Mutagenetix > Incidental Mutations

Incidental Mutation 'R3950:Pcx'

307910

Institutional Source

Beutler Lab

Gene Symbol

Pcx

Ensembl Gene

ENSMUSG00000024892

Gene Name

pyruvate carboxylase

Synonyms

MMRRC Submission

040930-MU

Accession Numbers

Is this an essential gene?

Essential (E-score: 1.000) question?

Stock #

R3950 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

4510472-4621752 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

C to T at 4617967 bp

Zygosity

Heterozygous

Amino Acid Change

Histidine to Tyrosine at position 506 (H506Y)

Ref Sequence

ENSEMBL: ENSMUSP00000153479 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000025823] [ENSMUST00000053597] [ENSMUST00000068004] [ENSMUST00000113822] [ENSMUST00000113825] [ENSMUST00000224707] [ENSMUST00000224726] [ENSMUST00000225476]

Predicted Effect

probably benign
Transcript: ENSMUST00000025823

SMART Domains

Protein: ENSMUSP00000025823
Gene: ENSMUSG00000024889

Domain	Start	End	E-Value	Type
transmembrane domain	34	56	N/A	INTRINSIC
low complexity region	72	88	N/A	INTRINSIC
transmembrane domain	112	134	N/A	INTRINSIC
Pfam:Abi	147	267	1.4e-19	PFAM
transmembrane domain	283	302	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000053597

SMART Domains

Protein: ENSMUSP00000050039
Gene: ENSMUSG00000045045

Domain	Start	End	E-Value	Type
LRRNT	16	52	1.16e0	SMART
LRR	71	94	3.86e0	SMART
LRR_TYP	95	118	9.44e-2	SMART
LRR	120	142	1.23e0	SMART
LRR	144	166	1.09e1	SMART
LRR_TYP	168	191	7.37e-4	SMART
LRR	192	215	1.45e1	SMART
LRRCT	234	279	1.27e-3	SMART
IGc2	293	358	3.35e-14	SMART
FN3	403	484	1.77e-2	SMART
transmembrane domain	517	539	N/A	INTRINSIC
low complexity region	565	585	N/A	INTRINSIC
low complexity region	614	626	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000068004
AA Change: H507Y

PolyPhen 2 Score 0.002 (Sensitivity: 0.99; Specificity: 0.30)

SMART Domains

Protein: ENSMUSP00000063825
Gene: ENSMUSG00000024892
AA Change: H507Y

Domain	Start	End	E-Value	Type
low complexity region	8	22	N/A	INTRINSIC
Pfam:CPSase_L_chain	37	147	3.3e-45	PFAM
Pfam:ATP-grasp_4	149	334	3.9e-19	PFAM
Pfam:CPSase_L_D2	152	361	7.2e-77	PFAM
Pfam:Dala_Dala_lig_C	161	329	1.5e-11	PFAM
Biotin_carb_C	376	483	1.21e-50	SMART
low complexity region	513	541	N/A	INTRINSIC
Pfam:HMGL-like	564	838	8.2e-29	PFAM
Pfam:PYC_OADA	862	1062	1.4e-72	PFAM
Pfam:Biotin_lipoyl	1111	1178	1.4e-20	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000113822

SMART Domains

Protein: ENSMUSP00000109453
Gene: ENSMUSG00000045045

Domain	Start	End	E-Value	Type
LRRNT	16	52	1.16e0	SMART
LRR	71	94	3.86e0	SMART
LRR_TYP	95	118	9.44e-2	SMART
LRR	120	142	1.23e0	SMART
LRR	144	166	1.09e1	SMART
LRR_TYP	168	191	7.37e-4	SMART
LRR	192	215	1.45e1	SMART
LRRCT	234	279	1.27e-3	SMART
IGc2	293	358	3.35e-14	SMART
FN3	403	484	1.77e-2	SMART
transmembrane domain	517	539	N/A	INTRINSIC
low complexity region	565	585	N/A	INTRINSIC
low complexity region	614	626	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000113825
AA Change: H506Y

PolyPhen 2 Score 0.002 (Sensitivity: 0.99; Specificity: 0.30)

SMART Domains

Protein: ENSMUSP00000109456
Gene: ENSMUSG00000024892
AA Change: H506Y

Domain	Start	End	E-Value	Type
low complexity region	7	21	N/A	INTRINSIC
Pfam:CPSase_L_chain	36	146	1.1e-43	PFAM
Pfam:ATP-grasp_4	148	332	2.9e-19	PFAM
Pfam:CPSase_L_D2	151	360	4.2e-77	PFAM
Pfam:Dala_Dala_lig_C	158	328	7.9e-13	PFAM
Biotin_carb_C	375	482	1.21e-50	SMART
low complexity region	512	540	N/A	INTRINSIC
Pfam:HMGL-like	571	821	3.4e-28	PFAM
Pfam:PYC_OADA	861	1062	3.4e-69	PFAM
Pfam:Biotin_lipoyl	1110	1177	1.8e-21	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000224707

Predicted Effect

probably benign
Transcript: ENSMUST00000224726
AA Change: H506Y

PolyPhen 2 Score 0.002 (Sensitivity: 0.99; Specificity: 0.30)

Predicted Effect

probably benign
Transcript: ENSMUST00000225476

Meta Mutation Damage Score

0.0942

Coding Region Coverage

1x: 99.2%
3x: 98.6%
10x: 97.3%
20x: 95.1%

Validation Efficiency

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes pyruvate carboxylase, which requires biotin and ATP to catalyse the carboxylation of pyruvate to oxaloacetate. The active enzyme is a homotetramer arranged in a tetrahedron which is located exclusively in the mitochondrial matrix. Pyruvate carboxylase is involved in gluconeogenesis, lipogenesis, insulin secretion and synthesis of the neurotransmitter glutamate. Mutations in this gene have been associated with pyruvate carboxylase deficiency. Alternatively spliced transcript variants with different 5' UTRs, but encoding the same protein, have been found for this gene. [provided by RefSeq, Jul 2008]

Allele List at MGI

Other mutations in this stock

Total: 59 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4932414N04Rik	T	C	2: 68,664,403		probably null	Het
Ahnak2	A	T	12: 112,785,789	I186N	probably damaging	Het
Appbp2	A	G	11: 85,194,706	I458T	probably damaging	Het
Arhgef25	T	C	10: 127,185,144	Y291C	probably damaging	Het
Ate1	T	C	7: 130,467,292	Y415C	probably damaging	Het
B4galt4	G	T	16: 38,768,022	A72S	probably benign	Het
C3	T	C	17: 57,225,286	R178G	probably benign	Het
Cdh23	T	C	10: 60,657,326	Y3C	probably benign	Het
Col11a1	T	C	3: 114,121,445		probably null	Het
Col22a1	A	G	15: 71,977,358	F294L	possibly damaging	Het
Dera	A	G	6: 137,837,120	Y100C	probably damaging	Het
Dync2h1	A	T	9: 7,112,061	Y276*	probably null	Het
Eea1	A	T	10: 96,042,134	N1389I	probably damaging	Het
Epha4	A	T	1: 77,399,716	Y509N	probably damaging	Het
Fat3	G	A	9: 15,998,271	S2145F	probably damaging	Het
Fezf1	T	A	6: 23,247,420	K219*	probably null	Het
Fsd1	G	A	17: 55,995,517		probably null	Het
Haspin	A	G	11: 73,136,395	Y623H	probably damaging	Het
Hsd3b1	C	T	3: 98,856,138	V56M	possibly damaging	Het
Hyou1	C	T	9: 44,385,227	T483I	probably damaging	Het
Kdm2a	A	G	19: 4,343,232	L365S	possibly damaging	Het
Kdm6b	G	T	11: 69,405,615	P609T	probably damaging	Het
Klhl18	T	A	9: 110,428,902	Y490F	probably damaging	Het
Ky	C	T	9: 102,542,428	Q545*	probably null	Het
L1td1	T	C	4: 98,737,353	L595P	probably benign	Het
Map3k20	T	G	2: 72,438,300	I550M	probably damaging	Het
Mug1	T	A	6: 121,878,530	V941E	probably damaging	Het
Ndst1	T	C	18: 60,697,139	N633S	probably benign	Het
Ninl	A	T	2: 150,952,488	I740K	possibly damaging	Het
Npepl1	A	G	2: 174,121,113	N431D	probably damaging	Het
Olfr1128	T	C	2: 87,545,065	T160A	probably damaging	Het
Pacs2	T	C	12: 113,061,113	S408P	probably damaging	Het
Pard6b	C	T	2: 168,099,194	T367I	probably damaging	Het
Pcdhga7	A	G	18: 37,716,515	E525G	probably damaging	Het
Pctp	A	G	11: 89,987,318	I130T	probably benign	Het
Pdhx	A	G	2: 103,035,241	S199P	probably damaging	Het
Pdia2	C	A	17: 26,197,616		probably null	Het
Pif1	C	A	9: 65,591,834	N445K	probably damaging	Het
Prickle4	T	C	17: 47,688,582	K349E	probably benign	Het
Ptch1	T	G	13: 63,524,959	E944A	probably benign	Het
Ptpdc1	A	T	13: 48,589,194	M173K	probably damaging	Het
Rb1	A	G	14: 73,262,662	L515P	probably damaging	Het
Rcvrn	A	G	11: 67,700,051	K154E	probably damaging	Het
Ros1	C	T	10: 52,066,388	V2059I	probably damaging	Het
Rtn4ip1	T	A	10: 43,909,897		probably null	Het
Sema5a	T	C	15: 32,689,338	Y1050H	probably damaging	Het
Slc25a28	C	T	19: 43,664,269	V318I	probably benign	Het
Srek1	G	A	13: 103,744,895	R408W	unknown	Het
Synrg	C	T	11: 83,989,815	T444I	probably damaging	Het
Ticrr	T	C	7: 79,682,069	L776S	probably damaging	Het
Tmem127	T	C	2: 127,248,657	L31P	probably damaging	Het
Tmprss15	T	A	16: 79,073,186	T190S	probably benign	Het
Trip10	T	A	17: 57,253,411		probably null	Het
Ttc6	A	G	12: 57,649,506	Y31C	probably damaging	Het
Unc80	A	T	1: 66,622,570	H1718L	possibly damaging	Het
Zbtb38	A	G	9: 96,687,546	F495S	probably damaging	Het
Zfp280d	G	T	9: 72,296,019	Q16H	possibly damaging	Het
Zfp521	A	G	18: 13,846,346	S337P	probably damaging	Het
Zswim9	T	A	7: 13,261,577	T218S	possibly damaging	Het

Other mutations in Pcx

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00924:Pcx	APN	19	4620937	missense	probably benign	0.02
IGL01339:Pcx	APN	19	4620235	splice site	probably null
IGL01373:Pcx	APN	19	4620235	splice site	probably null
IGL01704:Pcx	APN	19	4621060	missense	probably damaging	1.00
IGL02223:Pcx	APN	19	4601978	missense	probably damaging	1.00
PIT4151001:Pcx	UTSW	19	4603129	missense	probably damaging	1.00
R0098:Pcx	UTSW	19	4601747	splice site	probably benign
R0098:Pcx	UTSW	19	4601747	splice site	probably benign
R0211:Pcx	UTSW	19	4620199	missense	probably damaging	1.00
R0211:Pcx	UTSW	19	4620199	missense	probably damaging	1.00
R0398:Pcx	UTSW	19	4601610	missense	probably benign	0.35
R0414:Pcx	UTSW	19	4607642	missense	possibly damaging	0.60
R1402:Pcx	UTSW	19	4602030	missense	possibly damaging	0.59
R1402:Pcx	UTSW	19	4602030	missense	possibly damaging	0.59
R1479:Pcx	UTSW	19	4602024	missense	probably damaging	1.00
R1543:Pcx	UTSW	19	4602223	missense	probably damaging	1.00
R1559:Pcx	UTSW	19	4619086	missense	probably damaging	1.00
R1607:Pcx	UTSW	19	4603159	missense	possibly damaging	0.89
R1833:Pcx	UTSW	19	4619104	missense	probably damaging	0.98
R1866:Pcx	UTSW	19	4621221	missense	possibly damaging	0.58
R2131:Pcx	UTSW	19	4602551	missense	probably benign	0.00
R2172:Pcx	UTSW	19	4620881	missense	probably benign	0.17
R2224:Pcx	UTSW	19	4617998	missense	possibly damaging	0.46
R2226:Pcx	UTSW	19	4617998	missense	possibly damaging	0.46
R2280:Pcx	UTSW	19	4604543	missense	probably damaging	1.00
R3952:Pcx	UTSW	19	4617967	missense	probably benign	0.00
R4205:Pcx	UTSW	19	4619166	missense	possibly damaging	0.95
R4409:Pcx	UTSW	19	4610003	missense	possibly damaging	0.65
R4670:Pcx	UTSW	19	4619888	missense	probably damaging	1.00
R4691:Pcx	UTSW	19	4619477	missense	probably damaging	0.99
R4728:Pcx	UTSW	19	4603096	missense	probably damaging	1.00
R4808:Pcx	UTSW	19	4620928	missense	probably benign	0.00
R5200:Pcx	UTSW	19	4618504	missense	probably damaging	1.00
R5454:Pcx	UTSW	19	4602476	missense	probably damaging	1.00
R5621:Pcx	UTSW	19	4619167	missense	possibly damaging	0.59
R5990:Pcx	UTSW	19	4621266	missense	probably damaging	1.00
R6519:Pcx	UTSW	19	4602211	missense	possibly damaging	0.64
R6526:Pcx	UTSW	19	4604495	missense	probably benign	0.44
R7202:Pcx	UTSW	19	4602333	missense	possibly damaging	0.47
R7423:Pcx	UTSW	19	4621178	missense	probably benign	0.00
R7473:Pcx	UTSW	19	4619561	nonsense	probably null
R7654:Pcx	UTSW	19	4515669	splice site	probably null
R7963:Pcx	UTSW	19	4602006	missense	probably damaging	1.00
R8272:Pcx	UTSW	19	4601730	missense	probably damaging	1.00
Z1176:Pcx	UTSW	19	4619073	missense	possibly damaging	0.82

Predicted Primers

PCR Primer
(F):5'- GCTACATTACCTCGGTCTGC -3'
(R):5'- AGGATGTCCCTGAAACCAGC -3'

Sequencing Primer
(F):5'- GTACCCCTGCCCTTGTTAAG -3'
(R):5'- ATGTCCCTGAAACCAGCTGGAG -3'

Posted On

2015-04-17