Mutagenetix > Incidental Mutations

Incidental Mutation 'R5940:Ppargc1a'

462482

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

044132-MU

Accession Numbers

Is this an essential gene?

Probably essential (E-score: 0.773) question?

Stock #

R5940 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

51454250-51567726 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

C to T at 51473911 bp

Zygosity

Heterozygous

Amino Acid Change

Alanine to Threonine at position 459 (A459T)

Ref Sequence

ENSEMBL: ENSMUSP00000143553 (fasta)

Gene Model

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

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

probably damaging
Transcript: ENSMUST00000132734
AA Change: A459T

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000117040
Gene: ENSMUSG00000029167
AA Change: A459T

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 damaging
Transcript: ENSMUST00000196968
AA Change: A459T

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000143553
Gene: ENSMUSG00000029167
AA Change: A459T

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

Meta Mutation Damage Score

0.1330

Coding Region Coverage

1x: 99.9%
3x: 99.6%
10x: 98.2%
20x: 95.0%

Validation Efficiency

96% (88/92)

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: 79 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
0610037L13Rik	A	G	4: 107,893,288		probably benign	Het
1110008L16Rik	T	A	12: 55,304,874	W323R	probably damaging	Het
1500015O10Rik	C	T	1: 43,737,241	R41*	probably null	Het
3425401B19Rik	T	C	14: 32,662,688	Y440C	possibly damaging	Het
5430419D17Rik	A	T	7: 131,238,263	D638V	probably damaging	Het
Aasdh	G	T	5: 76,882,898	S618R	probably benign	Het
Alpk1	T	G	3: 127,670,946	T1228P	probably benign	Het
Ank3	T	C	10: 69,920,486	V850A	probably benign	Het
Apeh	A	T	9: 108,091,899		probably null	Het
Ash1l	C	T	3: 88,984,036	T1074I	probably damaging	Het
C3	G	A	17: 57,210,244	S1297F	possibly damaging	Het
Cchcr1	G	A	17: 35,524,993	R284Q	probably damaging	Het
Cd93	A	T	2: 148,442,232	I398N	probably benign	Het
Chrd	G	T	16: 20,734,586	R226L	probably null	Het
Clvs1	A	T	4: 9,449,443	N344I	possibly damaging	Het
Cyp4v3	A	T	8: 45,321,784	I111N	probably damaging	Het
Cysltr2	T	A	14: 73,029,949	Y107F	probably damaging	Het
Cysltr2	T	C	14: 73,029,491	K260E	probably benign	Het
Defb47	A	T	14: 63,000,910	E28D	probably benign	Het
Dnajc30	T	A	5: 135,064,559	Y103*	probably null	Het
Drap1	T	C	19: 5,423,000	T160A	probably benign	Het
Dsp	A	G	13: 38,196,026	E2249G	possibly damaging	Het
E2f8	T	A	7: 48,871,077	I499F	probably benign	Het
Ebf1	T	A	11: 44,621,221	Y116N	probably damaging	Het
Ect2	C	A	3: 27,115,465	E746D	probably benign	Het
Enpep	T	A	3: 129,312,578	Y333F	probably damaging	Het
Fat4	T	C	3: 38,889,649	V897A	probably benign	Het
Gja3	T	A	14: 57,035,860	S352C	probably damaging	Het
Gm884	T	C	11: 103,613,886	S243G	probably benign	Het
Gpr153	C	A	4: 152,283,375	P561Q	probably benign	Het
Hlcs	T	C	16: 94,134,712	M574V	probably damaging	Het
Hmcn1	A	G	1: 150,657,222	V3070A	probably benign	Het
Hsd3b2	G	T	3: 98,711,971	N219K	probably benign	Het
Htra3	T	C	5: 35,652,980	I453V	possibly damaging	Het
Klrc1	A	T	6: 129,674,935	M220K	possibly damaging	Het
Kntc1	T	G	5: 123,786,195	I1048S	probably benign	Het
Macf1	T	A	4: 123,432,881	D2822V	probably damaging	Het
Mcu	T	A	10: 59,456,732	I42F	possibly damaging	Het
Mkln1	T	A	6: 31,489,372	D521E	probably damaging	Het
Ms4a13	T	C	19: 11,192,966	N5D	possibly damaging	Het
Msh3	T	G	13: 92,249,843	N838T	probably damaging	Het
Msl2	T	A	9: 101,101,091	C221*	probably null	Het
Ncapd2	A	G	6: 125,168,869	S1310P	probably benign	Het
Ncoa6	A	T	2: 155,415,865	M586K	probably damaging	Het
Ndel1	C	T	11: 68,822,571		probably benign	Het
Ndst4	T	C	3: 125,561,419		probably benign	Het
Nes	T	G	3: 87,975,952	V506G	probably damaging	Het
Nrg1	T	C	8: 31,849,344	K200E	probably damaging	Het
Nt5c1b	A	G	12: 10,375,515	K295E	probably damaging	Het
Olfr1085	A	T	2: 86,658,050	M136K	probably damaging	Het
Olfr1278	G	A	2: 111,292,384	V39M	possibly damaging	Het
Olfr1487	T	A	19: 13,619,153		probably null	Het
Olfr750	T	A	14: 51,070,722	I224L	probably damaging	Het
Olfr878	C	T	9: 37,919,437	T260I	probably damaging	Het
Olfr919	G	T	9: 38,697,711	Y218*	probably null	Het
Otx1	C	A	11: 21,997,037	A91S	probably damaging	Het
Pde1a	A	G	2: 79,887,839		probably null	Het
Pds5a	A	G	5: 65,643,985		probably benign	Het
Plbd1	A	T	6: 136,613,721		probably benign	Het
Plod2	T	A	9: 92,591,397	V292E	probably benign	Het
Polg	A	G	7: 79,454,071	V879A	possibly damaging	Het
Psip1	T	C	4: 83,476,322	E83G	probably damaging	Het
Rhbdf1	T	C	11: 32,209,847	D843G	probably benign	Het
Rnpepl1	G	T	1: 92,917,712	C451F	probably damaging	Het
Rrp1	T	C	10: 78,405,415	D206G	probably damaging	Het
Setbp1	A	T	18: 78,755,488	D1492E	probably damaging	Het
Sh3bp5	C	A	14: 31,377,495	R265L	probably benign	Het
Slc16a6	C	T	11: 109,473,196		probably benign	Homo
Slc7a6os	A	G	8: 106,210,805	S37P	probably damaging	Het
Tenm4	T	A	7: 96,845,895	S1140T	probably damaging	Het
Thoc6	C	A	17: 23,670,341	R115L	probably benign	Het
Tmem63c	C	T	12: 87,075,172	H385Y	probably benign	Het
Trpm8	G	T	1: 88,351,415	E649*	probably null	Het
Usf1	A	G	1: 171,417,779	E253G	possibly damaging	Het
Vps13d	T	C	4: 145,074,975	T443A	probably benign	Het
Wdr86	T	C	5: 24,722,662	Y93C	probably damaging	Het
Zfp597	A	T	16: 3,865,821	I357N	probably damaging	Het
Zfp709	A	G	8: 71,890,220	I497V	possibly damaging	Het
Zxdc	T	C	6: 90,370,325	S223P	probably 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
R2211:Ppargc1a	UTSW	5	51474259	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
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
X0019:Ppargc1a	UTSW	5	51548678	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- ACAATGAATAGGGCTGCGTGC -3'
(R):5'- TCACAGGAGCTCCAAGACTC -3'

Sequencing Primer
(F):5'- CCAAGGGTAGCTCAGTTTATCAC -3'
(R):5'- TCTAGACAACTAGACTTCAAAGATGC -3'

Posted On

2017-02-28