DLAT

Chr 11AR

dihydrolipoamide S-acetyltransferase

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

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.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.861 OMIM phenotype
Clinical SummaryDLAT
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Gene-Disease Validity (ClinGen)
Leigh syndrome · ARModerate

Moderate evidence — consider for supplementary testing

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.86LOEUF
pLI 0.000
Z-score 2.14
OE 0.58 (0.390.86)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.42Z-score
OE missense 0.94 (0.861.03)
338 obs / 360.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.58 (0.390.86)
00.351.4
Missense OE0.94 (0.861.03)
00.61.4
Synonymous OE0.97
01.21.6
LoF obs/exp: 17 / 29.6Missense obs/exp: 338 / 360.3Syn Z: 0.23
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveDLAT-related pyruvate dehydrogenase E2 deficiencyLOFAR

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

DN
0.6840th %ile
GOF
0.5954th %ile
LOF
0.3940th %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

DLAT · 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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