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): 144 total — 1 likely-pathogenic
• GTEx eGene: eQTL in 45 tissues, sQTL in 0 (q < 0.05)
• Phenotypes (HPO): 30
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.95 (unconstrained)
• 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: 6 — 6 protein_coding

MANE Select: ENST00000310109

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 2: 2, TSL 3: 1

ENST00000310109, ENST00000527115, ENST00000528085, ENST00001120564, ENST00001120565, ENST00001143857

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.

Highest expression (Bgee): male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, testis, hindlimb stylopod muscle, calcaneal tendon.

Genetic regulation across tissues (GTEx eQTL / sQTL)

LIPT2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 45 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 45 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Skin Sun Exposed Lower leg	eqtl	2.0e-46	+0.51	11:74504237:G:A
Adipose Subcutaneous	eqtl	2.4e-46	+0.54	11:74494452:A:G
Skin Not Sun Exposed Suprapubic	eqtl	2.2e-39	+0.45	11:74489694:G:A
Muscle Skeletal	eqtl	5.3e-37	+0.30	11:74486857:G:A
Thyroid	eqtl	2.6e-32	+0.34	11:74491959:G:A
Nerve Tibial	eqtl	9.1e-30	+0.51	11:74494452:A:G
Artery Tibial	eqtl	2.5e-26	+0.48	11:74491959:G:A
Esophagus Mucosa	eqtl	3.4e-26	+0.35	11:74504237:G:A
Breast Mammary Tissue	eqtl	3.1e-25	+0.42	11:74504850:C:G
Cells Cultured fibroblasts	eqtl	6.3e-20	+0.46	11:74489694:G:A
Adipose Visceral Omentum	eqtl	7.4e-20	+0.34	11:74504237:G:A
Colon Transverse	eqtl	1.7e-18	+0.28	11:74489694:G:A
Stomach	eqtl	1.7e-18	+0.35	11:74489189:T:C
Lung	eqtl	1.1e-17	+0.25	11:74489694:G:A
Artery Aorta	eqtl	3.2e-15	+0.31	11:74504237:G:A
Heart Atrial Appendage	eqtl	1.3e-14	+0.31	11:74486281:A:C
Esophagus Gastroesophageal Junction	eqtl	2.0e-14	+0.36	11:74491959:G:A
Cells EBV-transformed lymphocytes	eqtl	3.0e-14	-0.44	11:74482113:A:G
Esophagus Muscularis	eqtl	9.9e-14	+0.31	11:74494471:T:A
Heart Left Ventricle	eqtl	2.3e-13	+0.36	11:74489694:G:A

FANTOM5 promoters

2 alternative TSS:

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

Top tissues by expression

showing 100 of 136 tissues 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
right uterine tube	UBERON:0001302	66.91	gold quality
gall bladder	UBERON:0002110	66.84	gold quality
liver	UBERON:0002107	66.64	gold quality
left adrenal gland	UBERON:0001234	66.59	gold quality
leukocyte	CL:0000738	66.57	gold quality
bone marrow	UBERON:0002371	66.53	gold quality
body of stomach	UBERON:0001161	66.36	gold quality
body of pancreas	UBERON:0001150	66.28	gold quality
endometrium	UBERON:0001295	66.21	gold quality
right ovary	UBERON:0002118	65.90	gold quality
metanephros cortex	UBERON:0010533	65.87	gold quality
small intestine	UBERON:0002108	65.84	gold quality
adrenal gland	UBERON:0002369	65.84	gold quality
small intestine Peyer’s patch	UBERON:0003454	65.83	gold quality
spleen	UBERON:0002106	65.79	gold quality
monocyte	CL:0000576	65.78	gold quality
bone marrow cell	CL:0002092	65.63	silver quality
vermiform appendix	UBERON:0001154	65.40	gold quality
ovary	UBERON:0000992	65.28	gold quality
stomach	UBERON:0000945	65.21	gold quality
left adrenal gland cortex	UBERON:0035825	65.10	gold quality
right lobe of thyroid gland	UBERON:0001119	65.05	gold quality
left lobe of thyroid gland	UBERON:0001120	65.00	gold quality
left uterine tube	UBERON:0001303	64.98	gold quality
mucosa of transverse colon	UBERON:0004991	64.97	gold quality
prefrontal cortex	UBERON:0000451	64.47	gold quality
thyroid gland	UBERON:0002046	64.37	gold quality
left ovary	UBERON:0002119	64.27	gold quality
esophagus mucosa	UBERON:0002469	64.14	gold quality
saliva-secreting gland	UBERON:0001044	63.94	gold quality
pituitary gland	UBERON:0000007	63.77	gold quality
stromal cell of endometrium	CL:0002255	63.74	gold quality
tonsil	UBERON:0002372	63.69	gold quality
right coronary artery	UBERON:0001625	63.62	gold quality
minor salivary gland	UBERON:0001830	63.55	gold quality
urinary bladder	UBERON:0001255	63.47	gold quality
adenohypophysis	UBERON:0002196	63.40	gold quality
mucosa of stomach	UBERON:0001199	63.29	gold quality
transverse colon	UBERON:0001157	63.28	gold quality
superior frontal gyrus	UBERON:0002661	62.93	gold quality
myometrium	UBERON:0001296	62.82	gold quality
intestine	UBERON:0000160	62.77	gold quality
right lung	UBERON:0002167	62.77	gold quality
fundus of stomach	UBERON:0001160	62.30	gold quality
material anatomical entity	UBERON:0000465	62.29	gold quality
multicellular organism	UBERON:0000468	62.29	gold quality
anatomical system	UBERON:0000467	62.28	gold quality
body of uterus	UBERON:0009853	62.23	gold quality
esophagus	UBERON:0001043	62.16	gold quality
heart left ventricle	UBERON:0002084	61.93	gold quality
prostate gland	UBERON:0002367	61.93	gold quality
blood	UBERON:0000178	61.58	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	61.54	gold quality
frontal cortex	UBERON:0001870	61.44	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	61.41	gold quality
colon	UBERON:0001155	61.38	gold quality
heart	UBERON:0000948	61.02	gold quality
cortical plate	UBERON:0005343	60.58	gold quality
thoracic mammary gland	UBERON:0005200	60.30	gold quality
lower esophagus	UBERON:0013473	60.04	gold quality
lower esophagus muscularis layer	UBERON:0035833	59.99	gold quality
endocervix	UBERON:0000458	59.87	gold quality
descending thoracic aorta	UBERON:0002345	59.86	gold quality
left coronary artery	UBERON:0001626	59.75	gold quality
cerebral cortex	UBERON:0000956	59.74	gold quality
nucleus accumbens	UBERON:0001882	59.69	gold quality
skin of abdomen	UBERON:0001416	59.67	gold quality
vagina	UBERON:0000996	59.35	gold quality
adipose tissue	UBERON:0001013	59.30	gold quality
subcutaneous adipose tissue	UBERON:0002190	59.20	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

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Skeletal muscle	tissue	7.5	medium
Frontal cortex	tissue	7.0
Tongue	tissue	6.6
Testis	tissue	6.2	high
Caudate putamen	tissue	4.7
Kidney	tissue	4.3	high
Nucleus accumbens	tissue	4.0
Hippocampus	tissue	4.0	high
Choroid plexus	tissue	3.6
Locus coeruleus	tissue	3.6
Cerebral cortex	tissue	3.5	high
Duodenum	tissue	3.5	high
Somatosensory cortex	tissue	3.5
Small intestine	tissue	3.4	high
Stomach 1	tissue	3.3	high
Hippocampal formation	tissue	3.3
Ovary	tissue	3.2	not detected
Occipital cortex	tissue	3.2
Postcentral gyrus	tissue	3.1
Temporal cortex	tissue	3.1
Epididymis	tissue	3.0	high
Entorhinal cortex	tissue	3.0
Fallopian tube	tissue	3.0	high
Amygdala	tissue	2.9
Superior colliculi	tissue	2.9
Prefrontal cortex	tissue	2.8
Thyroid gland	tissue	2.8	high
Retrosplenial and cingulate cortex	tissue	2.8
Pons	tissue	2.7
Pancreas	tissue	2.7	high
Motor cortex	tissue	2.7
Cerebellum	tissue	2.7
Septum	tissue	2.7
Insular cortex	tissue	2.7
Seminal vesicle	tissue	2.6	high
Basal ganglia	tissue	2.6	high
Thalamus	tissue	2.6
Ventral forebrain	tissue	2.6
Retrosplenial cortex	tissue	2.6
Midbrain	tissue	2.5
Thymus	tissue	2.5
Medulla oblongata	tissue	2.4
Hypothalamus	tissue	2.4
Periaqueductal gray	tissue	2.4
Breast	tissue	2.3	medium
Rectum	tissue	2.2	high
Putamen	tissue	2.2
Substantia nigra	tissue	2.2
Tonsil	tissue	2.1	medium
Pituitary gland	tissue	2.0
Lymph node	tissue	2.0	medium
Salivary gland	tissue	2.0	low
Parathyroid gland	tissue	2.0	high
Colon	tissue	2.0	high
Placenta	tissue	2.0	high
Spinal cord	tissue	2.0
Olfactory bulb	tissue	2.0
Bone marrow	tissue	1.9	medium
Retina	tissue	1.8
Gallbladder	tissue	1.8	high

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Occipital cortex (white matter) (7.8), Parahippocampal cortex (white matter) (7.6), Ventromedial nucleus (7.0), Dorsal funiculus (white matter) (6.8), Lateral funiculus (white matter) (6.2).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting LIPT2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 35 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 3.18e-08, LOEUF 1.95, missense Z -3.08 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000310109 — one region, missense o/e 1.22.

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

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1914414) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 20 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal heart morphology	1
abnormal heart looping	1
abnormal head morphology	1
abnormal somite shape	1
abnormal embryo size	1
pale yolk sac	1
abnormal neural tube morphology	1
abnormal chorioallantoic fusion	1
abnormal tail bud morphology	1
abnormal pharyngeal arch morphology	1
abnormal vitelline vasculature morphology	1
abnormal forebrain development	1
pallor	1
abnormal neural tube closure	1
abnormal midbrain development	1
embryonic growth retardation	1
abnormal limb bud morphology	1
abnormal hindbrain development	1
preweaning lethality, complete penetrance	1
embryonic lethality prior to tooth bud stage	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bacteroides fragilis NCTC 9343	Q5LDM3	99.5%	Diamond
Bacteroides fragilis YCH46	Q64UP8	99.5%	Diamond
Bacteroides thetaiotaomicron VPI-5482	Q8A8S8	85.0%	Diamond
Xenopus tropicalis	Q0VFH3	59.1%	Diamond
Schizosaccharomyces pombe 972h-	O36017	56.6%	Diamond
Maridesulfovibrio salexigens DSM 2638	C6BZY6	56.1%	Diamond
Arabidopsis thaliana	Q9SXP7	45.5%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
LIPT2-AS1	ncRNA	100287896
POLD3	protein-coding	10714
KCNE3	protein-coding	10008
MIR548AL	ncRNA	100616215

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)

• 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

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Metabolic proteins, Predicted intracellular proteins, Disease related genes, Potential drug targets, Human disease related genes, Congenital disorders of metabolism, Congenital disorders of cofactor/vitamin metabolism

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH approved

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)

Position	Role
185	acyl-thioester intermediate
151	lowers pka of active site cys

Ligand- & substrate-binding residues (3)

Position	Role
85–92	substrate
154–156	substrate
167–169	substrate

Mutagenesis-validated functional residues (1)

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

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 3; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

3 pathways:

ID	Pathway	Evidence
R-HSA-9857492	Protein lipoylation	curated
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 (2): protein lipoylation (GO:0009249), 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

2 top-level categories:

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

GO top-level categories

12 GO namespaces:

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

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 2 of 8 annotations. The rest are phylogenetic / computational / electronic (IEA).

2 experimentally-supported GO terms:

GO term	NS	Evidence
protein lipoylation	BP	mutant phenotype
mitochondrion	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 400 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LIPT2	LIPT1	Q9Y234	898
LIPT2	LIAS	O43766	868
LIPT2	GCSH	P23434	833
LIPT2	DLAT	P10515	743
LIPT2	SLC31A1	O15431	737
LIPT2	ATP7B	P35670	734
LIPT2	PDHB	P11177	722
LIPT2	FDX1	P10109	720
LIPT2	PDHA1	P08559	717
LIPT2	NFU1	Q9UMS0	667
LIPT2	GLS	O94925	650
LIPT2	ATP7A	Q04656	646
LIPT2	IBA57	Q5T440	644
LIPT2	GLS2	Q9UI32	633
LIPT2	ISCA2	Q86U28	628

IntAct

Human interaction partners of LIPT2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

1 partners by confidence:

Partner	Interaction type	MIscore	Records
ST14	association	0.350	1

BioGRID (7 interactions; top human partners by supporting records): BAP1 (Negative Genetic), BCAR1 (Affinity Capture-MS), EGFR (Negative Genetic), KRAS (Negative Genetic), RIT1 (Negative Genetic), ST14 (Affinity Capture-MS)

Disease & clinical

Genetic variants

Variant evidence for LIPT2: 144 ClinVar records (1 pathogenic / likely pathogenic); 1 GWAS association. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	95
Likely benign	29
Benign	10

Top pathogenic / likely-pathogenic (1)

Showing all 1 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
2502311	NM_001144869.3(LIPT2):c.1A>T (p.Met1Leu)	Likely pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore LIPT2’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 21 predictions of 220):

Position(s)	Effect	Δscore	Sites
11:74492365–74492366	acceptor_loss	0.9900	6
11:74493236–74493237	donor_loss	0.9800	6
11:74492367	acceptor_loss	0.9700
11:74493218	donor_gain	0.9600
11:74493233	donor_loss	0.9600
11:74493211	donor_gain	0.9400
11:74493233	donor_loss	0.9400	2
11:74492374	acceptor_loss	0.8000
11:74493234	donor_loss	0.8000
11:74492428	acceptor_gain	0.7700

AlphaMissense

436 missense substitutions predicted likely pathogenic (of 1,441 scored), across 125 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
H166	8	0.901	0.959
H92	8	0.895	0.977
N171	8	0.876	0.989
F216	8	0.863	0.967
F179	7	0.970	0.990
F91	7	0.957	0.994
W146	7	0.939	0.975
C185	7	0.928	0.967
K151	7	0.903	0.975
C172	7	0.856	0.973
Q96	7	0.840	0.957
G167	6	0.899	0.969
G144	6	0.886	0.951
E120	6	0.880	0.977
C153	6	0.877	0.984
G60	6	0.868	0.936
R85	6	0.860	0.972
W178	6	0.849	0.923
H115	6	0.845	0.922
C127	6	0.845	0.928

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Colon Adenocarcinoma (TCGA)	favorable	0.000169
Pancreatic Adenocarcinoma (validation)	favorable	0.00031
Colon Adenocarcinoma (validation)	unfavorable	0.000381

Disease associations

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

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
encephalopathy, neonatal severe, with lactic acidosis and brain abnormalities	Strong	Autosomal recessive	5
lipoyl transferase 1 deficiency	Strong	Autosomal recessive

ClinGen Gene-Disease Validity

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

1 validity classifications:

Disease	Classification	Inheritance
mitochondrial disease	Limited	AR

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (12 panels, 6 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

12 panels:

Panel	Rating
DDG2P	green
Fetal anomalies	green
Likely inborn error of metabolism	green
Mitochondrial disorders	green
Possible mitochondrial disorder, nuclear genes	green
Pyruvate dehydrogenase (PDH) deficiency	green
Early onset or syndromic epilepsy	amber
Hypotonic infant	amber
Intellectual disability	amber
Leukodystrophy, childhood onset	amber
Paediatric disorders	amber
Unexplained death in infancy and sudden unexplained death in childhood	amber

Mondo (2): encephalopathy, neonatal severe, with lactic acidosis and brain abnormalities (MONDO:0060562), lipoyl transferase 1 deficiency (MONDO:0014576)

Orphanet (1): Lipoyl transferase 2 deficiency (Orphanet:447795)

HPO phenotypes

30 phenotypes (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:

Study	Trait	p-value
GCST008829_1	Neuritic plaque	1e-6

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0006798	neuritic plaque measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

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 expression, decreases response to substance	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)

Via MONDO — disease-level, not drug-specific.