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    PDHX pyruvate dehydrogenase complex component X [ Homo sapiens (human) ]

    Gene ID: 8050, updated on 25-Apr-2024

    Summary

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    Official Symbol
    PDHXprovided by HGNC
    Official Full Name
    pyruvate dehydrogenase complex component Xprovided by HGNC
    Primary source
    HGNC:HGNC:21350
    See related
    Ensembl:ENSG00000110435 MIM:608769; AllianceGenome:HGNC:21350
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    E3BP; OPDX; PDX1; proX; DLDBP; PDHXD
    Summary
    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]
    Expression
    Ubiquitous expression in heart (RPKM 24.7), testis (RPKM 13.6) and 25 other tissues See more
    Orthologs
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    Genomic context

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    Location:
    11p13
    Exon count:
    13
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (34915920..34996128)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (35054373..35134137)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (34937985..35017675)

    Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC102723568 Neighboring gene uncharacterized LOC105376625 Neighboring gene uncharacterized LOC105376624 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3253 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3254 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4608 Neighboring gene APAF1 interacting protein Neighboring gene microRNA 1343 Neighboring gene uncharacterized LOC105376626 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4609 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr11:35051560-35052759 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4611 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4612 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4613 Neighboring gene uncharacterized LOC105376627 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4614 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4615 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4616

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Identification of PDHX as a metabolic target for esophageal squamous cell carcinoma. Inoue J, et al. Cancer Sci, 2021 Jul. PMID 33964039, Free PMC Article
    2. Founder p.Arg 446* mutation in the PDHX gene explains over half of cases with congenital lactic acidosis in Roma children. Ivanov IS, et al. Mol Genet Metab, 2014 Sep-Oct. PMID 25087164
    3. Pyruvate dehydrogenase deficiency caused by a new mutation of PDHX gene in two Moroccan patients. Tajir M, et al. Eur J Med Genet, 2012 Oct. PMID 22766002
    4. Pyruvate dehydrogenase E3 binding protein (protein X) deficiency. Brown RM, et al. Dev Med Child Neurol, 2006 Sep. PMID 16904023
    5. A novel gross deletion caused by non-homologous recombination of the PDHX gene in a patient with pyruvate dehydrogenase deficiency. Miné M, et al. Mol Genet Metab, 2006 Sep-Oct. PMID 16843025

    See all (88) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Cuproptosis-related gene PDHX and heat stress-related HSPD1 as potential key drivers associated with cell stemness, aberrant metabolism and immunosuppression in esophageal carcinoma.
      Title: Cuproptosis-related gene PDHX and heat stress-related HSPD1 as potential key drivers associated with cell stemness, aberrant metabolism and immunosuppression in esophageal carcinoma.
    2. Identification of PDHX as a metabolic target for esophageal squamous cell carcinoma.
      Title: Identification of PDHX as a metabolic target for esophageal squamous cell carcinoma.
    3. PDHX is a functional target of miR-27b and that this interaction has consequential effects on cell metabolism which facilitate cell growth and progression in breast cancer.
      Title: Suppression of PDHX by microRNA-27b deregulates cell metabolism and promotes growth in breast cancer.
    4. We propose testing for the R446* mutation in PDHX as a rapid first screening in Roma infants with metabolic acidosis.
      Title: Founder p.Arg 446* mutation in the PDHX gene explains over half of cases with congenital lactic acidosis in Roma children.
    5. MiR-26a regulates glucose metabolism of colorectal cancer cells by direct targeting PDHX.
      Title: MicroRNA-26a regulates glucose metabolism by direct targeting PDHX in colorectal cancer cells.
    6. New mutation in PDHX gene found in two unrelated patients with Pyruvate dehydrogenase deficiency.
      Title: Pyruvate dehydrogenase deficiency caused by a new mutation of PDHX gene in two Moroccan patients.
    7. genetic association with systemic lupus erythematosus to a haplotype between PDHX and CD44 was established.
      Title: Identification of a systemic lupus erythematosus susceptibility locus at 11p13 between PDHX and CD44 in a multiethnic study.
    8. Observational study of gene-disease association. (HuGE Navigator)
      Title: Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.
    9. determination that PDH and complex III exist at a steady-state ratio of 1:100, 1:128 and 1:202 in HeLa cell extracts, fibroblast mitochondria and heart tissue mitochondria, respectively
      Title: Quantitative proteomics: the copy number of pyruvate dehydrogenase is more than 10(2)-fold lower than that of complex III in human mitochondria.
    10. model of the pyruvate dehydrogenase complex formed by E2 and E2 plus the E3-binding protein and binding of the E1 and E3 components
      Title: Organization of the cores of the mammalian pyruvate dehydrogenase complex formed by E2 and E2 plus the E3-binding protein and their capacities to bind the E1 and E3 components.
    Submit: New GeneRIF Correction See all GeneRIFs (14)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables acyltransferase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    contributes_to pyruvate dehydrogenase (NAD+) activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    acts_upstream_of_or_within acetyl-CoA biosynthetic process from pyruvate IC
    Inferred by Curator
    more info
    		 PubMed 
    involved_in acetyl-CoA biosynthetic process from pyruvate IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in acetyl-CoA biosynthetic process from pyruvate ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Component Evidence Code Pubs
    located_in mitochondrial matrix TAS
    Traceable Author Statement
    more info
    		  
    is_active_in mitochondrion IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in mitochondrion NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    part_of pyruvate dehydrogenase complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    part_of pyruvate dehydrogenase complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of pyruvate dehydrogenase complex IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    part_of pyruvate dehydrogenase complex ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  

    General protein information

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    Preferred Names
    pyruvate dehydrogenase protein X component, mitochondrial
    Names
    dihydrolipoamide dehydrogenase-binding protein of pyruvate dehydrogenase complex
    lipoyl-containing pyruvate dehydrogenase complex component X
    pyruvate dehydrogenase complex, E3-binding protein subunit
    pyruvate dehydrogenase complex, lipoyl-containing component X

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_013368.1 RefSeqGene

      Range
      5489..84999
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001135024.2 → NP_001128496.2  pyruvate dehydrogenase protein X component, mitochondrial isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks a segment in the 5' region, resulting in upstream in-frame AUG start codon, as compared to variant 1. The resulting isoform (2) has a shorter and distinct N-terminus, as compared to isoform 1.
      Source sequence(s)
      AC107928, AL138810
      Consensus CDS
      CCDS44569.2
      UniProtKB/TrEMBL
      A0A8C8MSB2, B2R673
      Related
      ENSP00000389404.3, ENST00000448838.8
      Conserved Domains (1) summary
      TIGR01349
      Location:1 → 440
      PDHac_trf_mito; pyruvate dehydrogenase complex dihydrolipoamide acetyltransferase, long form

    2. NM_001166158.2 → NP_001159630.1  pyruvate dehydrogenase protein X component, mitochondrial isoform 3 precursor

      See identical proteins and their annotated locations for NP_001159630.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks multiple in-frame exons in the central coding region, compared to variant 1, resulting in a protein (isoform 3) that lacks 227 aa, compared to isoform 1.
      Source sequence(s)
      AA282215, AC107928, AF001437, BC010389
      Consensus CDS
      CCDS53616.1
      UniProtKB/Swiss-Prot
      O00330
      Related
      ENSP00000415695.2, ENST00000430469.6
      Conserved Domains (2) summary
      PRK11892
      Location:56 → 114
      PRK11892; pyruvate dehydrogenase subunit beta; Provisional
      pfam00198
      Location:109 → 273
      2-oxoacid_dh; 2-oxoacid dehydrogenases acyltransferase (catalytic domain)

    3. NM_003477.3 → NP_003468.2  pyruvate dehydrogenase protein X component, mitochondrial isoform 1 precursor

      See identical proteins and their annotated locations for NP_003468.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (1).
      Source sequence(s)
      AA282215, AC107928, AF001437, BC010389
      Consensus CDS
      CCDS7896.1
      UniProtKB/Swiss-Prot
      B4DW62, D3DR11, E9PB14, E9PBP7, O00330, O60221, Q96FV8, Q99783
      UniProtKB/TrEMBL
      B2R673
      Related
      ENSP00000227868.4, ENST00000227868.9
      Conserved Domains (1) summary
      TIGR01349
      Location:58 → 500
      PDHac_trf_mito; pyruvate dehydrogenase complex dihydrolipoamide acetyltransferase, long form

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000011.10 Reference GRCh38.p14 Primary Assembly

      Range
      34915920..34996128
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011520390.2 → XP_011518692.1  pyruvate dehydrogenase protein X component, mitochondrial isoform X1

      UniProtKB/TrEMBL
      A0A8C8MSB2, B2R673
      Conserved Domains (1) summary
      TIGR01349
      Location:1 → 440
      PDHac_trf_mito; pyruvate dehydrogenase complex dihydrolipoamide acetyltransferase, long form

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060935.1 Alternate T2T-CHM13v2.0

      Range
      35054373..35134137
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O00330.3 GenPept UniProtKB/Swiss-Prot:O00330

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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