Mutagenetix > Incidental Mutation

Incidental Mutation 'R7460:Pdhx'

578370

Institutional Source

Beutler Lab

Gene Symbol

Pdhx

Ensembl Gene

ENSMUSG00000010914

Gene Name

pyruvate dehydrogenase complex, component X

Synonyms

Pdx1

MMRRC Submission

045534-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R7460 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

102851420-102903858 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 102877124 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Threonine to Methionine at position 95 (T95M)

Ref Sequence

ENSEMBL: ENSMUSP00000011058 (fasta)

Gene Model

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

AlphaFold

Q8BKZ9

Predicted Effect

probably damaging
Transcript: ENSMUST00000011058
AA Change: T95M

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000011058
Gene: ENSMUSG00000010914
AA Change: T95M

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 damaging
Transcript: ENSMUST00000111183
AA Change: T95M

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000106814
Gene: ENSMUSG00000010914
AA Change: T95M

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 damaging
Transcript: ENSMUST00000132449
AA Change: T30M

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000119172
Gene: ENSMUSG00000010914
AA Change: T30M

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: 100.0%
10x: 99.8%
20x: 99.3%

Validation Efficiency

100% (64/64)

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: 63 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abi2	T	A	1: 60,473,466 (GRCm39)	V61D	probably damaging	Het
Agrn	C	A	4: 156,258,881 (GRCm39)	V915L	probably damaging	Het
Arhgap24	T	C	5: 103,040,212 (GRCm39)	V476A	probably benign	Het
Arhgef15	A	G	11: 68,837,861 (GRCm39)	L720P	probably damaging	Het
Atad2b	C	A	12: 5,002,660 (GRCm39)	R343S	probably benign	Het
Atxn3	T	A	12: 101,892,776 (GRCm39)	T313S	probably benign	Het
BC051665	T	C	13: 60,932,457 (GRCm39)	E76G	probably benign	Het
Birc2	A	T	9: 7,818,762 (GRCm39)	F610I	probably damaging	Het
Cdh16	A	T	8: 105,348,923 (GRCm39)	V58D	possibly damaging	Het
Cenpf	T	C	1: 189,386,247 (GRCm39)	D2011G	probably damaging	Het
Ddb1	T	C	19: 10,585,275 (GRCm39)		probably null	Het
Ddx1	A	G	12: 13,281,440 (GRCm39)		probably null	Het
Disp2	A	G	2: 118,620,261 (GRCm39)	H331R	probably damaging	Het
Dmxl1	A	G	18: 50,011,679 (GRCm39)	T1279A	probably benign	Het
Dync1i2	T	C	2: 71,081,230 (GRCm39)	I473T	probably damaging	Het
Fam114a1	T	G	5: 65,196,050 (GRCm39)	V520G	possibly damaging	Het
Fan1	T	A	7: 64,022,234 (GRCm39)	N340Y	probably damaging	Het
Fat2	T	A	11: 55,169,789 (GRCm39)	D2990V	probably damaging	Het
Fbh1	C	T	2: 11,761,496 (GRCm39)	G597D	probably benign	Het
Fdxr	A	C	11: 115,167,680 (GRCm39)	S12A	probably benign	Het
Fgf14	T	A	14: 124,914,105 (GRCm39)	R9W	possibly damaging	Het
Gnat3	A	T	5: 18,204,656 (GRCm39)	D103V		Het
Hepacam2	G	A	6: 3,487,199 (GRCm39)	P53S	probably benign	Het
Inhca	T	C	9: 103,131,847 (GRCm39)	N625D	probably benign	Het
Jmjd1c	A	G	10: 67,052,815 (GRCm39)	T21A	probably benign	Het
Lama1	T	C	17: 68,074,013 (GRCm39)	C930R		Het
Lrp1b	T	C	2: 40,488,478 (GRCm39)	T4536A		Het
Lrrc27	T	A	7: 138,803,574 (GRCm39)	V166E	probably damaging	Het
Mapk10	C	T	5: 103,186,443 (GRCm39)	V90I	probably benign	Het
Mfsd14b	C	T	13: 65,219,837 (GRCm39)	G339D	probably damaging	Het
Mnt	T	A	11: 74,734,109 (GRCm39)	M580K	unknown	Het
Mrc1	T	C	2: 14,253,680 (GRCm39)	S234P	probably damaging	Het
Mrps5	G	A	2: 127,433,811 (GRCm39)	V75I	not run	Het
Mrtfb	G	T	16: 13,218,840 (GRCm39)	Q495H	probably benign	Het
Myo10	A	G	15: 25,807,913 (GRCm39)	D1845G	probably damaging	Het
Or3a1c	A	T	11: 74,046,672 (GRCm39)	I231F	probably damaging	Het
Or51a25	A	T	7: 102,373,028 (GRCm39)	M223K	probably benign	Het
Or7a40	C	A	16: 16,491,030 (GRCm39)	A272S	possibly damaging	Het
Or8b3	T	C	9: 38,314,649 (GRCm39)	S160P	possibly damaging	Het
Pigb	C	T	9: 72,945,957 (GRCm39)	V72I	probably damaging	Het
Prr7	C	A	13: 55,620,166 (GRCm39)	P110Q	unknown	Het
Psg22	A	G	7: 18,458,329 (GRCm39)	D340G	probably benign	Het
Ptprn2	T	C	12: 117,212,301 (GRCm39)	S908P	probably benign	Het
Ros1	T	C	10: 51,994,299 (GRCm39)	Y1348C	probably damaging	Het
Rspry1	T	C	8: 95,376,963 (GRCm39)	I506T	probably benign	Het
Ryr2	T	A	13: 11,720,596 (GRCm39)	Y2684F	probably benign	Het
Sdr16c6	A	G	4: 4,076,575 (GRCm39)		probably null	Het
Senp7	A	G	16: 55,993,545 (GRCm39)	T743A	possibly damaging	Het
Slc6a20b	T	C	9: 123,434,014 (GRCm39)	I275V	probably benign	Het
Slc6a7	A	G	18: 61,134,674 (GRCm39)	I467T	probably benign	Het
Tacc2	A	G	7: 130,226,363 (GRCm39)	D1016G	probably benign	Het
Thsd7a	A	G	6: 12,554,933 (GRCm39)	V317A		Het
Tle3	A	G	9: 61,320,366 (GRCm39)	H598R	probably damaging	Het
Tmem102	A	G	11: 69,694,949 (GRCm39)	L341P	probably damaging	Het
Tmem94	G	T	11: 115,677,082 (GRCm39)	R118L	possibly damaging	Het
Trappc14	G	A	5: 138,260,991 (GRCm39)	T218M	probably benign	Het
Trhde	T	A	10: 114,249,168 (GRCm39)	D866V	probably damaging	Het
Ttn	A	G	2: 76,581,617 (GRCm39)	I23092T	probably damaging	Het
U2surp	C	A	9: 95,344,877 (GRCm39)	V944L	unknown	Het
Urgcp	T	C	11: 5,666,622 (GRCm39)	H615R	possibly damaging	Het
Vps45	T	A	3: 95,955,699 (GRCm39)	Y97F	probably benign	Het
Zc3h12c	T	C	9: 52,055,402 (GRCm39)	T136A	probably benign	Het
Zfp948	A	T	17: 21,808,677 (GRCm39)	H623L	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
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
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'- GGGCAATTACTACTAAGTTTTGGC -3'
(R):5'- TTCATGCTGTACACATGTTCATAC -3'

Sequencing Primer
(F):5'- TGGCACTAAGATATTGTAAAGATGTG -3'
(R):5'- GTAAGAAGGCTCAGTACTTGCCTC -3'

Posted On

2019-10-07