DLD

Chr 7AR

dihydrolipoamide dehydrogenase

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.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismARLOEUF 0.551 OMIM phenotype
Clinical SummaryDLD
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Gene-Disease Validity (ClinGen)
Leigh syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.
Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.55LOEUF
pLI 0.010
Z-score 3.42
OE 0.31 (0.190.55)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.10Z-score
OE missense 0.81 (0.730.91)
220 obs / 270.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.31 (0.190.55)
00.351.4
Missense OE0.81 (0.730.91)
00.61.4
Synonymous OE1.05
01.21.6
LoF obs/exp: 9 / 28.8Missense obs/exp: 220 / 270.9Syn Z: -0.34
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveDLD-related dihydrolipoamide dehydrogenase E3 deficiencyLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.7327th %ile
GOF
0.6735th %ile
LOF
0.3355th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

DLD · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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