Mutagenetix > Incidental Mutations

Incidental Mutation 'R1997:Acly'

224382

Institutional Source

Beutler Lab

Gene Symbol

Acly

Ensembl Gene

ENSMUSG00000020917

Gene Name

ATP citrate lyase

Synonyms

A730098H14Rik

MMRRC Submission

040007-MU

Accession Numbers

NCBI RefSeq: NM_001199296.1, NM_134037.3; MGI: 103251

Is this an essential gene?

Essential (E-score: 1.000) question?

Stock #

R1997 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

100476353-100528000 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 100519151 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Asparagine at position 185 (I185N)

Ref Sequence

ENSEMBL: ENSMUSP00000103008 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000007131] [ENSMUST00000107385] [ENSMUST00000107389] [ENSMUST00000165111]

AlphaFold

Q91V92

Predicted Effect

probably damaging
Transcript: ENSMUST00000007131
AA Change: I185N

PolyPhen 2 Score 0.970 (Sensitivity: 0.77; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000007131
Gene: ENSMUSG00000020917
AA Change: I185N

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: I185N

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000103008
Gene: ENSMUSG00000020917
AA Change: I185N

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: I185N

PolyPhen 2 Score 0.946 (Sensitivity: 0.80; Specificity: 0.95)

SMART Domains

Protein: ENSMUSP00000103012
Gene: ENSMUSG00000020917
AA Change: I185N

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: I185N

PolyPhen 2 Score 0.970 (Sensitivity: 0.77; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000127632
Gene: ENSMUSG00000020917
AA Change: I185N

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: 96.4%
20x: 92.2%

Validation Efficiency

MGI Phenotype

Strain: 5287022; 3036686
Lethality: E7-E8
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: 100 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1600015I10Rik	A	T	6: 48,932,429	Q536L	probably damaging	Het
3425401B19Rik	A	G	14: 32,660,048	F1320S	possibly damaging	Het
Aaas	C	T	15: 102,340,059	V241I	probably benign	Het
Abca17	A	G	17: 24,285,726	I1233T	probably benign	Het
Acin1	T	C	14: 54,646,699		probably null	Het
Adamts16	T	C	13: 70,753,267	D897G	probably benign	Het
Allc	A	C	12: 28,563,483	D153E	probably benign	Het
Ankrd12	A	G	17: 65,984,884	S1185P	probably damaging	Het
Ap1g2	T	C	14: 55,102,378	E448G	probably benign	Het
Atg9a	A	T	1: 75,189,626	V50D	probably benign	Het
Bace2	A	T	16: 97,415,089	D294V	possibly damaging	Het
Camsap2	T	C	1: 136,271,545	K708E	probably damaging	Het
Card10	G	A	15: 78,793,975	R358C	probably damaging	Het
Ccdc81	A	T	7: 89,898,063	V39E	probably damaging	Het
Cdh7	A	T	1: 110,048,938	D111V	probably damaging	Het
Cercam	C	A	2: 29,872,923	T223K	probably benign	Het
Cog5	A	G	12: 31,660,849	H76R	possibly damaging	Het
Col28a1	A	T	6: 7,999,644	N1024K	probably benign	Het
Csrnp3	A	T	2: 65,949,102	N41Y	probably damaging	Het
Cyp2t4	G	A	7: 27,157,613		probably null	Het
Dbn1	T	C	13: 55,482,441	H38R	probably damaging	Het
Dclre1b	A	G	3: 103,803,356	V287A	probably benign	Het
Dennd4c	A	G	4: 86,837,397	T1609A	probably benign	Het
Depdc5	T	A	5: 32,901,906		probably null	Het
Dhcr7	T	G	7: 143,847,430	D446E	probably damaging	Het
Dlx5	A	T	6: 6,879,680	M129K	possibly damaging	Het
Dnah11	C	G	12: 118,082,468	G1745A	possibly damaging	Het
Dnm3	T	C	1: 162,353,712	T133A	possibly damaging	Het
Eif3e	A	G	15: 43,265,609	L205P	probably damaging	Het
Fam166a	T	G	2: 25,220,205	L43R	probably damaging	Het
Fam91a1	A	G	15: 58,424,195		probably null	Het
Fank1	C	T	7: 133,862,225	T50I	probably damaging	Het
Fhod3	A	G	18: 25,090,416	T940A	possibly damaging	Het
Fkbp10	T	C	11: 100,416,015	F78L	probably damaging	Het
Gabbr2	A	C	4: 46,787,502	F387C	probably damaging	Het
Ggnbp2	A	T	11: 84,860,561	L138I	probably damaging	Het
Gm2832	T	A	14: 41,280,986		probably null	Het
Gm38394	A	G	1: 133,656,713	L962P	probably damaging	Het
Gm5084	T	A	13: 60,212,530		noncoding transcript	Het
Gm9979	T	C	13: 40,705,752		noncoding transcript	Het
Hepacam2	A	G	6: 3,487,241	S39P	probably damaging	Het
Hesx1	A	T	14: 27,001,383	N57Y	probably damaging	Het
Kcnh1	G	A	1: 192,276,935	V266I	probably damaging	Het
Kif24	T	C	4: 41,392,904	T1168A	possibly damaging	Het
Kng2	A	T	16: 23,024,876	F118I	possibly damaging	Het
Lig3	C	T	11: 82,787,666	P245S	probably benign	Het
Loxhd1	G	T	18: 77,295,769	W121C	probably damaging	Het
Ltn1	A	G	16: 87,381,637	V1568A	probably damaging	Het
Map3k4	A	T	17: 12,254,995		probably null	Het
Mcm10	C	T	2: 4,993,760	V790M	probably damaging	Het
Mia3	A	T	1: 183,344,286	F1223I	possibly damaging	Het
Mlec	C	A	5: 115,150,346	K150N	probably damaging	Het
Morn4	T	C	19: 42,076,538	K70R	possibly damaging	Het
Mphosph10	A	C	7: 64,387,447		probably null	Het
Myocd	G	A	11: 65,204,321	Q47*	probably null	Het
Nav2	T	A	7: 49,548,471	S1283T	probably benign	Het
Nbeal2	T	C	9: 110,632,198	H1599R	probably damaging	Het
Nek10	G	T	14: 14,827,003	G67V	probably benign	Het
Nlgn2	A	C	11: 69,828,050	V271G	probably damaging	Het
Olfr167	A	C	16: 19,515,042	V198G	probably damaging	Het
Olfr97	A	G	17: 37,231,632	V246A	probably damaging	Het
Pcolce2	A	T	9: 95,694,740	M355L	probably benign	Het
Per2	T	C	1: 91,440,859	E264G	probably damaging	Het
Phf2	A	G	13: 48,828,908	L113P	unknown	Het
Piwil2	A	G	14: 70,426,658	V14A	possibly damaging	Het
Plekha6	G	A	1: 133,263,818	A146T	probably benign	Het
Plxnb2	C	T	15: 89,158,768	V1473I	probably benign	Het
Pms2	T	C	5: 143,913,700	L111P	probably damaging	Het
Polg	A	G	7: 79,459,231	L533P	probably damaging	Het
Ppp1r12b	A	G	1: 134,846,355		probably benign	Het
Ppp2r1b	T	A	9: 50,867,371	M208K	possibly damaging	Het
Prdm5	A	G	6: 65,936,088	Y207C	probably damaging	Het
Prkar2b	A	G	12: 31,963,935	V314A	probably damaging	Het
Proser1	T	A	3: 53,478,871	S725T	probably benign	Het
Psg20	A	G	7: 18,682,610	F194L	probably benign	Het
Ptprz1	A	G	6: 23,050,497	I2255V	probably damaging	Het
Sardh	T	G	2: 27,244,397	T36P	probably damaging	Het
Sec23a	T	A	12: 59,002,007	I110L	probably benign	Het
Slc22a29	T	A	19: 8,217,798	I158L	probably benign	Het
Slc35c1	T	C	2: 92,454,639	D210G	probably benign	Het
Syde2	A	G	3: 145,998,991	N566S	probably benign	Het
Tcf20	G	A	15: 82,857,230	Q7*	probably null	Het
Terb2	T	A	2: 122,204,857	H186Q	possibly damaging	Het
Tet2	G	A	3: 133,486,589	Q695*	probably null	Het
Tnfaip1	T	C	11: 78,530,147	Y29C	probably damaging	Het
Traf3	A	G	12: 111,260,661	K328E	probably benign	Het
Uaca	A	G	9: 60,870,341	E668G	probably damaging	Het
Ube2o	T	A	11: 116,545,337	E326V	probably damaging	Het
Ubr1	C	T	2: 120,946,273		probably null	Het
Vmn1r19	T	A	6: 57,405,048	S195R	probably damaging	Het
Vmn1r213	T	G	13: 23,012,303	V352G	probably benign	Het
Vmn2r19	T	A	6: 123,315,921	D307E	probably damaging	Het
Wdfy3	T	C	5: 101,968,946	D76G	probably damaging	Het
Zan	A	T	5: 137,403,114	C4114*	probably null	Het
Zdhhc23	A	T	16: 43,978,942	C37S	probably damaging	Het
Zfp628	G	T	7: 4,918,832	G18W	probably damaging	Het
Zfp712	T	A	13: 67,042,050	K138*	probably null	Het
Zfp867	A	T	11: 59,463,591	V304D	probably damaging	Het
Zfp870	T	C	17: 32,884,053	T102A	possibly damaging	Het
Zmym5	G	A	14: 56,797,753	S286L	possibly damaging	Het

Other mutations in Acly

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01336:Acly	APN	11	100495910	missense	probably benign	0.00
IGL01661:Acly	APN	11	100514342	splice site	probably benign
IGL02349:Acly	APN	11	100519679	missense	probably benign	0.01
IGL02792:Acly	APN	11	100478410	missense	probably damaging	0.97
IGL03026:Acly	APN	11	100519690	missense	possibly damaging	0.94
IGL03144:Acly	APN	11	100515083	missense	possibly damaging	0.84
IGL03230:Acly	APN	11	100494059	missense	probably damaging	0.99
IGL03266:Acly	APN	11	100483752	missense	probably damaging	1.00
Coyote	UTSW	11	100479255	missense	probably damaging	0.99
lupine	UTSW	11	100515905	missense	probably damaging	1.00
P0014:Acly	UTSW	11	100484604	missense	probably benign	0.03
R0195:Acly	UTSW	11	100512974	missense	possibly damaging	0.56
R0319:Acly	UTSW	11	100504982	missense	probably damaging	1.00
R0598:Acly	UTSW	11	100478390	missense	probably damaging	1.00
R1115:Acly	UTSW	11	100479255	missense	probably damaging	0.99
R1201:Acly	UTSW	11	100493935	missense	probably damaging	1.00
R1498:Acly	UTSW	11	100483801	missense	probably benign	0.27
R1593:Acly	UTSW	11	100481755	missense	possibly damaging	0.74
R1804:Acly	UTSW	11	100515905	missense	probably damaging	1.00
R1817:Acly	UTSW	11	100495891	missense	probably benign	0.00
R1980:Acly	UTSW	11	100495876	missense	possibly damaging	0.87
R2125:Acly	UTSW	11	100523496	missense	probably benign	0.01
R3001:Acly	UTSW	11	100504227	missense	possibly damaging	0.91
R3002:Acly	UTSW	11	100504227	missense	possibly damaging	0.91
R3003:Acly	UTSW	11	100504227	missense	possibly damaging	0.91
R5194:Acly	UTSW	11	100523546	missense	probably benign
R5509:Acly	UTSW	11	100514979	missense	probably damaging	0.97
R5594:Acly	UTSW	11	100522120	splice site	probably null
R6077:Acly	UTSW	11	100519757	missense	probably benign
R6310:Acly	UTSW	11	100482220	missense	possibly damaging	0.92
R7099:Acly	UTSW	11	100492291	splice site	probably null
R7148:Acly	UTSW	11	100483782	missense	possibly damaging	0.49
R7149:Acly	UTSW	11	100484625	missense	probably damaging	1.00
R7349:Acly	UTSW	11	100521991	missense	probably benign
R7450:Acly	UTSW	11	100479275	missense	probably damaging	1.00
R7484:Acly	UTSW	11	100495963	missense	probably damaging	1.00
R7687:Acly	UTSW	11	100504854	critical splice donor site	probably null
R7728:Acly	UTSW	11	100516797	missense	probably damaging	1.00
R7728:Acly	UTSW	11	100519687	missense	probably benign	0.06
R7750:Acly	UTSW	11	100478013	critical splice donor site	probably null
R8042:Acly	UTSW	11	100514325	missense	probably damaging	1.00
R8221:Acly	UTSW	11	100519750	missense	probably damaging	1.00
R8407:Acly	UTSW	11	100494071	missense	possibly damaging	0.67
R8677:Acly	UTSW	11	100519743	missense	probably damaging	0.96
R8721:Acly	UTSW	11	100521980	critical splice donor site	probably null
R8861:Acly	UTSW	11	100484598	critical splice donor site	probably null
R8894:Acly	UTSW	11	100516813	missense	probably benign	0.21
R9171:Acly	UTSW	11	100516831	missense	probably benign
X0028:Acly	UTSW	11	100495933	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- TAAAGTTCTGTACTGCCTTCTGG -3'
(R):5'- TTCCGCCTCAGTGTTTGAAG -3'

Sequencing Primer
(F):5'- AAAGCGTGTTACCAAGGG -3'
(R):5'- CCTCAGTGTTTGAAGAGTGACAGC -3'

Posted On

2014-08-25