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GeneE
26 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
DLD
dihydrolipoamide dehydrogenase
Chromosome 7 Β· 7q31.1
NCBI Gene: 1738Ensembl: ENSG00000091140.15HGNC: HGNC:2898UniProt: A0A024R713
170PubMed Papers
21Diseases
0Drugs
139Pathogenic Variants
RESEARCH IMPACT
TrendingVariant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
pyruvate decarboxylation to acetyl-CoAdihydrolipoyl dehydrogenase (NADH) activityprotein bindingbranched-chain amino acid catabolic processpyruvate dehydrogenase E3 deficiencyLeigh syndromeulcerative colitisneurodegenerative disease
✦AI Summary

DLD (dihydrolipoamide dehydrogenase) is a mitochondrial flavin-dependent enzyme that functions as the E3 component of three alpha-ketoacid dehydrogenase complexes: pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase, and branched-chain amino acid dehydrogenase 12. As part of these complexes, DLD catalyzes reoxidation of the dihydrolipoyl moiety on E2 subunits using NAD+ as the ultimate electron acceptor 2345. This activity links cytoplasmic glycolysis to the mitochondrial tricarboxylic acid cycle. DLD also functions in the glycine cleavage system 1. Beyond its canonical role, a nuclear-localized fraction of the 2-oxoglutarate dehydrogenase complex containing DLD associates with histone acetyltransferase KAT2A to provide succinyl-CoA for histone succinylation, suggesting a role in epigenetic regulation 6. In monomeric form, DLD may possess serine protease activity 7. Mutations in DLD cause dihydrolipoamide dehydrogenase deficiency, a rare mitochondrial disease affecting energy metabolism and resulting in neurological complications. The DLD gene spans approximately 20 kb with 14 exons and contains multiple promoter elements including Sp1 and nuclear respiratory factor 1 binding sites 8.

Sources cited
1
DLD is a component of the glycine cleavage system and E3 component of alpha-ketoacid dehydrogenase complexes
PMID: 15712224
2
DLD catalyzes reoxidation of dihydrolipoyl moiety with NAD+ as electron acceptor
PMID: 16442803
3
DLD E3 component catalyzes reoxidation with NAD+ as ultimate electron acceptor
PMID: 16770810
4
DLD catalyzes reoxidation of dihydrolipoyl moiety with NAD+ as electron acceptor
PMID: 20160912
5
DLD catalyzes reoxidation of dihydrolipoyl moiety with NAD+ as electron acceptor
PMID: 20385101
6
Nuclear-localized DLD in 2-oxoglutarate dehydrogenase complex associates with KAT2A for histone succinylation
PMID: 29211711
7
DLD in monomeric form may have serine protease activity
PMID: 17404228
8
DLD gene structure: approximately 20 kb with 14 exons and multiple promoter elements
PMID: 8406489
Disease Associationsβ“˜21
pyruvate dehydrogenase E3 deficiencyOpen Targets
0.84Strong
Leigh syndromeOpen Targets
0.64Moderate
ulcerative colitisOpen Targets
0.48Moderate
neurodegenerative diseaseOpen Targets
0.48Moderate
inflammatory bowel diseaseOpen Targets
0.47Moderate
genetic disorderOpen Targets
0.47Moderate
Alzheimer diseaseOpen Targets
0.40Moderate
Parkinson diseaseOpen Targets
0.39Weak
multiple sclerosisOpen Targets
0.39Weak
lysosomal storage diseaseOpen Targets
0.39Weak
maple syrup urine disease type 1AOpen Targets
0.37Weak
ulcerative proctosigmoiditisOpen Targets
0.36Weak
lactic acidosisOpen Targets
0.34Weak
proctitisOpen Targets
0.28Weak
ulcer diseaseOpen Targets
0.25Weak
colitisOpen Targets
0.25Weak
enteritisOpen Targets
0.22Weak
ankylosing spondylitisOpen Targets
0.21Weak
pyruvate dehydrogenase deficiencyOpen Targets
0.19Weak
psoriasisOpen Targets
0.19Weak
Dihydrolipoamide dehydrogenase deficiencyUniProt
Pathogenic Variants139
NM_000108.5(DLD):c.1123G>A (p.Glu375Lys)Pathogenic
Pyruvate dehydrogenase E3 deficiency|not provided|Inborn genetic diseases|See cases|DLD-related disorder
β˜…β˜…β˜†β˜†2026β†’ Residue 375
NM_000108.5(DLD):c.737del (p.Gly246fs)Likely pathogenic
Pyruvate dehydrogenase E3 deficiency
β˜…β˜…β˜†β˜†2026β†’ Residue 246
NM_000108.5(DLD):c.104dup (p.Tyr35Ter)Pathogenic
Pyruvate dehydrogenase E3 deficiency|not provided
β˜…β˜…β˜†β˜†2026β†’ Residue 35
NM_000108.5(DLD):c.685G>T (p.Gly229Cys)Pathogenic
Pyruvate dehydrogenase E3 deficiency|not provided|Inborn genetic diseases|DLD-related disorder|Thyroid cancer, nonmedullary, 1
β˜…β˜…β˜†β˜†2026β†’ Residue 229
NM_000108.5(DLD):c.1344_1347del (p.Asp448fs)Pathogenic
Pyruvate dehydrogenase E3 deficiency
β˜…β˜…β˜†β˜†2025β†’ Residue 448
NM_000108.5(DLD):c.1464+1G>APathogenic
Pyruvate dehydrogenase E3 deficiency
β˜…β˜…β˜†β˜†2025
NM_000108.5(DLD):c.285_286del (p.His96fs)Pathogenic
Pyruvate dehydrogenase E3 deficiency
β˜…β˜…β˜†β˜†2025β†’ Residue 96
NM_000108.5(DLD):c.1058T>C (p.Ile353Thr)Pathogenic
Pyruvate dehydrogenase E3 deficiency
β˜…β˜…β˜†β˜†2025β†’ Residue 353
NM_000108.5(DLD):c.633dup (p.Val212fs)Pathogenic
Pyruvate dehydrogenase E3 deficiency
β˜…β˜…β˜†β˜†2025β†’ Residue 212
NM_000108.5(DLD):c.1463C>T (p.Pro488Leu)Likely pathogenic
Pyruvate dehydrogenase E3 deficiency
β˜…β˜…β˜†β˜†2025β†’ Residue 488
NM_000108.5(DLD):c.1436A>T (p.Asp479Val)Pathogenic
Pyruvate dehydrogenase E3 deficiency|Lactic acidosis
β˜…β˜…β˜†β˜†2025β†’ Residue 479
NM_000108.5(DLD):c.946C>T (p.Arg316Ter)Pathogenic
Pyruvate dehydrogenase E3 deficiency
β˜…β˜…β˜†β˜†2025β†’ Residue 316
NM_000108.5(DLD):c.259C>T (p.Pro87Ser)Likely pathogenic
Pyruvate dehydrogenase E3 deficiency
β˜…β˜…β˜†β˜†2025β†’ Residue 87
NM_000108.5(DLD):c.405_407del (p.Gly137del)Pathogenic
not provided|Pyruvate dehydrogenase E3 deficiency
β˜…β˜…β˜†β˜†2025β†’ Residue 137
NM_000108.5(DLD):c.875+1G>APathogenic
Pyruvate dehydrogenase E3 deficiency
β˜…β˜…β˜†β˜†2025
NM_000108.5(DLD):c.1081A>G (p.Met361Val)Likely pathogenic
Pyruvate dehydrogenase E3 deficiency
β˜…β˜…β˜†β˜†2025β†’ Residue 361
NM_000108.5(DLD):c.1036A>T (p.Lys346Ter)Likely pathogenic
Pyruvate dehydrogenase E3 deficiency
β˜…β˜…β˜†β˜†2024β†’ Residue 346
NM_000108.5(DLD):c.803_804del (p.Gln268fs)Pathogenic
not provided|Pyruvate dehydrogenase E3 deficiency
β˜…β˜…β˜†β˜†2024β†’ Residue 268
NM_000108.5(DLD):c.1182C>G (p.Tyr394Ter)Pathogenic
Pyruvate dehydrogenase E3 deficiency
β˜…β˜…β˜†β˜†2024β†’ Residue 394
NM_000108.5(DLD):c.821dup (p.Leu274fs)Pathogenic
Pyruvate dehydrogenase E3 deficiency
β˜…β˜…β˜†β˜†2024β†’ Residue 274
View on ClinVar β†—
Related Genes
UQCRC2Protein interaction100%BCKDHAProtein interaction100%DBTProtein interaction100%BCKDHBProtein interaction100%NDUFS1Protein interaction100%AMTProtein interaction100%
Tissue Expression6 tissues
Heart
100%
Brain
25%
Liver
21%
Bone Marrow
18%
Lung
13%
Ovary
9%
Gene Interaction Network
Click a node to explore
DLDUQCRC2BCKDHADBTBCKDHBNDUFS1AMT
PROTEIN STRUCTURE
Preparing viewer…
PDB6I4R Β· 1.44 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.73LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.53 [0.39–0.73]
RankingsWhere DLD stands among ~20K protein-coding genes
  • #2,595of 20,598
    Most Researched170 Β· top quartile
  • #550of 5,498
    Most Pathogenic Variants139 Β· top quartile
  • #5,639of 17,882
    Most Constrained (LOEUF)0.73
Genes detectedDLD
Sources retrieved26 papers
Response timeβ€”
πŸ“„ Sources
26β–Ό
1
How We Fail Children With Developmental Language Disorder.
PMID: 32755505
Lang Speech Hear Serv Sch Β· 2020
1.00
2
Editorial Perspective: Maximising the benefits of intervention research for children and young people with developmental language disorder (DLD) - a call for international consensus on standards of reporting in intervention studies for children with and at risk for DLD.
PMID: 36127873
J Child Psychol Psychiatry Β· 2023
0.90
3
Synthesis and Characterization of Sulfonamide-Schiff Bases, and Investigation of Cytotoxic, Antioxidant, HDAC, and Apoptotic Activities in Human Colon Cancer Cells (DLD-1 and HT-29).
PMID: 41961883
Arch Pharm (Weinheim) Β· 2026
0.80
4
Editorial: New frontiers in the scientific study of developmental language disorders.
PMID: 28921545
J Child Psychol Psychiatry Β· 2017
0.80
5
Vietnamese children with and without DLD: Classifier use and grammaticality over time.
PMID: 36587459
J Commun Disord Β· 2023
0.70