Human Gene PDHA1 (ENST00000540249.5) from GENCODE V44
  Description: Homo sapiens pyruvate dehydrogenase E1 subunit alpha 1 (PDHA1), transcript variant 4, mRNA; nuclear gene for mitochondrial product. (from RefSeq NM_001173456)
RefSeq Summary (NM_000284): The pyruvate dehydrogenase (PDH) complex is a nuclear-encoded mitochondrial multienzyme complex that catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and provides the primary link between glycolysis and the tricarboxylic acid (TCA) cycle. The PDH complex is composed of multiple copies of three enzymatic components: pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (E2) and lipoamide dehydrogenase (E3). The E1 enzyme is a heterotetramer of two alpha and two beta subunits. This gene encodes the E1 alpha 1 subunit containing the E1 active site, and plays a key role in the function of the PDH complex. Mutations in this gene are associated with pyruvate dehydrogenase E1-alpha deficiency and X-linked Leigh syndrome. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2010].
Gencode Transcript: ENST00000540249.5
Gencode Gene: ENSG00000131828.14
Transcript (Including UTRs)
   Position: hg38 chrX:19,343,893-19,361,705 Size: 17,813 Total Exon Count: 10 Strand: +
Coding Region
   Position: hg38 chrX:19,344,038-19,359,653 Size: 15,616 Coding Exon Count: 10 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesGeneReviewsMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chrX:19,343,893-19,361,705)mRNA (may differ from genome)Protein (359 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
BioGPSEnsemblEntrez GeneExonPrimerGencodeGeneCards
HGNCHPRDLynxMalacardsMGIneXtProt
OMIMPubMedReactomeUniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: ODPA_HUMAN
DESCRIPTION: RecName: Full=Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial; EC=1.2.4.1; AltName: Full=PDHE1-A type I; Flags: Precursor;
FUNCTION: The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2). It contains multiple copies of three enzymatic components: pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (E2) and lipoamide dehydrogenase (E3).
CATALYTIC ACTIVITY: Pyruvate + [dihydrolipoyllysine-residue acetyltransferase] lipoyllysine = [dihydrolipoyllysine-residue acetyltransferase] S-acetyldihydrolipoyllysine + CO(2).
COFACTOR: Thiamine pyrophosphate.
ENZYME REGULATION: E1 activity is regulated by phosphorylation (inactivation) and dephosphorylation (activation) of the alpha subunit.
SUBUNIT: Tetramer of 2 alpha and 2 beta subunits.
SUBCELLULAR LOCATION: Mitochondrion matrix.
TISSUE SPECIFICITY: Ubiquitous.
PTM: Phosphorylation at Ser-293 by PDK family kinases blocks the access to active site, and inactivates the enzyme.
DISEASE: Defects in PDHA1 are a cause of pyruvate dehydrogenase E1-alpha deficiency (PDHAD) [MIM:312170]. An enzymatic defect causing primary lactic acidosis in children. It is associated with a broad clinical spectrum ranging from fatal lactic acidosis in the newborn to chronic neurologic dysfunction with structural abnormalities in the central nervous system without systemic acidosis.
DISEASE: Defects in PDHA1 are the cause of X-linked Leigh syndrome (X-LS) [MIM:308930]. X-LS is an early-onset progressive neurodegenerative disorder with a characteristic neuropathology consisting of focal, bilateral lesions in one or more areas of the central nervous system, including the brainstem, thalamus, basal ganglia, cerebellum, and spinal cord. The lesions are areas of demyelination, gliosis, necrosis, spongiosis, or capillary proliferation. Clinical symptoms depend on which areas of the central nervous system are involved. The most common underlying cause is a defect in oxidative phosphorylation. LS may be a feature of a deficiency of any of the mitochondrial respiratory chain complexes.
SEQUENCE CAUTION: Sequence=AAA60055.1; Type=Erroneous initiation; Sequence=AAB59581.1; Type=Frameshift; Positions=106, 175;
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/PDHA1";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: PDHA1
Diseases sorted by gene-association score: pyruvate dehydrogenase e1-alpha deficiency* (1714), leigh syndrome with leukodystrophy* (124), x-linked leigh syndrome* (119), coffin-lowry syndrome (23), lactic acidosis (18), x-linked disease (11), alpha-ketoglutarate dehydrogenase deficiency (10), leigh syndrome (8), periventricular leukomalacia (7), leukomalacia (5), mitochondrial metabolism disease (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 94.41 RPKM in Heart - Left Ventricle
Total median expression: 1083.68 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -61.00145-0.421 Picture PostScript Text
3' UTR -567.602052-0.277 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR001017 - DH_E1
IPR017597 - Pyrv_DH_E1_asu_subgrp-y

Pfam Domains:
PF00676 - Dehydrogenase E1 component

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1NI4 - X-ray MuPIT 2OZL - X-ray MuPIT 3EXE - X-ray MuPIT 3EXF - X-ray MuPIT 3EXG - X-ray MuPIT 3EXH - X-ray MuPIT 3EXI - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P08559
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0004738 pyruvate dehydrogenase activity
GO:0004739 pyruvate dehydrogenase (acetyl-transferring) activity
GO:0005515 protein binding
GO:0016491 oxidoreductase activity
GO:0016624 oxidoreductase activity, acting on the aldehyde or oxo group of donors, disulfide as acceptor
GO:0034604 pyruvate dehydrogenase (NAD+) activity

Biological Process:
GO:0005975 carbohydrate metabolic process
GO:0006006 glucose metabolic process
GO:0006086 acetyl-CoA biosynthetic process from pyruvate
GO:0006099 tricarboxylic acid cycle
GO:0008152 metabolic process
GO:0055114 oxidation-reduction process
GO:0061732 mitochondrial acetyl-CoA biosynthetic process from pyruvate

Cellular Component:
GO:0005634 nucleus
GO:0005730 nucleolus
GO:0005739 mitochondrion
GO:0005759 mitochondrial matrix
GO:0043209 myelin sheath
GO:0043231 intracellular membrane-bounded organelle
GO:0045254 pyruvate dehydrogenase complex


-  Descriptions from all associated GenBank mRNAs
  AK312263 - Homo sapiens cDNA, FLJ92558, highly similar to Homo sapiens pyruvate dehydrogenase (lipoamide) alpha 1 (PDHA1), mRNA.
AK293250 - Homo sapiens cDNA FLJ59461 complete cds, highly similar to Pyruvate dehydrogenase E1 component alpha subunit, somatic form, mitochondrial precursor (EC 1.2.4.1).
AK296341 - Homo sapiens cDNA FLJ54787 complete cds, highly similar to Pyruvate dehydrogenase E1 component alpha subunit, somatic form, mitochondrial precursor (EC 1.2.4.1).
AK222988 - Homo sapiens mRNA for pyruvate dehydrogenase (lipoamide) alpha 1 variant, clone: HSI04186.
L13318 - Human pyruvate dehydrogenase E1-alpha subunit (PDHA1) mRNA, complete cds.
L48690 - Homo sapiens pyruvate dehydrogenase E1-alpha subunit precursor (PDHA1) mRNA, complete cds.
AK129887 - Homo sapiens cDNA FLJ26377 fis, clone HRT06382, highly similar to Pyruvate dehydrogenase E1 component alpha subunit, somatic form, mitochondrial precursor (EC 1.2.4.1).
AK222740 - Homo sapiens mRNA for pyruvate dehydrogenase (lipoamide) alpha 1 variant, clone: DMC00706.
J03503 - Human pyruvate dehydrogenase E1-alpha subunit mRNA, cds.
AK296457 - Homo sapiens cDNA FLJ52314 complete cds, highly similar to Pyruvate dehydrogenase E1 component alpha subunit, somatic form, mitochondrial precursor (EC 1.2.4.1).
BC002406 - Homo sapiens pyruvate dehydrogenase (lipoamide) alpha 1, mRNA (cDNA clone MGC:8609 IMAGE:2961286), complete cds.
X52710 - Human mRNA for liver pyruvate dehydrogenase (EC 1.2.4.1) E1' subunit.
X52709 - Human mRNA for brain pyruvate dehydrogenase (EC 1.2.4.1).
J03575 - Human pyruvate dehydrogenase alpha subunit mRNA, complete cds.
M24848 - Human pyruvate dehydrogenase alpha subunit mRNA, complete cds.
JD178558 - Sequence 159582 from Patent EP1572962.
EF590117 - Homo sapiens clone IMAGE:1925777 mitochondrial PDHA1 (PDHA1) mRNA, complete cds; nuclear gene for mitochondrial product.
JD458293 - Sequence 439317 from Patent EP1572962.
DQ895054 - Synthetic construct Homo sapiens clone IMAGE:100009514; FLH180718.01L; RZPDo839F04133D pyruvate dehydrogenase (lipoamide) alpha 1 (PDHA1) gene, encodes complete protein.
DQ895057 - Synthetic construct Homo sapiens clone IMAGE:100009517; FLH263696.01L; RZPDo839F08133D pyruvate dehydrogenase (lipoamide) alpha 1 (PDHA1) gene, encodes complete protein.
DQ891865 - Synthetic construct clone IMAGE:100004495; FLH180722.01X; RZPDo839F04134D pyruvate dehydrogenase (lipoamide) alpha 1 (PDHA1) gene, encodes complete protein.
KJ891769 - Synthetic construct Homo sapiens clone ccsbBroadEn_01163 PDHA1 gene, encodes complete protein.
KR709999 - Synthetic construct Homo sapiens clone CCSBHm_00008815 PDHA1 (PDHA1) mRNA, encodes complete protein.
KR710000 - Synthetic construct Homo sapiens clone CCSBHm_00008820 PDHA1 (PDHA1) mRNA, encodes complete protein.
KR710001 - Synthetic construct Homo sapiens clone CCSBHm_00008840 PDHA1 (PDHA1) mRNA, encodes complete protein.
KR710002 - Synthetic construct Homo sapiens clone CCSBHm_00008867 PDHA1 (PDHA1) mRNA, encodes complete protein.
EF576990 - Homo sapiens PDHA1 (PDHA1) mRNA, partial cds.
JD020790 - Sequence 1814 from Patent EP1572962.
JD031605 - Sequence 12629 from Patent EP1572962.
JD025081 - Sequence 6105 from Patent EP1572962.
AM746210 - Homo sapiens partial mRNA for PDHA1/LOC79064 protein.
EF590116 - Homo sapiens clone IMAGE:1571916 PDHA1 mRNA, complete sequence.
JD027232 - Sequence 8256 from Patent EP1572962.
JD034040 - Sequence 15064 from Patent EP1572962.
S81593 - pyruvate dehydrogenase complex alpha subunit {exon 11} [human, female pyruvate dehydrogenase deficiency patient, skin fibroblasts, mRNA Partial Mutant, 149 nt].
S56181 - E1 alpha =pyruvate dehydrogenase alpha subunit {3'region} [human, mRNA Partial Mutant, 67 nt].
S57358 - pyruvate dehydrogenase alpha subunit {3'region} [human, mRNA Partial Mutant, 129 nt].
JD046589 - Sequence 27613 from Patent EP1572962.
JD552190 - Sequence 533214 from Patent EP1572962.
AK092210 - Homo sapiens cDNA FLJ34891 fis, clone NT2NE2017562.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa00010 - Glycolysis / Gluconeogenesis
hsa00020 - Citrate cycle (TCA cycle)
hsa00290 - Valine, leucine and isoleucine biosynthesis
hsa00620 - Pyruvate metabolism
hsa00650 - Butanoate metabolism
hsa01100 - Metabolic pathways

BioCarta from NCI Cancer Genome Anatomy Project
h_malatexPathway - Shuttle for transfer of acetyl groups from mitochondria to the cytosol

Reactome (by CSHL, EBI, and GO)

Protein P08559 (Reactome details) participates in the following event(s):

R-HSA-203946 PDK isoforms phosphorylate lipo-PDH
R-HSA-204169 PDP dephosphorylates p-lipo-PDH
R-HSA-6792572 LIPT1 transfers lipoyl group from lipoyl-GCSH to DHs
R-HSA-71397 lipo-PDH decarboxylates PYR to Ac-CoA
R-HSA-204174 Regulation of pyruvate dehydrogenase (PDH) complex
R-HSA-5362517 Signaling by Retinoic Acid
R-HSA-389661 Glyoxylate metabolism and glycine degradation
R-HSA-70268 Pyruvate metabolism
R-HSA-9006931 Signaling by Nuclear Receptors
R-HSA-71291 Metabolism of nitrogenous molecules
R-HSA-71406 Pyruvate metabolism and Citric Acid (TCA) cycle
R-HSA-162582 Signal Transduction
R-HSA-1430728 Metabolism
R-HSA-1428517 The citric acid (TCA) cycle and respiratory electron transport

-  Other Names for This Gene
  Alternate Gene Symbols: A5YVE9, B7Z3T7, B7Z3X5, ENST00000540249.1, ENST00000540249.2, ENST00000540249.3, ENST00000540249.4, NM_001173456, ODPA_HUMAN, P08559, PHE1A, Q53H41, Q5JPT8, Q9NP12, Q9UBJ8, Q9UBU0, Q9UNG4, Q9UNG5, uc011mjd.1, uc011mjd.2, uc011mjd.3
UCSC ID: ENST00000540249.5
RefSeq Accession: NM_000284
Protein: P08559 (aka ODPA_HUMAN)
CCDS: CCDS55382.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene PDHA1:
pdhc-def-ov (Primary Pyruvate Dehydrogenase Complex Deficiency Overview)

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.