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DLD dihydrolipoamide dehydrogenase [ Homo sapiens (human) ]

Gene ID: 1738, updated on 13-Nov-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
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Genomic context

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See DLD in Genome Data Viewer
Location:
7q31.1
Exon count:
14
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 7 NC_000007.14 (107891107..107921198)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 7 NC_060931.1 (109209306..109239391)
RS_2024_09 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. A novel mutation in the dihydrolipoamide dehydrogenase E3 subunit gene (DLD) resulting in an atypical form of alpha-ketoglutarate dehydrogenase deficiency. Odièvre MH, et al. Hum Mutat, 2005 Mar. PMID 15712224
  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. 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
  5. Dihydrolipoamide Dehydrogenase Deficiency. Adam MP, et al. , 1993. PMID 25032271

See all (154) 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
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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)

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
involved_in 2-oxoglutarate metabolic process IBA
Inferred from Biological aspect of Ancestor
more info
  
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 pyruvate metabolic process IBA
Inferred from Biological aspect of Ancestor
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
  
part_of branched-chain alpha-ketoacid dehydrogenase complex IDA
Inferred from Direct Assay
more info
 PubMed 
part_of branched-chain alpha-ketoacid dehydrogenase complex IPI
Inferred from Physical Interaction
more info
 PubMed 
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 
located_in mitochondrion HTP 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 oxoadipate dehydrogenase complex 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 
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
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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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_2024_08

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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