DLD dihydrolipoamide dehydrogenase [Homo sapiens (human)] - Gene

Summary

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
NEW: Try the new Gene table
Try the new Transcript table

Genomic context

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_000007.14 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help

See details

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

Go to the top of the page Help

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Pan-Cancer Analysis of the Cuproptosis-Related Gene DLD.
Title: Pan-Cancer Analysis of the Cuproptosis-Related Gene DLD.
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.
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.
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.
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.
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.
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.
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.
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.
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

Go to the top of the page Help

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

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

Go to the top of the page Help

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

Interactions

Go to the top of the page Help

Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

Go to the top of the page Help

Markers

RH103475 (e-PCR)
- UniSTS:97800

D7S2771 (e-PCR)
- UniSTS:7702

G54025 (e-PCR)
- UniSTS:109407

RH80342 (e-PCR)
- UniSTS:91000

WIAF-2151 (e-PCR)
- UniSTS:79785

D7S2064E (e-PCR)
- UniSTS:60841

RH130917 (e-PCR)
- UniSTS:214201

D7S1572 (e-PCR)
- UniSTS:15830

IB1079 (e-PCR)
- UniSTS:9180

RH102910 (e-PCR)
- UniSTS:97244

DLD (e-PCR)
- UniSTS:33264

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 more info	PubMed
located_in mitochondrion	HTP more info	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

Go to the top of the page Help

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; pyruvate dehydrogenase complex subunit E3, 2-oxo-glutarate complex, branched chain keto acid dehydrogenase complex, glycine cleavage system protein L

NP_000099.2

EC 1.8.1.4

NP_001276679.1

EC 1.8.1.4

NP_001276680.1

EC 1.8.1.4

NP_001276681.1

EC 1.8.1.4

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

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

NG_008045.1 RefSeqGene

Range

5043..35058

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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
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
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