CPT2

Chr 1ADAR

carnitine palmitoyltransferase 2

Also known as: CPT1, CPTASE, IIAE4

The protein is transported to the mitochondrial inner membrane where it works with carnitine palmitoyltransferase I to oxidize long-chain fatty acids. Mutations cause CPT II deficiency with autosomal recessive inheritance, presenting as lethal neonatal, infantile, or myopathic stress-induced forms, as well as susceptibility to acute infection-induced encephalopathy with autosomal dominant inheritance. The pathogenic mechanism involves impaired mitochondrial long-chain fatty acid oxidation.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismAD/ARLOEUF 1.174 OMIM phenotypes
Clinical SummaryCPT2
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Gene-Disease Validity (ClinGen)
carnitine palmitoyltransferase II deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.17LOEUF
pLI 0.000
Z-score 0.95
OE 0.78 (0.531.17)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.40Z-score
OE missense 0.94 (0.861.03)
337 obs / 358.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.78 (0.531.17)
00.351.4
Missense OE0.94 (0.861.03)
00.61.4
Synonymous OE1.12
01.21.6
LoF obs/exp: 17 / 21.8Missense obs/exp: 337 / 358.1Syn Z: -1.17
DN
0.6163th %ile
GOF
0.4283th %ile
LOF
0.3260th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and loss-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DN1 literature citation
LOF1 literature citation

Literature Evidence

DNIn vitro studies by Yao et al. (2008) demonstrated that the F352C/V368I variant proteins exerted a dominant-negative effect on the CPT2 homotetramer and had shortened half-lives compared to wildtype, consistent with intracellular instability.PMID:18306170
LOFThe heterozygous knockout of CPT2 resulted in thymus FAO haploinsufficiency and an approximately 30% improvement in survival time, paralleling the antiproliferative signaling observed with MB disruption.PMID:32958587

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

CPT2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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