LIPT1

Chr 2AR

lipoyltransferase 1

Also known as: LIPT1D

NCBI Gene: 51601ENSG00000144182UniProt: Q9Y234

The process of transferring lipoic acid to proteins is a two-step process. The first step is the activation of lipoic acid by lipoate-activating enzyme to form lipoyl-AMP. For the second step, the protein encoded by this gene transfers the lipoyl moiety to apoproteins. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 13. Read-through transcription also exists between this gene and the neighboring downstream mitochondrial ribosomal protein L30 (MRPL30) gene. [provided by RefSeq, Mar 2011]

Primary Disease Associations & Inheritance

Lipoyltransferase 1 deficiencyMIM #616299
AR
157
ClinVar variants
23
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— LIPT1
🧬
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.
📋
ClinVar Variants
23 Pathogenic / Likely Pathogenic· 78 VUS of 157 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.71LOEUF
pLI 0.000
Z-score -0.20
OE 1.07 (0.67–1.71)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.34Z-score
OE missense 0.93 (0.82–1.05)
178 obs / 191.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.1.07 (0.67–1.71)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.93 (0.82–1.05)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.91
0≤1.21.6
LoF obs/exp: 11 / 10.3Missense obs/exp: 178 / 191.2Syn Z: 0.58

ClinVar Variant Classifications

157 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic13
Likely Pathogenic10
VUS78
Likely Benign27
Benign22
Conflicting7
13
Pathogenic
10
Likely Pathogenic
78
VUS
27
Likely Benign
22
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
12
0
13
Likely Pathogenic
0
3
7
0
10
VUS
3
68
7
0
78
Likely Benign
0
2
6
19
27
Benign
0
1
17
4
22
Conflicting
—7
Total3754923157

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

View in ClinVar →

Protein Context — Lollipop Plot

LIPT1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

LIPT1-related Leigh syndrome with secondary deficiency for pyruvate and alpha-ketoglutarate dehydrogenase

strong
ARUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Lipoyltransferase 1 deficiency

MIM #616299

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — LIPT1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Endoplasmic reticulum stress related super-enhancers suppress cuproptosis via glycolysis reprogramming in lung adenocarcinoma.
Gu Y et al.·Cell Death Dis
2025
Lipoic acid biosynthesis defects.
Mayr JA et al.·J Inherit Metab Dis
2014Review
Exploring and clinical validation of prognostic significance and therapeutic implications of copper homeostasis-related gene dysregulation in acute myeloid leukemia.
Abulimiti M et al.·Ann Hematol
2024
Engineered bacterial lipoate protein ligase A (lplA) restores lipoylation in cell models of lipoylation deficiency.
Bick NR et al.·J Biol Chem
2024Functional
Differential diagnosis of lipoic acid synthesis defects.
Tort F et al.·J Inherit Metab Dis
2016Review
Cuproptosis-Related Genes MTF1 and LIPT1 as Novel Prognostic Biomarker in Acute Myeloid Leukemia.
Li Y et al.·Biochem Genet
2024
System analysis based on the cuproptosis-related genes identifies LIPT1 as a novel therapy target for liver hepatocellular carcinoma.
Yan C et al.·J Transl Med
2022
LIPT1 deficiency presenting as early infantile epileptic encephalopathy, Leigh disease, and secondary pyruvate dehydrogenase complex deficiency.
Stowe RC et al.·Am J Med Genet A
2018Case report
Aberrant expression of cuproptosis‑related gene LIPT1 is associated with metabolic dysregulation of fatty acid and prognosis in hepatocellular carcinoma.
Li J et al.·J Cancer Res Clin Oncol
2023
Identification of Cuproptosis-Related Genes and Their Potential Role in COPD Pathogenesis: A Bioinformatics Analysis.
Shen Q et al.·Int J Chron Obstruct Pulmon Dis
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools