LIPT2

lipoyl(octanoyl) transferase 2

Basic information

Region (hg38): 11:74490519-74493724

Links

ENSG00000175536 ∙ NCBI:387787 ∙ OMIM:617659 ∙ HGNC:37216 ∙ Uniprot:A6NK58 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• encephalopathy, neonatal severe, with lactic acidosis and brain abnormalities (Strong), mode of inheritance: AR
• lipoyl transferase 1 deficiency (Strong), mode of inheritance: AR
• encephalopathy, neonatal severe, with lactic acidosis and brain abnormalities (Limited), mode of inheritance: AR
• encephalopathy, neonatal severe, with lactic acidosis and brain abnormalities (Strong), mode of inheritance: AR
• encephalopathy, neonatal severe, with lactic acidosis and brain abnormalities (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Encephalopathy, neonatal severe, with lactic acidosis and brain abnormalities	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Neurologic	28757203

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LIPT2 gene.

• not_provided (84 variants)
• not_specified (49 variants)
• Encephalopathy,_neonatal_severe,_with_lactic_acidosis_and_brain_abnormalities (12 variants)
• LIPT2-related_disorder (8 variants)
• Early-onset_progressive_encephalopathy-hearing_loss-pons_hypoplasia-brain_atrophy_syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LIPT2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001144869.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	22	1	24
missense		3	84	3	1	91
nonsense						0
start loss		1				1
frameshift			2			2
splice donor/acceptor (+/-2bp)						0
Total	0	4	87	25	2

Highest pathogenic variant AF is 0.000299984

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LIPT2	protein_coding	protein_coding	ENST00000310109	2	2022

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.626	0.346	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.120	85	81.9	1.04	0.00000446	1385
Missense in Polyphen		18	26.941	0.66813		422
Synonymous	0.0827	38	38.7	0.983	0.00000237	530
Loss of Function	1.64	0	3.13	0.00	1.34e-7	62

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the transfer of endogenously produced octanoic acid from octanoyl-acyl-carrier-protein onto the lipoyl domains of lipoate-dependent enzymes, which catalyze essential redox reactions (PubMed:28757203). Lipoyl-ACP can also act as a substrate although octanoyl-ACP is likely to be the physiological substrate (By similarity). {ECO:0000250, ECO:0000269|PubMed:28757203}.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:28757203}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Lipoic acid metabolism - Homo sapiens (human);Metabolism of amino acids and derivatives;Metabolism;Glyoxylate metabolism and glycine degradation (Consensus)

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.813

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Lipt2

Gene ontology

• Biological process: protein lipoylation;cellular nitrogen compound metabolic process;positive regulation of oxygen metabolic process
• Cellular component: mitochondrion;mitochondrial matrix
• Molecular function: ligase activity;lipoyl(octanoyl) transferase activity;octanoyl transferase activity (acting on glycine-cleavage complex H protein)