Mutagenetix > Incidental Mutation

Incidental Mutation 'R9712:Pdp1'

730234

Institutional Source

Beutler Lab

Gene Symbol

Pdp1

Ensembl Gene

ENSMUSG00000049225

Gene Name

pyruvate dehyrogenase phosphatase catalytic subunit 1

Synonyms

LOC381511, Ppm2c

MMRRC Submission

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R9712 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

11958184-11966452 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 11961607 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Histidine to Tyrosine at position 254 (H254Y)

Ref Sequence

ENSEMBL: ENSMUSP00000103936 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000056050] [ENSMUST00000095144] [ENSMUST00000108297] [ENSMUST00000108299] [ENSMUST00000108301] [ENSMUST00000108302]

AlphaFold

Q3UV70

Predicted Effect

probably benign
Transcript: ENSMUST00000056050
AA Change: H195Y

PolyPhen 2 Score 0.415 (Sensitivity: 0.89; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000050521
Gene: ENSMUSG00000049225
AA Change: H195Y

Domain	Start	End	E-Value	Type
PP2Cc	99	523	3.36e-97	SMART
PP2C_SIG	177	525	2.77e0	SMART

Predicted Effect

possibly damaging
Transcript: ENSMUST00000095144
AA Change: H220Y

PolyPhen 2 Score 0.896 (Sensitivity: 0.82; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000092766
Gene: ENSMUSG00000049225
AA Change: H220Y

Domain	Start	End	E-Value	Type
PP2Cc	124	548	3.36e-97	SMART
PP2C_SIG	202	550	2.77e0	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000108297
AA Change: H195Y

PolyPhen 2 Score 0.415 (Sensitivity: 0.89; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000103932
Gene: ENSMUSG00000049225
AA Change: H195Y

Domain	Start	End	E-Value	Type
PP2Cc	99	523	3.36e-97	SMART
PP2C_SIG	177	525	2.77e0	SMART

Predicted Effect

possibly damaging
Transcript: ENSMUST00000108299
AA Change: H220Y

PolyPhen 2 Score 0.896 (Sensitivity: 0.82; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000103934
Gene: ENSMUSG00000049225
AA Change: H220Y

Domain	Start	End	E-Value	Type
PP2Cc	124	548	3.36e-97	SMART
PP2C_SIG	202	550	2.77e0	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000108301
AA Change: H254Y

PolyPhen 2 Score 0.415 (Sensitivity: 0.89; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000103936
Gene: ENSMUSG00000049225
AA Change: H254Y

Domain	Start	End	E-Value	Type
low complexity region	11	18	N/A	INTRINSIC
PP2Cc	158	582	3.36e-97	SMART
PP2C_SIG	236	584	2.77e0	SMART

Predicted Effect

possibly damaging
Transcript: ENSMUST00000108302
AA Change: H235Y

PolyPhen 2 Score 0.715 (Sensitivity: 0.86; Specificity: 0.92)

SMART Domains

Protein: ENSMUSP00000103937
Gene: ENSMUSG00000049225
AA Change: H235Y

Domain	Start	End	E-Value	Type
PP2Cc	139	563	3.36e-97	SMART
PP2C_SIG	217	565	2.77e0	SMART

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.6%
20x: 98.6%

Validation Efficiency

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] Pyruvate dehydrogenase (E1) is one of the three components (E1, E2, and E3) of the large pyruvate dehydrogenase complex. Pyruvate dehydrogenase kinases catalyze phosphorylation of serine residues of E1 to inactivate the E1 component and inhibit the complex. Pyruvate dehydrogenase phosphatases catalyze the dephosphorylation and activation of the E1 component to reverse the effects of pyruvate dehydrogenase kinases. Pyruvate dehydrogenase phosphatase is a heterodimer consisting of catalytic and regulatory subunits. Two catalytic subunits have been reported; one is predominantly expressed in skeletal muscle and another one is is much more abundant in the liver. The catalytic subunit, encoded by this gene, is the former, and belongs to the protein phosphatase 2C (PP2C) superfamily. Along with the pyruvate dehydrogenase complex and pyruvate dehydrogenase kinases, this enzyme is located in the mitochondrial matrix. Mutation in this gene causes pyruvate dehydrogenase phosphatase deficiency. Multiple alternatively spliced transcript variants encoding different isoforms have been identified.[provided by RefSeq, Jun 2009]

Allele List at MGI

Other mutations in this stock

Total: 84 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1810055G02Rik	A	T	19: 3,715,784	M20L	probably benign	Het
9430007A20Rik	C	T	4: 144,528,784	A258V	probably benign	Het
Abca8b	T	A	11: 109,942,337	D1241V	probably benign	Het
Adam20	G	A	8: 40,795,453	R200H	probably benign	Het
Adcy10	T	C	1: 165,513,112	F229L	probably damaging	Het
Adsl	A	T	15: 80,955,639	N126I	probably benign	Het
Ahnak	AGATCTC	A	19: 9,007,028		probably benign	Het
Ahnak	GATCTCTAT	GAT	19: 9,007,029		probably benign	Het
Aktip	G	A	8: 91,129,727	P41S	probably damaging	Het
Alkbh3	C	A	2: 93,980,973	R258L	probably damaging	Het
Arfgap3	A	G	15: 83,313,533	Y341H	probably benign	Het
Arhgef26	C	T	3: 62,423,613	L583F	probably damaging	Het
Arhgef40	T	C	14: 51,988,958	I153T	probably damaging	Het
Atp1a1	T	C	3: 101,591,441	S179G	probably benign	Het
Bok	T	C	1: 93,686,507	S21P	probably damaging	Het
C130060K24Rik	A	G	6: 65,456,140	I315V	probably benign	Het
Ccdc136	A	G	6: 29,417,442	E754G	probably benign	Het
Cers3	A	G	7: 66,773,630	K108E	probably benign	Het
Cmya5	T	C	13: 93,065,373		probably null	Het
Col19a1	T	C	1: 24,328,067	E478G	possibly damaging	Het
Colec10	T	A	15: 54,459,784	S134R	possibly damaging	Het
Ctnnb1	A	T	9: 120,955,829	I514F	probably damaging	Het
Cux1	C	T	5: 136,309,819	E664K	probably benign	Het
Dars	T	C	1: 128,405,462	Q75R	probably benign	Het
Disp1	T	A	1: 183,135,815	S16C	probably damaging	Het
Dnah7a	A	T	1: 53,559,140	V1412E	probably benign	Het
Ect2l	C	T	10: 18,168,434	V226I	probably benign	Het
Ep400	T	A	5: 110,756,643	H30L	unknown	Het
Ephx4	A	G	5: 107,419,781	I202V	probably benign	Het
Exoc3	A	T	13: 74,192,908	F259Y	probably damaging	Het
Ezr	T	C	17: 6,752,995	E229G	probably damaging	Het
Fat1	A	T	8: 45,017,380	I1472L	probably benign	Het
Fsd1l	T	G	4: 53,679,972	D223E	probably benign	Het
Gata6	A	T	18: 11,059,064	D377V	possibly damaging	Het
Gm12185	A	T	11: 48,907,389	M759K	probably benign	Het
Gm21994	C	T	2: 150,254,576	R311Q	probably benign	Het
Gm9922	C	T	14: 101,729,457	A120T	unknown	Het
Hectd4	A	T	5: 121,310,681	Y364F	probably benign	Het
Hnrnph1	A	G	11: 50,385,869	S465G	unknown	Het
Ifi204	T	C	1: 173,749,358	Y559C	probably damaging	Het
Ift88	T	C	14: 57,481,396	S613P	probably damaging	Het
Kif21a	G	C	15: 90,985,325	A441G	probably damaging	Het
Kif21a	G	T	15: 90,995,512	T191K	probably benign	Het
Lrit1	T	A	14: 37,060,127	C252*	probably null	Het
Ncbp1	T	A	4: 46,144,837	D29E	probably benign	Het
Nlrp10	A	T	7: 108,925,528	D248E	probably damaging	Het
Nphp4	T	G	4: 152,547,064	V807G	probably benign	Het
Nsd1	T	C	13: 55,246,043	S589P	possibly damaging	Het
Oas1b	T	A	5: 120,814,485	N80K	probably damaging	Het
Olfr1055	G	A	2: 86,347,239	H176Y	probably benign	Het
Olfr1135	A	T	2: 87,671,761	I202N	probably benign	Het
Oprk1	T	A	1: 5,598,873	C181S	probably damaging	Het
Oprl1	T	A	2: 181,718,419	N89K	probably damaging	Het
Pdcd11	A	G	19: 47,129,302	K1697E	probably damaging	Het
Pds5b	A	T	5: 150,805,663	D1419V	possibly damaging	Het
Per1	G	T	11: 69,100,649	G3V	probably benign	Het
Pex16	C	A	2: 92,376,643	N55K	probably damaging	Het
Phldb2	C	A	16: 45,774,977	L862F	probably benign	Het
Pld5	T	A	1: 175,964,006	D478V	probably benign	Het
Pms2	T	C	5: 143,914,796	I177T	probably damaging	Het
Pou1f1	A	T	16: 65,529,872	E119D	probably benign	Het
Ppp2r1a	A	C	17: 20,958,796	E295A	probably damaging	Het
Rad51ap2	A	T	12: 11,457,592	N505I	possibly damaging	Het
Rasal3	A	C	17: 32,396,562	V434G	probably damaging	Het
Rasgrf2	C	T	13: 91,987,973	V6M		Het
Rwdd1	A	T	10: 34,001,156	D197E		Het
Scn11a	A	T	9: 119,790,010	C755*	probably null	Het
Skil	T	C	3: 31,116,860	S443P	probably benign	Het
Slc12a6	T	C	2: 112,356,472	C939R	probably damaging	Het
Slc25a36	A	G	9: 97,079,177	S269P	probably benign	Het
Srrm4	T	A	5: 116,482,393	H92L	unknown	Het
Styk1	CTCTTCATGATTTTCTT	CTCTT	6: 131,301,649		probably benign	Het
Tbc1d4	A	T	14: 101,507,410	V260E	probably benign	Het
Tbc1d8	T	C	1: 39,385,232	N593D	probably damaging	Het
Trex1	C	A	9: 109,058,737	R62L	probably damaging	Het
Trpm3	A	T	19: 22,715,352	D269V	possibly damaging	Het
Trpv4	G	T	5: 114,633,150	Y439*	probably null	Het
Ttn	G	A	2: 76,734,248	T28515I	probably damaging	Het
Ucn2	G	A	9: 108,986,503	G111D	probably damaging	Het
Uhrf2	A	G	19: 30,056,481	I212V	possibly damaging	Het
Usp24	T	A	4: 106,347,367	M261K	probably benign	Het
Vmn1r235	A	T	17: 21,261,698	D95V	probably benign	Het
Vwf	G	A	6: 125,624,573	R826Q		Het
Zfp28	T	C	7: 6,393,879	C438R	probably damaging	Het

Other mutations in Pdp1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL02243:Pdp1	APN	4	11961873	missense	probably benign	0.20
IGL02643:Pdp1	APN	4	11962062	missense	probably benign
R1931:Pdp1	UTSW	4	11962074	missense	probably benign	0.01
R2162:Pdp1	UTSW	4	11961123	missense	probably damaging	0.98
R2418:Pdp1	UTSW	4	11961838	missense	probably damaging	0.98
R3843:Pdp1	UTSW	4	11961961	missense	probably benign	0.00
R5699:Pdp1	UTSW	4	11960907	missense	possibly damaging	0.79
R6479:Pdp1	UTSW	4	11961327	missense	probably damaging	1.00
R7221:Pdp1	UTSW	4	11961004	missense	probably damaging	0.99
R7263:Pdp1	UTSW	4	11960821	missense	possibly damaging	0.82
R8483:Pdp1	UTSW	4	11961982	missense	probably benign
R9184:Pdp1	UTSW	4	11962143	missense	possibly damaging	0.80
Z1177:Pdp1	UTSW	4	11961639	missense	possibly damaging	0.67

Predicted Primers

PCR Primer
(F):5'- CAACTTGAGCCTCCAATGAAATG -3'
(R):5'- AATGCACCCATAGAGGACCG -3'

Sequencing Primer
(F):5'- GTCATTATCGAGTCTCTTGAAAGC -3'
(R):5'- CAGACCAGAGGGATGCTCTTG -3'

Posted On

2022-10-06