CPT2

Chr 1ADAR

carnitine palmitoyltransferase 2

Also known as: CPT1, CPTASE, IIAE4

NCBI Gene: 1376ENSG00000157184UniProt: P23786

The protein encoded by this gene is a nuclear protein which is transported to the mitochondrial inner membrane. Together with carnitine palmitoyltransferase I, the encoded protein oxidizes long-chain fatty acids in the mitochondria. Defects in this gene are associated with mitochondrial long-chain fatty-acid (LCFA) oxidation disorders. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

{Encephalopathy, acute, infection-induced, 4, susceptibility to}MIM #614212
ADAR
CPT II deficiency, infantileMIM #600649
AR
CPT II deficiency, lethal neonatalMIM #608836
AR
CPT II deficiency, myopathic, stress-inducedMIM #255110
ADAR
UniProtCarnitine palmitoyltransferase 2 deficiency, myopathic, stress-induced
UniProtCarnitine palmitoyltransferase 2 deficiency, infantile
UniProtCarnitine palmitoyltransferase 2 deficiency, lethal neonatal
0
Active trials
94
Pathogenic / LP
498
ClinVar variants
85
Pubs (1 yr)
0.4
Missense Z
1.17
LOEUF
Clinical Summary— CPT2
🧬
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.
📋
ClinVar Variants
94 Pathogenic / Likely Pathogenic· 182 VUS of 498 total submissions
📖
GeneReview available — CPT2
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.17LOEUF
pLI 0.000
Z-score 0.95
OE 0.78 (0.53–1.17)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.40Z-score
OE missense 0.94 (0.86–1.03)
337 obs / 358.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.78 (0.53–1.17)
0≤0.351.4
Missense OE0.94 (0.86–1.03)
0≤0.61.4
Synonymous OE1.12
0≤1.21.6
LoF obs/exp: 17 / 21.8Missense obs/exp: 337 / 358.1Syn Z: -1.17
LOFDN
DN
0.6163th %ile
GOF
0.4283th %ile
LOF
0.3260th %ile

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and dominant-negative). The Badonyi & Marsh model scores dominant-negative highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOF1 literature citation · 59% of P/LP variants are LoF
DN1 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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

498 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic48
Likely Pathogenic46
VUS182
Likely Benign218
Benign1
Conflicting3
48
Pathogenic
46
Likely Pathogenic
182
VUS
218
Likely Benign
1
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
25
2
21
0
48
Likely Pathogenic
30
5
11
0
46
VUS
3
166
7
6
182
Likely Benign
0
1
41
176
218
Benign
0
0
1
0
1
Conflicting
—3
Total5817481182498

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

View in ClinVar →

CPT2 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
SOX8/CPT2 axis regulates lipid metabolism to support enzalutamide resistance in prostate cancer.
Liu S et al.·Cancer Cell Int
2026
CPT2 inhibition enhances selective autophagy and proliferation in colorectal cancer via GPAT4-dependent glycerophospholipid biosynthesis.
Li K et al.·Commun Biol
2025Open Access
Porphyromonas gingivalis extracellular vesicles exacerbated osteoporosis by disrupting osteoblast mitochondrial dynamics and inhibiting Cpt2-regulated fatty acid oxidation.
Qiu Q et al.·J Nanobiotechnology
2025Open Access
SIRT3 mediates CPT2 delactylation to enhance mitochondrial function and proliferation in goat granulosa cells.
Song S et al.·J Anim Sci Biotechnol
2025Open Access
SLC44A2 negatively regulates mitochondrial fatty acid oxidation to suppress colorectal progression by blocking the MUL1-CPT2 interaction.
Yang Y et al.·Cell Death Dis
2025Open Access
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients