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    PGD phosphogluconate dehydrogenase [ Homo sapiens (human) ]

    Gene ID: 5226, updated on 10-Dec-2024

    Summary

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    Official Symbol
    PGDprovided by HGNC
    Official Full Name
    phosphogluconate dehydrogenaseprovided by HGNC
    Primary source
    HGNC:HGNC:8891
    See related
    Ensembl:ENSG00000142657 MIM:172200; AllianceGenome:HGNC:8891
    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
    6PGD
    Summary
    6-phosphogluconate dehydrogenase is the second dehydrogenase in the pentose phosphate shunt. Deficiency of this enzyme is generally asymptomatic, and the inheritance of this disorder is autosomal dominant. Hemolysis results from combined deficiency of 6-phosphogluconate dehydrogenase and 6-phosphogluconolactonase suggesting a synergism of the two enzymopathies. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2015]
    Expression
    Broad expression in esophagus (RPKM 163.6), bone marrow (RPKM 118.1) and 22 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See PGD in Genome Data Viewer
    Location:
    1p36.22
    Exon count:
    13
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (10399064..10420511)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (9942673..9964125)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (10459121..10480568)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene kinesin family member 1B Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:10367507-10368007 Neighboring gene MPRA-validated peak67 silencer Neighboring gene RNA, U6 small nuclear 37, pseudogene Neighboring gene RNA, 7SL, cytoplasmic 731, pseudogene Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr1:10378039-10378580 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr1:10385546-10386745 Neighboring gene MPRA-validated peak69 silencer Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:10437772-10438272 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 244 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 146 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 147 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 245 Neighboring gene ReSE screen-validated silencer GRCh37_chr1:10459711-10459887 Neighboring gene MPRA-validated peak70 silencer Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:10485963-10486568 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:10486569-10487174 Neighboring gene Sharpr-MPRA regulatory region 15261 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 246 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 148 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:10493213-10493793 Neighboring gene CENPS-CORT readthrough Neighboring gene centromere protein S Neighboring gene cortistatin

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: Tissue-specific circular RNA induction during human fetal development
    • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
    • BioProject: PRJNA270632
    • Publication: PMID 26076956
    • Analysis date: Mon Apr 2 22:54:59 2018

    Bibliography

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    Related articles in PubMed

    1. 6-Phosphogluconate dehydrogenase promotes glycolysis and fatty acid synthesis by inhibiting the AMPK pathway in lung adenocarcinoma cells. Wu J, et al. Cancer Lett, 2024 Oct 1. PMID 39179096
    2. 1p36.22 region containing PGD gene is frequently gained in human cervical cancer. Lee M, et al. J Obstet Gynaecol Res, 2014 Feb. PMID 24125036
    3. 6PGD Upregulation is Associated with Chemo- and Immuno-Resistance of Renal Cell Carcinoma via AMPK Signaling-Dependent NADPH-Mediated Metabolic Reprograming. Cao J, et al. Am J Med Sci, 2020 Sep. PMID 32829780
    4. [Intensity of pentose phosphate metabolism of carbohydrates in various brain areas in normal and starved animals]. Kerimov BF. Vopr Med Khim, 2002 Sep-Oct. PMID 12498092
    5. Inhibiting 6-phosphogluconate dehydrogenase reverses doxorubicin resistance in anaplastic thyroid cancer via inhibiting NADPH-dependent metabolic reprogramming. Ma L, et al. Biochem Biophys Res Commun, 2018 Apr 15. PMID 29534964

    See all (116) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. 6-Phosphogluconate dehydrogenase promotes glycolysis and fatty acid synthesis by inhibiting the AMPK pathway in lung adenocarcinoma cells.
      Title: 6-Phosphogluconate dehydrogenase promotes glycolysis and fatty acid synthesis by inhibiting the AMPK pathway in lung adenocarcinoma cells.
    2. Critical Role of 6-Phosphogluconate Dehydrogenase in TAp73-Mediated Cancer Cell Proliferation.
      Title: Critical Role of 6-Phosphogluconate Dehydrogenase in TAp73-Mediated Cancer Cell Proliferation.
    3. HIF-1alpha regulates cellular metabolism, and Imatinib resistance by targeting phosphogluconate dehydrogenase in gastrointestinal stromal tumors.
      Title: HIF-1α regulates cellular metabolism, and Imatinib resistance by targeting phosphogluconate dehydrogenase in gastrointestinal stromal tumors.
    4. 6PGD Upregulation is Associated with Chemo- and Immuno-Resistance of Renal Cell Carcinoma via AMPK Signaling-Dependent NADPH-Mediated Metabolic Reprograming.
      Title: 6PGD Upregulation is Associated with Chemo- and Immuno-Resistance of Renal Cell Carcinoma via AMPK Signaling-Dependent NADPH-Mediated Metabolic Reprograming.
    5. 6-phosphogluconate dehydrogenase (6PGD) is aberrantly upregulated and activated in cervical cancer cells and patient tissues compared to normal counterparts. 6PGD inhibition decreases growth and migration, and enhances chemosensitivity in cervical cancer. Inhibition of 6PGD activates AMP-activated protein kinase and decreases rhoA GTP-binding protein and rac1 GTP-binding protein activities.
      Title: Inhibiting 6-phosphogluconate dehydrogenase enhances chemotherapy efficacy in cervical cancer via AMPK-independent inhibition of RhoA and Rac1.
    6. identified that 6-phosphogluconate dehydrogenase (6PGD) is critically involved in the development of anaplastic thyroid cancer (ATC) resistance to doxorubicin. 6PGD inhibition disrupts metabolic reprogramming in doxorubicin-resistant ATC cells.
      Title: Inhibiting 6-phosphogluconate dehydrogenase reverses doxorubicin resistance in anaplastic thyroid cancer via inhibiting NADPH-dependent metabolic reprogramming.
    7. Studies indicate link between the 6-phosphogluconate dehydrogenase, oxidative pentose phosphate pathway (PPP) and lipogenesis through Ru-5-P-dependent inhibition of serine/threonine protein kinase LKB1-AMPK signalling.
      Title: 6-Phosphogluconate dehydrogenase links oxidative PPP, lipogenesis and tumour growth by inhibiting LKB1-AMPK signalling.
    8. copy number gain of the PGD gene was consistently identified in cervical cancers but not in the normal tissues
      Title: 1p36.22 region containing PGD gene is frequently gained in human cervical cancer.
    9. Results show that 6PGD activity is upregulated with increased lysine acetylation in primary leukemia cells from human patients, providing mechanistic insights into 6PGD upregulation in cancer cells.
      Title: Lysine acetylation activates 6-phosphogluconate dehydrogenase to promote tumor growth.
    10. Expression of 6PGD positively correlates with advancing stage of lung carcinoma. Knockdown of 6PGD by shRNA potently inhibits c-Met tyrosine phosphorylation.
      Title: 6-Phosphogluconate dehydrogenase regulates tumor cell migration in vitro by regulating receptor tyrosine kinase c-Met.
    Submit: New GeneRIF Correction See all GeneRIFs (17)

    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

    EBI GWAS Catalog

    Description
    Genome-wide association study identifies 1p36.22 as a new susceptibility locus for hepatocellular carcinoma in chronic hepatitis B virus carriers.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    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 NADP binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables phosphogluconate dehydrogenase (decarboxylating) activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables phosphogluconate dehydrogenase (decarboxylating) activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Process Evidence Code Pubs
    involved_in D-gluconate catabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in pentose biosynthetic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in pentose-phosphate shunt ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in pentose-phosphate shunt, oxidative branch IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in pentose-phosphate shunt, oxidative branch IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    is_active_in cytosol IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in extracellular exosome HDA PubMed 
    located_in nucleus HDA PubMed 

    General protein information

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    Preferred Names
    6-phosphogluconate dehydrogenase, decarboxylating
    NP_001291380.1
    NP_001291381.1
    NP_002622.2

    NCBI Reference Sequences (RefSeq)

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    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.

    mRNA and Protein(s)

    1. NM_001304451.2 → NP_001291380.1  6-phosphogluconate dehydrogenase, decarboxylating isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is shorter compared to isoform 1.
      Source sequence(s)
      AK304423, AL139424, BC000368, HY049516, HY245069
      UniProtKB/TrEMBL
      B4E2U0
      Conserved Domains (3) summary
      COG0362
      Location:1 → 453
      Gnd; 6-phosphogluconate dehydrogenase [Carbohydrate transport and metabolism]
      pfam00393
      Location:158 → 447
      6PGD; 6-phosphogluconate dehydrogenase, C-terminal domain
      pfam03446
      Location:3 → 154
      NAD_binding_2; NAD binding domain of 6-phosphogluconate dehydrogenase

    2. NM_001304452.2 → NP_001291381.1  6-phosphogluconate dehydrogenase, decarboxylating isoform 3

      See identical proteins and their annotated locations for NP_001291381.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (3) is shorter at the N-terminus compared to isoform 1.
      Source sequence(s)
      AK298830, AL139424, BC000368, HY245069
      UniProtKB/TrEMBL
      B4E2U0
      Conserved Domains (3) summary
      PRK09287
      Location:1 → 460
      PRK09287; 6-phosphogluconate dehydrogenase; Validated
      pfam00393
      Location:167 → 456
      6PGD; 6-phosphogluconate dehydrogenase, C-terminal domain
      pfam03446
      Location:1 → 163
      NAD_binding_2; NAD binding domain of 6-phosphogluconate dehydrogenase

    3. NM_002631.4 → NP_002622.2  6-phosphogluconate dehydrogenase, decarboxylating isoform 1

      See identical proteins and their annotated locations for NP_002622.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (1).
      Source sequence(s)
      AL139424, BC000368, HY049516, HY245069
      Consensus CDS
      CCDS113.1
      UniProtKB/Swiss-Prot
      A8K2Y9, B4DQJ8, P52209, Q9BWD8
      UniProtKB/TrEMBL
      B4E2U0
      Related
      ENSP00000270776.8, ENST00000270776.13
      Conserved Domains (1) summary
      PRK09287
      Location:14 → 473
      PRK09287; 6-phosphogluconate dehydrogenase; Validated

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000001.11 Reference GRCh38.p14 Primary Assembly

      Range
      10399064..10420511
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060925.1 Alternate T2T-CHM13v2.0

      Range
      9942673..9964125
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P52209.3 GenPept UniProtKB/Swiss-Prot:P52209

    Gene LinkOut

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

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