LIPT2

Chr 11AR

lipoyl(octanoyl) transferase 2

NCBI Gene: 387787 ENSG00000175536 UniProt: A6NK58 OMIM: 617659

The protein catalyzes the transfer of octanoic acid to lipoate-dependent enzymes in mitochondria, which is essential for proper mitochondrial metabolism. Autosomal recessive mutations cause neonatal severe encephalopathy with lactic acidosis and brain abnormalities due to impaired mitochondrial function.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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. [provided by RefSeq, Aug 2016]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Encephalopathy, neonatal severe, with lactic acidosis and brain abnormalitiesMIM #617668

Clinical highlights

Gene–disease validity (ClinGen)

Limited · mitochondrial disease · AR · ClinGen 2024

not for standalone diagnostic reporting

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.94

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.94LOEUF

pLI 0.626

Z-score 1.64

OE 0.00 (0.00–0.94)

Moderately constrained

Typical tolerance to LoF variation

Missense Constraint?

-0.12Z-score

OE missense 1.04 (0.87–1.24)

85 obs / 81.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.94)

0≤0.351.4

Missense OE?1.04 (0.87–1.24)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 0 / 3.1Missense obs/exp: 85 / 81.9Syn Z: 0.08

Background carrier burden — how many people carry a rare variant somewhere in LIPT2?

gnomAD v4 · ~700k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

486 rare PASS variants

Rare truncating (LoF)

1 in 1,600

79 rare PASS variants

Rare synonymous (reference)

1 in 250

200 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for LIPT2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~540k	1 in 150	1 in 1,700
South Asian	~40k	1 in 190	1 in 5,000
Remaining (unassigned)	~29k	1 in 190	1 in 450
European (Finnish)	~25k	1 in 440	≈ 1 in 7,000
African / African American	~21k	1 in 110	1 in 360
East Asian	~18k	1 in 190	1 in 1,000
Admixed American	~18k	1 in 110	1 in 1,300
Ashkenazi Jewish	~13k	1 in 340	none seen
Middle Eastern	~2,850	1 in 140	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 1 of 2 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 2.? see exons ↓