LIPT1

lipoyltransferase 1

Basic information

Region (hg38): 2:99154955-99163157

Links

ENSG00000144182 ∙ NCBI:51601 ∙ OMIM:610284 ∙ HGNC:29569 ∙ Uniprot:Q9Y234 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• lipoyl transferase 1 deficiency (Strong), mode of inheritance: AR
• lipoyl transferase 1 deficiency (Moderate), mode of inheritance: AR
• Leigh syndrome with leukodystrophy (Supportive), mode of inheritance: AR
• lipoyl transferase 1 deficiency (Supportive), mode of inheritance: AR
• lipoyl transferase 1 deficiency (Strong), mode of inheritance: AR
• Leigh syndrome (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Lipoyltransferase 1 deficiency	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	24256811; 24341803

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LIPT1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LIPT1 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				18	4	22
missense		1	44		1	46
nonsense		2	1			3
start loss		1				1
frameshift			4			4
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding				4	12	16
Total	0	4	49	22	17

Variants in LIPT1

This is a list of pathogenic ClinVar variants found in the LIPT1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-99155036-C-T			Likely benign (Aug 01, 2018)
2-99155039-C-T		not specified	Likely benign (Dec 27, 2017)
2-99155070-C-T		not specified	Benign (Dec 02, 2015)
2-99155118-C-T			Likely benign (Jun 29, 2018)
2-99155127-G-T			Benign (Jun 29, 2018)
2-99155218-G-C			Benign (Jun 29, 2018)
2-99155507-C-A			Benign (Jul 22, 2019)
2-99156388-C-T		not specified	Benign (Feb 05, 2018)
2-99156389-G-A		not specified	Benign (Mar 01, 2016)
2-99156412-T-C		not specified	Benign (Dec 04, 2015)
2-99156738-T-G			Benign (Jun 29, 2018)
2-99156969-A-G			Benign (Jun 29, 2018)
2-99158360-A-C			Benign (Jun 29, 2018)
2-99158468-C-A			Benign (Jun 29, 2018)
2-99161677-GA-G			Benign (Oct 09, 2018)
2-99161958-A-T		LIPT1-related disorder	Benign/Likely benign (Dec 01, 2022)
2-99161959-T-C			Likely pathogenic (Oct 24, 2019)
2-99162014-C-T			Likely benign (Oct 04, 2023)
2-99162029-T-TA			Conflicting classifications of pathogenicity (Jun 14, 2022)
2-99162066-A-G			Uncertain significance (Nov 11, 2022)
2-99162066-A-T		Inborn genetic diseases	Uncertain significance (Oct 03, 2022)
2-99162078-G-A			Uncertain significance (Sep 27, 2022)
2-99162088-A-G		Lipoyl transferase 1 deficiency • Inborn genetic diseases	Likely pathogenic (Aug 05, 2022)
2-99162097-T-C			Uncertain significance (Aug 17, 2022)
2-99162107-G-T			Uncertain significance (Apr 25, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LIPT1	protein_coding	protein_coding	ENST00000393477	1	8203

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.83e-8	0.109	125468	0	274	125742	0.00109

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.340	178	191	0.931	0.00000895	2480
Missense in Polyphen		52	60.578	0.85839		772
Synonymous	0.582	62	68.1	0.910	0.00000312	700
Loss of Function	-0.196	11	10.3	1.07	4.30e-7	151

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000632	0.000630
Ashkenazi Jewish	0.00278	0.00278
East Asian	0.000163	0.000163
Finnish	0.000142	0.000139
European (Non-Finnish)	0.00188	0.00187
Middle Eastern	0.000163	0.000163
South Asian	0.000295	0.000294
Other	0.000492	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the transfer of the lipoyl group from lipoyl- AMP to the specific lysine residue of lipoyl domains of lipoate- dependent enzymes. {ECO:0000250}.
• Pathway: Lipoic acid metabolism - Homo sapiens (human);Metabolism of amino acids and derivatives;Metabolism;lipoate salvage;Glyoxylate metabolism and glycine degradation;lipoate biosynthesis and incorporation (Consensus)

Recessive Scores

• pRec: 0.182

Intolerance Scores

• loftool: 0.143
• rvis_EVS: -0.27
• rvis_percentile_EVS: 34.32

Haploinsufficiency Scores

• pHI: 0.125
• hipred: N
• hipred_score: 0.350
• ghis: 0.433

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.00158

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Lipt1

Gene ontology

• Biological process: cellular protein modification process;lipid metabolic process;protein lipoylation;cellular nitrogen compound metabolic process
• Cellular component: mitochondrion;mitochondrial matrix
• Molecular function: transferase activity, transferring acyl groups