DLD

Summary

DLD (dihydrolipoamide dehydrogenase, HGNC:2898) is a protein-coding gene on chromosome 7q31.1, encoding Dihydrolipoyl dehydrogenase, mitochondrial (P09622). Lipoamide dehydrogenase is a component of the glycine cleavage system as well as an E3 component of three alpha-ketoacid dehydrogenase complexes (pyruvate-, alpha-ketoglutarate-, and branched-chain amino acid-dehydrogenase complex). It is a selective cancer dependency (DepMap: 22.4% of cell lines).

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.

Source: NCBI Gene 1738 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Leigh syndrome (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 9
• Clinical variants (ClinVar): 746 total — 39 pathogenic, 87 likely-pathogenic
• Phenotypes (HPO): 43
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 22.4% of screened cell lines
• MANE Select transcript: NM_000108

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2898
Approved symbol	DLD
Name	dihydrolipoamide dehydrogenase
Location	7q31.1
Locus type	gene with protein product
Status	Approved
Aliases	DLDH, E3, OGDC-E3
Ensembl gene	ENSG00000091140
Ensembl biotype	protein_coding
OMIM	238331
Entrez	1738

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 13 protein_coding, 4 nonsense_mediated_decay, 4 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000205402, ENST00000415325, ENST00000417551, ENST00000437604, ENST00000440410, ENST00000450038, ENST00000451081, ENST00000453354, ENST00000460577, ENST00000478414, ENST00000485066, ENST00000489184, ENST00000494441, ENST00000880447, ENST00000880448, ENST00000880449, ENST00000880450, ENST00000880451, ENST00000880452, ENST00000924908, ENST00000924909, ENST00000924910, ENST00000957323

RefSeq mRNA: 4 — MANE Select: NM_000108 NM_000108, NM_001289750, NM_001289751, NM_001289752

CCDS: CCDS5749, CCDS78268, CCDS78269

Canonical transcript exons

ENST00000205402 — 14 exons

Exon	Start	End
ENSE00001876887	107891183	107891289
ENSE00003490343	107906267	107906368
ENSE00003503135	107904958	107905058
ENSE00003506893	107915506	107915696
ENSE00003517425	107916794	107916964
ENSE00003528162	107917273	107917462
ENSE00003533170	107905361	107905504
ENSE00003556190	107919010	107919099
ENSE00003594323	107917924	107918061
ENSE00003603060	107901738	107901817
ENSE00003619167	107893200	107893278
ENSE00003623156	107902325	107902393
ENSE00003624603	107903478	107903547
ENSE00003643561	107919194	107921198

Expression profiles

Bgee: expression breadth ubiquitous, 301 present calls, max score 99.46.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 38.5458 / max 1130.1496, expressed in 1810 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
80477	38.5458	1810

Top tissues by expression

301 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
heart right ventricle	UBERON:0002080	99.46	gold quality
biceps brachii	UBERON:0001507	98.95	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	98.79	gold quality
diaphragm	UBERON:0001103	98.76	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.69	gold quality
vastus lateralis	UBERON:0001379	98.52	gold quality
body of tongue	UBERON:0011876	98.43	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.35	gold quality
jejunal mucosa	UBERON:0000399	98.26	gold quality
colonic mucosa	UBERON:0000317	98.25	gold quality
rectum	UBERON:0001052	98.24	gold quality
adrenal tissue	UBERON:0018303	98.23	gold quality
quadriceps femoris	UBERON:0001377	98.13	gold quality
cardiac ventricle	UBERON:0002082	98.10	gold quality
heart left ventricle	UBERON:0002084	98.07	gold quality
triceps brachii	UBERON:0001509	97.91	gold quality
right adrenal gland cortex	UBERON:0035827	97.84	gold quality
muscle organ	UBERON:0001630	97.83	gold quality
skeletal muscle organ	UBERON:0014892	97.83	gold quality
right adrenal gland	UBERON:0001233	97.82	gold quality
gastrocnemius	UBERON:0001388	97.78	gold quality
muscle of leg	UBERON:0001383	97.74	gold quality
skeletal muscle tissue	UBERON:0001134	97.64	gold quality
jejunum	UBERON:0002115	97.62	gold quality
apex of heart	UBERON:0002098	97.60	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.40	gold quality
left adrenal gland	UBERON:0001234	97.35	gold quality
duodenum	UBERON:0002114	97.31	gold quality
gluteal muscle	UBERON:0002000	97.22	gold quality
adrenal gland	UBERON:0002369	97.20	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-CURD-53	no	65.77
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, EGR1, ETS1, FOS, GABPA, GLI3, HIF1A, HR, MYOD1, NEUROD1, NEUROG3, PAX1, RNF2, TBX15, TCF3, ZFPM1, ZFPM2

miRNA regulators (miRDB)

110 targeting DLD, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 22.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 26)

• the E3 binding protein component of the pyruvate dehydrogenase complex appear to be a rare cause of pyruvate dehydrogenase deficiency (PMID:11935326)
• Activity of human dihydrolipoamide dehydrogenase is reduced by mutation at threonine-44 of FAD-binding region to valine. (PMID:12297006)
• model of the pyruvate dehydrogenase complex formed by E2 and E2 plus the E3-binding protein and binding of the E1 and E3 components (PMID:14638692)
• A c.1444A>G substitution in E3 exon 13, predictive of a p.R482G (or R447G in the processed gene product) substitution in a highly conserved domain of the protein was found. (PMID:15712224)
• Asparagine-473 residue is important for the catalytic function of dihydrolipoamide dehydrogenase. (PMID:15826505)
• the disease-causing mutations of E3 occur at three locations in the human enzyme: the dimer interface, the active site, and the FAD and NAD(+)-binding sites (PMID:15946682)
• specificity of pairing for human E3BP with E3 from its subcomplex structure to be most likely due to conformational rigidity of the binding fragment of the E3-binding domain of E3BP and its exquisite amino acid match with the E3 target interface (PMID:16263718)
• dihydrolipoamide dehydrogenase (PMID:16442803)
• The conservation of the Ile-51 residue with Ala using site-directed mutagenesis in human Dihydrolipoamide dehydrogenase(E3) was very important to the efficient catalytic function of the enzyme. (PMID:16584639)
• These results suggest that N286 and D320 play a role in the catalytic function of the E3. (PMID:17171578)
• Certain DLD mutations can simultaneously induce the loss of a primary metabolic activity and the gain of a moonlighting proteolytic activity thus contributing to the metabolic derangement associated with DLD deficiency. (PMID:17404228)
• Human, mouse, and pig Dld has moonlighting function as a protease in addition to its canonical function as a a dehydrogenase. (PMID:17404228)
• kinetic studies suggest that T148 is not important to E3 catalytic function and R281 plays a role in the catalytic function of E3 (PMID:17960497)
• This protein has been found differentially expressed in the Wernicke’s Area from patients with schizophrenia. (PMID:19405953)
• Case Report: novel mutation in the DLD interface giving rise to DLD deficiency. (PMID:20652410)
• Structural and thermodynamic basis for weak interactions between dihydrolipoamide dehydrogenase and subunit-binding domain of the branched-chain alpha-ketoacid dehydrogenase complex. (PMID:21543315)
• the cryptic activities of DLD promote oxidative damage to neighboring molecules and thus contribute to the clinical severity of DLD mutations (PMID:21930696)
• ATP consumption is demonstrated in respiration-impaired isolated and in situ neuronal somal mitochondria from transgenic mice that exhibit a 20-48% decrease in alpha-ketoglutarate dehydrogenase activity. (PMID:23475850)
• 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. (PMID:24012808)
• IgA autoantibody against DLD could be a novel diagnostic marker for endometrial cancer. (PMID:25202086)
• Mitochondrial dihydrolipoamide dehydrogenase is upregulated in response to the brain intermittent hypoxic preconditioning. (PMID:26078703)
• 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 (PMID:27303803)
• Molecular characterization of dihydrolipoamide dehydrogenase binding sites to titanium dioxide has been reported. (PMID:28247484)
• Dihydrolipoamide dehydrogenase regulates cystine deprivation-induced ferroptosis in head and neck cancer. (PMID:31931284)
• Lipoamide dehydrogenase (LADH) deficiency: medical perspectives of the structural and functional characterization of LADH and its pathogenic variants. (PMID:36842090)
• Pan-Cancer Analysis of the Cuproptosis-Related Gene DLD. (PMID:38077227)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	dldh	ENSDARG00000008785
mus_musculus	Dld	ENSMUSG00000020664
rattus_norvegicus	Dld	ENSRNOG00000006364
drosophila_melanogaster	CG7430	FBGN0036762
caenorhabditis_elegans		WBGENE00010794

Paralogs (7): GSR (ENSG00000104687), PYROXD1 (ENSG00000121350), AIFM1 (ENSG00000156709), AIFM3 (ENSG00000183773), TXNRD2 (ENSG00000184470), TXNRD3 (ENSG00000197763), TXNRD1 (ENSG00000198431)

Protein

Protein identifiers

Dihydrolipoyl dehydrogenase, mitochondrial — P09622 (reviewed: P09622)

Alternative names: Dihydrolipoamide dehydrogenase, Glycine cleavage system L protein

All UniProt accessions (6): P09622, A0A024R713, E9PEX6, F2Z2E3, F8WDM5, F8WDY5

UniProt curated annotations — full annotation on UniProt →

Function. Lipoamide dehydrogenase is a component of the glycine cleavage system as well as an E3 component of three alpha-ketoacid dehydrogenase complexes (pyruvate-, alpha-ketoglutarate-, and branched-chain amino acid-dehydrogenase complex). The 2-oxoglutarate dehydrogenase complex is mainly active in the mitochondrion. A fraction of the 2-oxoglutarate dehydrogenase complex also localizes in the nucleus and is required for lysine succinylation of histones: associates with KAT2A on chromatin and provides succinyl-CoA to histone succinyltransferase KAT2A. In monomeric form may have additional moonlighting function as serine protease. Involved in the hyperactivation of spermatazoa during capacitation and in the spermatazoal acrosome reaction. The pyruvate dehydrogenase (PDH) complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links cytoplasmic glycolysis and the mitochondrial tricarboxylic acid (TCA) cycle. It contains multiple copies of three enzymatic components: pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (E2) and dihydrolipoamide dehydrogenase (E3). The E3 subunit catalyzes reoxidation of the dihydrolipoyl moiety on lipoyl-bearing domains (LBDs) of E2 with NAD+ as the ultimate electron acceptor.

Subunit / interactions. Homodimer. Part of the multimeric pyruvate dehydrogenase (PDH) complex that contains multiple copies of pyruvate dehydrogenase (subunits PDHA (PDHA1 or PDHA2) and PDHB, E1), dihydrolipoamide acetyltransferase (DLAT, E2) and lipoamide dehydrogenase (DLD, E3). These subunits are bound to an inner core composed of about 48 DLAT and 12 PDHX molecules (by non covalent bonds). The 2-oxoglutarate dehydrogenase complex is composed of OGDH (2-oxoglutarate dehydrogenase; E1), DLST (dihydrolipoamide succinyltransferase; E2), DLD (dihydrolipoamide dehydrogenase; E3) and the assembly factor KGD4. It contains multiple copies of the three enzymatic components (E1, E2 and E3). In the nucleus, the 2-oxoglutarate dehydrogenase complex associates with KAT2A. Interacts with PDHX.

Subcellular location. Mitochondrion matrix. Nucleus. Cell projection. Cilium. Flagellum. Cytoplasmic vesicle. Secretory vesicle. Acrosome.

Post-translational modifications. Tyrosine phosphorylated.

Disease relevance. Dihydrolipoamide dehydrogenase deficiency (DLDD) [MIM:246900] An autosomal recessive metabolic disorder characterized biochemically by a combined deficiency of the branched-chain alpha-keto acid dehydrogenase complex (BCKDC), pyruvate dehydrogenase complex (PDC), and alpha-ketoglutarate dehydrogenase complex (KGDC). Clinically, affected individuals have lactic acidosis and neurologic deterioration due to sensitivity of the central nervous system to defects in oxidative metabolism. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Disruption of native heterodimer state inhibits primary dihydrolipoamide dehydrogenase activity and induces serine protease activity.

Cofactor. Binds 1 FAD per subunit.

Miscellaneous. The active site is a redox-active disulfide bond.

Similarity. Belongs to the class-I pyridine nucleotide-disulfide oxidoreductase family.

Isoforms (3)

UniProt ID	Names	Canonical?
P09622-1	1	yes
P09622-2	2
P09622-3	3

RefSeq proteins (4): NP_000099, NP_001276679, NP_001276680, NP_001276681 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001100	Pyr_nuc-diS_OxRdtase	Family
IPR004099	Pyr_nucl-diS_OxRdtase_dimer	Domain
IPR006258	Lipoamide_DH	Family
IPR012999	Pyr_OxRdtase_I_AS	Active_site
IPR016156	FAD/NAD-linked_Rdtase_dimer_sf	Homologous_superfamily
IPR023753	FAD/NAD-binding_dom	Domain
IPR036188	FAD/NAD-bd_sf	Homologous_superfamily
IPR050151	Class-I_Pyr_Nuc-Dis_Oxidored	Family

Pfam: PF02852, PF07992

Enzyme classification (BRENDA):

• EC 1.2.1.104 — pyruvate dehydrogenase system (BRENDA: 46 organisms, 32 substrates, 100 inhibitors, 83 Km, 12 kcat entries)
• EC 1.2.1.105 — 2-oxoglutarate dehydrogenase system (BRENDA: 28 organisms, 44 substrates, 119 inhibitors, 83 Km, 16 kcat entries)
• EC 1.4.1.27 — glycine cleavage system (BRENDA: 15 organisms, 4 substrates, 5 inhibitors, 6 Km, 0 kcat entries)
• EC 1.8.1.4 — dihydrolipoyl dehydrogenase (BRENDA: 77 organisms, 163 substrates, 92 inhibitors, 268 Km, 86 kcat entries)

Substrate kinetics (BRENDA)

57 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
NAD+	0.024–4.1	76
DIHYDROLIPOAMIDE	0.0107–43.6	73
2-OXOGLUTARATE	0.0025–10.1	50
PYRUVATE	0.0002–1	44
NADH	0.0032–84	37
LIPOAMIDE	0.05–16	26
NAD+	0.01–0.27	14
COA	0.0005–0.61	12
COA	0.0032–0.075	11
NAD+	0.0249–0.3	11
2-OXOVALERATE	0.0063–0.0163	5
FORMALDOXIME	2.73–17.82	4
GLYCEROL TRINITRATE	0.9–16.93	4
THIAMINE DIPHOSPHATE	0.0016–0.05	3
2,6-DICHLOROPHENOLINDOPHENOL	0.015–0.12	3

Catalyzed reactions (Rhea), 1 shown:

• N(6)-[(R)-dihydrolipoyl]-L-lysyl-[protein] + NAD(+) = N(6)-[(R)-lipoyl]-L-lysyl-[protein] + NADH + H(+) (RHEA:15045)

UniProt features (118 total): strand 25, modified residue 25, helix 18, mutagenesis site 15, sequence variant 13, binding site 10, sequence conflict 3, site 2, splice variant 2, transit peptide 1, chain 1, turn 1, active site 1, disulfide bond 1

Structure

Experimental structures (PDB)

17 structures.

PDB	Method	Resolution (Å)
6I4R	X-RAY DIFFRACTION	1.44
6I4P	X-RAY DIFFRACTION	1.6
6I4Q	X-RAY DIFFRACTION	1.75
6I4S	X-RAY DIFFRACTION	1.75
6HG8	X-RAY DIFFRACTION	1.76
6I4T	X-RAY DIFFRACTION	1.82
5J5Z	X-RAY DIFFRACTION	1.84
6I4U	X-RAY DIFFRACTION	1.84
1ZMD	X-RAY DIFFRACTION	2.08
2F5Z	X-RAY DIFFRACTION	2.18
5NHG	X-RAY DIFFRACTION	2.27
6I4Z	X-RAY DIFFRACTION	2.34
3RNM	X-RAY DIFFRACTION	2.4
7PSC	X-RAY DIFFRACTION	2.44
1ZMC	X-RAY DIFFRACTION	2.53
1ZY8	X-RAY DIFFRACTION	2.59
7ZYT	X-RAY DIFFRACTION	2.89

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P09622-F1	93.69	0.92

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (3): 448 (important for interaction with pdhx and activity of multienzyme pyruvate dehydrogenase complex); 473 (important for interaction with pdhx and activity of multienzyme pyruvate dehydrogenase complex); 487 (proton acceptor)

Ligand- & substrate-binding residues (10): 314; 355; 361–364; 71–80; 89; 154; 183–185; 220–227; 243; 278

Post-translational modifications (25): 66, 66, 104, 104, 122, 122, 132, 132, 143, 143, 159, 166, 273, 277, 285, 297, 346, 410, 410, 417 …

Disulfide bonds (1): 80–85

Mutagenesis-validated functional residues (15):

Position	Phenotype
89	abolishes dihydrolipoyl dehydrogenase activity. does not affect interaction with pdhx.
383	reduces dihydrolipoyl dehydrogenase activity.
448	reduces interaction with pdhx. inhibits multienzyme pyruvate dehydrogenase complex activity. does not affect dihydrolipo
448	does not affect dihydrolipoyl dehydrogenase activity.
466	decreases dehydrogenase activity. loss of proteolytic activity.
473	reduces interaction with pdhx. inhibits multienzyme pyruvate dehydrogenase complex activity. does not affect dihydrolipo
473	does not affect dihydrolipoyl dehydrogenase activity.
482	does not affect dihydrolipoyl dehydrogenase activity.
482	does not affect interaction with pdhx.
485	loss of dehydrogenase activity. increases proteolytic activity.
491	loss of proteolytic activity. does not affect dehydrogenase activity.
492	reduces dihydrolipoyl dehydrogenase activity. does not affect interaction with pdhx.
505	reduces dihydrolipoyl dehydrogenase activity. does not affect interaction with pdhx.

Function

Pathways and Gene Ontology

Reactome pathways

13 pathways

ID	Pathway
R-HSA-204174	Regulation of pyruvate dehydrogenase (PDH) complex
R-HSA-5362517	Signaling by Retinoic Acid
R-HSA-6783984	Glycine degradation
R-HSA-70895	Branched-chain amino acid catabolism
R-HSA-9837999	Mitochondrial protein degradation
R-HSA-9853506	OGDH complex synthesizes succinyl-CoA from 2-OG
R-HSA-9858328	OADH complex synthesizes glutaryl-CoA from 2-OA
R-HSA-9859138	BCKDH synthesizes BCAA-CoA from KIC, KMVA, KIV
R-HSA-9861559	PDH complex synthesizes acetyl-CoA from PYR
R-HSA-9865113	Loss-of-function mutations in DBT cause MSUD2
R-HSA-9907570	Loss-of-function mutations in DLD cause MSUD3/DLDD
R-HSA-9912481	Branched-chain ketoacid dehydrogenase kinase deficiency
R-HSA-9912529	H139Hfs13* PPM1K causes a mild variant of MSUD

MSigDB gene sets: 342 (showing top): TGCGCANK_UNKNOWN, GOCC_SECRETORY_GRANULE, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, MORF_RAD21, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, MORF_HDAC2, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_MALE_GAMETE_GENERATION, KEGG_GLYCOLYSIS_GLUCONEOGENESIS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_ACETYL_COA_METABOLIC_PROCESS, MORF_PSMC2, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, KEGG_VALINE_LEUCINE_AND_ISOLEUCINE_DEGRADATION, GOBP_DICARBOXYLIC_ACID_METABOLIC_PROCESS

GO Biological Process (12): pyruvate decarboxylation to acetyl-CoA (GO:0006086), 2-oxoglutarate metabolic process (GO:0006103), mitochondrial electron transport, NADH to ubiquinone (GO:0006120), proteolysis (GO:0006508), gastrulation (GO:0007369), branched-chain amino acid catabolic process (GO:0009083), obsolete L-lysine catabolic process to acetyl-CoA (GO:0019474), regulation of membrane potential (GO:0042391), sperm capacitation (GO:0048240), 2-oxoglutarate decarboxylation to succinyl-CoA (GO:0120551), branched-chain alpha-keto acid decarboxylation to branched-chain acyl-CoA (GO:0120552), tricarboxylic acid cycle (GO:0006099)

GO Molecular Function (6): dihydrolipoyl dehydrogenase (NADH) activity (GO:0004148), flavin adenine dinucleotide binding (GO:0050660), nucleotide binding (GO:0000166), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on a sulfur group of donors, NAD(P) as acceptor (GO:0016668)

GO Cellular Component (14): nucleus (GO:0005634), mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), motile cilium (GO:0031514), acrosomal matrix (GO:0043159), oxoglutarate dehydrogenase complex (GO:0045252), pyruvate dehydrogenase complex (GO:0045254), branched-chain alpha-ketoacid dehydrogenase complex (GO:0160157), oxoadipate dehydrogenase complex (GO:0160167), acrosomal vesicle (GO:0001669), cytoplasm (GO:0005737), cilium (GO:0005929), cytoplasmic vesicle (GO:0031410), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
Maple Syrup Urine Disease	3
Regulation of pyruvate metabolism	1
Signaling by Nuclear Receptors	1
Glyoxylate metabolism and glycine degradation	1
Metabolism of amino acids and derivatives	1
Metabolism of proteins	1
Citric acid cycle (TCA cycle)	1
Lysine catabolism	1
Branched-chain amino acid catabolism	1
Pyruvate metabolism	1
Diseases of branched-chain amino acid catabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
alpha-ketoacid dehydrogenase complex	4
cellular anatomical structure	3
transferase complex	3
aerobic respiration	2
intracellular membrane-bounded organelle	2
cytoplasm	2
dihydrolipoyl dehydrogenase (NADH) activity	1
pyruvate dehydrogenase (acetyl-transferring) activity	1
dihydrolipoyllysine-residue acetyltransferase activity	1
acetyl-CoA biosynthetic process	1
pyruvate metabolic process	1
dicarboxylic acid metabolic process	1
aerobic electron transport chain	1
mitochondrial ATP synthesis coupled electron transport	1
protein metabolic process	1
ectoderm formation	1
endoderm formation	1
mesoderm formation	1
embryonic morphogenesis	1
amino acid catabolic process	1
branched-chain amino acid metabolic process	1
carboxylic acid catabolic process	1
monoatomic ion transmembrane transport	1
regulation of biological quality	1
developmental process involved in reproduction	1
spermatid development	1
cellular process involved in reproduction in multicellular organism	1
cell maturation	1
tricarboxylic acid cycle	1
2-oxoglutarate metabolic process	1
succinyl-CoA biosynthetic process	1
branched-chain amino acid catabolic process	1
carboxylic acid metabolic process	1
fatty-acyl-CoA metabolic process	1
primary metabolic process	1
oxidoreductase activity, acting on a sulfur group of donors, NAD(P) as acceptor	1
nucleotide binding	1
anion binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1

Protein interactions and networks

STRING

4304 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DLD	PDHX	O00330	995
DLD	OGDH	Q02218	995
DLD	PDHA1	P08559	991
DLD	DLAT	P10515	987
DLD	DLST	P36957	980
DLD	BCKDHA	P12694	971
DLD	BCKDHB	P21953	949
DLD	AMT	P48728	900
DLD	PDHB	P11177	891
DLD	DBT	P11182	861
DLD	GCSH	P23434	860
DLD	AASDHPPT	Q9NRN7	814
DLD	PDHA2	P29803	798
DLD	GLDC	P23378	792
DLD	DHTKD1	Q96HY7	759

IntAct

104 interactions, top by confidence:

A	B	Type	Score
PDHX	DLD	psi-mi:“MI:0407”(direct interaction)	0.880
DLD	PDHX	psi-mi:“MI:0914”(association)	0.880
PDHX	DLD	psi-mi:“MI:0915”(physical association)	0.880
DLD	PDHX	psi-mi:“MI:0407”(direct interaction)	0.880
PPP6C	ANKRD28	psi-mi:“MI:0914”(association)	0.870
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
KGD4	DLD	psi-mi:“MI:0914”(association)	0.640
ITGB1BP1	DLD	psi-mi:“MI:0915”(physical association)	0.560
DLD	HTT	psi-mi:“MI:0915”(physical association)	0.560
DLD	PDHB	psi-mi:“MI:0914”(association)	0.530
GATA2	BANF1	psi-mi:“MI:0914”(association)	0.530
DLD	PRDX6	psi-mi:“MI:0915”(physical association)	0.500
DLD	YWHAE	psi-mi:“MI:0915”(physical association)	0.500
NDUFAB1	MIEF1	psi-mi:“MI:0915”(physical association)	0.490
BMP2K	DLD	psi-mi:“MI:0915”(physical association)	0.490
sseJ	AGPS	psi-mi:“MI:0914”(association)	0.460
CDK1	DLD	psi-mi:“MI:0403”(colocalization)	0.430
DLD	Nfkbie	psi-mi:“MI:0915”(physical association)	0.400
TXNDC16	DLD	psi-mi:“MI:0915”(physical association)	0.400
TAF1	DLD	psi-mi:“MI:0915”(physical association)	0.400
CALD1	DLD	psi-mi:“MI:0915”(physical association)	0.400
SIRT4	VWA8	psi-mi:“MI:0914”(association)	0.350

BioGRID (633): DLD (Affinity Capture-MS), DLD (Affinity Capture-MS), DLD (Affinity Capture-MS), DLD (Affinity Capture-MS), DLST (Affinity Capture-MS), OGDHL (Affinity Capture-MS), OGDH (Affinity Capture-MS), HLTF (Affinity Capture-MS), PDK3 (Affinity Capture-MS), DLAT (Affinity Capture-MS), SORL1 (Affinity Capture-MS), PARS2 (Affinity Capture-MS), PDHA1 (Affinity Capture-MS), NFS1 (Affinity Capture-MS), FBXO21 (Affinity Capture-MS)

ESM2 similar proteins: B9A1H3, F1N206, O04955, O08749, O62768, O89049, P00390, P09622, P09623, P13110, P27456, P28593, P30635, P39040, P39050, P39051, P41921, P47791, P48640, P48641, P48642, P49819, P70619, P78965, P91938, Q16881, Q41219, Q43154, Q5NVA2, Q5R4B1, Q60HG3, Q6BPI1, Q6C5H4, Q6FRV2, Q6HA23, Q6P6R2, Q74ZK4, Q811C4, Q873E8, Q8CIZ7

Diamond homologs: A6V3A6, A7FD10, A8MS68, B2JZF3, B7UZU5, D0VWY5, D9J041, F1N206, F4JLP5, G0SB20, O00087, O05139, O05940, O08749, O17953, O18480, O34324, O50286, O50311, O84561, P09063, P09622, P09623, P09624, P0A0E4, P0A0E5, P0A0E6, P0A0E7, P0A0E8, P0A9P0, P0A9P1, P0A9P2, P0A9P3, P11959, P14218, P16171, P18925, P21880, P23189, P27456

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
DLD	“form complex”	OGDC	binding
DLD	“form complex”	PDH	binding
DLD	“form complex”	“Glycine cleavage system”	binding
RIPK3	“up-regulates activity”	DLD	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

746 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	39
Likely pathogenic	87
Uncertain significance	178
Likely benign	338
Benign	38

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1072157	NM_000108.5(DLD):c.1396G>T (p.Glu466Ter)	Pathogenic
11966	NM_000108.5(DLD):c.685G>T (p.Gly229Cys)	Pathogenic
1353559	NM_000108.5(DLD):c.459T>G (p.Tyr153Ter)	Pathogenic
1359450	NM_000108.5(DLD):c.783del (p.Gln262fs)	Pathogenic
1392784	NM_000108.5(DLD):c.24C>G (p.Tyr8Ter)	Pathogenic
1398789	NC_000007.13:g.(?107556049)(107558012_?)del	Pathogenic
1424970	NM_000108.5(DLD):c.1245_1249del (p.Tyr416fs)	Pathogenic
1454310	NM_000108.5(DLD):c.362del (p.Asp121fs)	Pathogenic
2017211	NM_000108.5(DLD):c.647del (p.Met216fs)	Pathogenic
2028124	NM_000108.5(DLD):c.987dup (p.Glu330Ter)	Pathogenic
2030397	NM_000108.5(DLD):c.1232_1233del (p.Glu411fs)	Pathogenic
2057359	NM_000108.5(DLD):c.1116_1117del (p.Ile372fs)	Pathogenic
2069354	NM_000108.5(DLD):c.1158C>G (p.Tyr386Ter)	Pathogenic
2113162	NM_000108.5(DLD):c.1139del (p.Gly380fs)	Pathogenic
2422364	NC_000007.13:g.(?107412489)(107559714_?)del	Pathogenic
2674859	NM_000108.5(DLD):c.184C>T (p.Gln62Ter)	Pathogenic
2707325	NM_000108.5(DLD):c.813del (p.Lys271fs)	Pathogenic
2715363	NM_000108.5(DLD):c.104del (p.Tyr35fs)	Pathogenic
2744285	NM_000108.5(DLD):c.988G>T (p.Glu330Ter)	Pathogenic
2752254	NM_000108.5(DLD):c.854C>G (p.Ser285Ter)	Pathogenic
2793857	NM_000108.5(DLD):c.529A>T (p.Lys177Ter)	Pathogenic
2865401	NM_000108.5(DLD):c.3G>A (p.Met1Ile)	Pathogenic
2914891	NM_000108.5(DLD):c.105C>A (p.Tyr35Ter)	Pathogenic
2976179	NM_000108.5(DLD):c.380del (p.Lys127fs)	Pathogenic
3245827	NC_000007.13:g.(?107531696)(107533743_?)del	Pathogenic
3245828	NC_000007.13:g.(?107542163)(107559704_?)del	Pathogenic
3594235	NM_000108.5(DLD):c.1A>C (p.Met1Leu)	Pathogenic
370072	NM_000108.5(DLD):c.104dup (p.Tyr35Ter)	Pathogenic
370700	NM_000108.5(DLD):c.112C>T (p.Gln38Ter)	Pathogenic
40187	NM_000108.5(DLD):c.1444A>G (p.Arg482Gly)	Pathogenic

SpliceAI

2631 predictions. Top by Δscore:

Variant	Effect	Δscore
7:107893196:CTA:C	acceptor_loss	1.0000
7:107893198:A:AG	acceptor_gain	1.0000
7:107893199:G:GG	acceptor_gain	1.0000
7:107893199:GA:G	acceptor_gain	1.0000
7:107893199:GAGA:G	acceptor_gain	1.0000
7:107893274:GCCGA:G	donor_gain	1.0000
7:107893275:CCGA:C	donor_gain	1.0000
7:107893275:CCGAG:C	donor_loss	1.0000
7:107893276:CGA:C	donor_gain	1.0000
7:107893276:CGAG:C	donor_loss	1.0000
7:107893277:GA:G	donor_gain	1.0000
7:107893277:GAG:G	donor_gain	1.0000
7:107893277:GAGT:G	donor_loss	1.0000
7:107893278:AG:A	donor_loss	1.0000
7:107893279:G:C	donor_loss	1.0000
7:107893279:G:GG	donor_gain	1.0000
7:107893280:T:A	donor_loss	1.0000
7:107893281:AA:A	donor_loss	1.0000
7:107893282:AGT:A	donor_loss	1.0000
7:107901736:A:AG	acceptor_gain	1.0000
7:107901736:AGTT:A	acceptor_gain	1.0000
7:107901737:G:GG	acceptor_gain	1.0000
7:107901737:GTT:G	acceptor_gain	1.0000
7:107901737:GTTG:G	acceptor_gain	1.0000
7:107902323:A:AG	acceptor_gain	1.0000
7:107902324:G:GG	acceptor_gain	1.0000
7:107902324:GACA:G	acceptor_gain	1.0000
7:107903466:A:AG	acceptor_gain	1.0000
7:107903467:A:AG	acceptor_gain	1.0000
7:107903472:CTTTA:C	acceptor_loss	1.0000

AlphaMissense

3305 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:107902364:T:C	C80R	1.000
7:107902379:T:C	C85R	1.000
7:107902393:G:C	K89N	1.000
7:107902393:G:T	K89N	1.000
7:107916854:C:G	C312W	1.000
7:107901756:T:A	V46D	0.999
7:107901762:G:A	G48D	0.999
7:107901768:G:A	G50D	0.999
7:107901777:G:A	G53E	0.999
7:107901786:C:A	A56D	0.999
7:107901788:G:C	A57P	0.999
7:107901789:C:A	A57D	0.999
7:107902333:C:G	C69W	0.999
7:107902355:G:C	G77R	0.999
7:107902356:G:A	G77D	0.999
7:107902356:G:T	G77V	0.999
7:107902359:G:A	G78E	0.999
7:107902359:G:T	G78V	0.999
7:107902365:G:A	C80Y	0.999
7:107902366:C:G	C80W	0.999
7:107902368:T:G	L81W	0.999
7:107902376:G:C	G84R	0.999
7:107902377:G:A	G84D	0.999
7:107902380:G:A	C85Y	0.999
7:107902381:T:G	C85W	0.999
7:107902386:C:A	P87H	0.999
7:107902389:C:A	S88Y	0.999
7:107902389:C:T	S88F	0.999
7:107902391:A:G	K89E	0.999
7:107903485:T:C	L92S	0.999

dbSNP variants (sampled 300 via entrez): RS1000057822 (7:107897060 C>T), RS1000108310 (7:107896898 G>A), RS1000165051 (7:107912046 GTT>G,GT,GTTT,GTTTT), RS1000267401 (7:107921170 C>T), RS1000344536 (7:107914338 T>C), RS1000494779 (7:107908567 T>C), RS1000804050 (7:107896235 G>A), RS1000842625 (7:107914669 CTT>C,CT), RS1001072632 (7:107916777 C>T), RS1001090914 (7:107910168 T>G), RS1001099600 (7:107902270 G>A,T), RS1001172755 (7:107911567 T>G), RS1001173763 (7:107896403 C>A,T), RS1001316927 (7:107890920 A>G), RS1001361356 (7:107905183 C>T)

Disease associations

OMIM: gene MIM:238331 | disease phenotypes: MIM:246900, MIM:256000, MIM:312170

GenCC curated gene-disease

Disease	Classification	Inheritance
pyruvate dehydrogenase E3 deficiency	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Leigh syndrome	Definitive	AR
pyruvate dehydrogenase E3 deficiency	Definitive	AR

Mondo (4): pyruvate dehydrogenase E3 deficiency (MONDO:0009529), Leigh syndrome (MONDO:0009723), pyruvate dehydrogenase deficiency (MONDO:0019169), lactic acidosis (MONDO:0006040)

Orphanet (4): Pyruvate dehydrogenase E3 deficiency (Orphanet:2394), Pyruvate dehydrogenase deficiency (Orphanet:765), Leigh syndrome (Orphanet:506), Pyruvate dehydrogenase E1-alpha deficiency (Orphanet:79243)

HPO phenotypes

43 total (30 of 43 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000708	Atypical behavior
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001254	Lethargy
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001290	Generalized hypotonia
HP:0001298	Encephalopathy
HP:0001332	Dystonia
HP:0001399	Hepatic failure
HP:0001410	Decreased liver function
HP:0001508	Failure to thrive
HP:0001638	Cardiomyopathy
HP:0001639	Hypertrophic cardiomyopathy
HP:0001942	Metabolic acidosis
HP:0001943	Hypoglycemia
HP:0001987	Hyperammonemia
HP:0001993	Ketoacidosis
HP:0002013	Vomiting
HP:0002151	Increased circulating lactate concentration
HP:0002240	Hepatomegaly
HP:0002480	Hepatic encephalopathy
HP:0002910	Elevated circulating hepatic transaminase concentration
HP:0003128	Lactic acidosis
HP:0003234	Decreased circulating carnitine concentration
HP:0003394	Muscle spasm
HP:0003542	Increased circulating pyruvate concentration

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST000311_10	Ulcerative colitis	7.000000e-06
GCST000311_5	Ulcerative colitis	1.000000e-06
GCST000311_6	Ulcerative colitis	9.000000e-06
GCST000624_19	Ulcerative colitis	8.000000e-08
GCST001728_4	Ulcerative colitis	2.000000e-26
GCST004131_45	Inflammatory bowel disease	8.000000e-16
GCST004133_10	Ulcerative colitis	9.000000e-21
GCST005956_26	Waist-to-hip ratio adjusted for BMI	2.000000e-08
GCST005962_48	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	2.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D000140	Acidosis, Lactic	C18.452.076.176.180
D007888	Leigh Disease	C10.228.140.163.100.412; C16.320.565.189.412; C16.320.565.202.810.444; C18.452.132.100.412; C18.452.648.189.412; C18.452.648.202.810.444; C18.452.660.520

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066969 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

57 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, affects cotreatment, increases methylation, decreases expression	3
Resveratrol	affects cotreatment, increases expression, affects secretion	3
Cadmium Chloride	decreases expression, increases abundance, increases expression	3
methacrylaldehyde	increases expression, increases abundance, affects cotreatment	2
Acrolein	affects cotreatment, increases expression, increases abundance	2
Air Pollutants	affects cotreatment, increases abundance, increases expression, decreases expression	2
Vehicle Emissions	increases methylation, decreases expression, increases abundance	2
Cadmium	decreases expression, increases abundance, increases expression	2
Ozone	affects cotreatment, increases expression, increases abundance	2
Tobacco Smoke Pollution	affects expression, decreases expression, increases expression	2
Particulate Matter	increases abundance, decreases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
oxybenzone	increases expression	1
alpha-pinene	increases abundance, affects cotreatment, increases expression	1
sodium arsenate	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, increases expression	1
perfluorooctanoic acid	increases expression	1
ochratoxin A	increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
chromium hexavalent ion	affects expression	1
bisphenol B	increases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	increases expression	1
bisphenol AF	increases expression	1
Temozolomide	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651286	Binding	Binding affinity to human DLD incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1Q5	Abcam HeLa DLD KO	Cancer cell line	Female

Clinical trials (associated diseases)

41 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00202228	PHASE4	COMPLETED	Lactate Metabolism Study in HIV Infected Persons
NCT01354652	PHASE4	TERMINATED	Lactic Acidosis During Entecavir(ETV)Treatment
NCT02616484	PHASE3	ACTIVE_NOT_RECRUITING	Trial of Dichloroacetate in Pyruvate Dehydrogenase Complex Deficiency:
NCT00004490	PHASE3	COMPLETED	Phase III Randomized Study of Sodium Dichloroacetate in Children With Congenital Lactic Acidosis
NCT01721733	PHASE2	COMPLETED	Safety and Efficacy Study of EPI-743 in Children With Leigh Syndrome
NCT02352896	PHASE2	COMPLETED	Long-Term Safety and Efficacy Evaluation of EPI-743 in Children With Leigh Syndrome
NCT03747328	PHASE2	WITHDRAWN	ABI-009 (Nab-sirolimus) in Patients With Genetically-confirmed Leigh or Leigh-like Syndrome
NCT06843811	PHASE2	ENROLLING_BY_INVITATION	Sirolimus for Leigh Syndrome
NCT06990984	PHASE2	NOT_YET_RECRUITING	A Dose-ranging Study of TTI-0102 in Adults and Children With Leigh Syndrome Spectrum (LSS)
NCT03734263	PHASE2	COMPLETED	Use of Phenylbutyrate Therapy for Patients With Pyruvate Dehydrogenase Complex Deficiency.
NCT00004493	PHASE2	COMPLETED	Phase II Pilot Randomized Study of Sodium Dichloroacetate in Patients With Congenital Lactic Acidemia
NCT01973504	PHASE2	WITHDRAWN	Phase 2c Dose Comparison Study of MP4OX in Trauma
NCT02974257	PHASE2	TERMINATED	Thiamine vs. Placebo to Increase Oxygen Consumption After Cardiac Arrest
NCT02544217	PHASE1	COMPLETED	A Dose-escalating Clinical Trial With KH176
NCT06340685	PHASE1	RECRUITING	Triheptanoin for Children With Primary-Specific Pyruvate Dehydrogenase Complex (PDC) Deficiency
NCT03122678	PHASE1	WITHDRAWN	Thiamine Supplementation in Patients With Septic Shock
NCT04378075	PHASE2/PHASE3	TERMINATED	A Study to Evaluate Efficacy and Safety of Vatiquinone for Treating Mitochondrial Disease in Participants With Refractory Epilepsy
NCT01780168	Not specified	RECRUITING	The NIH MINI Study: Metabolism, Infection, and Immunity in Inborn Errors of Metabolism
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT01803906	Not specified	ENROLLING_BY_INVITATION	Tissue Sample Study for Mitochondrial Disorders
NCT03137355	Not specified	RECRUITING	The International Registry for Leigh Syndrome
NCT05277363	Not specified	WITHDRAWN	A Study of the Natural Course of SURF1 Deficiency
NCT05554835	Not specified	RECRUITING	Global Registry and Natural History Study for Mitochondrial Disorders
NCT06967831	Not specified	RECRUITING	Drug Repurposing for Mitochondrial Disorders Using iPSCs Derived Neural Cells
NCT05257005	Not specified	UNKNOWN	Natural History Study of Pyruvate Dehydrogenase Deficiency
NCT06931262	Not specified	AVAILABLE	Expanded Access Treatment Protocol With DCA for Patients With PDCD
NCT03466528	PHASE2/PHASE3	COMPLETED	Alcohol: Thiamine and or Magnesium 1
NCT00004353	Not specified	COMPLETED	Study of the Metabolism of Pyruvate and Related Problems in Patients With Lactic Acidemia
NCT00015015	Not specified	COMPLETED	Dichloroacetate Kinetics, Metabolism and Toxicology
NCT00638040	Not specified	WITHDRAWN	The Gene Expression Studies of the Role of Tumor Microenvironments in Tumor Progression
NCT00874276	Not specified	COMPLETED	Pharmacotoxicology of Trichloroethylene Metabolites
NCT00942123	Not specified	COMPLETED	Study On the Role of Mitochondrial Dysfunction in the Pathogenesis of Metformin-associated Lactic Acidosis
NCT01139463	Not specified	COMPLETED	Study of Blood Lactate Levels in Patients Treated With Antipsychotics
NCT01873859	Not specified	COMPLETED	Safety of Continuing Metformin in Diabetic Patients With Normal Kidney Function Receiving Contrast Media
NCT01901419	Not specified	COMPLETED	Nitroglycerin Infusion During Cardiac Surgery
NCT03126890	Not specified	UNKNOWN	Investigation of the Correlation Between Plasma Concentration of Linezolid Antibiotic and Treatment Response and Adverse Reactions
NCT03723993	Not specified	WITHDRAWN	Remote Ischemic Preconditioning During Cardiopulmonary Bypass
NCT04975906	Not specified	COMPLETED	The Threshold of Serum Anion Gap as a Screening Tool for Organic Acidosis
NCT05984186	Not specified	COMPLETED	Effect of High Velocity/Hyperoxic Breathing Therapy on Blood Lactate Decline
NCT06727318	Not specified	COMPLETED	Comparison of Peripheral Perfusion Indicators and Lactate Levels