DLST
dihydrolipoamide S-succinyltransferase
Basic information
Region (hg38): 14:74881891-74903743
Previous symbols: [ "DLTS" ]
Links
Phenotypes
GenCC
Source:
- pheochromocytoma/paraganglioma syndrome 7 (Limited), mode of inheritance: AD
- hereditary pheochromocytoma-paraganglioma (Supportive), mode of inheritance: AD
- pyruvate dehydrogenase E1-alpha deficiency (No Known Disease Relationship), mode of inheritance: AR
- pheochromocytoma/paraganglioma syndrome 7 (Limited), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Pheochromocytoma/paraganglioma syndrome 7 | AD | Oncologic | The condition can involve increased risk of certain types of neoplasms, and awareness may allow early detection and management, which can reduce morbidity and mortality | Oncologic | 30929736 |
ClinVar
This is a list of variants' phenotypes submitted to
- not_provided (77 variants)
- not_specified (50 variants)
- DLST-related_disorder (12 variants)
- Pheochromocytoma/paraganglioma_syndrome_7 (3 variants)
- Hereditary_pheochromocytoma-paraganglioma (1 variants)
- Oxoglutaricaciduria (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the DLST gene is commonly pathogenic or not. These statistics are base on transcript: NM_000001933.5. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 13 | |||||
| missense | 71 | 77 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 1 | 0 | 78 | 8 | 4 |
Highest pathogenic variant AF is 0.000004956359
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| DLST | protein_coding | protein_coding | ENST00000334220 | 15 | 21855 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.485 | 0.515 | 125741 | 0 | 7 | 125748 | 0.0000278 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.585 | 239 | 266 | 0.899 | 0.0000145 | 2915 |
| Missense in Polyphen | 82 | 106.38 | 0.7708 | 1143 | ||
| Synonymous | -0.778 | 103 | 93.4 | 1.10 | 0.00000515 | 933 |
| Loss of Function | 3.53 | 5 | 23.4 | 0.213 | 0.00000108 | 284 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.0000993 | 0.0000992 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.0000463 | 0.0000462 |
| European (Non-Finnish) | 0.0000352 | 0.0000352 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000327 | 0.0000327 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Dihydrolipoamide succinyltransferase (E2) component of the 2-oxoglutarate dehydrogenase complex (By similarity). The 2- oxoglutarate dehydrogenase complex catalyzes the overall conversion of 2-oxoglutarate to succinyl-CoA and CO(2) (By similarity). The 2-oxoglutarate dehydrogenase complex is mainly active in the mitochondrion (PubMed:29211711). 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 (PubMed:29211711). {ECO:0000250|UniProtKB:Q9N0F1, ECO:0000269|PubMed:29211711}.;
- Pathway
- Citrate cycle (TCA cycle) - Homo sapiens (human);Lysine degradation - Homo sapiens (human);Warburg Effect;Lysine Degradation;Hyperlysinemia I, Familial;The oncogenic action of Succinate;The oncogenic action of Fumarate;2-aminoadipic 2-oxoadipic aciduria;Pyruvate dehydrogenase deficiency (E3);Pyruvate dehydrogenase deficiency (E2);2-ketoglutarate dehydrogenase complex deficiency;Mitochondrial complex II deficiency;Fumarase deficiency;Congenital lactic acidosis;Citric Acid Cycle;Pyridoxine dependency with seizures;Saccharopinuria/Hyperlysinemia II;Glutaminolysis and Cancer;The oncogenic action of 2-hydroxyglutarate;Glutaric Aciduria Type I;The oncogenic action of L-2-hydroxyglutarate in Hydroxygluaricaciduria;The oncogenic action of D-2-hydroxyglutarate in Hydroxygluaricaciduria ;Hyperlysinemia II or Saccharopinuria;TCA Cycle and Deficiency of Pyruvate Dehydrogenase complex (PDHc);Amino Acid metabolism;TCA Cycle;Citrate cycle;Lysine catabolism;Citric acid cycle (TCA cycle);Pyruvate metabolism and Citric Acid (TCA) cycle;Histidine, lysine, phenylalanine, tyrosine, proline and tryptophan catabolism;Metabolism of amino acids and derivatives;The citric acid (TCA) cycle and respiratory electron transport;Metabolism;TCA cycle;Lysine metabolism;TCA cycle;Glyoxylate metabolism and glycine degradation;superpathway of conversion of glucose to acetyl CoA and entry into the TCA cycle;2-oxoglutarate decarboxylation to succinyl-CoA
(Consensus)
Recessive Scores
- pRec
- 0.466
Intolerance Scores
- loftool
- 0.476
- rvis_EVS
- -0.71
- rvis_percentile_EVS
- 14.57
Haploinsufficiency Scores
- pHI
- hipred
- Y
- hipred_score
- 0.699
- ghis
- 0.563
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- E
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.995
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Dlst
- Phenotype
- nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); homeostasis/metabolism phenotype; growth/size/body region phenotype;
Zebrafish Information Network
- Gene name
- dlst
- Affected structure
- nucleate erythrocyte
- Phenotype tag
- abnormal
- Phenotype quality
- decreased amount
Gene ontology
- Biological process
- generation of precursor metabolites and energy;tricarboxylic acid cycle;2-oxoglutarate metabolic process;succinyl-CoA metabolic process;L-lysine catabolic process to acetyl-CoA via saccharopine;histone succinylation
- Cellular component
- nucleus;mitochondrion;mitochondrial matrix;membrane;myelin sheath;oxoglutarate dehydrogenase complex
- Molecular function
- dihydrolipoyllysine-residue succinyltransferase activity;protein binding