DLAT

dihydrolipoamide S-acetyltransferase, the group of Pyruvate dehydrogenase complex

Basic information

Region (hg38): 11:112025033-112064404

Previous symbols: [ "DLTA" ]

Links

ENSG00000150768 ∙ NCBI:1737 ∙ OMIM:608770 ∙ HGNC:2896 ∙ Uniprot:P10515 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• pyruvate dehydrogenase E2 deficiency (Definitive), mode of inheritance: AR
• pyruvate dehydrogenase E2 deficiency (Strong), mode of inheritance: AR
• pyruvate dehydrogenase E2 deficiency (Moderate), mode of inheritance: AR
• pyruvate dehydrogenase E2 deficiency (Strong), mode of inheritance: AR
• pyruvate dehydrogenase E2 deficiency (Supportive), mode of inheritance: AR
• Leigh syndrome (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pyruvate dehydrogenase E2 deficiency	AR	Biochemical	Medical treatment (eg, with lipoic acid, thiamine, and ketogenic diet) has been reported as resulting in marked clinical improvement	Biochemical; Neurologic	2112155; 2112155; 20022530; 22896851; 23021068

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DLAT gene.

• Pyruvate dehydrogenase E2 deficiency (5 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DLAT 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				53	2	55
missense		2	101	8	6	117
nonsense	3					3
start loss						0
frameshift	2	2	1			5
inframe indel			3			3
splice donor/acceptor (+/-2bp)		3				3
splice region		1	8	6	2	17
non coding			1	52	34	87
Total	5	7	106	113	42

Highest pathogenic variant AF is 0.00000658

Variants in DLAT

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

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

Position	Type	Phenotype	Significance	ClinVar
11-112025316-G-A			Likely benign (Oct 09, 2018)
11-112025317-C-G			Likely benign (Oct 09, 2018)
11-112025458-G-A			Likely benign (May 03, 2018)
11-112025481-C-T		Pyruvate dehydrogenase E2 deficiency	Likely benign (Sep 13, 2023)
11-112025492-G-T		Inborn genetic diseases	Uncertain significance (Mar 19, 2024)
11-112025504-A-C		Pyruvate dehydrogenase E2 deficiency	Uncertain significance (Jul 19, 2022)
11-112025518-G-A		not specified • Pyruvate dehydrogenase E2 deficiency	Benign (Jan 07, 2024)
11-112025526-C-A		Pyruvate dehydrogenase E2 deficiency	Likely benign (Jul 20, 2022)
11-112025527-G-C		not specified • Pyruvate dehydrogenase E2 deficiency • DLAT-related disorder	Benign (Jul 01, 2024)
11-112025550-G-A			Likely benign (Dec 19, 2018)
11-112025555-T-C			Uncertain significance (Feb 04, 2020)
11-112025570-G-A		Pyruvate dehydrogenase E2 deficiency	Uncertain significance (Aug 10, 2022)
11-112025579-C-G		Inborn genetic diseases	Uncertain significance (Oct 02, 2023)
11-112025581-C-G		Pyruvate dehydrogenase E2 deficiency	Conflicting classifications of pathogenicity (May 09, 2023)
11-112025600-C-T		not specified • Pyruvate dehydrogenase E2 deficiency	Benign (Feb 01, 2024)
11-112025603-G-T		Inborn genetic diseases	Uncertain significance (May 16, 2022)
11-112025616-G-A		Pyruvate dehydrogenase E2 deficiency	Likely benign (Dec 31, 2019)
11-112025618-C-T		Pyruvate dehydrogenase E2 deficiency	Uncertain significance (Oct 20, 2023)
11-112025632-G-T		Pyruvate dehydrogenase E2 deficiency	Uncertain significance (Nov 02, 2021)
11-112025637-C-G		not specified • Pyruvate dehydrogenase E2 deficiency	Conflicting classifications of pathogenicity (Oct 16, 2023)
11-112025639-G-C		Inborn genetic diseases • Pyruvate dehydrogenase E2 deficiency	Uncertain significance (Aug 02, 2022)
11-112025641-G-T		Pyruvate dehydrogenase E2 deficiency	Uncertain significance (Mar 29, 2022)
11-112025649-C-T		Pyruvate dehydrogenase E2 deficiency	Likely benign (Jan 20, 2023)
11-112025660-C-T		Pyruvate dehydrogenase E2 deficiency	Uncertain significance (Jun 05, 2022)
11-112025680-C-T		not specified	Uncertain significance (May 03, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DLAT	protein_coding	protein_coding	ENST00000280346	14	39577

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.30e-8	0.974	125702	0	46	125748	0.000183

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.417	338	360	0.938	0.0000176	4132
Missense in Polyphen		113	150.24	0.75212		1868
Synonymous	0.230	126	129	0.974	0.00000666	1377
Loss of Function	2.14	17	29.6	0.575	0.00000135	361

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000206	0.000206
Ashkenazi Jewish	0.00	0.00
East Asian	0.000110	0.000109
Finnish	0.0000929	0.0000924
European (Non-Finnish)	0.000212	0.000211
Middle Eastern	0.000110	0.000109
South Asian	0.000261	0.000261
Other	0.000666	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle.
• Disease: DISEASE: Note=Primary biliary cirrhosis is a chronic, progressive cholestatic liver disease characterized by the presence of antimitochondrial autoantibodies in patients' serum. It manifests with inflammatory obliteration of intra-hepatic bile duct, leading to liver cell damage and cirrhosis. Patients with primary biliary cirrhosis show autoantibodies against the E2 component of pyruvate dehydrogenase complex.; DISEASE: Pyruvate dehydrogenase E2 deficiency (PDHE2 deficiency) [MIM:245348]: Pyruvate dehydrogenase (PDH) deficiency is a major cause of primary lactic acidosis and neurological dysfunction in infancy and early childhood. In this form of PDH deficiency episodic dystonia is the major neurological manifestation, with other more common features of pyruvate dehydrogenase deficiency, such as hypotonia and ataxia, being less prominent. {ECO:0000269|PubMed:16049940}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Citrate cycle (TCA cycle) - Homo sapiens (human);Pyruvate metabolism - Homo sapiens (human);Glycolysis / Gluconeogenesis - Homo sapiens (human);Warburg Effect;Pyruvate Dehydrogenase Complex Deficiency;The oncogenic action of Succinate;The oncogenic action of Fumarate;Primary hyperoxaluria II, PH2;Pyruvate kinase deficiency;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;Leigh Syndrome;Glutaminolysis and Cancer;The oncogenic action of 2-hydroxyglutarate;Pyruvate Metabolism;The oncogenic action of L-2-hydroxyglutarate in Hydroxygluaricaciduria;The oncogenic action of D-2-hydroxyglutarate in Hydroxygluaricaciduria ;Pyruvate Decarboxylase E1 Component Deficiency (PDHE1 Deficiency);TCA Cycle and Deficiency of Pyruvate Dehydrogenase complex (PDHc);Glycolysis and Gluconeogenesis;Signal Transduction;Butanoate metabolism;Regulation of pyruvate dehydrogenase (PDH) complex;Pyruvate metabolism;Pyruvate metabolism and Citric Acid (TCA) cycle;Metabolism of amino acids and derivatives;The citric acid (TCA) cycle and respiratory electron transport;Glycolysis and Gluconeogenesis;Metabolism;pyruvate decarboxylation to acetyl CoA;Glyoxylate metabolism and glycine degradation;Pyruvate metabolism;Signaling by Retinoic Acid;Signaling by Nuclear Receptors;superpathway of conversion of glucose to acetyl CoA and entry into the TCA cycle (Consensus)

Recessive Scores

• pRec: 0.423

Intolerance Scores

• loftool: 0.919
• rvis_EVS: 0.36
• rvis_percentile_EVS: 74.63

Haploinsufficiency Scores

• pHI: 0.803
• hipred: Y
• hipred_score: 0.501
• ghis: 0.502

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.872

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Dlat

Zebrafish Information Network

• Gene name: dlat
• Affected structure: pigment cell
• Phenotype tag: abnormal
• Phenotype quality: quality

Gene ontology

• Biological process: glucose metabolic process;acetyl-CoA biosynthetic process from pyruvate;tricarboxylic acid cycle;sleep
• Cellular component: mitochondrion;mitochondrial matrix;mitochondrial pyruvate dehydrogenase complex;myelin sheath;pyruvate dehydrogenase complex
• Molecular function: dihydrolipoyllysine-residue acetyltransferase activity;protein binding;pyruvate dehydrogenase (NAD+) activity;identical protein binding