DLD

Chr 7AR

dihydrolipoamide dehydrogenase

Also known as: DLDD, DLDH, E3, GCSL, LAD, OGDC-E3, PHE3

NCBI Gene: 1738 ENSG00000091140 UniProt: P09622 OMIM: 238331

The protein functions as a dehydrogenase in homodimeric form within mitochondrial multi-enzyme complexes that regulate energy metabolism, and as a protease in monomeric form. Mutations cause dihydrolipoamide dehydrogenase deficiency and E3-deficient maple syrup urine disease through an autosomal recessive inheritance pattern. The pathogenic mechanism involves dominant-negative effects.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a member of the class-I pyridine nucleotide-disulfide oxidoreductase family. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. In homodimeric form, the encoded protein functions as a dehydrogenase and is found in several multi-enzyme complexes that regulate energy metabolism. However, as a monomer, this protein can function as a protease. Mutations in this gene have been identified in patients with E3-deficient maple syrup urine disease and lipoamide dehydrogenase deficiency. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Dihydrolipoamide dehydrogenase deficiencyMIM #246900

Clinical highlights

Gene-disease validity (ClinGen)

Leigh syndrome · ARDefinitivesufficient evidence for diagnostic panels2 gene-disease associations curated in total

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

667

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.55

LOEUF

LOF

Mechanism· G2P

📖