Mutagenetix > Incidental Mutation

Incidental Mutation 'R1543:Pcx'

171961

Institutional Source

Beutler Lab

Gene Symbol

Pcx

Ensembl Gene

ENSMUSG00000024892

Gene Name

pyruvate carboxylase

Synonyms

MMRRC Submission

039582-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R1543 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

4560500-4671780 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 4652251 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Aspartic acid to Valine at position 112 (D112V)

Ref Sequence

ENSEMBL: ENSMUSP00000152918 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000068004] [ENSMUST00000113825] [ENSMUST00000224726] [ENSMUST00000225189]

AlphaFold

no structure available at present

Predicted Effect

probably damaging
Transcript: ENSMUST00000068004
AA Change: D113V

PolyPhen 2 Score 0.978 (Sensitivity: 0.76; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000063825
Gene: ENSMUSG00000024892
AA Change: D113V

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 damaging
Transcript: ENSMUST00000113825
AA Change: D112V

PolyPhen 2 Score 0.978 (Sensitivity: 0.76; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000109456
Gene: ENSMUSG00000024892
AA Change: D112V

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 damaging
Transcript: ENSMUST00000224726
AA Change: D112V

PolyPhen 2 Score 0.978 (Sensitivity: 0.76; Specificity: 0.96)

Predicted Effect

probably damaging
Transcript: ENSMUST00000225189
AA Change: D112V

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

Meta Mutation Damage Score

0.9269

Coding Region Coverage

1x: 99.0%
3x: 98.1%
10x: 95.7%
20x: 90.2%

Validation Efficiency

95% (77/81)

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: 77 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1810009J06Rik	G	A	6: 40,945,138 (GRCm39)	V206I	probably damaging	Het
Abca8b	A	C	11: 109,865,500 (GRCm39)	M319R	probably damaging	Het
Abcc6	T	C	7: 45,665,928 (GRCm39)	R231G	probably benign	Het
Acadm	A	G	3: 153,635,209 (GRCm39)	Y302H	probably damaging	Het
Acox3	C	A	5: 35,760,352 (GRCm39)	R423S	probably damaging	Het
Adam7	T	A	14: 68,759,371 (GRCm39)		probably benign	Het
Adgrb3	A	C	1: 25,527,169 (GRCm39)	M589R	probably benign	Het
Adgrl2	A	C	3: 148,564,909 (GRCm39)	F224V	probably damaging	Het
Adm2	G	C	15: 89,208,282 (GRCm39)	G74A	probably damaging	Het
Aen	T	A	7: 78,552,370 (GRCm39)	V15E	probably damaging	Het
Ankzf1	T	A	1: 75,169,160 (GRCm39)	V22D	possibly damaging	Het
Arap2	T	A	5: 62,763,498 (GRCm39)	K1549*	probably null	Het
Arhgef11	G	A	3: 87,620,324 (GRCm39)	R430H	probably benign	Het
Asb17	T	G	3: 153,550,148 (GRCm39)	L60W	probably damaging	Het
BC035044	T	C	6: 128,867,948 (GRCm39)		probably benign	Het
Bltp2	A	G	11: 78,166,000 (GRCm39)	T1422A	probably benign	Het
Cacna2d1	A	T	5: 16,471,716 (GRCm39)	M254L	possibly damaging	Het
Celf6	T	C	9: 59,511,160 (GRCm39)		probably benign	Het
Cemip2	G	T	19: 21,789,937 (GRCm39)	A668S	probably benign	Het
Coro2b	C	T	9: 62,333,123 (GRCm39)	V120I	probably benign	Het
Cyp20a1	C	A	1: 60,415,353 (GRCm39)		probably benign	Het
Cyp2c67	C	A	19: 39,631,708 (GRCm39)		probably benign	Het
Dclk3	A	G	9: 111,297,122 (GRCm39)	H222R	probably benign	Het
Deaf1	A	G	7: 140,904,060 (GRCm39)	S109P	possibly damaging	Het
Dlg5	T	A	14: 24,194,516 (GRCm39)	D1675V	probably damaging	Het
Dsg2	T	A	18: 20,727,268 (GRCm39)	V605E	probably benign	Het
Dync2i1	T	C	12: 116,195,404 (GRCm39)		probably benign	Het
Frem2	A	T	3: 53,479,876 (GRCm39)	I1939N	possibly damaging	Het
Fsip2	A	T	2: 82,811,931 (GRCm39)	Y2750F	possibly damaging	Het
Gpr39	T	A	1: 125,800,161 (GRCm39)	I304N	probably damaging	Het
Hdac7	G	A	15: 97,707,410 (GRCm39)		probably benign	Het
Hipk1	T	C	3: 103,685,480 (GRCm39)	H45R	probably benign	Het
Hyal2	T	C	9: 107,447,386 (GRCm39)	L13P	probably damaging	Het
Kdm1b	C	T	13: 47,221,997 (GRCm39)	R479W	probably damaging	Het
Lilrb4b	A	G	10: 51,357,517 (GRCm39)	T118A	probably damaging	Het
Lin7a	C	A	10: 107,247,930 (GRCm39)	F78L	possibly damaging	Het
Lpin3	A	G	2: 160,737,310 (GRCm39)	D119G	possibly damaging	Het
Lrp2	G	A	2: 69,331,074 (GRCm39)	R1661C	probably damaging	Het
Lrrc45	A	G	11: 120,610,844 (GRCm39)	K527E	probably benign	Het
Map10	C	T	8: 126,397,611 (GRCm39)	P335S	probably benign	Het
Mast3	A	G	8: 71,244,955 (GRCm39)	S2P	possibly damaging	Het
Mbtps1	A	G	8: 120,268,808 (GRCm39)		probably benign	Het
Mms22l	T	A	4: 24,591,084 (GRCm39)	N1018K	probably benign	Het
Nckipsd	C	A	9: 108,689,571 (GRCm39)	A244D	possibly damaging	Het
Nt5el	A	T	13: 105,248,877 (GRCm39)	R364*	probably null	Het
Or12k5	C	A	2: 36,895,139 (GRCm39)	L162F	probably damaging	Het
Or1j1	A	T	2: 36,703,069 (GRCm39)	F12I	probably damaging	Het
Or4k44	A	G	2: 111,368,142 (GRCm39)	V164A	probably benign	Het
Or52j3	T	A	7: 102,836,421 (GRCm39)	F204L	probably benign	Het
Or8b12c	T	A	9: 37,715,243 (GRCm39)	I12N	possibly damaging	Het
Phf14	G	A	6: 11,987,682 (GRCm39)		probably null	Het
Pkd1l1	A	G	11: 8,851,200 (GRCm39)	I744T	probably damaging	Het
Ppip5k2	A	G	1: 97,668,607 (GRCm39)	L560P	probably damaging	Het
Psmd14	A	T	2: 61,615,874 (GRCm39)	M248L	probably benign	Het
Ryr1	T	G	7: 28,782,962 (GRCm39)	E1884A	possibly damaging	Het
Scn4b	T	A	9: 45,061,727 (GRCm39)	S204R	probably damaging	Het
Slc12a1	A	T	2: 125,026,777 (GRCm39)	M471L	possibly damaging	Het
Slc17a5	A	G	9: 78,468,082 (GRCm39)	V236A	probably benign	Het
Sobp	T	C	10: 42,897,720 (GRCm39)	T622A	probably damaging	Het
Spata31d1a	G	T	13: 59,850,056 (GRCm39)	R691S	probably benign	Het
Speg	A	G	1: 75,398,595 (GRCm39)	E2014G	probably damaging	Het
Steap4	A	G	5: 8,025,902 (GRCm39)		probably benign	Het
Tas2r144	G	A	6: 42,192,537 (GRCm39)	M92I	probably benign	Het
Tbc1d5	T	C	17: 51,242,560 (GRCm39)	Q179R	probably benign	Het
Tcf25	T	C	8: 124,115,326 (GRCm39)	Y188H	probably benign	Het
Tmem200a	G	A	10: 25,954,518 (GRCm39)		probably benign	Het
Trappc9	G	A	15: 72,897,816 (GRCm39)	R377W	probably damaging	Het
Tssk5	T	C	15: 76,256,409 (GRCm39)	T337A	probably benign	Het
Ttc23	T	C	7: 67,328,743 (GRCm39)	V228A	probably benign	Het
Tulp1	A	T	17: 28,581,645 (GRCm39)		probably benign	Het
Uqcc3	A	G	19: 8,858,117 (GRCm39)	F25L	probably damaging	Het
Vmn2r1	G	A	3: 63,996,994 (GRCm39)	G217S	probably damaging	Het
Vmn2r120	C	T	17: 57,829,374 (GRCm39)	E508K	probably benign	Het
Wdfy3	C	A	5: 101,991,947 (GRCm39)	V3451L	probably benign	Het
Wdr19	G	A	5: 65,382,033 (GRCm39)	V418I	probably benign	Het
Xirp2	C	T	2: 67,338,383 (GRCm39)	T208I	probably benign	Het
Xpnpep1	A	G	19: 52,980,107 (GRCm39)	V639A	probably benign	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
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
R7423:Pcx	UTSW	19	4,671,206 (GRCm39)	missense	probably benign	0.00
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'- CAGGCAGAAAGCTGATGAAGCCTAC -3'
(R):5'- AGAATCCTCACGCCATCTTGTCAC -3'

Sequencing Primer
(F):5'- TTCCAGACATCATCAAGGTGGC -3'
(R):5'- CCATCTTGTCACAGGCCC -3'

Posted On

2014-04-13