LIPT2

Summary

LIPT2 (lipoyl(octanoyl) transferase 2, HGNC:37216) is a protein-coding gene on chromosome 11q13.4, encoding Octanoyl-[acyl-carrier-protein]:protein N-octanoyltransferase LIPT2, mitochondrial (A6NK58). Catalyzes the transfer of endogenously produced octanoic acid from octanoyl-acyl-carrier-protein (octanoyl-ACP) onto the lipoyl domains of lipoate-dependent enzymes such as the protein H of the glycine cleavage system (GCSH).

This gene encodes a mitochondrial protein that catalyzes the transfer of octanoic acid to lipoate-dependent enzymes such as octanoyl-ACP. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 387787 — RefSeq curated summary.

At a glance

• Gene–disease (curated): encephalopathy, neonatal severe, with lactic acidosis and brain abnormalities (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 142 total — 1 likely-pathogenic
• Phenotypes (HPO): 30
• MANE Select transcript: NM_001144869

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:37216
Approved symbol	LIPT2
Name	lipoyl(octanoyl) transferase 2
Location	11q13.4
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000175536
Ensembl biotype	protein_coding
OMIM	617659
Entrez	387787

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000310109, ENST00000527115, ENST00000528085

RefSeq mRNA: 3 — MANE Select: NM_001144869 NM_001144869, NM_001329941, NM_001329942

CCDS: CCDS44679

Canonical transcript exons

ENST00000310109 — 2 exons

Exon	Start	End
ENSE00001184042	74490519	74492364
ENSE00001325760	74493238	74493724

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 80.77.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 2.0836 / max 39.5547, expressed in 960 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
121320	1.4598	771
121319	0.6238	354

Top tissues by expression

136 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.77	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.40	gold quality
left testis	UBERON:0004533	77.77	gold quality
hindlimb stylopod muscle	UBERON:0004252	77.63	gold quality
testis	UBERON:0000473	77.56	gold quality
right testis	UBERON:0004534	76.89	gold quality
calcaneal tendon	UBERON:0003701	76.64	gold quality
muscle of leg	UBERON:0001383	74.07	gold quality
gastrocnemius	UBERON:0001388	72.80	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	72.75	gold quality
duodenum	UBERON:0002114	72.19	gold quality
placenta	UBERON:0001987	71.02	gold quality
skeletal muscle tissue	UBERON:0001134	70.92	gold quality
adult mammalian kidney	UBERON:0000082	70.87	gold quality
islet of Langerhans	UBERON:0000006	70.79	gold quality
granulocyte	CL:0000094	70.76	gold quality
kidney	UBERON:0002113	69.93	gold quality
right lobe of liver	UBERON:0001114	69.32	gold quality
cortex of kidney	UBERON:0001225	69.32	gold quality
adrenal tissue	UBERON:0018303	69.05	gold quality
ventricular zone	UBERON:0003053	68.66	gold quality
rectum	UBERON:0001052	68.31	gold quality
fallopian tube	UBERON:0003889	68.20	gold quality
right adrenal gland cortex	UBERON:0035827	68.02	gold quality
right adrenal gland	UBERON:0001233	67.92	gold quality
muscle tissue	UBERON:0002385	67.91	gold quality
pancreas	UBERON:0001264	67.62	gold quality
apex of heart	UBERON:0002098	67.60	gold quality
ganglionic eminence	UBERON:0004023	67.49	gold quality
lymph node	UBERON:0000029	67.34	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-6058	no	55.69
E-ANND-3	no	2.86

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

35 targeting LIPT2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4458	99.96	71.64	1650
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-5580-3P	99.70	69.41	2052
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-4687-3P	99.48	66.41	968
HSA-MIR-4519	99.48	66.10	859
HSA-MIR-491-5P	99.13	65.98	1468
HSA-MIR-222-5P	98.75	69.17	1242
HSA-MIR-5094	98.63	67.11	1062
HSA-MIR-3670	97.88	64.39	763

Literature-anchored findings (GeneRIF, showing 1)

• The authors report on the identification of biallelic LIPT2 mutations in three affected individuals from two families with severe neonatal encephalopathy where a normalization of lipoylation was observed after expression of wild-type LIPT2, arguing for LIPT2 requirement in intramitochondrial lipoate synthesis. (PMID:28757203)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	lipt2	ENSDARG00000069852
mus_musculus	Lipt2	ENSMUSG00000030725
rattus_norvegicus	Lipt2	ENSRNOG00000016906
drosophila_melanogaster	Lipt2	FBGN0037251
caenorhabditis_elegans		WBGENE00003066

Protein

Protein identifiers

Octanoyl-[acyl-carrier-protein]:protein N-octanoyltransferase LIPT2, mitochondrial — A6NK58 (reviewed: A6NK58)

Alternative names: Lipoate-protein ligase B, Lipoyl/octanoyl transferase, Lipoyltransferase 2, Octanoyl-[acyl-carrier-protein]-protein N-octanoyltransferase

All UniProt accessions (3): A6NK58, H0YC96, H0YD50

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the transfer of endogenously produced octanoic acid from octanoyl-acyl-carrier-protein (octanoyl-ACP) onto the lipoyl domains of lipoate-dependent enzymes such as the protein H of the glycine cleavage system (GCSH). Lipoyl-ACP can also act as a substrate although octanoyl-ACP is likely to be the physiological substrate.

Subcellular location. Mitochondrion.

Disease relevance. Encephalopathy, neonatal severe, with lactic acidosis and brain abnormalities (NELABA) [MIM:617668] An autosomal recessive disorder characterized by severe encephalopathy with neonatal onset, metabolic features including lactic acidosis, little or no psychomotor development, and brain abnormalities including cerebral atrophy, cysts, and white matter abnormalities. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Protein modification; protein lipoylation via endogenous pathway; protein N(6)-(lipoyl)lysine from octanoyl-[acyl-carrier-protein]: step 1/2.

Miscellaneous. In the reaction, the free carboxyl group of octanoic acid is attached via an amide linkage to the epsilon-amino group of a specific lysine residue of lipoyl domains of lipoate-dependent enzymes.

Similarity. Belongs to the LipB family.

RefSeq proteins (3): NP_001138341, NP_001316870, NP_001316871 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000544	Octanoyltransferase	Family
IPR004143	BPL_LPL_catalytic	Domain
IPR045864	aa-tRNA-synth_II/BPL/LPL	Homologous_superfamily

Pfam: PF21948

Enzyme classification (BRENDA):

• EC 2.3.1.181 — lipoyl(octanoyl) transferase (BRENDA: 14 organisms, 31 substrates, 1 inhibitors, 3 Km, 2 kcat entries)

Substrate kinetics (BRENDA)

3 substrates with measured Km, best-characterized 3. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
APO-H PROTEIN	0.0132	1
LIPOYL-[ACYL-CARRIER PROTEIN]	0.001	1
OCTANOYL-[ACYL-CARRIER PROTEIN]	0.0102	1

Catalyzed reactions (Rhea), 1 shown:

• octanoyl-[ACP] + L-lysyl-[protein] = N(6)-octanoyl-L-lysyl-[protein] + holo-[ACP] + H(+) (RHEA:17665)

UniProt features (12 total): sequence variant 3, binding site 3, transit peptide 1, chain 1, mutagenesis site 1, domain 1, active site 1, site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NK58-F1	93.37	0.87

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2): 185 (acyl-thioester intermediate); 151 (lowers pka of active site cys)

Ligand- & substrate-binding residues (3): 85–92; 154–156; 167–169

Mutagenesis-validated functional residues (1):

Position	Phenotype
1–31	mislocalization to the cytosol; induces apoptotic cell death.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-9857492	Protein lipoylation
R-HSA-392499	Metabolism of proteins
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 166 (showing top): chr11q13, GOBP_PEPTIDYL_LYSINE_MODIFICATION, GOBP_PROTEIN_MATURATION, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM6, GOCC_MITOCHONDRIAL_MATRIX, GOMF_ACYLTRANSFERASE_ACTIVITY, REACTOME_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, FEVR_CTNNB1_TARGETS_DN, ARID5B_TARGET_GENES, FOXD2_TARGET_GENES, KAT2A_TARGET_GENES, KAT5_TARGET_GENES, NAB2_TARGET_GENES, NFKBIA_TARGET_GENES, NPAT_TARGET_GENES

GO Biological Process (3): protein lipoylation (GO:0009249), obsolete positive regulation of oxygen metabolic process (GO:2000376), protein modification process (GO:0036211)

GO Molecular Function (4): ligase activity (GO:0016874), lipoyl(octanoyl) transferase activity (GO:0033819), transferase activity (GO:0016740), acyltransferase activity (GO:0016746)

GO Cellular Component (2): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Post-translational protein modification	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
catalytic activity	2
peptidyl-lysine modification	1
protein maturation	1
protein metabolic process	1
macromolecule modification	1
acyltransferase activity, transferring groups other than amino-acyl groups	1
catalytic activity, acting on a protein	1
transferase activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

608 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LIPT2	LIPT1	Q9Y234	913
LIPT2	LIAS	O43766	846
LIPT2	NFU1	Q9UMS0	771
LIPT2	SMIM34	A8MWV9	716
LIPT2	A0A1W2PS29	A0A1W2PS29	684
LIPT2	BOLA3	Q53S33	669
LIPT2	A0A1W2PPQ1	A0A1W2PPQ1	664
LIPT2	GCSH	P23434	664
LIPT2	IBA57	Q5T440	646
LIPT2	MECR	Q9BV79	592
LIPT2	ISCA2	Q86U28	591
LIPT2	PDHX	O00330	543
LIPT2	TPK1	Q9H3S4	542
LIPT2	DLAT	P10515	531
LIPT2	MYBPH	Q13203	505

IntAct

2 interactions, top by confidence:

A	B	Type	Score
ST14	LIPT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (7): LIPT2 (Affinity Capture-MS), LIPT2 (Affinity Capture-MS), LIPT2 (Negative Genetic), LIPT2 (Negative Genetic), LIPT2 (Negative Genetic), LIPT2 (Negative Genetic), LIPT2 (Protein-peptide)

ESM2 similar proteins: A1A4L8, A2BDX3, A4RPM5, A5GFZ6, A6NK58, B4FAT0, B4NXF7, B6TNK6, O19179, O43323, O95396, O95571, P19971, P55203, P85971, Q02846, Q05922, Q08DH8, Q0VFH3, Q14BV6, Q17CA7, Q1WNP0, Q3KQV9, Q3TW96, Q3UQ84, Q561R2, Q58E95, Q5PQQ1, Q5ZKI2, Q61488, Q66JK4, Q6PAT0, Q7PY41, Q86U10, Q8AWD2, Q8NFV4, Q8VBZ0, Q8VDG5, Q923K4, Q96EY9

Diamond homologs: A0LIW0, A0LTE0, A0M5H7, A0PNH8, A0QEY7, A0R074, A1KKQ9, A1TB25, A1UIB3, A1VF78, A3MW04, A3Q1S7, A4J246, A4QFS2, A4TBJ9, A4XA20, A4XHV1, A5CQA0, A5FIL6, A5GAC4, A5GJ90, A5MZJ0, A5U4P5, A5US49, A6GYW1, A6L9E1, A6NK58, A6TWD0, A8LYF4, A9NDX7, B0K3J8, B0K8D0, B0RE23, B1VZM4, B2HHL3, B2IVM2, B5EDZ5, B6IZL5, B6J7S2, B8G783

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

142 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	96
Likely benign	28
Benign	10

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2502311	NM_001144869.3(LIPT2):c.1A>T (p.Met1Leu)	Likely pathogenic

SpliceAI

322 predictions. Top by Δscore:

Variant	Effect	Δscore
11:74492362:CTC:C	acceptor_gain	1.0000
11:74492365:C:CC	acceptor_gain	0.9900
11:74493231:CGCT:C	donor_loss	0.9900
11:74493232:GCTC:G	donor_loss	0.9900
11:74493233:CTCA:C	donor_loss	0.9900
11:74493234:TCA:T	donor_loss	0.9900
11:74493235:CA:C	donor_loss	0.9900
11:74493236:A:AC	donor_gain	0.9900
11:74493237:C:CC	donor_gain	0.9900
11:74493237:C:CG	donor_loss	0.9900
11:74492364:CCTG:C	acceptor_loss	0.9800
11:74492365:C:CG	acceptor_loss	0.9800
11:74492366:T:A	acceptor_loss	0.9800
11:74492363:TC:T	acceptor_gain	0.9700
11:74492364:CC:C	acceptor_gain	0.9700
11:74493237:CCGAT:C	donor_gain	0.9700
11:74492367:G:C	acceptor_loss	0.9600
11:74493218:C:A	donor_gain	0.9600
11:74492360:GACTC:G	acceptor_gain	0.9500
11:74493211:G:C	donor_gain	0.9500
11:74493214:ACCGC:A	donor_gain	0.9300
11:74493215:CCGCC:C	donor_gain	0.9300
11:74493208:TCAGG:T	donor_gain	0.9200
11:74493216:CGCCC:C	donor_gain	0.9200
11:74492361:ACTC:A	acceptor_gain	0.8800
11:74492362:CTCC:C	acceptor_gain	0.8800
11:74492363:TCCT:T	acceptor_gain	0.8800
11:74493303:T:TA	donor_gain	0.8200
11:74492374:A:T	acceptor_loss	0.7800
11:74493150:T:TA	donor_gain	0.7800

AlphaMissense

1441 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:74493431:G:C	F91L	0.994
11:74493431:G:T	F91L	0.994
11:74493433:A:G	F91L	0.994
11:74492294:A:C	F179L	0.990
11:74492294:A:T	F179L	0.990
11:74492296:A:G	F179L	0.990
11:74492318:G:C	N171K	0.989
11:74492318:G:T	N171K	0.989
11:74493245:G:C	C153W	0.984
11:74493344:C:A	E120D	0.977
11:74493344:C:G	E120D	0.977
11:74493430:G:C	H92D	0.977
11:74493246:C:T	C153Y	0.975
11:74493251:C:A	K151N	0.975
11:74493251:C:G	K151N	0.975
11:74493266:C:A	W146C	0.975
11:74493266:C:G	W146C	0.975
11:74492315:G:C	C172W	0.973
11:74493247:A:G	C153R	0.972
11:74493336:G:T	A123D	0.972
11:74493451:G:T	R85S	0.972
11:74492295:A:C	F179C	0.971
11:74492364:C:T	G156E	0.971
11:74492251:A:G	S194P	0.970
11:74492331:C:T	G167D	0.969
11:74493535:A:C	Y57D	0.969
11:74492340:G:T	T164K	0.968
11:74492183:A:C	F216L	0.967
11:74492183:A:T	F216L	0.967
11:74492185:A:G	F216L	0.967

dbSNP variants (sampled 300 via entrez): RS1000313437 (11:74490696 TA>T,TAA), RS1000601574 (11:74491077 T>C), RS1000663254 (11:74492703 T>A,C), RS1000716548 (11:74492840 C>T), RS1001033723 (11:74495067 T>A,C), RS1001717042 (11:74491437 C>A,T), RS1001765713 (11:74493862 C>T), RS1002980598 (11:74490097 G>A), RS1003244204 (11:74495713 A>G,T), RS1003785594 (11:74491457 G>A), RS1003831909 (11:74494377 C>T), RS1004183103 (11:74494138 C>G,T), RS1004852304 (11:74495437 C>T), RS1004902928 (11:74495658 G>A), RS1005499670 (11:74494609 T>A)

Disease associations

OMIM: gene MIM:617659 | disease phenotypes: MIM:617668, MIM:617669

GenCC curated gene-disease

Disease	Classification	Inheritance
encephalopathy, neonatal severe, with lactic acidosis and brain abnormalities	Strong	Autosomal recessive
lipoyl transferase 1 deficiency	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
mitochondrial disease	Limited	AR

Mondo (3): encephalopathy, neonatal severe, with lactic acidosis and brain abnormalities (MONDO:0060562), early-onset progressive encephalopathy-hearing loss-pons hypoplasia-brain atrophy syndrome (MONDO:0044696), lipoyl transferase 1 deficiency (MONDO:0014576)

Orphanet (2): Lipoyl transferase 2 deficiency (Orphanet:447795), Early-onset progressive encephalopathy-hearing loss-pons hypoplasia-brain atrophy syndrome (Orphanet:500144)

HPO phenotypes

30 total (30 of 30 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001285	Spastic tetraparesis
HP:0001298	Encephalopathy
HP:0001332	Dystonia
HP:0001344	Absent speech
HP:0001522	Death in infancy
HP:0002093	Respiratory insufficiency
HP:0002119	Ventriculomegaly
HP:0002120	Cerebral cortical atrophy
HP:0002151	Increased circulating lactate concentration
HP:0002154	Hyperglycinemia
HP:0002188	Delayed CNS myelination
HP:0002194	Delayed gross motor development
HP:0003128	Lactic acidosis
HP:0003348	Hyperalaninemia
HP:0003542	Increased circulating pyruvate concentration
HP:0003623	Neonatal onset
HP:0006956	Lateral ventricle dilatation
HP:0007109	Periventricular cysts
HP:0008936	Axial hypotonia
HP:0009879	Simplified gyral pattern
HP:0011968	Feeding difficulties
HP:0012707	Elevated brain lactate level by MRS
HP:0012736	Profound global developmental delay
HP:0031518	Absent posterior alpha rhythm
HP:6000830	Diminished alpha-ketoglutarate dehydrogenase activity in cultured fibroblasts

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008829_1	Neuritic plaque	1.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006798	neuritic plaque measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aminomethylphosphonic acid (AMPA)	decreases expression	1
propionaldehyde	decreases expression	1
sodium arsenite	affects expression	1
ferrous chloride	decreases expression	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Potassium Chloride	decreases expression, decreases response to substance	1
Dronabinol	decreases response to substance, decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1
2,4-Dichlorophenoxyacetic Acid	decreases expression	1
Cadmium Chloride	decreases expression	1
Acrylamide	decreases expression	1
Particulate Matter	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E2B5	HAP1 LIPT2 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.