Mutagenetix > Incidental Mutation

Incidental Mutation 'R4744:Pdhx'

356554

Institutional Source

Beutler Lab

Gene Symbol

Pdhx

Ensembl Gene

ENSMUSG00000010914

Gene Name

pyruvate dehydrogenase complex, component X

Synonyms

Pdx1

MMRRC Submission

042027-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R4744 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

102851420-102903858 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 102872641 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Valine to Aspartic acid at position 147 (V147D)

Ref Sequence

ENSEMBL: ENSMUSP00000106814 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000011058] [ENSMUST00000111183] [ENSMUST00000132449]

AlphaFold

Q8BKZ9

Predicted Effect

probably benign
Transcript: ENSMUST00000011058
AA Change: V147D

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

SMART Domains

Protein: ENSMUSP00000011058
Gene: ENSMUSG00000010914
AA Change: V147D

Domain	Start	End	E-Value	Type
low complexity region	13	28	N/A	INTRINSIC
Pfam:Biotin_lipoyl	57	131	1.3e-21	PFAM
low complexity region	148	172	N/A	INTRINSIC
Pfam:E3_binding	182	217	5e-9	PFAM
low complexity region	233	249	N/A	INTRINSIC
Pfam:2-oxoacid_dh	272	501	8.4e-74	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000111183
AA Change: V147D

PolyPhen 2 Score 0.012 (Sensitivity: 0.96; Specificity: 0.78)

SMART Domains

Protein: ENSMUSP00000106814
Gene: ENSMUSG00000010914
AA Change: V147D

Domain	Start	End	E-Value	Type
low complexity region	13	28	N/A	INTRINSIC
Pfam:Biotin_lipoyl	57	131	1.8e-21	PFAM
low complexity region	148	172	N/A	INTRINSIC
Pfam:E3_binding	180	216	6.9e-12	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000132449
AA Change: V82D

PolyPhen 2 Score 0.003 (Sensitivity: 0.98; Specificity: 0.44)

SMART Domains

Protein: ENSMUSP00000119172
Gene: ENSMUSG00000010914
AA Change: V82D

Domain	Start	End	E-Value	Type
Pfam:Biotin_lipoyl	5	66	1.3e-14	PFAM
low complexity region	83	107	N/A	INTRINSIC
Pfam:E3_binding	115	153	6.1e-14	PFAM
low complexity region	168	184	N/A	INTRINSIC

Meta Mutation Damage Score

0.0898

Coding Region Coverage

1x: 99.1%
3x: 98.5%
10x: 96.9%
20x: 94.3%

Validation Efficiency

99% (82/83)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The pyruvate dehydrogenase (PDH) complex is located in the mitochondrial matrix and catalyzes the conversion of pyruvate to acetyl coenzyme A. The PDH complex thereby links glycolysis to Krebs cycle. The PDH complex contains three catalytic subunits, E1, E2, and E3, two regulatory subunits, E1 kinase and E1 phosphatase, and a non-catalytic subunit, E3 binding protein (E3BP). This gene encodes the E3 binding protein subunit; also known as component X of the pyruvate dehydrogenase complex. This protein tethers E3 dimers to the E2 core of the PDH complex. Defects in this gene are a cause of pyruvate dehydrogenase deficiency which results in neurological dysfunction and lactic acidosis in infancy and early childhood. This protein is also a minor antigen for antimitochondrial antibodies. These autoantibodies are present in nearly 95% of patients with the autoimmune liver disease primary biliary cirrhosis (PBC). In PBC, activated T lymphocytes attack and destroy epithelial cells in the bile duct where this protein is abnormally distributed and overexpressed. PBC eventually leads to cirrhosis and liver failure. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Oct 2009]

Allele List at MGI

Other mutations in this stock

Total: 70 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4930519G04Rik	T	C	5: 115,017,617 (GRCm39)	S143P	possibly damaging	Het
4933427D14Rik	T	C	11: 72,066,365 (GRCm39)	K614E	probably damaging	Het
Aatk	A	G	11: 119,906,948 (GRCm39)	M155T	possibly damaging	Het
Acvr2b	T	C	9: 119,260,328 (GRCm39)	L333P	probably damaging	Het
Adam22	T	C	5: 8,128,699 (GRCm39)	E865G	probably damaging	Het
Add2	A	G	6: 86,087,870 (GRCm39)	S358G	probably damaging	Het
Agap2	T	C	10: 126,926,072 (GRCm39)		probably null	Het
Alkbh8	G	A	9: 3,344,604 (GRCm39)	W49*	probably null	Het
AU015228	A	T	2: 129,942,549 (GRCm39)		noncoding transcript	Het
Bank1	G	T	3: 135,953,450 (GRCm39)	R102S	probably benign	Het
Brap	T	A	5: 121,800,193 (GRCm39)	D27E	probably damaging	Het
Cyb5r2	G	T	7: 107,349,484 (GRCm39)	H276N	possibly damaging	Het
Dhh	A	G	15: 98,792,139 (GRCm39)	F290L	possibly damaging	Het
Dhrs7	T	A	12: 72,699,025 (GRCm39)	N319I	possibly damaging	Het
Ebpl	A	G	14: 61,597,682 (GRCm39)	V53A	probably damaging	Het
Eif3j2	TGCCGCCGCCGCCGCCGCCGCCGCCGCC	TGCCGCCGCCGCCGCCGCCGCCGCC	18: 43,610,782 (GRCm39)		probably benign	Het
Etnk1	A	C	6: 143,132,319 (GRCm39)	N220T	probably damaging	Het
F11r	T	A	1: 171,288,166 (GRCm39)	V64D	probably benign	Het
Fam171a1	T	C	2: 3,225,946 (GRCm39)	S360P	probably damaging	Het
Fignl1	A	G	11: 11,751,585 (GRCm39)	M490T	probably damaging	Het
Fpr-rs7	A	T	17: 20,334,265 (GRCm39)	M75K	probably benign	Het
Fzd7	T	A	1: 59,523,595 (GRCm39)	F493I	possibly damaging	Het
Galnt14	G	T	17: 73,814,828 (GRCm39)	P412T	probably damaging	Het
Gcg	T	A	2: 62,308,975 (GRCm39)	S60C	probably damaging	Het
Ggt1	A	G	10: 75,421,733 (GRCm39)	K527E	probably benign	Het
Gm16551	T	A	9: 74,758,153 (GRCm39)		noncoding transcript	Het
Gm9972	A	G	11: 42,927,517 (GRCm39)	K55E	unknown	Het
Gpr141	T	A	13: 19,935,884 (GRCm39)	D297V	probably benign	Het
Grin2b	G	A	6: 135,755,697 (GRCm39)	S539L	probably damaging	Het
Hhipl1	A	T	12: 108,286,238 (GRCm39)	N515I	possibly damaging	Het
Hmcn1	T	G	1: 150,453,363 (GRCm39)	E5317D	probably damaging	Het
Hsf5	T	A	11: 87,513,617 (GRCm39)	N227K	probably benign	Het
Igfn1	A	T	1: 135,910,196 (GRCm39)	D129E	probably benign	Het
Invs	T	C	4: 48,397,609 (GRCm39)	F339L	probably damaging	Het
Jak2	T	A	19: 29,239,656 (GRCm39)	S17T	probably benign	Het
Mdga2	T	A	12: 66,844,501 (GRCm39)	I166F	probably benign	Het
Nck1	T	C	9: 100,388,797 (GRCm39)	I6V	probably benign	Het
Neb	T	C	2: 52,040,589 (GRCm39)	D6624G	probably benign	Het
Nmur2	A	G	11: 55,931,661 (GRCm39)	Y17H	probably benign	Het
Nwd2	T	C	5: 63,964,310 (GRCm39)	L1298P	probably damaging	Het
Ocel1	A	G	8: 71,825,397 (GRCm39)	E161G	probably damaging	Het
Or1j16	A	T	2: 36,530,991 (GRCm39)		probably null	Het
Pabpc2	A	G	18: 39,907,881 (GRCm39)	Y382C	probably benign	Het
Panx1	A	G	9: 14,921,594 (GRCm39)		probably benign	Het
Pigz	A	T	16: 31,764,151 (GRCm39)	H403L	probably damaging	Het
Pilra	T	C	5: 137,833,769 (GRCm39)		probably null	Het
Rbm47	T	C	5: 66,184,036 (GRCm39)	D189G	probably damaging	Het
Rhobtb2	A	G	14: 70,031,451 (GRCm39)	L558P	probably damaging	Het
Scarf2	G	A	16: 17,621,380 (GRCm39)	R322H	probably damaging	Het
Septin3	T	C	15: 82,174,658 (GRCm39)		probably null	Het
Sirt2	T	C	7: 28,476,438 (GRCm39)	F26L	probably damaging	Het
Slc1a1	A	T	19: 28,871,925 (GRCm39)	T133S	probably benign	Het
Slc1a2	A	G	2: 102,568,214 (GRCm39)	I84V	probably benign	Het
Slc28a2b	A	T	2: 122,353,286 (GRCm39)	K489*	probably null	Het
Slc6a9	A	T	4: 117,725,092 (GRCm39)	Q562L	probably benign	Het
Snx29	C	T	16: 11,167,773 (GRCm39)	Q25*	probably null	Het
St6galnac6	A	G	2: 32,508,555 (GRCm39)	I231V	probably damaging	Het
Stard9	A	G	2: 120,526,604 (GRCm39)	T954A	probably benign	Het
Sufu	A	G	19: 46,472,069 (GRCm39)	M443V	possibly damaging	Het
Sv2b	T	C	7: 74,856,266 (GRCm39)	D8G	probably benign	Het
Tapbpl	G	A	6: 125,205,248 (GRCm39)	R233W	probably damaging	Het
Tex10	A	G	4: 48,469,990 (GRCm39)	L25S	probably benign	Het
Trp53bp1	A	T	2: 121,041,794 (GRCm39)	V1254D	probably damaging	Het
Ugt3a1	T	A	15: 9,310,639 (GRCm39)	I307N	probably benign	Het
Unc13c	T	C	9: 73,839,126 (GRCm39)	D575G	probably damaging	Het
Usf2	A	T	7: 30,654,197 (GRCm39)	D166E	probably damaging	Het
Usp25	T	A	16: 76,911,877 (GRCm39)	L969M	probably damaging	Het
Usp32	G	A	11: 84,885,219 (GRCm39)	P1276L	probably damaging	Het
Vmn2r8	T	A	5: 108,956,447 (GRCm39)	E58D	probably benign	Het
Zfp462	G	T	4: 55,011,598 (GRCm39)	C40F	probably damaging	Het

Other mutations in Pdhx

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL02147:Pdhx	APN	2	102,860,686 (GRCm39)	unclassified	probably benign
IGL02450:Pdhx	APN	2	102,872,594 (GRCm39)	missense	probably benign	0.00
R0152:Pdhx	UTSW	2	102,858,625 (GRCm39)	missense	probably benign	0.04
R0317:Pdhx	UTSW	2	102,858,625 (GRCm39)	missense	probably benign	0.04
R2351:Pdhx	UTSW	2	102,854,562 (GRCm39)	nonsense	probably null
R3937:Pdhx	UTSW	2	102,852,564 (GRCm39)	missense	probably damaging	1.00
R3950:Pdhx	UTSW	2	102,865,586 (GRCm39)	missense	probably damaging	0.99
R4546:Pdhx	UTSW	2	102,903,742 (GRCm39)	missense	probably null	0.99
R4677:Pdhx	UTSW	2	102,903,811 (GRCm39)	splice site	probably null
R4996:Pdhx	UTSW	2	102,860,657 (GRCm39)	missense	probably damaging	1.00
R5000:Pdhx	UTSW	2	102,871,385 (GRCm39)	splice site	probably null
R5076:Pdhx	UTSW	2	102,871,422 (GRCm39)	missense	probably damaging	0.99
R5682:Pdhx	UTSW	2	102,865,685 (GRCm39)	missense	probably benign	0.00
R6246:Pdhx	UTSW	2	102,877,137 (GRCm39)	missense	probably damaging	1.00
R6850:Pdhx	UTSW	2	102,871,445 (GRCm39)	missense	probably damaging	1.00
R7141:Pdhx	UTSW	2	102,903,659 (GRCm39)	missense	probably benign	0.21
R7219:Pdhx	UTSW	2	102,858,760 (GRCm39)	missense	probably benign	0.01
R7460:Pdhx	UTSW	2	102,877,124 (GRCm39)	missense	probably damaging	1.00
R7552:Pdhx	UTSW	2	102,877,099 (GRCm39)	missense	probably benign	0.01
R8325:Pdhx	UTSW	2	102,872,597 (GRCm39)	missense	probably benign	0.08
R9163:Pdhx	UTSW	2	102,852,561 (GRCm39)	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- TGGATGATGCTGATTTCAAACCC -3'
(R):5'- GAAGAGCCCTCTGTCTTCAG -3'

Sequencing Primer
(F):5'- TGTTCACATAAACGCACTC -3'
(R):5'- CAGTGTCCTTTAGCTCAGGTC -3'

Posted On

2015-11-11