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10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
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LIPT2
lipoyl(octanoyl) transferase 2
Chromosome 11 Β· 11q13.4
NCBI Gene: 387787Ensembl: ENSG00000175536.7HGNC: HGNC:37216UniProt: A6NK58
14PubMed Papers
21Diseases
0Drugs
2Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein lipoylationmitochondrionlipoyl(octanoyl) transferase activitymitochondrial matrixOsteopetrosis with renal tubular acidosiscardiomyopathyearly-onset progressive encephalopathy-hearing loss-pons hypoplasia-brain atrophy syndromecancer
✦AI Summary

LIPT2 (lipoyl(octanoyl) transferase 2) is a mitochondrial enzyme that catalyzes the transfer of octanoic acid from octanoyl-acyl-carrier-protein (octanoyl-ACP) to lipoyl domains of lipoate-dependent enzymes, initiating lipoic acid assembly on protein cofactors 1. This process is essential for lipoylating the H protein of the glycine cleavage system and the E2 subunits of alpha-ketoglutarate dehydrogenase, which are critical for mitochondrial energy metabolism 23. LIPT2 functions as part of a three-enzyme pathway with LIAS and LIPT1 that synthesizes and attaches lipoic acid cofactors to five redox-active enzymatic complexes 3. Mutations in LIPT2 cause severe neonatal encephalopathy with lactic acidosis and brain abnormalities, reflecting the vital role of lipoic acid in cellular respiration 4. In Huntington's disease, LIPT2 degradation via the E3 ubiquitin ligase NEDD4L impairs mitochondrial function and neuronal survival; restoring LIPT2 levels or supplementing lipoic acid mitigates disease phenotypes 2. Emerging evidence indicates LIPT2 dysregulation may influence cancer progression and prognosis across multiple tumor types 56. LIPT2 represents a targetable node in lipoic acid metabolism for treating mitochondrial and neurodegenerative diseases 7.

Sources cited
1
LIPT2 encodes an octanoyl transferase that initiates lipoyl group assembly on cognate enzyme proteins
PMID: 29987032
2
LIPT2 degradation in Huntington's disease impairs lipoic acid biosynthesis and alpha-ketoglutarate dehydrogenase lipoylation; LIPT2 overexpression or lipoic acid supplementation mitigates neurodegeneration
PMID: 40663606
3
LIPT2 catalyzes octanoic acid transfer as part of the three-step lipoate synthesis pathway essential for five redox enzymes in mitochondrial and amino acid metabolism
PMID: 24777537
4
LIPT2 mutations cause lipoic acid synthesis defects associated with severe mitochondrial metabolic disorders presenting in infancy
PMID: 27586888
5
LIPT2 is dramatically overexpressed in most cancers and has differential prognostic significance across cancer types
PMID: 38129565
6
LIPT2 is a cuproptosis-related gene differentially expressed in glioma with potential biomarker and therapeutic significance
PMID: 40355831
7
Bacterial lipoate protein ligases can functionally compensate for LIPT2 deficiency and rescue mitochondrial dysfunction in animal models
PMID: 41337580
Disease Associationsβ“˜21
Osteopetrosis with renal tubular acidosisOpen Targets
0.77Strong
cardiomyopathyOpen Targets
0.21Weak
early-onset progressive encephalopathy-hearing loss-pons hypoplasia-brain atrophy syndromeOpen Targets
0.12Weak
cancerOpen Targets
0.08Suggestive
neoplasmOpen Targets
0.08Suggestive
benign colon neoplasmOpen Targets
0.06Suggestive
Huntington diseaseOpen Targets
0.04Suggestive
glioblastoma multiformeOpen Targets
0.03Suggestive
muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 10Open Targets
0.03Suggestive
gliomaOpen Targets
0.03Suggestive
benign neoplasmOpen Targets
0.02Suggestive
hepatocellular carcinomaOpen Targets
0.01Suggestive
lung adenocarcinomaOpen Targets
0.01Suggestive
bladder transitional cell carcinomaOpen Targets
0.01Suggestive
neonatal encephalopathyOpen Targets
0.01Suggestive
cholangiocarcinomaOpen Targets
0.01Suggestive
esophageal carcinomaOpen Targets
0.01Suggestive
pancreatic adenocarcinomaOpen Targets
0.01Suggestive
retinoblastomaOpen Targets
0.01Suggestive
Testicular Germ Cell TumorOpen Targets
0.01Suggestive
Encephalopathy, neonatal severe, with lactic acidosis and brain abnormalitiesUniProt
Pathogenic Variants2
NM_001144869.3(LIPT2):c.314T>G (p.Leu105Arg)Pathogenic
Encephalopathy, neonatal severe, with lactic acidosis and brain abnormalities|not provided
β˜…β˜…β˜†β˜†2020β†’ Residue 105
NM_001144869.3(LIPT2):c.1A>T (p.Met1Leu)Likely pathogenic
Encephalopathy, neonatal severe, with lactic acidosis and brain abnormalities
β˜…β˜†β˜†β˜†β†’ Residue 1
View on ClinVar β†—
Related Genes
GCSHProtein interaction92%FASNProtein interaction92%MECRProtein interaction92%OXSMProtein interaction92%NFU1Protein interaction77%ART3Protein interaction72%
Tissue Expression6 tissues
Liver
100%
Bone Marrow
73%
Heart
64%
Ovary
64%
Brain
57%
Lung
36%
Gene Interaction Network
Click a node to explore
LIPT2GCSHFASNMECROXSMNFU1ART3
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt A6NK58
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
1.95LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF1.69 [1.09–1.95]
RankingsWhere LIPT2 stands among ~20K protein-coding genes
  • #15,908of 20,598
    Most Researched14
  • #4,578of 5,498
    Most Pathogenic Variants2
  • #17,701of 17,882
    Most Constrained (LOEUF)1.95
Genes detectedLIPT2
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
NEDD4L induces mitochondrial dysfunction and neurodegeneration by promoting LIPT2 degradation in Huntington's disease.
PMID: 40663606
Proc Natl Acad Sci U S A Β· 2025
1.00
2
Comprehensive analysis of the potential biological significance of cuproptosis-related gene LIPT2 in pan-cancer prognosis and immunotherapy.
PMID: 38129565
Sci Rep Β· 2023
0.90
3
Lipoic acid biosynthesis defects.
PMID: 24777537
J Inherit Metab Dis Β· 2014
0.80
4
Targeting multiple genetic defects of mitochondrial diseases with a single bacterial lipoate protein ligase.
PMID: 41337580
Sci Adv Β· 2025
0.70
5
Protein moonlighting elucidates the essential human pathway catalyzing lipoic acid assembly on its cognate enzymes.
PMID: 29987032
Proc Natl Acad Sci U S A Β· 2018
0.60