Mutagenetix > Incidental Mutation

Incidental Mutation 'P0008:Agpat3'

7554

Institutional Source

Beutler Lab

Gene Symbol

Agpat3

Ensembl Gene

ENSMUSG00000001211

Gene Name

1-acylglycerol-3-phosphate O-acyltransferase 3

Synonyms

D10Jhu12e, LPAAT3

MMRRC Submission

038264-MU

Accession Numbers

Essential gene?

Probably non essential (E-score: 0.129) question?

Stock #

P0008 (G1)

Quality Score

Status

Validated

Chromosome

Chromosomal Location

78105012-78188323 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 78123710 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Asparagine to Serine at position 50 (N50S)

Ref Sequence

ENSEMBL: ENSMUSP00000114657 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000001240] [ENSMUST00000105387] [ENSMUST00000105388] [ENSMUST00000105389] [ENSMUST00000105390] [ENSMUST00000138035] [ENSMUST00000139282] [ENSMUST00000166360] [ENSMUST00000150828] [ENSMUST00000146899] [ENSMUST00000219932]

AlphaFold

Q9D517

Predicted Effect

possibly damaging
Transcript: ENSMUST00000001240
AA Change: N50S

PolyPhen 2 Score 0.816 (Sensitivity: 0.84; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000001240
Gene: ENSMUSG00000001211
AA Change: N50S

Domain	Start	End	E-Value	Type
transmembrane domain	15	37	N/A	INTRINSIC
PlsC	90	212	3.14e-21	SMART
transmembrane domain	308	330	N/A	INTRINSIC
transmembrane domain	335	357	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000105387
AA Change: N50S

PolyPhen 2 Score 0.816 (Sensitivity: 0.84; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000101026
Gene: ENSMUSG00000001211
AA Change: N50S

Domain	Start	End	E-Value	Type
transmembrane domain	15	37	N/A	INTRINSIC
PlsC	90	212	3.14e-21	SMART
transmembrane domain	308	330	N/A	INTRINSIC
transmembrane domain	335	357	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000105388
AA Change: N50S

PolyPhen 2 Score 0.816 (Sensitivity: 0.84; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000101027
Gene: ENSMUSG00000001211
AA Change: N50S

Domain	Start	End	E-Value	Type
transmembrane domain	15	37	N/A	INTRINSIC
PlsC	90	212	3.14e-21	SMART
transmembrane domain	308	330	N/A	INTRINSIC
transmembrane domain	335	357	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000105389
AA Change: N50S

PolyPhen 2 Score 0.816 (Sensitivity: 0.84; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000101028
Gene: ENSMUSG00000001211
AA Change: N50S

Domain	Start	End	E-Value	Type
transmembrane domain	15	37	N/A	INTRINSIC
PlsC	90	212	3.14e-21	SMART
transmembrane domain	308	330	N/A	INTRINSIC
transmembrane domain	335	357	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000105390
AA Change: N50S

PolyPhen 2 Score 0.816 (Sensitivity: 0.84; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000101029
Gene: ENSMUSG00000001211
AA Change: N50S

Domain	Start	End	E-Value	Type
transmembrane domain	15	37	N/A	INTRINSIC
PlsC	90	212	3.14e-21	SMART
transmembrane domain	308	330	N/A	INTRINSIC
transmembrane domain	335	357	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000138035
AA Change: N50S

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

SMART Domains

Protein: ENSMUSP00000121052
Gene: ENSMUSG00000001211
AA Change: N50S

Domain	Start	End	E-Value	Type
transmembrane domain	15	37	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000139282
AA Change: N50S

PolyPhen 2 Score 0.952 (Sensitivity: 0.79; Specificity: 0.95)

SMART Domains

Protein: ENSMUSP00000119713
Gene: ENSMUSG00000001211
AA Change: N50S

Domain	Start	End	E-Value	Type
transmembrane domain	15	37	N/A	INTRINSIC
Pfam:Acyltransferase	72	144	3.1e-7	PFAM

Predicted Effect

possibly damaging
Transcript: ENSMUST00000166360
AA Change: N50S

PolyPhen 2 Score 0.816 (Sensitivity: 0.84; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000132954
Gene: ENSMUSG00000001211
AA Change: N50S

Domain	Start	End	E-Value	Type
transmembrane domain	15	37	N/A	INTRINSIC
PlsC	90	212	3.14e-21	SMART
Pfam:Acyltransf_C	241	314	2.1e-29	PFAM
transmembrane domain	335	357	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000150828
AA Change: N50S

PolyPhen 2 Score 0.930 (Sensitivity: 0.81; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000114885
Gene: ENSMUSG00000001211
AA Change: N50S

Domain	Start	End	E-Value	Type
transmembrane domain	15	37	N/A	INTRINSIC
Blast:PlsC	90	129	5e-20	BLAST

Predicted Effect

probably damaging
Transcript: ENSMUST00000146899
AA Change: N50S

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

SMART Domains

Protein: ENSMUSP00000114657
Gene: ENSMUSG00000001211
AA Change: N50S

Domain	Start	End	E-Value	Type
transmembrane domain	15	37	N/A	INTRINSIC

Predicted Effect

silent
Transcript: ENSMUST00000219932

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000219907

Meta Mutation Damage Score

0.2996

Coding Region Coverage

1x: 86.8%
3x: 83.1%
10x: 72.7%
20x: 59.5%

Validation Efficiency

70% (420/599)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene is an acyltransferase that converts lysophosphatidic acid into phosphatidic acid, which is the second step in the de novo phospholipid biosynthetic pathway. The encoded protein may be an integral membrane protein. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]
PHENOTYPE: Mice homozygous for a knock-out allele exhibit male infertility with oligozoospermia, teratozoospermia. [provided by MGI curators]

Allele List at MGI

All alleles(14) : Targeted(2) Gene trapped(12)

Other mutations in this stock

Total: 9 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Cfap70	A	T	14: 20,466,600 (GRCm39)	F550I	probably damaging	Het
Dmpk	G	A	7: 18,821,987 (GRCm39)	R315H	possibly damaging	Het
Dnah5	T	A	15: 28,302,533 (GRCm39)	Y1597N	probably damaging	Het
Mocos	A	T	18: 24,812,663 (GRCm39)	Q519L	probably benign	Het
Mycbpap	T	A	11: 94,394,893 (GRCm39)	D270V	probably damaging	Het
Pkp1	T	C	1: 135,803,421 (GRCm39)	M712V	probably benign	Het
Sgtb	T	C	13: 104,260,782 (GRCm39)	V77A	probably damaging	Het
Srpk2	T	C	5: 23,718,976 (GRCm39)	Y613C	probably damaging	Het
Wwc1	T	C	11: 35,744,178 (GRCm39)		probably benign	Het

Other mutations in Agpat3

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00557:Agpat3	APN	10	78,109,516 (GRCm39)	utr 3 prime	probably benign
IGL02621:Agpat3	APN	10	78,120,900 (GRCm39)	missense	probably damaging	1.00
IGL02725:Agpat3	APN	10	78,113,889 (GRCm39)	missense	probably benign	0.02
PIT4445001:Agpat3	UTSW	10	78,109,927 (GRCm39)	missense	possibly damaging	0.94
R0041:Agpat3	UTSW	10	78,123,881 (GRCm39)	unclassified	probably benign
R0126:Agpat3	UTSW	10	78,113,890 (GRCm39)	missense	probably null	0.59
R0226:Agpat3	UTSW	10	78,113,863 (GRCm39)	missense	possibly damaging	0.89
R1520:Agpat3	UTSW	10	78,123,857 (GRCm39)	start codon destroyed	probably null	1.00
R2118:Agpat3	UTSW	10	78,113,918 (GRCm39)	missense	probably damaging	1.00
R5493:Agpat3	UTSW	10	78,120,069 (GRCm39)	missense	possibly damaging	0.89
R5599:Agpat3	UTSW	10	78,110,103 (GRCm39)	missense	probably benign	0.39
R6280:Agpat3	UTSW	10	78,120,872 (GRCm39)	missense	probably damaging	1.00
R7528:Agpat3	UTSW	10	78,123,746 (GRCm39)	missense	probably damaging	1.00
R7895:Agpat3	UTSW	10	78,119,034 (GRCm39)	missense	probably benign	0.34
R8351:Agpat3	UTSW	10	78,110,086 (GRCm39)	missense	probably damaging	1.00
R8425:Agpat3	UTSW	10	78,118,211 (GRCm39)	missense	possibly damaging	0.89
R8949:Agpat3	UTSW	10	78,118,989 (GRCm39)	missense	probably benign	0.00
R9136:Agpat3	UTSW	10	78,120,893 (GRCm39)	missense	probably damaging	1.00
X0003:Agpat3	UTSW	10	78,110,007 (GRCm39)	nonsense	probably null

Protein Function and Prediction

AGPAT3 (1-acyl-sn-glycerol 3-phosphate acyltransferase 3; alternatively lysophosphatidic acid acyltransferase (Lpaat3)) is one of the five isoforms of AGPAT (1). Agpat3 is a 376-aa protein that contains four transmembrane domains (2). The AGPAT family, including Agpat3, catalyze the acylation of lysophosphatidic acid to phosphatidic acid, the precursor of all glycerolipids, in de novo and remodeling pathways (1). Agpat3 is induced during germ cell development and contributes to the accumulation of polyunsaturated fatty acids in testicular phospholipids (3). This indicates that Agpat3 may function in sperm cell production (3).

Expression/Localization

RT-PCR determined that Agpat3 is ubiquitously expressed with some tissue variation (1). In the mouse, quantitative real-time PCR analysis revealed that Agpat3 expression in the testis increases significantly in an age-dependent manner (2). The Agpat3 protein was predominant in the testis, liver, and kidney (2). Due to the presence of a C-terminal KKXX sequence motif, it is proposed that Agpat3 localizes to the endoplasmic reticulum (ER) (2). Confocal microscopy of a FLAG-Agpat3 construct confirmed that Agpat3 was expressed predominantly in the ER fraction (2).

References

1. Lu, B., Jiang, Y. J., Zhou, Y., Xu, F. Y., Hatch, G. M., and Choy, P. C. (2005) Cloning and Characterization of Murine 1-Acyl-Sn-Glycerol 3-Phosphate Acyltransferases and their Regulation by PPARalpha in Murine Heart. Biochem J. 385, 469-477.

2. Yuki, K., Shindou, H., Hishikawa, D., and Shimizu, T. (2009) Characterization of Mouse Lysophosphatidic Acid Acyltransferase 3: An Enzyme with Dual Functions in the Testis. J Lipid Res. 50, 860-869.

3. Koeberle, A., Shindou, H., Harayama, T., Yuki, K., and Shimizu, T. (2012) Polyunsaturated Fatty Acids are Incorporated into Maturating Male Mouse Germ Cells by Lysophosphatidic Acid Acyltransferase 3. FASEB J. 26, 169-180.

Posted On

2012-10-04

Science Writer

Anne Murray