DLST Gene: Dihydrolipoamide S-Succinyltransferase
Key component of the mitochondrial alpha-ketoglutarate dehydrogenase complex (KGDHC) involved in the TCA cycle and associated with metabolic and neurodegenerative disorders.
Gene Information Card
| Symbol | DLST |
|---|---|
| Full Name | Dihydrolipoamide S-Succinyltransferase |
| Gene Type | Protein coding |
| Chromosomal Location | 14q24.3 |
| NCBI Gene ID | 1743 ncbi.nlm.nih.gov/gene/1743 |
| Ensembl ID | ENSG00000119689 |
| UniProt ID | P36957 |
| OMIM ID | 126063 |
| HGNC ID | 2917 |
| Aliases | DLTS, E2K, KGDHC, OGDC-E2 |
Description
The DLST gene encodes the dihydrolipoamide S-succinyltransferase (E2) component of the mitochondrial alpha-ketoglutarate dehydrogenase complex (KGDHC). This enzyme catalyzes the conversion of alpha-ketoglutarate to succinyl-CoA and CO2 in the tricarboxylic acid (TCA) cycle. DLST is essential for energy metabolism and is implicated in various metabolic and neurodegenerative conditions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Alpha-ketoglutarate dehydrogenase deficiency | Loss-of-function mutations in DLST impair KGDHC activity, leading to accumulation of alpha-ketoglutarate and metabolic acidosis. | OMIM #203740; ClinVar |
| Huntington disease | Reduced KGDHC activity due to DLST dysregulation contributes to mitochondrial dysfunction and neuronal death. | NCBI Gene; PubMed studies |
| Alzheimer disease | Decreased DLST expression and KGDHC activity are associated with oxidative stress and neurodegeneration. | UniProt; PubMed studies |
| Succinyl-CoA:3-ketoacid CoA transferase deficiency | Indirect involvement via disrupted ketone body metabolism. | OMIM #245050 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 45.2 | High |
| Skeletal Muscle | 38.1 | High |
| Liver | 32.5 | High |
| Brain | 28.7 | Medium |
| Kidney | 25.3 | Medium |
| Lung | 15.8 | Medium |
| Pancreas | 12.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 42.1 | Liver cancer cell line |
| K562 | 35.6 | Leukemia cell line |
| HeLa | 30.2 | Cervical cancer cell line |
| A549 | 28.9 | Lung cancer cell line |
| MCF7 | 22.4 | Breast cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1135C>T (p.Arg379*) | Nonsense | <0.01% | Loss of function; truncated protein |
| c.788A>G (p.Tyr263Cys) | Missense | <0.01% | Reduced enzyme activity |
| c.1024G>A (p.Glu342Lys) | Missense | <0.01% | Impaired complex assembly |
| c.1246_1247del (p.Leu416fs) | Frameshift | <0.01% | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg379*, p.Leu416fs) lead to truncated or absent protein, reducing KGDHC activity.
Gain of Function (GOF)
No gain-of-function mutations reported for DLST.
Dominant Negative (DN)
Missense mutations (e.g., p.Tyr263Cys, p.Glu342Lys) may interfere with complex assembly, acting in a dominant-negative manner.
View complete mutation data：
Gene Ontology (GO)
Pathways
• KEGG: hsa00020 - Citrate cycle (TCA cycle)
• KEGG: hsa00280 - Valine
• leucine and isoleucine degradation
• KEGG: hsa00640 - Propanoate metabolism
• Reactome: R-HSA-71403 - Citric acid cycle (TCA cycle)
Protein Summary
The DLST protein (dihydrolipoamide S-succinyltransferase, E2) is a 453-amino acid mitochondrial enzyme that forms the core of the alpha-ketoglutarate dehydrogenase complex. It contains a lipoyl-binding domain, a peripheral subunit-binding domain, and a catalytic domain. The protein transfers succinyl groups from dihydrolipoamide to coenzyme A, producing succinyl-CoA. Post-translational modifications include lipoylation and acetylation, which regulate activity.
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