Mutagenetix > Incidental Mutation

Incidental Mutation 'R9712:Pdp1'

730234

Institutional Source

Beutler Lab

Gene Symbol

Pdp1

Ensembl Gene

ENSMUSG00000049225

Gene Name

pyruvate dehydrogenase 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

11958183-11966450 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 11961607 bp (GRCm39)

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: 3,765,784 (GRCm39)	M20L	probably benign	Het
Aadacl4fm1	C	T	4: 144,255,354 (GRCm39)	A258V	probably benign	Het
Abca8b	T	A	11: 109,833,163 (GRCm39)	D1241V	probably benign	Het
Adam20	G	A	8: 41,248,490 (GRCm39)	R200H	probably benign	Het
Adcy10	T	C	1: 165,340,681 (GRCm39)	F229L	probably damaging	Het
Adsl	A	T	15: 80,839,840 (GRCm39)	N126I	probably benign	Het
Ahnak	GATCTCTAT	GAT	19: 8,984,393 (GRCm39)		probably benign	Het
Ahnak	AGATCTC	A	19: 8,984,392 (GRCm39)		probably benign	Het
Aktip	G	A	8: 91,856,355 (GRCm39)	P41S	probably damaging	Het
Alkbh3	C	A	2: 93,811,318 (GRCm39)	R258L	probably damaging	Het
Arfgap3	A	G	15: 83,197,734 (GRCm39)	Y341H	probably benign	Het
Arhgef26	C	T	3: 62,331,034 (GRCm39)	L583F	probably damaging	Het
Arhgef40	T	C	14: 52,226,415 (GRCm39)	I153T	probably damaging	Het
Atp1a1	T	C	3: 101,498,757 (GRCm39)	S179G	probably benign	Het
Bok	T	C	1: 93,614,229 (GRCm39)	S21P	probably damaging	Het
Ccdc136	A	G	6: 29,417,441 (GRCm39)	E754G	probably benign	Het
Cers3	A	G	7: 66,423,378 (GRCm39)	K108E	probably benign	Het
Cmya5	T	C	13: 93,201,881 (GRCm39)		probably null	Het
Col19a1	T	C	1: 24,367,148 (GRCm39)	E478G	possibly damaging	Het
Colec10	T	A	15: 54,323,180 (GRCm39)	S134R	possibly damaging	Het
Ctnnb1	A	T	9: 120,784,895 (GRCm39)	I514F	probably damaging	Het
Cux1	C	T	5: 136,338,673 (GRCm39)	E664K	probably benign	Het
Dars1	T	C	1: 128,333,199 (GRCm39)	Q75R	probably benign	Het
Disp1	T	A	1: 182,917,379 (GRCm39)	S16C	probably damaging	Het
Dnah7a	A	T	1: 53,598,299 (GRCm39)	V1412E	probably benign	Het
Ect2l	C	T	10: 18,044,182 (GRCm39)	V226I	probably benign	Het
Ep400	T	A	5: 110,904,509 (GRCm39)	H30L	unknown	Het
Ephx4	A	G	5: 107,567,647 (GRCm39)	I202V	probably benign	Het
Exoc3	A	T	13: 74,341,027 (GRCm39)	F259Y	probably damaging	Het
Ezr	T	C	17: 7,020,394 (GRCm39)	E229G	probably damaging	Het
Fat1	A	T	8: 45,470,417 (GRCm39)	I1472L	probably benign	Het
Fsd1l	T	G	4: 53,679,972 (GRCm39)	D223E	probably benign	Het
Gata6	A	T	18: 11,059,064 (GRCm39)	D377V	possibly damaging	Het
Gm12185	A	T	11: 48,798,216 (GRCm39)	M759K	probably benign	Het
Gm9922	C	T	14: 101,966,893 (GRCm39)	A120T	unknown	Het
Hectd4	A	T	5: 121,448,744 (GRCm39)	Y364F	probably benign	Het
Hnrnph1	A	G	11: 50,276,696 (GRCm39)	S465G	unknown	Het
Ifi204	T	C	1: 173,576,924 (GRCm39)	Y559C	probably damaging	Het
Ift88	T	C	14: 57,718,853 (GRCm39)	S613P	probably damaging	Het
Kif21a	G	C	15: 90,869,528 (GRCm39)	A441G	probably damaging	Het
Kif21a	G	T	15: 90,879,715 (GRCm39)	T191K	probably benign	Het
Lrit1	T	A	14: 36,782,084 (GRCm39)	C252*	probably null	Het
Ncbp1	T	A	4: 46,144,837 (GRCm39)	D29E	probably benign	Het
Nlrp10	A	T	7: 108,524,735 (GRCm39)	D248E	probably damaging	Het
Nphp4	T	G	4: 152,631,521 (GRCm39)	V807G	probably benign	Het
Nsd1	T	C	13: 55,393,856 (GRCm39)	S589P	possibly damaging	Het
Oas1b	T	A	5: 120,952,550 (GRCm39)	N80K	probably damaging	Het
Oprk1	T	A	1: 5,669,096 (GRCm39)	C181S	probably damaging	Het
Oprl1	T	A	2: 181,360,212 (GRCm39)	N89K	probably damaging	Het
Or5w12	A	T	2: 87,502,105 (GRCm39)	I202N	probably benign	Het
Or8k53	G	A	2: 86,177,583 (GRCm39)	H176Y	probably benign	Het
Pdcd11	A	G	19: 47,117,741 (GRCm39)	K1697E	probably damaging	Het
Pds5b	A	T	5: 150,729,128 (GRCm39)	D1419V	possibly damaging	Het
Per1	G	T	11: 68,991,475 (GRCm39)	G3V	probably benign	Het
Pex16	C	A	2: 92,206,988 (GRCm39)	N55K	probably damaging	Het
Phldb2	C	A	16: 45,595,340 (GRCm39)	L862F	probably benign	Het
Pld5	T	A	1: 175,791,572 (GRCm39)	D478V	probably benign	Het
Pms2	T	C	5: 143,851,614 (GRCm39)	I177T	probably damaging	Het
Pou1f1	A	T	16: 65,326,758 (GRCm39)	E119D	probably benign	Het
Ppp2r1a	A	C	17: 21,179,058 (GRCm39)	E295A	probably damaging	Het
Qrfprl	A	G	6: 65,433,124 (GRCm39)	I315V	probably benign	Het
Rad51ap2	A	T	12: 11,507,593 (GRCm39)	N505I	possibly damaging	Het
Rasal3	A	C	17: 32,615,536 (GRCm39)	V434G	probably damaging	Het
Rasgrf2	C	T	13: 92,136,092 (GRCm39)	V6M		Het
Rwdd1	A	T	10: 33,877,152 (GRCm39)	D197E		Het
Scn11a	A	T	9: 119,619,076 (GRCm39)	C755*	probably null	Het
Skil	T	C	3: 31,171,009 (GRCm39)	S443P	probably benign	Het
Slc12a6	T	C	2: 112,186,817 (GRCm39)	C939R	probably damaging	Het
Slc25a36	A	G	9: 96,961,230 (GRCm39)	S269P	probably benign	Het
Srrm4	T	A	5: 116,620,452 (GRCm39)	H92L	unknown	Het
Styk1	CTCTTCATGATTTTCTT	CTCTT	6: 131,278,612 (GRCm39)		probably benign	Het
Tbc1d4	A	T	14: 101,744,846 (GRCm39)	V260E	probably benign	Het
Tbc1d8	T	C	1: 39,424,313 (GRCm39)	N593D	probably damaging	Het
Trex1	C	A	9: 108,887,805 (GRCm39)	R62L	probably damaging	Het
Trpm3	A	T	19: 22,692,716 (GRCm39)	D269V	possibly damaging	Het
Trpv4	G	T	5: 114,771,211 (GRCm39)	Y439*	probably null	Het
Ttn	G	A	2: 76,564,592 (GRCm39)	T28515I	probably damaging	Het
Ucn2	G	A	9: 108,815,571 (GRCm39)	G111D	probably damaging	Het
Uhrf2	A	G	19: 30,033,881 (GRCm39)	I212V	possibly damaging	Het
Usp24	T	A	4: 106,204,564 (GRCm39)	M261K	probably benign	Het
Vmn1r235	A	T	17: 21,481,960 (GRCm39)	D95V	probably benign	Het
Vwf	G	A	6: 125,601,536 (GRCm39)	R826Q		Het
Zfp1002	C	T	2: 150,096,496 (GRCm39)	R311Q	probably benign	Het
Zfp28	T	C	7: 6,396,878 (GRCm39)	C438R	probably damaging	Het

Other mutations in Pdp1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL02243:Pdp1	APN	4	11,961,873 (GRCm39)	missense	probably benign	0.20
IGL02643:Pdp1	APN	4	11,962,062 (GRCm39)	missense	probably benign
R1931:Pdp1	UTSW	4	11,962,074 (GRCm39)	missense	probably benign	0.01
R2162:Pdp1	UTSW	4	11,961,123 (GRCm39)	missense	probably damaging	0.98
R2418:Pdp1	UTSW	4	11,961,838 (GRCm39)	missense	probably damaging	0.98
R3843:Pdp1	UTSW	4	11,961,961 (GRCm39)	missense	probably benign	0.00
R5699:Pdp1	UTSW	4	11,960,907 (GRCm39)	missense	possibly damaging	0.79
R6479:Pdp1	UTSW	4	11,961,327 (GRCm39)	missense	probably damaging	1.00
R7221:Pdp1	UTSW	4	11,961,004 (GRCm39)	missense	probably damaging	0.99
R7263:Pdp1	UTSW	4	11,960,821 (GRCm39)	missense	possibly damaging	0.82
R8483:Pdp1	UTSW	4	11,961,982 (GRCm39)	missense	probably benign
R9184:Pdp1	UTSW	4	11,962,143 (GRCm39)	missense	possibly damaging	0.80
Z1177:Pdp1	UTSW	4	11,961,639 (GRCm39)	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