Mutagenetix > Incidental Mutation

Incidental Mutation 'R2211:Ppargc1a'

239363

Institutional Source

Beutler Lab

Gene Symbol

Ppargc1a

Ensembl Gene

ENSMUSG00000029167

Gene Name

peroxisome proliferative activated receptor, gamma, coactivator 1 alpha

Synonyms

A830037N07Rik, Gm11133, Pgco1, Pgc1, PPAR Gamma Coactivator-1, Pgc-1alpha, Pgc-1alphaa

MMRRC Submission

040213-MU

Accession Numbers

Essential gene?

Possibly essential (E-score: 0.706) question?

Stock #

R2211 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

51454250-51567726 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to C at 51474259 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Serine to Alanine at position 343 (S343A)

Ref Sequence

ENSEMBL: ENSMUSP00000117040 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000031059] [ENSMUST00000132734] [ENSMUST00000151104] [ENSMUST00000196968]

AlphaFold

O70343

PDB Structure

SF-1 LBD bound by phosphatidylcholine [X-RAY DIFFRACTION]

Predicted Effect

probably benign
Transcript: ENSMUST00000031059

SMART Domains

Protein: ENSMUSP00000138397
Gene: ENSMUSG00000029167

Domain	Start	End	E-Value	Type
low complexity region	23	40	N/A	INTRINSIC
low complexity region	141	147	N/A	INTRINSIC
PDB:3D24\|D	197	218	1e-7	PDB

Predicted Effect

possibly damaging
Transcript: ENSMUST00000132734
AA Change: S343A

PolyPhen 2 Score 0.475 (Sensitivity: 0.89; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000117040
Gene: ENSMUSG00000029167
AA Change: S343A

Domain	Start	End	E-Value	Type
low complexity region	23	40	N/A	INTRINSIC
low complexity region	141	147	N/A	INTRINSIC
PDB:3D24\|D	197	218	4e-7	PDB
low complexity region	294	300	N/A	INTRINSIC
low complexity region	558	613	N/A	INTRINSIC
low complexity region	615	636	N/A	INTRINSIC
RRM	677	746	4.61e-5	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000151104

SMART Domains

Protein: ENSMUSP00000116566
Gene: ENSMUSG00000029167

Domain	Start	End	E-Value	Type
low complexity region	19	36	N/A	INTRINSIC
low complexity region	137	143	N/A	INTRINSIC
PDB:3D24\|D	193	214	1e-7	PDB

Predicted Effect

probably benign
Transcript: ENSMUST00000196968
AA Change: S343A

PolyPhen 2 Score 0.128 (Sensitivity: 0.93; Specificity: 0.86)

SMART Domains

Protein: ENSMUSP00000143553
Gene: ENSMUSG00000029167
AA Change: S343A

Domain	Start	End	E-Value	Type
low complexity region	23	40	N/A	INTRINSIC
low complexity region	141	147	N/A	INTRINSIC
PDB:3D24\|D	197	218	4e-7	PDB
low complexity region	294	300	N/A	INTRINSIC
low complexity region	558	613	N/A	INTRINSIC
low complexity region	615	636	N/A	INTRINSIC

Coding Region Coverage

1x: 99.1%
3x: 98.5%
10x: 97.1%
20x: 94.5%

Validation Efficiency

MGI Phenotype

FUNCTION: This gene encodes a transcriptional coactivator that induces and coordinates gene expression regulating mitochondrial biogenesis, respiration, hepatic gluconeogenesis, thermogenic program in brown fat and muscle fiber-type switching. Mice lacking the encoded protein exhibit reduced thermogenic capacity, hyperactivity and resistance to diet-induced obesity. Mice lacking the encoded protein specifically in the heart exhibit peripartum cardiomyopathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]
PHENOTYPE: Homozygous null mice display partial postnatal lethality, abnormal glucose and insulin homeostasis, resistance to diet induced obesity, increased oxygen consumption, spongiform encephalopathy, hyperactivity, increased startle reflex, and limb grasping. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 71 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
A430078G23Rik	T	C	8: 3,387,680	S268P	possibly damaging	Het
Adam18	A	G	8: 24,628,155	S34P	probably damaging	Het
Adam23	T	A	1: 63,573,129		probably benign	Het
Adcy10	A	T	1: 165,518,212	I277F	probably damaging	Het
Arfgef3	A	T	10: 18,592,245	S1736T	possibly damaging	Het
Arhgap21	A	T	2: 20,881,640	M242K	possibly damaging	Het
Astn1	A	G	1: 158,657,306	R4G	probably benign	Het
AU041133	G	A	10: 82,150,921	C135Y	probably damaging	Het
Cdc42bpb	A	G	12: 111,301,854	V53A	probably benign	Het
Cdh23	T	C	10: 60,466,004	D428G	possibly damaging	Het
Cebpa	T	C	7: 35,120,466	S350P	probably damaging	Het
Cftr	A	G	6: 18,214,280	M152V	probably null	Het
Cpa4	A	G	6: 30,583,650	N255S	possibly damaging	Het
Ddx51	T	A	5: 110,655,768	D343E	probably damaging	Het
Dnah7a	T	C	1: 53,479,773	I2942V	probably benign	Het
Dnajc1	G	T	2: 18,392,475	A9E	probably damaging	Het
Dpysl5	G	A	5: 30,791,597	D399N	probably damaging	Het
Edem3	A	G	1: 151,804,702	D526G	possibly damaging	Het
Emc10	G	A	7: 44,493,192	R109W	probably damaging	Het
Etaa1	G	A	11: 17,952,686	Q84*	probably null	Het
Fabp3	C	T	4: 130,312,387	T57I	probably benign	Het
Fam149a	G	A	8: 45,341,009	T674I	probably damaging	Het
Fam98a	A	G	17: 75,538,945		probably null	Het
Fat4	A	G	3: 38,891,527	N1523S	possibly damaging	Het
Fbxw10	A	G	11: 62,867,535	T529A	probably damaging	Het
Gzf1	C	T	2: 148,684,950	A447V	probably damaging	Het
Hap1	G	A	11: 100,354,724	T138M	probably benign	Het
Hic1	T	A	11: 75,169,384	R46W	possibly damaging	Het
Id4	T	A	13: 48,261,802	L102Q	probably damaging	Het
Il3ra	T	C	14: 14,355,029	C271R	probably benign	Het
Ints4	T	C	7: 97,509,750	I443T	possibly damaging	Het
Lmln	A	G	16: 33,109,778	E535G	probably benign	Het
Lrrtm4	A	G	6: 80,022,640	H345R	probably benign	Het
Ltbp3	T	C	19: 5,753,962	I834T	possibly damaging	Het
Mnd1	C	A	3: 84,134,109	C62F	probably benign	Het
Mpp5	A	T	12: 78,797,248	K75N	possibly damaging	Het
Ms4a18	C	A	19: 10,997,305	V341L	probably benign	Het
Nbr1	T	C	11: 101,567,264		probably null	Het
Nf1	T	C	11: 79,444,064	M914T	probably benign	Het
Notch3	T	A	17: 32,147,978	H861L	probably benign	Het
Nupl1	A	G	14: 60,232,640	F341L	probably damaging	Het
Ogfod2	C	A	5: 124,112,780		probably null	Het
Oit3	T	C	10: 59,428,070	D414G	probably damaging	Het
Olfr1079	T	C	2: 86,538,513	Y132C	probably damaging	Het
Olfr1497	T	A	19: 13,795,369	M81L	probably benign	Het
Olfr787	A	T	10: 129,462,940	K88M	probably damaging	Het
Olfr804	A	G	10: 129,705,451	H191R	probably benign	Het
Pcbp4	C	A	9: 106,460,734	H74Q	probably benign	Het
Pip5k1b	A	T	19: 24,378,850	D241E	probably damaging	Het
Plcb2	T	C	2: 118,723,534	D102G	probably benign	Het
Plekha5	G	A	6: 140,525,861	E4K	possibly damaging	Het
Ppwd1	G	A	13: 104,207,142	S585L	probably benign	Het
Rarg	T	C	15: 102,239,524	N284S	probably benign	Het
Rnpepl1	C	T	1: 92,916,380	L278F	probably damaging	Het
Rp1	A	C	1: 4,348,139	S917A	probably damaging	Het
Rsf1	ATGGCG	ATGGCGAGGGTGGCG	7: 97,579,904		probably benign	Het
Rsph3b	T	C	17: 6,941,740	S189G	probably benign	Het
Sec31b	A	T	19: 44,523,150	L604Q	probably damaging	Het
Sema6b	T	A	17: 56,124,741	I641F	probably benign	Het
Slc35f5	A	T	1: 125,579,264	I309F	possibly damaging	Het
Smarca4	A	G	9: 21,686,029	E1360G	probably damaging	Het
Spata31d1c	T	C	13: 65,035,939	S432P	probably benign	Het
Spsb3	T	C	17: 24,890,937		probably null	Het
Sptbn4	T	C	7: 27,367,609	D1960G	probably damaging	Het
Srgap1	A	G	10: 121,853,740	V345A	possibly damaging	Het
Tiam2	C	A	17: 3,414,918	C307*	probably null	Het
Trim43b	T	A	9: 89,085,249	T444S	possibly damaging	Het
Trmt13	A	G	3: 116,594,754	I11T	probably benign	Het
Ylpm1	A	T	12: 85,044,378	R1073*	probably null	Het
Zfp524	T	C	7: 5,017,919	S149P	probably damaging	Het
Zfp777	T	C	6: 48,043,885	I312V	possibly damaging	Het

Other mutations in Ppargc1a

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01016:Ppargc1a	APN	5	51498031	splice site	probably null
IGL01063:Ppargc1a	APN	5	51474322	missense	probably benign	0.43
IGL01800:Ppargc1a	APN	5	51494721	missense	probably damaging	1.00
IGL02179:Ppargc1a	APN	5	51473711	missense	possibly damaging	0.90
IGL02336:Ppargc1a	APN	5	51495726	nonsense	probably null
IGL02368:Ppargc1a	APN	5	51474156	missense	probably benign	0.05
BB007:Ppargc1a	UTSW	5	51472922	missense	unknown
BB017:Ppargc1a	UTSW	5	51472922	missense	unknown
R1300:Ppargc1a	UTSW	5	51548672	missense	probably damaging	1.00
R2048:Ppargc1a	UTSW	5	51548516	missense	probably damaging	1.00
R2054:Ppargc1a	UTSW	5	51473788	missense	possibly damaging	0.47
R2848:Ppargc1a	UTSW	5	51473809	missense	probably benign	0.02
R4094:Ppargc1a	UTSW	5	51490064	missense	possibly damaging	0.47
R4419:Ppargc1a	UTSW	5	51494702	missense	probably damaging	1.00
R4552:Ppargc1a	UTSW	5	51463215	intron	probably benign
R4702:Ppargc1a	UTSW	5	51495696	missense	possibly damaging	0.73
R4855:Ppargc1a	UTSW	5	51474222	missense	possibly damaging	0.89
R5287:Ppargc1a	UTSW	5	51462825	intron	probably benign
R5313:Ppargc1a	UTSW	5	51458239	utr 3 prime	probably benign
R5403:Ppargc1a	UTSW	5	51462825	intron	probably benign
R5711:Ppargc1a	UTSW	5	51474220	missense	probably damaging	1.00
R5918:Ppargc1a	UTSW	5	51463237	intron	probably benign
R5940:Ppargc1a	UTSW	5	51473911	missense	probably damaging	1.00
R6170:Ppargc1a	UTSW	5	51473911	missense	probably damaging	1.00
R6415:Ppargc1a	UTSW	5	51462834	intron	probably benign
R7718:Ppargc1a	UTSW	5	51498162	missense	probably damaging	1.00
R7755:Ppargc1a	UTSW	5	51473541	missense	unknown
R7793:Ppargc1a	UTSW	5	51462509	splice site	probably null
R7849:Ppargc1a	UTSW	5	51548513	missense	probably benign	0.45
R7930:Ppargc1a	UTSW	5	51472922	missense	unknown
R8169:Ppargc1a	UTSW	5	51473684	missense	probably benign	0.19
R8497:Ppargc1a	UTSW	5	51490228	missense	probably damaging	1.00
R8862:Ppargc1a	UTSW	5	51473893	missense	possibly damaging	0.88
R8907:Ppargc1a	UTSW	5	51490228	missense	probably damaging	0.99
R9017:Ppargc1a	UTSW	5	51472909	missense	unknown
R9142:Ppargc1a	UTSW	5	51494804	missense	possibly damaging	0.86
R9475:Ppargc1a	UTSW	5	51495738	missense	probably damaging	1.00
R9580:Ppargc1a	UTSW	5	51462797	missense	unknown
R9655:Ppargc1a	UTSW	5	51548510	critical splice donor site	probably null
X0019:Ppargc1a	UTSW	5	51548678	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- CTAGAGTCTTGGAGCTCCTGTG -3'
(R):5'- GTCCTTGAAGAACATTATCTCCATCTC -3'

Sequencing Primer
(F):5'- GGAGCTCCTGTGATATGTTAATGAG -3'
(R):5'- TTTCCCCTCCTACATTTCTTTTTG -3'

Posted On

2014-10-15