Mutagenetix > Incidental Mutation

Incidental Mutation 'R7219:Pdhx'

561637

Institutional Source

Beutler Lab

Gene Symbol

Pdhx

Ensembl Gene

ENSMUSG00000010914

Gene Name

pyruvate dehydrogenase complex, component X

Synonyms

Pdx1

MMRRC Submission

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R7219 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

103021075-103073513 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 103028415 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Valine to Alanine at position 348 (V348A)

Ref Sequence

ENSEMBL: ENSMUSP00000011058 (fasta)

Gene Model

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

AlphaFold

Q8BKZ9

Predicted Effect

probably benign
Transcript: ENSMUST00000011058
AA Change: V348A

PolyPhen 2 Score 0.013 (Sensitivity: 0.96; Specificity: 0.78)

SMART Domains

Protein: ENSMUSP00000011058
Gene: ENSMUSG00000010914
AA Change: V348A

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: ENSMUST00000132449

SMART Domains

Protein: ENSMUSP00000119172
Gene: ENSMUSG00000010914

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: 99.7%
20x: 99.0%

Validation Efficiency

97% (77/79)

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: 79 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4930562C15Rik	T	C	16: 4,849,644	S300P	unknown	Het
Abhd17a	T	A	10: 80,584,174	K226*	probably null	Het
Alkbh7	T	A	17: 56,998,508	H108Q	probably damaging	Het
Ankrd44	A	C	1: 54,766,910	H112Q	probably damaging	Het
Capn3	A	G	2: 120,503,454	E790G	probably damaging	Het
Cd47	C	A	16: 49,908,077	N330K	possibly damaging	Het
Cd55	A	G	1: 130,462,606	S22P	possibly damaging	Het
Cdc25a	A	G	9: 109,889,086	I373V	probably damaging	Het
Cfap43	T	C	19: 47,791,473	I514V	probably benign	Het
Cfap73	A	T	5: 120,630,135	M186K	probably benign	Het
Chd9	A	G	8: 91,001,766	D1270G	unknown	Het
Ciita	A	G	16: 10,512,257	T802A	probably benign	Het
Dlgap2	A	G	8: 14,743,296	E430G	probably benign	Het
Dlx1	C	A	2: 71,530,169	S59*	probably null	Het
Dnaaf3	T	C	7: 4,528,077	N119S	probably damaging	Het
Dnah11	T	G	12: 118,041,095	I2164L	possibly damaging	Het
Dnah11	T	C	12: 118,126,889	K1079R	probably benign	Het
Dnah12	C	T	14: 26,854,880	T3029I	probably damaging	Het
Dppa3	A	T	6: 122,629,959	Y136F	probably damaging	Het
Enox1	T	A	14: 77,720,844	M611K	probably benign	Het
Fam149a	A	T	8: 45,350,563	I378N	possibly damaging	Het
Fam208b	T	A	13: 3,590,521	L205F	probably damaging	Het
Farp2	T	C	1: 93,560,318	F89S	probably damaging	Het
Fbn2	C	T	18: 58,053,027	V1750M	probably benign	Het
Frs3	A	G	17: 47,702,695	T181A	probably damaging	Het
Heatr4	T	A	12: 83,957,870	I726F	possibly damaging	Het
Ighg1	T	G	12: 113,326,596	E375A		Het
Ikzf4	G	T	10: 128,634,383	Q476K	possibly damaging	Het
Kcnh1	G	T	1: 192,505,637	C829F	probably benign	Het
Krtap19-4	T	C	16: 88,884,909	Y53C	unknown	Het
Lor	C	A	3: 92,081,398	G194C	unknown	Het
Lrp1	A	C	10: 127,557,228	D2720E	probably benign	Het
Lrp4	A	G	2: 91,492,023	Y1068C	probably damaging	Het
Mbnl1	A	G	3: 60,603,823	N67D	probably benign	Het
Mrpl21	A	G	19: 3,286,998	E123G	probably benign	Het
Mst1	A	T	9: 108,081,286	D65V	probably damaging	Het
Myo15b	T	A	11: 115,877,095		probably null	Het
Myo5a	A	G	9: 75,120,770	Y79C	probably damaging	Het
Oas1c	A	T	5: 120,802,892	W279R	probably damaging	Het
Olfr1283	A	T	2: 111,369,537	I302L	probably benign	Het
Olfr1291-ps1	A	T	2: 111,500,187	M312L	probably benign	Het
Olfr561	A	G	7: 102,781,706	I77V	probably benign	Het
Pcdh9	C	T	14: 93,015,780	G1149D	possibly damaging	Het
Pcid2	G	A	8: 13,079,907	T283I	probably benign	Het
Pi16	C	A	17: 29,319,234	P7Q	possibly damaging	Het
Psmb3	T	A	11: 97,711,197	M131K	probably null	Het
Raph1	A	G	1: 60,502,873	Y309H	unknown	Het
Rasgrf1	A	G	9: 89,984,288	N593S	probably damaging	Het
Rbm38	A	C	2: 173,022,197	E53A	possibly damaging	Het
Rufy3	A	G	5: 88,649,856	T631A	probably benign	Het
Sbno1	A	T	5: 124,405,659	D272E	probably benign	Het
Scamp1	T	A	13: 94,224,907	Y207F	probably damaging	Het
Scn8a	T	A	15: 100,969,103	S263R	probably damaging	Het
Setbp1	T	G	18: 78,755,745	T1407P	probably damaging	Het
Skor2	T	C	18: 76,860,401	L606P	possibly damaging	Het
Slc35f6	A	G	5: 30,657,452	N241S	probably benign	Het
Slc36a2	T	G	11: 55,168,918	D247A	probably benign	Het
Smim10l1	T	A	6: 133,107,932	F87L	unknown	Het
Son	T	C	16: 91,665,001	S2265P	unknown	Het
Spta1	A	G	1: 174,222,637	N1748D	probably damaging	Het
Sptbn2	A	G	19: 4,724,173	D84G	probably damaging	Het
Tbc1d24	G	A	17: 24,185,292	R293C	probably damaging	Het
Tex15	A	G	8: 33,546,240	T65A	probably benign	Het
Thyn1	A	G	9: 27,005,210	Y97C	probably damaging	Het
Tmem64	T	C	4: 15,266,700	L250P	probably damaging	Het
Tnfrsf9	A	T	4: 150,935,534	K217N	probably damaging	Het
Tnxb	A	G	17: 34,679,065	T896A	probably benign	Het
Trpm1	T	A	7: 64,204,585	I285N	possibly damaging	Het
Try5	T	A	6: 41,311,703	D194V	probably damaging	Het
U2surp	G	A	9: 95,490,162	R316*	probably null	Het
Ubr2	G	T	17: 46,935,434	S1618*	probably null	Het
Ugp2	T	C	11: 21,323,271	I449M	probably damaging	Het
Umodl1	A	G	17: 30,982,262		probably null	Het
Vmn2r31	C	T	7: 7,387,106	V538I	probably benign	Het
Vmn2r31	A	T	7: 7,394,398	M287K	probably damaging	Het
Wwc2	A	G	8: 47,858,884	V748A	unknown	Het
Zfp800	A	C	6: 28,243,663	H434Q	probably benign	Het
Zfp869	A	G	8: 69,706,706	C406R	probably damaging	Het
Zhx1	A	G	15: 58,054,337	V171A	probably benign	Het

Other mutations in Pdhx

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL02147:Pdhx	APN	2	103030341	unclassified	probably benign
IGL02450:Pdhx	APN	2	103042249	missense	probably benign	0.00
R0152:Pdhx	UTSW	2	103028280	missense	probably benign	0.04
R0317:Pdhx	UTSW	2	103028280	missense	probably benign	0.04
R2351:Pdhx	UTSW	2	103024217	nonsense	probably null
R3937:Pdhx	UTSW	2	103022219	missense	probably damaging	1.00
R3950:Pdhx	UTSW	2	103035241	missense	probably damaging	0.99
R4546:Pdhx	UTSW	2	103073397	missense	probably null	0.99
R4677:Pdhx	UTSW	2	103073466	splice site	probably null
R4744:Pdhx	UTSW	2	103042296	missense	probably benign	0.01
R4996:Pdhx	UTSW	2	103030312	missense	probably damaging	1.00
R5000:Pdhx	UTSW	2	103041040	splice site	probably null
R5076:Pdhx	UTSW	2	103041077	missense	probably damaging	0.99
R5682:Pdhx	UTSW	2	103035340	missense	probably benign	0.00
R6246:Pdhx	UTSW	2	103046792	missense	probably damaging	1.00
R6850:Pdhx	UTSW	2	103041100	missense	probably damaging	1.00
R7141:Pdhx	UTSW	2	103073314	missense	probably benign	0.21
R7460:Pdhx	UTSW	2	103046779	missense	probably damaging	1.00
R7552:Pdhx	UTSW	2	103046754	missense	probably benign	0.01
R8325:Pdhx	UTSW	2	103042252	missense	probably benign	0.08
R9163:Pdhx	UTSW	2	103022216	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- ACAGTTTGAAAGCAGTCTTCTGG -3'
(R):5'- CGTCAGGATTTTCTTAGTCATGC -3'

Sequencing Primer
(F):5'- TGGACACATACCTTTACAGAGTCAG -3'
(R):5'- AGTCATGCGTACTGCTGAAC -3'

Posted On

2019-06-26