DLD

Chr 7

dihydrolipoamide dehydrogenase

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

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]

GeneReviewsResearchGenerating clinical summary…
LOFmechanismLOEUF 0.55
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.
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ClinVar Variants
144 unique Pathogenic / Likely Pathogenic· 177 VUS of 745 total submissions
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GeneReview available — DLD
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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 OE?0.31 (0.190.55)
00.351.4
Missense OE?0.81 (0.730.91)
00.61.4
Synonymous OE?1.05
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

This gene — mechanism propensity

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

745 submitted variants in ClinVar

Classification Summary

Pathogenic38
Likely Pathogenic106
VUS177
Likely Benign349
Benign38
Conflicting23
38
Pathogenic
106
Likely Pathogenic
177
VUS
349
Likely Benign
38
Benign
23
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
30
3
5
0
38
Likely Pathogenic
92
13
1
0
106
VUS
2
136
33
6
177
Likely Benign
0
4
173
172
349
Benign
0
0
34
4
38
Conflicting
23
Total124156246182731

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

20 pathogenic / likely-pathogenic (of 26) ClinVar copy-number / structural variants overlap DLD — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

DLD · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →