Mutagenetix > Incidental Mutation

Incidental Mutation 'R9622:Acly'

724895

Institutional Source

Beutler Lab

Gene Symbol

Acly

Ensembl Gene

ENSMUSG00000020917

Gene Name

ATP citrate lyase

Synonyms

A730098H14Rik

MMRRC Submission

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R9622 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

100367179-100418826 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 100395785 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Threonine to Alanine at position 412 (T412A)

Ref Sequence

ENSEMBL: ENSMUSP00000103012 (fasta)

Gene Model

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

AlphaFold

Q91V92

Predicted Effect

probably damaging
Transcript: ENSMUST00000007131
AA Change: T412A

PolyPhen 2 Score 0.987 (Sensitivity: 0.73; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000007131
Gene: ENSMUSG00000020917
AA Change: T412A

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: T412A

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

SMART Domains

Protein: ENSMUSP00000103008
Gene: ENSMUSG00000020917
AA Change: T412A

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: T412A

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000103012
Gene: ENSMUSG00000020917
AA Change: T412A

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: T412A

PolyPhen 2 Score 0.987 (Sensitivity: 0.73; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000127632
Gene: ENSMUSG00000020917
AA Change: T412A

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: 100.0%
3x: 99.9%
10x: 99.7%
20x: 99.2%

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: 80 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Ablim2	A	G	5: 36,006,889 (GRCm39)	K435E	probably damaging	Het
Aldh3b2	T	A	19: 4,029,489 (GRCm39)	D287E	probably benign	Het
Asphd1	G	A	7: 126,547,974 (GRCm39)	P110S		Het
Atg7	T	C	6: 114,654,993 (GRCm39)	L142P	probably benign	Het
Atp13a4	T	C	16: 29,239,277 (GRCm39)	I796V		Het
Bbx	A	G	16: 50,095,022 (GRCm39)	V98A	probably damaging	Het
Brca2	T	C	5: 150,480,410 (GRCm39)	S2727P	probably damaging	Het
Camk1	T	A	6: 113,318,850 (GRCm39)	D21V	possibly damaging	Het
Cdc5l	A	T	17: 45,715,709 (GRCm39)	D634E	probably benign	Het
Cfap418	T	C	4: 10,893,304 (GRCm39)	I141T	possibly damaging	Het
Cyfip1	A	T	7: 55,528,853 (GRCm39)	D275V	possibly damaging	Het
Cyp4a30b	A	G	4: 115,328,162 (GRCm39)	E477G	probably damaging	Het
Cyp4f16	C	T	17: 32,769,246 (GRCm39)	P379S	probably damaging	Het
Dchs2	C	T	3: 83,263,766 (GRCm39)	Q3345*	probably null	Het
Dnaaf1	A	G	8: 120,315,001 (GRCm39)	T270A	possibly damaging	Het
Dnah3	A	G	7: 119,561,356 (GRCm39)	V334A		Het
Dnhd1	T	C	7: 105,353,342 (GRCm39)	F2832L	probably benign	Het
Dock8	A	G	19: 25,098,545 (GRCm39)	N623S	probably null	Het
Eif4enif1	T	C	11: 3,165,714 (GRCm39)	I97T	probably benign	Het
Elmo1	C	G	13: 20,392,310 (GRCm39)	P29A	probably benign	Het
Erich6	G	C	3: 58,544,162 (GRCm39)	P142A	possibly damaging	Het
Fam135b	T	C	15: 71,397,686 (GRCm39)	R125G	probably damaging	Het
Fcrla	T	A	1: 170,749,808 (GRCm39)	H83L	probably damaging	Het
Flt3	C	T	5: 147,303,841 (GRCm39)	E366K	possibly damaging	Het
Gabbr2	C	T	4: 46,724,283 (GRCm39)		probably null	Het
Gigyf1	T	A	5: 137,522,926 (GRCm39)	L809*	probably null	Het
Glg1	C	T	8: 111,899,133 (GRCm39)	G711R	probably damaging	Het
Gp1bb	T	C	16: 18,439,527 (GRCm39)	E189G	probably benign	Het
H2-Q1	A	T	17: 35,542,532 (GRCm39)	I326F	probably benign	Het
Hoxb3	A	T	11: 96,235,420 (GRCm39)	K116*	probably null	Het
Kcnb1	T	C	2: 167,030,161 (GRCm39)	Y128C	probably damaging	Het
Kif5b	G	A	18: 6,225,672 (GRCm39)	R171C	probably damaging	Het
Lcn4	G	A	2: 26,561,228 (GRCm39)	Q18*	probably null	Het
Lrp1b	G	A	2: 40,779,354 (GRCm39)	Q2677*	probably null	Het
Map4k3	T	A	17: 80,958,538 (GRCm39)	T145S	probably damaging	Het
Mas1	T	C	17: 13,060,898 (GRCm39)	E175G	probably benign	Het
Metap2	T	C	10: 93,707,366 (GRCm39)	T202A	probably benign	Het
Mras	A	T	9: 99,275,054 (GRCm39)	M131K	probably benign	Het
Mtor	T	C	4: 148,568,169 (GRCm39)	V1092A	probably damaging	Het
Mug2	T	C	6: 122,028,751 (GRCm39)	S582P	probably benign	Het
Myo5b	A	G	18: 74,848,017 (GRCm39)	N1085S	probably damaging	Het
Nav3	T	C	10: 109,603,103 (GRCm39)	T1149A	probably benign	Het
Nipbl	A	T	15: 8,366,373 (GRCm39)	S1239T	probably benign	Het
Nkpd1	C	A	7: 19,257,867 (GRCm39)	R549S	probably benign	Het
Or10a3m	T	A	7: 108,312,677 (GRCm39)	M39K	probably benign	Het
Or10p1	G	A	10: 129,444,084 (GRCm39)	H89Y	probably benign	Het
Or1j1	A	G	2: 36,702,621 (GRCm39)	L161P	probably damaging	Het
Or51i2	T	A	7: 103,689,522 (GRCm39)	V173D	probably damaging	Het
Pcdh18	T	C	3: 49,711,229 (GRCm39)	N29D	probably benign	Het
Pdzrn4	T	C	15: 92,294,949 (GRCm39)	W52R	probably benign	Het
Plekhb1	T	C	7: 100,304,588 (GRCm39)	K39E	probably damaging	Het
Pramel28	A	G	4: 143,692,348 (GRCm39)	S218P	probably benign	Het
Psmb4	C	A	3: 94,792,285 (GRCm39)	E212D	probably benign	Het
Rcc1l	A	G	5: 134,205,348 (GRCm39)	L69P	probably damaging	Het
Robo2	T	C	16: 73,729,952 (GRCm39)	R1082G	probably benign	Het
Rorb	T	C	19: 18,955,115 (GRCm39)	Y167C	probably damaging	Het
Sanbr	T	A	11: 23,534,590 (GRCm39)	K589I	probably damaging	Het
Sbsn	GGAAATATGGCAGACAAGTTTGGTCAGGGGGCCCACCATGCTTTTGGTCAGGGCAG	GG	7: 30,452,067 (GRCm39)		probably benign	Het
Scaf8	T	A	17: 3,248,170 (GRCm39)	F1164L	probably benign	Het
Scn10a	A	T	9: 119,438,046 (GRCm39)	M1940K	probably benign	Het
Serpinb2	A	G	1: 107,452,298 (GRCm39)	N292S	probably benign	Het
Sparcl1	C	A	5: 104,234,998 (GRCm39)	V506L	possibly damaging	Het
Stt3a	A	G	9: 36,661,025 (GRCm39)	V262A	possibly damaging	Het
Syt17	C	A	7: 118,036,191 (GRCm39)	M58I	probably benign	Het
Tas2r134	A	C	2: 51,518,358 (GRCm39)	N279T	possibly damaging	Het
Tbc1d2	T	C	4: 46,609,065 (GRCm39)	E724G	probably damaging	Het
Teddm1b	T	A	1: 153,750,620 (GRCm39)	L143Q		Het
Tlk1	T	A	2: 70,617,281 (GRCm39)	R66S	probably damaging	Het
Tmem139	A	T	6: 42,240,176 (GRCm39)		probably null	Het
Tom1l2	T	C	11: 60,151,942 (GRCm39)	Y155C	possibly damaging	Het
Trmt1l	C	A	1: 151,304,710 (GRCm39)	S28*	probably null	Het
Ttf2	T	C	3: 100,859,918 (GRCm39)	I679V	probably benign	Het
Unc13b	T	G	4: 43,172,513 (GRCm39)	F1114V		Het
Vmn2r25	T	A	6: 123,816,579 (GRCm39)	D334V	probably damaging	Het
Vps13c	T	G	9: 67,856,715 (GRCm39)	Y2581D	probably damaging	Het
Xkr5	A	G	8: 18,984,247 (GRCm39)	S432P	probably benign	Het
Zc2hc1b	G	A	10: 13,043,677 (GRCm39)	P73S	possibly damaging	Het
Zfhx2	A	C	14: 55,303,483 (GRCm39)	F1500L	probably benign	Het
Zfp3	T	G	11: 70,662,739 (GRCm39)	S233A	possibly damaging	Het
Zmat5	T	C	11: 4,687,453 (GRCm39)	W169R	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
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
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'- CAGGAGAGGAACATTGTGTCC -3'
(R):5'- ACTTTTGGCACGTGATCTGTAG -3'

Sequencing Primer
(F):5'- AGAGGAACATTGTGTCCTGTGTAG -3'
(R):5'- GTAGATGAACAGTCTTGTCCTCACAG -3'

Posted On

2022-09-12