DLAT

Chr 11AR

dihydrolipoamide S-acetyltransferase

Also known as: DLTA, E2, PBC, PDC-E2, PDCE2

NCBI Gene: 1737 ENSG00000150768 UniProt: P10515 OMIM: 608770

Dihydrolipoamide acetyltransferase (E2 component) transfers acetyl groups from pyruvate to coenzyme A within the mitochondrial pyruvate dehydrogenase complex, which converts pyruvate to acetyl-CoA for energy metabolism. Autosomal recessive mutations cause pyruvate dehydrogenase E2 deficiency, resulting in primary lactic acidosis in infancy and early childhood due to impaired cellular energy production. The pathogenic mechanism involves defective mitochondrial pyruvate metabolism leading to lactate accumulation and metabolic acidosis.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes component E2 of the multi-enzyme pyruvate dehydrogenase complex (PDC). PDC resides in the inner mitochondrial membrane and catalyzes the conversion of pyruvate to acetyl coenzyme A. The protein product of this gene, dihydrolipoamide acetyltransferase, accepts acetyl groups formed by the oxidative decarboxylation of pyruvate and transfers them to coenzyme A. Dihydrolipoamide acetyltransferase is the antigen for antimitochondrial antibodies. These autoantibodies are present in nearly 95% of patients with the autoimmune liver disease primary biliary cirrhosis (PBC). In PBC, activated T lymphocytes attack and destroy epithelial cells in the bile duct where this protein is abnormally distributed and overexpressed. PBC enventually leads to cirrhosis and liver failure. Mutations in this gene are also a cause of pyruvate dehydrogenase E2 deficiency which causes primary lactic acidosis in infancy and early childhood.[provided by RefSeq, Oct 2009]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Pyruvate dehydrogenase E2 deficiencyMIM #245348

Clinical highlights

Gene-disease validity (ClinGen)

Leigh syndrome · ARModerateconsider for supplementary testing

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

274

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.86

LOEUF

LOF

Mechanism· G2P

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