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    DLD dihydrolipoamide dehydrogenase [ Homo sapiens (human) ]

    Gene ID: 1738, updated on 5-May-2024

    Summary

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    Official Symbol
    DLDprovided by HGNC
    Official Full Name
    dihydrolipoamide dehydrogenaseprovided by HGNC
    Primary source
    HGNC:HGNC:2898
    See related
    Ensembl:ENSG00000091140 MIM:238331; AllianceGenome:HGNC:2898
    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
    E3; LAD; DLDD; DLDH; GCSL; PHE3; OGDC-E3
    Summary
    This gene encodes a member of the class-I pyridine nucleotide-disulfide oxidoreductase family. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. In homodimeric form, the encoded protein functions as a dehydrogenase and is found in several multi-enzyme complexes that regulate energy metabolism. However, as a monomer, this protein can function as a protease. Mutations in this gene have been identified in patients with E3-deficient maple syrup urine disease and lipoamide dehydrogenase deficiency. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]
    Expression
    Ubiquitous expression in heart (RPKM 53.0), fat (RPKM 39.4) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    7q31.1
    Exon count:
    14
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 7 NC_000007.14 (107891107..107921198)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 7 NC_060931.1 (109209306..109239391)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 7 NC_000007.13 (107531552..107561643)

    Chromosome 7 - NC_000007.14Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105375444 Neighboring gene uncharacterized LOC105375445 Neighboring gene H3K27ac hESC enhancer GRCh37_chr7:107531366-107532048 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26499 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:107572237-107572884 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr7:107573531-107574176 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:107572885-107573530 Neighboring gene VISTA enhancer hs2081 Neighboring gene laminin subunit beta 1 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:107593919-107594462 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:107595007-107595549 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:107616823-107617323 Neighboring gene uncharacterized LOC124901861 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:107641444-107642044 Neighboring gene uncharacterized LOC107986834 Neighboring gene laminin subunit beta 4

    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. Lipoamide dehydrogenase (LADH) deficiency: medical perspectives of the structural and functional characterization of LADH and its pathogenic variants. Szabó E, et al. Biol Futur, 2023 Jun. PMID 36842090
    2. Dihydrolipoamide dehydrogenase regulates cystine deprivation-induced ferroptosis in head and neck cancer. Shin D, et al. Redox Biol, 2020 Feb. PMID 31931284, Free PMC Article
    3. The involvement of coordinative interactions in the binding of dihydrolipoamide dehydrogenase to titanium dioxide-Localization of a putative binding site. Dayan A, et al. J Mol Recognit, 2017 Aug. PMID 28247484
    4. Hepatitis B Virus Core Promoter Double Mutations (A1762T, G1764A) Are Associated with Lower Levels of Serum Dihydrolipoyl Dehydrogenase. Jiang ZH, et al. Intervirology, 2016. PMID 27303803, Free PMC Article
    5. Proteomic identification of dihydrolipoamide dehydrogenase as a target of autoantibodies in patients with endometrial cancer. Yoneyama K, et al. Anticancer Res, 2014 Sep. PMID 25202086

    See all (133) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Pan-Cancer Analysis of the Cuproptosis-Related Gene DLD.
      Title: Pan-Cancer Analysis of the Cuproptosis-Related Gene DLD.
    2. Lipoamide dehydrogenase (LADH) deficiency: medical perspectives of the structural and functional characterization of LADH and its pathogenic variants.
      Title: Lipoamide dehydrogenase (LADH) deficiency: medical perspectives of the structural and functional characterization of LADH and its pathogenic variants.
    3. Dihydrolipoamide dehydrogenase regulates cystine deprivation-induced ferroptosis in head and neck cancer.
      Title: Dihydrolipoamide dehydrogenase regulates cystine deprivation-induced ferroptosis in head and neck cancer.
    4. Molecular characterization of dihydrolipoamide dehydrogenase binding sites to titanium dioxide has been reported.
      Title: The involvement of coordinative interactions in the binding of dihydrolipoamide dehydrogenase to titanium dioxide-Localization of a putative binding site.
    5. study found that individuals infected with HBV withwith basal core promoter (BCP) double mutations (A1762T, G1764A)have lower concentrations of serum DLD than those with the wild-type BCP
      Title: Hepatitis B Virus Core Promoter Double Mutations (A1762T, G1764A) Are Associated with Lower Levels of Serum Dihydrolipoyl Dehydrogenase.
    6. Mitochondrial dihydrolipoamide dehydrogenase is upregulated in response to the brain intermittent hypoxic preconditioning.
      Title: Mitochondrial Dihydrolipoamide Dehydrogenase is Upregulated in Response to Intermittent Hypoxic Preconditioning.
    7. IgA autoantibody against DLD could be a novel diagnostic marker for endometrial cancer.
      Title: Proteomic identification of dihydrolipoamide dehydrogenase as a target of autoantibodies in patients with endometrial cancer.
    8. Case Report: novel mutation in the DLD interface giving rise to DLD deficiency.
      Title: Dihydrolipoamide dehydrogenase (DLD) deficiency in a Spanish patient with myopathic presentation due to a new mutation in the interface domain.
    9. Human, mouse, and pig Dld has moonlighting function as a protease in addition to its canonical function as a a dehydrogenase.
      Title: Cryptic proteolytic activity of dihydrolipoamide dehydrogenase.
    10. This molecular dynamics study proposes the structural changes that may lead to the modulation in reactive oxygen species generation by pathogenic mutants of human dihydrolipoamide dehydrogenase.
      Title: Molecular dynamics study of the structural basis of dysfunction and the modulation of reactive oxygen species generation by pathogenic mutants of human dihydrolipoamide dehydrogenase.
    Submit: New GeneRIF Correction See all GeneRIFs (27)

    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

    Associated conditions

    Description Tests
    Pyruvate dehydrogenase E3 deficiency
    MedGen: C5574660 OMIM: 246900 GeneReviews: Dihydrolipoamide Dehydrogenase Deficiency
    		Compare labs

    EBI GWAS Catalog

    Description
    Genome-wide association identifies multiple ulcerative colitis susceptibility loci.
    EBI GWAS Catalog
    Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
    EBI GWAS Catalog
    Ulcerative colitis-risk loci on chromosomes 1p36 and 12q15 found by genome-wide association study.
    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)

    Genotypes

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    retropepsin gag-pol Positional proteomics analysis identifies the cleavage of human dihydrolipoamide dehydrogenase (DLD) at amino acid residues 470-471 by the HIV-1 protease PubMed

    Go to the HIV-1, Human Interaction Database

    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
    contributes_to branched-chain alpha-keto acid dehydrogenase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables dihydrolipoyl dehydrogenase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables dihydrolipoyl dehydrogenase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables flavin adenine dinucleotide binding IBA
    Inferred from Biological aspect of Ancestor
    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
    		  
    involved_in branched-chain amino acid catabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in gastrulation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in mitochondrial electron transport, NADH to ubiquinone IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in proteolysis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of membrane potential IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in sperm capacitation IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    part_of acetyltransferase complex IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in acrosomal matrix IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in mitochondrial matrix NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    located_in mitochondrial matrix TAS
    Traceable Author Statement
    more info
    		  
    located_in mitochondrion HDA PubMed 
    is_active_in mitochondrion IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in mitochondrion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in mitochondrion NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    located_in motile cilium IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of oxoglutarate dehydrogenase complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    part_of oxoglutarate dehydrogenase complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of pyruvate dehydrogenase complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    dihydrolipoyl dehydrogenase, mitochondrial
    Names
    E3 component of pyruvate dehydrogenase complex, 2-oxo-glutarate complex, branched chain keto acid dehydrogenase complex
    diaphorase
    epididymis secretory sperm binding protein
    glycine cleavage system L protein
    glycine cleavage system protein L
    lipoamide dehydrogenase
    lipoamide reductase
    lipoyl dehydrogenase
    NP_000099.2
    NP_001276679.1
    NP_001276680.1
    NP_001276681.1

    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_008045.1 RefSeqGene

      Range
      5043..35058
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000108.5 → NP_000099.2  dihydrolipoyl dehydrogenase, mitochondrial isoform 1 precursor

      See identical proteins and their annotated locations for NP_000099.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
      Source sequence(s)
      AC005046, AK312346, BC018648
      Consensus CDS
      CCDS5749.1
      UniProtKB/Swiss-Prot
      B2R5X0, B4DHG0, B4DT69, P09622, Q14131, Q14167, Q59EV8, Q8WTS4
      UniProtKB/TrEMBL
      A0A024R713, B4DMK9
      Related
      ENSP00000205402.3, ENST00000205402.10
      Conserved Domains (1) summary
      cl27343
      Location:43 → 509
      Pyr_redox_dim; Pyridine nucleotide-disulphide oxidoreductase, dimerisation domain

    2. NM_001289750.1 → NP_001276679.1  dihydrolipoyl dehydrogenase, mitochondrial isoform 2

      See identical proteins and their annotated locations for NP_001276679.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks part of the 5' coding region, and uses a downstream start codon, compared to variant 1. The encoded isoform (2) has a shorter N-terminus, compared to isoform 1.
      Source sequence(s)
      AC005046, AK295080, DC354209
      UniProtKB/TrEMBL
      B4DFL1
      Conserved Domains (1) summary
      cl39093
      Location:4 → 410
      Pyr_redox_2; Pyridine nucleotide-disulphide oxidoreductase

    3. NM_001289751.1 → NP_001276680.1  dihydrolipoyl dehydrogenase, mitochondrial isoform 3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks an in-frame exon in the 5' coding region, compared to variant 1. The encoded isoform (3) is shorter, compared to isoform 1.
      Source sequence(s)
      AC005046, AK312346, BC018648, DC354209
      Consensus CDS
      CCDS78269.1
      UniProtKB/TrEMBL
      B4DMK9, E9PEX6
      Related
      ENSP00000417016.1, ENST00000440410.5
      Conserved Domains (1) summary
      cl27343
      Location:43 → 486
      Pyr_redox_dim; Pyridine nucleotide-disulphide oxidoreductase, dimerisation domain

    4. NM_001289752.1 → NP_001276681.1  dihydrolipoyl dehydrogenase, mitochondrial isoform 4

      See identical proteins and their annotated locations for NP_001276681.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) lacks an in-frame exon in the central coding region, compared to variant 1. The encoded isoform (4) is shorter, compared to isoform 1.
      Source sequence(s)
      AC005046, AK312346, BC018648, DC354209
      Consensus CDS
      CCDS78268.1
      UniProtKB/TrEMBL
      B4DMK9
      Related
      ENSP00000387542.2, ENST00000437604.6
      Conserved Domains (1) summary
      cl27343
      Location:43 → 461
      Pyr_redox_dim; Pyridine nucleotide-disulphide oxidoreductase, dimerisation domain

    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_000007.14 Reference GRCh38.p14 Primary Assembly

      Range
      107891107..107921198
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060931.1 Alternate T2T-CHM13v2.0

      Range
      109209306..109239391
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P09622.2 GenPept UniProtKB/Swiss-Prot:P09622

    Gene LinkOut

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

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