Mutagenetix > Incidental Mutation

Incidental Mutation 'R8325:Pdhx'

644035

Institutional Source

Beutler Lab

Gene Symbol

Pdhx

Ensembl Gene

ENSMUSG00000010914

Gene Name

pyruvate dehydrogenase complex, component X

Synonyms

Pdx1

MMRRC Submission

067857-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R8325 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

102851420-102903858 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

G to T at 102872597 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Proline to Threonine at position 162 (P162T)

Ref Sequence

ENSEMBL: ENSMUSP00000011058 (fasta)

Gene Model

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

AlphaFold

Q8BKZ9

Predicted Effect

probably benign
Transcript: ENSMUST00000011058
AA Change: P162T

PolyPhen 2 Score 0.075 (Sensitivity: 0.93; Specificity: 0.85)

SMART Domains

Protein: ENSMUSP00000011058
Gene: ENSMUSG00000010914
AA Change: P162T

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: P162T

PolyPhen 2 Score 0.323 (Sensitivity: 0.90; Specificity: 0.89)

SMART Domains

Protein: ENSMUSP00000106814
Gene: ENSMUSG00000010914
AA Change: P162T

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: P97T

PolyPhen 2 Score 0.353 (Sensitivity: 0.90; Specificity: 0.89)

SMART Domains

Protein: ENSMUSP00000119172
Gene: ENSMUSG00000010914
AA Change: P97T

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

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.4%
20x: 98.2%

Validation Efficiency

100% (51/51)

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: 54 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Acr	T	C	15: 89,453,954 (GRCm39)	V97A	probably benign	Het
Agrn	C	T	4: 156,258,119 (GRCm39)	G1081D	probably benign	Het
Ang2	A	G	14: 51,432,960 (GRCm39)	S141P	probably damaging	Het
Ap3b2	T	C	7: 81,134,237 (GRCm39)		probably null	Het
Apba2	A	T	7: 64,345,730 (GRCm39)	T307S	probably benign	Het
Cadm2	T	A	16: 66,612,338 (GRCm39)	N84Y	possibly damaging	Het
Camsap1	T	C	2: 25,829,375 (GRCm39)	D783G	probably benign	Het
Ccdc62	T	C	5: 124,092,448 (GRCm39)	C478R	probably benign	Het
Cep290	A	C	10: 100,353,670 (GRCm39)	H801P	probably benign	Het
Chfr	T	A	5: 110,310,629 (GRCm39)	Y555*	probably null	Het
Cmas	T	C	6: 142,717,065 (GRCm39)		probably null	Het
Cmtm7	T	C	9: 114,592,415 (GRCm39)	I61V	probably benign	Het
Cyb5d2	A	G	11: 72,669,651 (GRCm39)	S236P	possibly damaging	Het
Dcp1b	C	T	6: 119,192,397 (GRCm39)	Q438*	probably null	Het
Dgcr8	T	C	16: 18,076,149 (GRCm39)	Q678R	probably damaging	Het
Emc1	T	A	4: 139,092,521 (GRCm39)	M487K	possibly damaging	Het
Gm7361	T	C	5: 26,467,154 (GRCm39)	S258P	probably damaging	Het
Hbs1l	A	G	10: 21,183,548 (GRCm39)	I96M	probably benign	Het
Ifi27l2a	G	A	12: 103,409,144 (GRCm39)	A49V	unknown	Het
Igkv10-96	T	C	6: 68,609,088 (GRCm39)	Y69C	possibly damaging	Het
Igsf10	A	T	3: 59,225,954 (GRCm39)	V2573D	probably damaging	Het
Kcng3	T	C	17: 83,939,007 (GRCm39)	N14S	possibly damaging	Het
Kif20a	A	G	18: 34,759,975 (GRCm39)	T94A	possibly damaging	Het
Lcp2	T	A	11: 34,032,394 (GRCm39)	V324E	probably benign	Het
Lmod3	T	C	6: 97,224,379 (GRCm39)	K481E	probably benign	Het
Met	A	G	6: 17,571,671 (GRCm39)	E1330G	probably damaging	Het
Mroh1	GCCCAGGCCCC	GCC	15: 76,316,415 (GRCm39)		probably null	Het
Mss51	T	C	14: 20,534,771 (GRCm39)	D333G	possibly damaging	Het
Nav3	A	G	10: 109,541,464 (GRCm39)	V1933A	probably benign	Het
Nbas	A	G	12: 13,338,796 (GRCm39)	Y212C	probably damaging	Het
Nkapd1	T	C	9: 50,521,608 (GRCm39)	I104M	probably benign	Het
Npsr1	C	T	9: 24,198,118 (GRCm39)		probably benign	Het
Nt5e	A	G	9: 88,245,615 (GRCm39)	E295G	probably benign	Het
Or6b1	T	C	6: 42,815,124 (GRCm39)	F103S	probably damaging	Het
Or9m1b	A	T	2: 87,836,537 (GRCm39)	L186Q	probably damaging	Het
Papss1	A	G	3: 131,288,372 (GRCm39)	T136A	probably benign	Het
Pcdha1	A	T	18: 37,063,867 (GRCm39)	D177V	possibly damaging	Het
Pcolce2	A	T	9: 95,574,973 (GRCm39)	S308C	probably damaging	Het
Plin3	C	T	17: 56,593,268 (GRCm39)	R98Q	probably benign	Het
Prr36	T	C	8: 4,262,982 (GRCm39)	T895A	probably benign	Het
Repin1	G	T	6: 48,574,279 (GRCm39)	E403*	probably null	Het
Rnf213	A	G	11: 119,321,271 (GRCm39)	N1243S		Het
Serpinb1b	A	T	13: 33,277,584 (GRCm39)	K272N	probably benign	Het
Sez6l	A	T	5: 112,575,982 (GRCm39)		probably null	Het
Syne1	A	T	10: 5,096,257 (GRCm39)	M739K	probably benign	Het
Tbc1d9	G	A	8: 83,966,667 (GRCm39)		probably null	Het
Trp53inp1	A	G	4: 11,164,561 (GRCm39)	D35G	probably damaging	Het
Trpc7	A	G	13: 56,952,524 (GRCm39)	V549A	probably damaging	Het
Usp18	T	C	6: 121,230,769 (GRCm39)	L66S	probably damaging	Het
Vmn1r238	C	T	18: 3,122,529 (GRCm39)	S295N	probably benign	Het
Vmn2r29	T	C	7: 7,244,941 (GRCm39)	D311G	probably damaging	Het
Vmn2r91	C	A	17: 18,356,625 (GRCm39)	A764D	probably damaging	Het
Wdfy4	T	A	14: 32,689,444 (GRCm39)	I3031F		Het
Wdr7	A	G	18: 63,911,535 (GRCm39)		probably null	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
R4744:Pdhx	UTSW	2	102,872,641 (GRCm39)	missense	probably benign	0.01
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
R9163:Pdhx	UTSW	2	102,852,561 (GRCm39)	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- TCTACACTGAGCAAGCAAGG -3'
(R):5'- GTGACTTCATGTGACCCTGG -3'

Sequencing Primer
(F):5'- GGCTTTTAGATTCTAGCCCAAAC -3'
(R):5'- GACTTCATGTGACCCTGGGTTTTTC -3'

Posted On

2020-09-02