39) |
R125S |
probably damaging |
Het |
Fbxl5 |
A |
T |
5: 43,928,140 (GRCm39) |
L40Q |
probably damaging |
Het |
Git1 |
T |
A |
11: 77,391,899 (GRCm39) |
D240E |
probably benign |
Het |
Glp2r |
T |
A |
11: 67,600,534 (GRCm39) |
K438N |
probably damaging |
Het |
Hivep1 |
T |
A |
13: 42,309,629 (GRCm39) |
I623N |
probably benign |
Het |
Il17re |
A |
G |
6: 113,443,098 (GRCm39) |
E312G |
probably damaging |
Het |
Itgb7 |
G |
A |
15: 102,130,618 (GRCm39) |
|
probably benign |
Het |
Itpr3 |
A |
G |
17: 27,333,088 (GRCm39) |
Y1900C |
probably damaging |
Het |
Krt1c |
G |
A |
15: 101,721,626 (GRCm39) |
Q472* |
probably null |
Het |
Krtap5-1 |
A |
C |
7: 141,850,434 (GRCm39) |
C125G |
unknown |
Het |
Macf1 |
A |
G |
4: 123,328,709 (GRCm39) |
S2554P |
probably damaging |
Het |
Marchf10 |
C |
T |
11: 105,276,351 (GRCm39) |
G646R |
probably damaging |
Het |
Mrpl48 |
A |
C |
7: 100,195,560 (GRCm39) |
|
probably benign |
Het |
Myo16 |
A |
T |
8: 10,365,538 (GRCm39) |
|
probably benign |
Het |
Nrcam |
A |
T |
12: 44,631,628 (GRCm39) |
E1060D |
probably benign |
Het |
Nsd3 |
T |
A |
8: 26,170,709 (GRCm39) |
C731S |
probably damaging |
Het |
Nup85 |
T |
G |
11: 115,455,357 (GRCm39) |
M1R |
probably null |
Het |
Nxnl2 |
G |
T |
13: 51,325,483 (GRCm39) |
R42L |
probably damaging |
Het |
Oas3 |
G |
A |
5: 120,894,210 (GRCm39) |
R39C |
probably damaging |
Het |
Or13c25 |
G |
A |
4: 52,910,849 (GRCm39) |
T315M |
probably benign |
Het |
Orc1 |
C |
T |
4: 108,471,505 (GRCm39) |
R786* |
probably null |
Het |
P2ry6 |
A |
T |
7: 100,587,904 (GRCm39) |
W152R |
probably damaging |
Het |
Pex5l |
T |
C |
3: 33,047,102 (GRCm39) |
N283D |
possibly damaging |
Het |
Pgk2 |
T |
C |
17: 40,518,622 (GRCm39) |
I269V |
probably benign |
Het |
Phgdh |
T |
G |
3: 98,223,866 (GRCm39) |
|
probably benign |
Het |
Pzp |
A |
T |
6: 128,464,441 (GRCm39) |
L1362Q |
probably damaging |
Het |
Rbbp9 |
T |
C |
2: 144,390,026 (GRCm39) |
|
probably benign |
Het |
Rffl |
A |
G |
11: 82,700,989 (GRCm39) |
L244P |
probably damaging |
Het |
Serpina11 |
T |
C |
12: 103,952,131 (GRCm39) |
Y213C |
probably damaging |
Het |
Spopfm1 |
A |
G |
3: 94,173,229 (GRCm39) |
Y79C |
possibly damaging |
Het |
Srsf11 |
A |
G |
3: 157,742,172 (GRCm39) |
|
probably benign |
Het |
Sspo |
T |
A |
6: 48,463,570 (GRCm39) |
V3785E |
probably benign |
Het |
Svep1 |
A |
T |
4: 58,089,514 (GRCm39) |
S1632T |
possibly damaging |
Het |
Tm4sf1 |
T |
A |
3: 57,200,480 (GRCm39) |
D74V |
probably damaging |
Het |
Tmprss15 |
T |
A |
16: 78,831,222 (GRCm39) |
T393S |
probably benign |
Het |
Tnfaip3 |
A |
G |
10: 18,881,461 (GRCm39) |
L275P |
probably damaging |
Het |
Trim30c |
A |
G |
7: 104,031,636 (GRCm39) |
V393A |
probably benign |
Het |
Tssk2 |
T |
A |
16: 17,717,439 (GRCm39) |
S281T |
probably benign |
Het |
Tubb4a |
A |
G |
17: 57,388,499 (GRCm39) |
S176P |
probably damaging |
Het |
Unc45b |
T |
A |
11: 82,828,654 (GRCm39) |
M785K |
probably damaging |
Het |
Vldlr |
A |
T |
19: 27,215,786 (GRCm39) |
D261V |
probably damaging |
Het |
Vmn1r176 |
G |
T |
7: 23,535,010 (GRCm39) |
Q48K |
probably benign |
Het |
Vmn2r110 |
A |
T |
17: 20,794,317 (GRCm39) |
L784Q |
probably benign |
Het |
Vps13b |
A |
G |
15: 35,472,045 (GRCm39) |
T783A |
probably benign |
Het |
Zfp800 |
A |
G |
6: 28,243,846 (GRCm39) |
M373T |
probably damaging |
Het |
Zmym1 |
A |
G |
4: 126,941,704 (GRCm39) |
F895L |
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 |
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 |
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'- TACCCAGCACACTACTGGGCATAG -3'
(R):5'- ATTGCGGATGGCAGTCCTCTTG -3'
Sequencing Primer
(F):5'- gctcaattcccagcatccac -3'
(R):5'- CTGTATGGTCACACACTGGG -3'
|
Posted On |
2013-04-16 |