Mutagenetix > Incidental Mutation

Incidental Mutation 'R7423:Pcx'

575882

Institutional Source

Beutler Lab

Gene Symbol

Pcx

Ensembl Gene

ENSMUSG00000024892

Gene Name

pyruvate carboxylase

Synonyms

MMRRC Submission

045501-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R7423 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

4560500-4671780 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 4671206 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Methionine to Leucine at position 1144 (M1144L)

Ref Sequence

ENSEMBL: ENSMUSP00000063825 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000025823] [ENSMUST00000068004] [ENSMUST00000113825] [ENSMUST00000177696] [ENSMUST00000224675] [ENSMUST00000224707] [ENSMUST00000224726] [ENSMUST00000225264] [ENSMUST00000225375] [ENSMUST00000225476] [ENSMUST00000225896]

AlphaFold

no structure available at present

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: ENSMUST00000068004
AA Change: M1144L

PolyPhen 2 Score 0.005 (Sensitivity: 0.97; Specificity: 0.74)

SMART Domains

Protein: ENSMUSP00000063825
Gene: ENSMUSG00000024892
AA Change: M1144L

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: ENSMUST00000113825
AA Change: M1143L

PolyPhen 2 Score 0.005 (Sensitivity: 0.97; Specificity: 0.74)

SMART Domains

Protein: ENSMUSP00000109456
Gene: ENSMUSG00000024892
AA Change: M1143L

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: ENSMUST00000177696

SMART Domains

Protein: ENSMUSP00000136515
Gene: ENSMUSG00000071691

Domain	Start	End	E-Value	Type
low complexity region	65	79	N/A	INTRINSIC
low complexity region	106	122	N/A	INTRINSIC
low complexity region	128	140	N/A	INTRINSIC
Pfam:DUF4554	274	719	5.3e-206	PFAM
low complexity region	720	731	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000224675

Predicted Effect

probably benign
Transcript: ENSMUST00000224707

Predicted Effect

probably benign
Transcript: ENSMUST00000224726
AA Change: M1143L

PolyPhen 2 Score 0.005 (Sensitivity: 0.97; Specificity: 0.74)

Predicted Effect

probably benign
Transcript: ENSMUST00000225264

Predicted Effect

probably benign
Transcript: ENSMUST00000225375

Predicted Effect

probably benign
Transcript: ENSMUST00000225476

Predicted Effect

probably benign
Transcript: ENSMUST00000225896

Coding Region Coverage

1x: 100.0%
3x: 100.0%
10x: 99.7%
20x: 98.8%

Validation Efficiency

96% (91/95)

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: 93 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Acsbg2	A	T	17: 57,175,257 (GRCm39)	M85K	probably benign	Het
Actn4	C	T	7: 28,593,680 (GRCm39)	A905T	probably damaging	Het
Aff1	T	A	5: 103,994,967 (GRCm39)	V1055D	probably damaging	Het
Aox3	A	G	1: 58,160,228 (GRCm39)	E137G	possibly damaging	Het
Apaf1	A	T	10: 90,895,468 (GRCm39)	D443E	probably damaging	Het
Arl5b	C	A	2: 15,072,983 (GRCm39)	A28E	probably damaging	Het
Atg16l1	T	C	1: 87,714,023 (GRCm39)	V478A	probably damaging	Het
Atp6v1f	G	C	6: 29,468,105 (GRCm39)	E13Q	probably null	Het
Atpaf1	A	T	4: 115,647,827 (GRCm39)	K162M	probably damaging	Het
C3	A	T	17: 57,521,767 (GRCm39)	L1100Q	probably damaging	Het
Ccr1	A	G	9: 123,764,422 (GRCm39)	L36P	probably damaging	Het
Cct3	T	C	3: 88,216,503 (GRCm39)	L153S	probably benign	Het
Chd4	A	G	6: 125,105,822 (GRCm39)	D1813G	possibly damaging	Het
Chrm3	T	C	13: 9,928,845 (GRCm39)	I64V	probably benign	Het
Cnot2	A	T	10: 116,328,303 (GRCm39)	V477E	probably damaging	Het
Csf2rb2	T	A	15: 78,176,760 (GRCm39)	I211F	possibly damaging	Het
Dnah8	T	C	17: 30,923,743 (GRCm39)	L1237P	possibly damaging	Het
Dnttip2	T	C	3: 122,069,175 (GRCm39)	V130A	probably benign	Het
Dock10	G	A	1: 80,501,497 (GRCm39)	A1852V	possibly damaging	Het
Dock3	A	G	9: 106,844,370 (GRCm39)	V910A	probably damaging	Het
Drgx	A	G	14: 32,350,778 (GRCm39)	S205G	probably damaging	Het
Fbrs	G	A	7: 127,088,633 (GRCm39)	W738*	probably null	Het
Fmnl3	T	A	15: 99,227,281 (GRCm39)	D162V	probably damaging	Het
Fosl2	A	G	5: 32,307,807 (GRCm39)	R133G	probably damaging	Het
Frmpd1	A	G	4: 45,256,948 (GRCm39)	Q172R	probably damaging	Het
Fsd1l	A	T	4: 53,686,406 (GRCm39)	D273V	probably damaging	Het
Fstl4	T	A	11: 52,959,382 (GRCm39)	M141K	possibly damaging	Het
Gcfc2	A	G	6: 81,923,541 (GRCm39)	D535G	probably damaging	Het
Gm19410	A	C	8: 36,271,761 (GRCm39)	D1277A	probably benign	Het
Gnmt	T	A	17: 47,037,066 (GRCm39)	N211Y	probably damaging	Het
Hic2	A	G	16: 17,075,993 (GRCm39)	D274G	probably damaging	Het
Hnrnpu	A	G	1: 178,156,849 (GRCm39)		probably benign	Het
Icam5	T	C	9: 20,948,201 (GRCm39)	S670P	probably benign	Het
Ighv5-4	A	T	12: 113,561,120 (GRCm39)	L100Q	probably damaging	Het
Il17rb	A	T	14: 29,719,072 (GRCm39)	S337T	probably damaging	Het
Inf2	G	T	12: 112,576,172 (GRCm39)	R883L	unknown	Het
Inhbc	C	T	10: 127,193,275 (GRCm39)	C247Y	probably damaging	Het
Ints4	A	G	7: 97,156,926 (GRCm39)	K333E	probably damaging	Het
Iyd	A	T	10: 3,497,088 (GRCm39)	I148F	probably damaging	Het
Klk1b26	A	T	7: 43,664,193 (GRCm39)	D16V	probably damaging	Het
Krt15	A	T	11: 100,026,386 (GRCm39)	V100E	possibly damaging	Het
Lama2	A	T	10: 27,088,222 (GRCm39)	S852T	probably benign	Het
Mbtd1	A	G	11: 93,834,622 (GRCm39)	E600G	probably benign	Het
Mfap3	T	G	11: 57,420,329 (GRCm39)	N103K	probably damaging	Het
Mtor	G	A	4: 148,640,801 (GRCm39)	E2536K	possibly damaging	Het
Mug2	G	A	6: 122,056,685 (GRCm39)	S1210N	probably benign	Het
Nat8	G	A	6: 85,807,477 (GRCm39)	L219F	probably benign	Het
Nisch	A	G	14: 30,893,658 (GRCm39)	V1305A	probably benign	Het
Nup153	A	T	13: 46,850,120 (GRCm39)		probably null	Het
Or3a1b	G	A	11: 74,012,811 (GRCm39)	R232H	probably benign	Het
Otud6b	A	T	4: 14,825,858 (GRCm39)		probably null	Het
Pbld2	A	G	10: 62,883,783 (GRCm39)	T83A	probably damaging	Het
Pdpk1	C	A	17: 24,329,874 (GRCm39)	R81L	probably benign	Het
Pik3cd	A	T	4: 149,736,220 (GRCm39)		probably null	Het
Plch2	A	C	4: 155,068,194 (GRCm39)	D1477E	probably damaging	Het
Plek2	A	G	12: 78,946,884 (GRCm39)	I51T	probably damaging	Het
Plekhn1	A	G	4: 156,315,142 (GRCm39)	V505A	probably benign	Het
Pofut2	T	C	10: 77,098,273 (GRCm39)	S129P	possibly damaging	Het
Prdx5	C	A	19: 6,887,370 (GRCm39)		probably benign	Het
Proca1	G	T	11: 78,085,643 (GRCm39)		probably benign	Het
Ptprs	A	C	17: 56,721,793 (GRCm39)	Y1752D	probably damaging	Het
Pum1	G	A	4: 130,501,856 (GRCm39)	V1127M	probably damaging	Het
Ralbp1	T	C	17: 66,165,976 (GRCm39)	R403G	probably damaging	Het
Reps1	A	T	10: 17,969,635 (GRCm39)	H246L	possibly damaging	Het
Rps6kc1	A	C	1: 190,531,293 (GRCm39)	M903R	probably damaging	Het
Rubcnl	A	G	14: 75,287,083 (GRCm39)	T584A	probably benign	Het
Samd9l	A	T	6: 3,374,408 (GRCm39)	V951E	probably damaging	Het
Sbf2	A	G	7: 110,038,055 (GRCm39)	F463L	possibly damaging	Het
Sdr16c6	G	A	4: 4,076,921 (GRCm39)		probably benign	Het
Shoc1	A	T	4: 59,076,264 (GRCm39)	S560T	probably benign	Het
Slc26a8	A	G	17: 28,867,177 (GRCm39)	I548T	probably benign	Het
Slc2a13	T	A	15: 91,456,883 (GRCm39)	I140F	probably damaging	Het
Smtn	A	T	11: 3,481,200 (GRCm39)		probably null	Het
Sobp	G	T	10: 42,898,564 (GRCm39)	C340*	probably null	Het
Sox6	A	T	7: 115,149,258 (GRCm39)	V413E	probably benign	Het
Spin1	T	C	13: 51,277,326 (GRCm39)		probably null	Het
Sra1	T	C	18: 36,800,536 (GRCm39)	T224A	probably benign	Het
Sv2c	A	T	13: 96,185,056 (GRCm39)	F207Y	probably benign	Het
Tcp10c	T	A	17: 13,581,503 (GRCm39)		probably null	Het
Tkt	G	A	14: 30,292,992 (GRCm39)	G490S	possibly damaging	Het
Tpgs1	G	T	10: 79,511,655 (GRCm39)	A266S	probably damaging	Het
Tprg1	T	G	16: 25,241,003 (GRCm39)	S260A	probably damaging	Het
Trdv2-1	T	A	14: 54,183,935 (GRCm39)	W56R	probably damaging	Het
Trgv6	G	T	13: 19,374,814 (GRCm39)	G40W	possibly damaging	Het
Trpc4	T	A	3: 54,225,450 (GRCm39)	V933E	probably benign	Het
Ulk4	A	T	9: 120,932,687 (GRCm39)	M1051K	possibly damaging	Het
Unc119b	A	G	5: 115,272,743 (GRCm39)	L76P	probably damaging	Het
Vmn2r15	G	A	5: 109,445,394 (GRCm39)	S10F	probably benign	Het
Vwce	A	G	19: 10,641,704 (GRCm39)	E810G	probably benign	Het
Wdr7	T	A	18: 63,910,451 (GRCm39)		probably null	Het
Wnk2	T	A	13: 49,191,608 (GRCm39)	E1283V	probably benign	Het
Zfp28	T	C	7: 6,396,956 (GRCm39)	C464R	probably damaging	Het
Zpld1	C	T	16: 55,054,027 (GRCm39)	C255Y	probably damaging	Het

Other mutations in Pcx

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00924:Pcx	APN	19	4,670,965 (GRCm39)	missense	probably benign	0.02
IGL01339:Pcx	APN	19	4,670,263 (GRCm39)	splice site	probably null
IGL01373:Pcx	APN	19	4,670,263 (GRCm39)	splice site	probably null
IGL01704:Pcx	APN	19	4,671,088 (GRCm39)	missense	probably damaging	1.00
IGL02223:Pcx	APN	19	4,652,006 (GRCm39)	missense	probably damaging	1.00
PIT4151001:Pcx	UTSW	19	4,653,157 (GRCm39)	missense	probably damaging	1.00
R0098:Pcx	UTSW	19	4,651,775 (GRCm39)	splice site	probably benign
R0098:Pcx	UTSW	19	4,651,775 (GRCm39)	splice site	probably benign
R0211:Pcx	UTSW	19	4,670,227 (GRCm39)	missense	probably damaging	1.00
R0211:Pcx	UTSW	19	4,670,227 (GRCm39)	missense	probably damaging	1.00
R0398:Pcx	UTSW	19	4,651,638 (GRCm39)	missense	probably benign	0.35
R0414:Pcx	UTSW	19	4,657,670 (GRCm39)	missense	possibly damaging	0.60
R1402:Pcx	UTSW	19	4,652,058 (GRCm39)	missense	possibly damaging	0.59
R1402:Pcx	UTSW	19	4,652,058 (GRCm39)	missense	possibly damaging	0.59
R1479:Pcx	UTSW	19	4,652,052 (GRCm39)	missense	probably damaging	1.00
R1543:Pcx	UTSW	19	4,652,251 (GRCm39)	missense	probably damaging	1.00
R1559:Pcx	UTSW	19	4,669,114 (GRCm39)	missense	probably damaging	1.00
R1607:Pcx	UTSW	19	4,653,187 (GRCm39)	missense	possibly damaging	0.89
R1833:Pcx	UTSW	19	4,669,132 (GRCm39)	missense	probably damaging	0.98
R1866:Pcx	UTSW	19	4,671,249 (GRCm39)	missense	possibly damaging	0.58
R2131:Pcx	UTSW	19	4,652,579 (GRCm39)	missense	probably benign	0.00
R2172:Pcx	UTSW	19	4,670,909 (GRCm39)	missense	probably benign	0.17
R2224:Pcx	UTSW	19	4,668,026 (GRCm39)	missense	possibly damaging	0.46
R2226:Pcx	UTSW	19	4,668,026 (GRCm39)	missense	possibly damaging	0.46
R2280:Pcx	UTSW	19	4,654,571 (GRCm39)	missense	probably damaging	1.00
R3950:Pcx	UTSW	19	4,667,995 (GRCm39)	missense	probably benign	0.00
R3952:Pcx	UTSW	19	4,667,995 (GRCm39)	missense	probably benign	0.00
R4205:Pcx	UTSW	19	4,669,194 (GRCm39)	missense	possibly damaging	0.95
R4409:Pcx	UTSW	19	4,660,031 (GRCm39)	missense	possibly damaging	0.65
R4670:Pcx	UTSW	19	4,669,916 (GRCm39)	missense	probably damaging	1.00
R4691:Pcx	UTSW	19	4,669,505 (GRCm39)	missense	probably damaging	0.99
R4728:Pcx	UTSW	19	4,653,124 (GRCm39)	missense	probably damaging	1.00
R4808:Pcx	UTSW	19	4,670,956 (GRCm39)	missense	probably benign	0.00
R5200:Pcx	UTSW	19	4,668,532 (GRCm39)	missense	probably damaging	1.00
R5454:Pcx	UTSW	19	4,652,504 (GRCm39)	missense	probably damaging	1.00
R5621:Pcx	UTSW	19	4,669,195 (GRCm39)	missense	possibly damaging	0.59
R5990:Pcx	UTSW	19	4,671,294 (GRCm39)	missense	probably damaging	1.00
R6519:Pcx	UTSW	19	4,652,239 (GRCm39)	missense	possibly damaging	0.64
R6526:Pcx	UTSW	19	4,654,523 (GRCm39)	missense	probably benign	0.44
R7202:Pcx	UTSW	19	4,652,361 (GRCm39)	missense	possibly damaging	0.47
R7473:Pcx	UTSW	19	4,669,589 (GRCm39)	nonsense	probably null
R7654:Pcx	UTSW	19	4,565,697 (GRCm39)	splice site	probably null
R7963:Pcx	UTSW	19	4,652,034 (GRCm39)	missense	probably damaging	1.00
R8272:Pcx	UTSW	19	4,651,758 (GRCm39)	missense	probably damaging	1.00
R8693:Pcx	UTSW	19	4,652,039 (GRCm39)	missense	probably damaging	1.00
R8781:Pcx	UTSW	19	4,670,980 (GRCm39)	missense	probably damaging	1.00
R8829:Pcx	UTSW	19	4,651,968 (GRCm39)	missense	probably damaging	1.00
R9084:Pcx	UTSW	19	4,669,868 (GRCm39)	missense	probably damaging	1.00
R9334:Pcx	UTSW	19	4,670,532 (GRCm39)	missense	probably benign	0.31
R9462:Pcx	UTSW	19	4,651,970 (GRCm39)	missense	probably benign	0.00
R9540:Pcx	UTSW	19	4,651,682 (GRCm39)	missense	probably benign
R9650:Pcx	UTSW	19	4,657,714 (GRCm39)	missense	probably damaging	1.00
Z1176:Pcx	UTSW	19	4,669,101 (GRCm39)	missense	possibly damaging	0.82

Predicted Primers

PCR Primer
(F):5'- AGGCCATGAAGGTATAGTGCC -3'
(R):5'- TGCACAGCTTCTGTTGAGAGG -3'

Sequencing Primer
(F):5'- CCATGAAGGTATAGTGCCACCAG -3'
(R):5'- AGAGGCTTGGGGTAGGGTC -3'

Posted On

2019-10-07