LIPT1

Chr 2AR

lipoyltransferase 1

Also known as: LIPT1D

NCBI Gene: 51601 ENSG00000144182 OMIM: 610284

The protein transfers lipoyl moieties to apoproteins in the second step of lipoic acid attachment to mitochondrial proteins. Mutations cause lipoyltransferase 1 deficiency, which is inherited in an autosomal recessive pattern. The pathogenic mechanism involves impaired lipoylation of mitochondrial enzyme complexes that require lipoic acid as a cofactor for proper function.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

The process of transferring lipoic acid to proteins is a two-step process. The first step is the activation of lipoic acid by lipoate-activating enzyme to form lipoyl-AMP. For the second step, the protein encoded by this gene transfers the lipoyl moiety to apoproteins. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 13. Read-through transcription also exists between this gene and the neighboring downstream mitochondrial ribosomal protein L30 (MRPL30) gene. [provided by RefSeq, Mar 2011]

GeneReviews OMIM ResearchGenerating clinical summary…

ARLOEUF 1.711 OMIM phenotype

Clinical Summary— LIPT1

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Gene-Disease Validity (ClinGen)

Leigh syndrome · ARModerate

Moderate evidence — consider for supplementary testing

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

7 unique Pathogenic / Likely Pathogenic· 73 VUS of 140 total submissions

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GeneReview available — LIPT1

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.71LOEUF

pLI 0.000

Z-score -0.20

OE 1.07 (0.67–1.71)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.34Z-score

OE missense 0.93 (0.82–1.05)

178 obs / 191.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.07 (0.67–1.71)

0≤0.351.4

Missense OE?0.93 (0.82–1.05)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 11 / 10.3Missense obs/exp: 178 / 191.2Syn Z: 0.58

ClinVar Variant Classifications

140 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

Likely Pathogenic6

VUS73

Likely Benign27

Benign22

Conflicting7

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	1	0	0	1
Likely Pathogenic	3	3	0	0	6
VUS	4	68	1	0	73
Likely Benign	0	2	6	19	27
Benign	0	1	17	4	22
Conflicting	—				7
Total	7	75	24	23	136

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

16 pathogenic / likely-pathogenic (of 21) ClinVar copy-number / structural variants overlap LIPT1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →