LIAS

Chr 4AR

lipoic acid synthetase

This mitochondrial iron-sulfur enzyme catalyzes the final step in lipoic acid biosynthesis, a potent antioxidant essential for cellular metabolism. Mutations cause autosomal recessive hyperglycinemia, lactic acidosis, and seizures through loss of function. The condition presents with neonatal-onset epilepsy and metabolic derangements due to deficient lipoic acid synthesis.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
DNmechanismARLOEUF 0.841 OMIM phenotype
Clinical SummaryLIAS
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Gene-Disease Validity (ClinGen)
Leigh syndrome · ARLimited

Limited evidence — not for standalone diagnostic reporting

2 total gene-disease associations curated

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

Tolerant — LoF & missense variants common in population
LoF Constraint
0.84LOEUF
pLI 0.000
Z-score 2.11
OE 0.51 (0.320.84)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.25Z-score
OE missense 0.75 (0.660.86)
153 obs / 203.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.51 (0.320.84)
00.351.4
Missense OE0.75 (0.660.86)
00.61.4
Synonymous OE0.91
01.21.6
LoF obs/exp: 11 / 21.6Missense obs/exp: 153 / 203.3Syn Z: 0.62
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongLIAS-related neonatal-onset epilepsy, defective mitochondrial energy metabolism and glycine elevationOTHERAR

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

DN
0.75top 25%
GOF
0.4974th %ile
LOF
0.3648th %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

LIAS · 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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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗