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) question?
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

DomainStartEndE-ValueType
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

DomainStartEndE-ValueType
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

DomainStartEndE-ValueType
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

DomainStartEndE-ValueType
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 question?
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
GeneRefVarChr/LocMutationPredicted EffectZygosity
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
AlleleSourceChrCoordTypePredicted EffectPPH 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