DLST

dihydrolipoamide S-succinyltransferase

Basic information

Region (hg38): 14:74881891-74903743

Previous symbols: [ "DLTS" ]

Links

ENSG00000119689 ∙ NCBI:1743 ∙ OMIM:126063 ∙ HGNC:2911 ∙ Uniprot:P36957 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• paragangliomas 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
• paragangliomas 7 (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

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 ClinVar and linked to the DLST gene.

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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				2	2	4
missense			33	2	2	37
nonsense				1		1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1	1		2
non coding			3	7	5	15
Total	0	0	36	12	9

Variants in DLST

This is a list of pathogenic ClinVar variants found in the DLST region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
14-74881944-C-T		DLST-related disorder	Likely benign (Jun 20, 2019)
14-74881947-C-A		DLST-related disorder	Likely benign (Mar 31, 2022)
14-74881948-G-A			Uncertain significance (Nov 03, 2021)
14-74881950-C-G			Uncertain significance (Jun 01, 2021)
14-74881960-T-C		not specified	Uncertain significance (Sep 22, 2023)
14-74881961-C-T		not specified	Uncertain significance (Nov 10, 2024)
14-74881963-C-G		not specified	Uncertain significance (Sep 30, 2024)
14-74881964-G-A			Uncertain significance (Jul 01, 2022)
14-74881965-A-G		DLST-related disorder	Uncertain significance (Nov 17, 2023)
14-74881969-C-A		not specified	Uncertain significance (Nov 10, 2024)
14-74881981-C-T		not specified	Uncertain significance (Sep 26, 2024)
14-74881989-C-T			Likely benign (Jan 20, 2024)
14-74882598-G-A		not specified	Uncertain significance (Mar 13, 2023)
14-74882601-C-T		DLST-related disorder	Uncertain significance (Feb 20, 2024)
14-74885599-C-G		not specified	Uncertain significance (May 18, 2022)
14-74885633-G-A		DLST-related disorder	Likely benign (Dec 18, 2023)
14-74889078-G-A			Likely benign (Feb 01, 2024)
14-74889078-G-C			Conflicting classifications of pathogenicity (Jan 09, 2024)
14-74889305-C-T		not specified	Uncertain significance (Apr 12, 2022)
14-74889365-C-CT			Likely benign (Dec 30, 2023)
14-74889367-A-T			Likely benign (Jan 25, 2024)
14-74889888-T-C			Uncertain significance (Jan 28, 2024)
14-74889938-A-G		DLST-related disorder	Uncertain significance (Oct 04, 2022)
14-74889971-C-T			Benign (Jan 30, 2024)
14-74891062-G-T			Uncertain significance (Nov 03, 2021)

GnomAD

Source: gnomAD

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: dbNSFP

• 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

• 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