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CPT2
carnitine palmitoyltransferase 2
The CPT2 gene provides instructions for making carnitine palmitoyltransferase 2, an enzyme vital for metabolising fatty acids into energy, particularly for muscles and during fasting. The CPT2 gene encodes the enzyme carnitine palmitoyltransferase 2, which is critical for fatty acid oxidation, a process that converts fats into usable energy for the body.
CPT2 is located on the short (p) arm of chromosome 1, at band 1p32.3. Arm ratio per GRCh38 - banding schematic.
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Overview
The CPT2 gene provides the genetic blueprint for carnitine palmitoyltransferase 2, an enzyme that plays a central role in the body's energy production. This enzyme facilitates fatty acid oxidation, a multi-step metabolic pathway that breaks down fats to generate energy.
Fats, particularly long-chain fatty acids, are a significant energy source for various tissues, including the heart and skeletal muscles. During prolonged periods without food, fatty acids also become a crucial energy supply for the liver and other organs.
What the gene does
The carnitine palmitoyltransferase 2 enzyme, encoded by the CPT2 gene, is integral to the process of fatty acid oxidation, which occurs within the mitochondria, the energy-producing organelles in cells. Specifically, it enables long-chain fatty acids to be transported into the mitochondrial matrix where they can be metabolised.
Before entering the mitochondria, long-chain fatty acids must first bind to a molecule called carnitine. Once this complex is inside the mitochondria, carnitine palmitoyltransferase 2 removes the carnitine from the fatty acid and attaches coenzyme A instead. This attachment to coenzyme A is a necessary step, preparing the fatty acid for subsequent metabolic reactions that will convert it into energy.
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Chromosome location
The CPT2 gene is located on chromosome 1, specifically within the short arm (p) at position 32.3. This genomic address, 1p32.3, precisely pinpoints the gene's physical position within the human genome.
Protein structure
The protein encoded by the CPT2 gene is carnitine palmitoyltransferase 2, which consists of 658 amino acids. Domain architecture has not been experimentally characterised in detail for this protein.
Key variants
Variants within the CPT2 gene can alter the function of the carnitine palmitoyltransferase 2 enzyme. These genetic changes can affect the enzyme's ability to process fatty acids, potentially disrupting the body's energy metabolism. Such variants are inherited in an autosomal recessive pattern.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.1143_1144del | p.Arg382fs | Pathogenic/Likely pathogenic | ★★☆☆ | Carnitine palmitoyltransferase II deficiency |
c.1273_1274del | p.Thr425fs | Pathogenic | ★★☆☆ | Carnitine palmitoyltransferase II deficiency |
c.1444_1447del | p.Thr482fs | Pathogenic | ★★☆☆ | Carnitine palmitoyltransferase II deficiency |
c.1528_1529del | p.Lys510fs | Pathogenic/Likely pathogenic | ★★☆☆ | Carnitine palmitoyltransferase II deficiency |
c.1741C>T | p.Gln581Ter | Pathogenic | ★★☆☆ | Carnitine palmitoyltransferase II deficiency |
c.1806del | p.Phe602fs | Pathogenic/Likely pathogenic | ★★☆☆ | Carnitine palmitoyltransferase II deficiency |
c.340+1G>C | - | Pathogenic/Likely pathogenic | ★★☆☆ | CPT2-related disorder |
c.595_596del | p.Leu199fs | Pathogenic/Likely pathogenic | ★★☆☆ | Carnitine palmitoyltransferase II deficiency |
c.646C>T | p.Gln216Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Carnitine palmitoyltransferase II deficiency |
c.975_976del | p.Cys326fs | Pathogenic/Likely pathogenic | ★★☆☆ | Carnitine palmitoyltransferase II deficiency |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Pathogenic variants in the CPT2 gene are known to cause Carnitine palmitoyltransferase II deficiency. This condition impairs the body's capacity to utilise certain fats for energy, leading to a range of health issues. Symptoms often manifest during fasting or periods of increased energy demand.
Inheritance pattern
Conditions caused by pathogenic CPT2 variants typically follow autosomal recessive inheritance.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
UK clinical status
In the UK, the CPT2 gene is included on several NHS national genomic testing panels, reflecting its clinical significance. It is recognised in panels for Acute rhabdomyolysis (R419), Foetal anomalies (R21), Hyperammonaemia, Likely inborn error of metabolism (R98), Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies (R82), Paediatric or syndromic cardiomyopathy (R135), Rhabdomyolysis and metabolic muscle disorders, and Undiagnosed metabolic disorders.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What does the CPT2 gene do?
The CPT2 gene provides instructions for making an enzyme called carnitine palmitoyltransferase 2. This enzyme is crucial for breaking down fatty acids into energy, especially for the heart and muscles, and during fasting periods.
What is Carnitine palmitoyltransferase II deficiency?
Carnitine palmitoyltransferase II deficiency is a condition caused by changes in the CPT2 gene. It prevents the body from effectively using certain fats as an energy source, which can lead to various health problems, particularly during fasting.
How is CPT2 gene variation inherited?
Variants in the CPT2 gene that cause Carnitine palmitoyltransferase II deficiency are inherited in an autosomal recessive pattern. This means an individual must inherit two copies of the altered gene (one from each parent) to develop the condition.
References
- Corti S, Bordoni A, Ronchi D. Clinical features and new molecular findings in Carnitine Palmitoyltransferase II (CPT II) deficiency. Journal of the neurological sciences. 2008. PMID: 17936304
- Isackson PJ, Bennett MJ, Lichter-Konecki U. CPT2 gene mutations resulting in lethal neonatal or severe infantile carnitine palmitoyltransferase II deficiency. Molecular genetics and metabolism. 2008. PMID: 18550408
- Illsinger S, Lücke T, Peter M. Carnitine-palmitoyltransferase 2 deficiency: novel mutations and relevance of newborn screening. American journal of medical genetics. Part A. 2008. PMID: 18925671
- Longo N, Amat di San Filippo C, Pasquali M. Disorders of carnitine transport and the carnitine cycle. American journal of medical genetics. Part C, Seminars in medical genetics. 2006. PMID: 16602102
- Ørngreen MC, Dunø M, Ejstrup R. Fuel utilization in subjects with carnitine palmitoyltransferase 2 gene mutations. Annals of neurology. 2005. PMID: 15622536
- Deschauer M, Wieser T, Zierz S. Muscle carnitine palmitoyltransferase II deficiency: clinical and molecular genetic features and diagnostic aspects. Archives of neurology. 2005. PMID: 15642848
- Ramsay RR, Zammit VA. Carnitine acyltransferases and their influence on CoA pools in health and disease. Molecular aspects of medicine. 2004. PMID: 15363637
- Olpin SE, Afifi A, Clark S. Mutation and biochemical analysis in carnitine palmitoyltransferase type II (CPT II) deficiency. Journal of inherited metabolic disease. 2003. PMID: 14605500
- Sigauke E, Rakheja D, Kitson K. Carnitine palmitoyltransferase II deficiency: a clinical, biochemical, and molecular review. Laboratory investigation; a journal of technical methods and pathology. 2003. PMID: 14615409
- Adam MP, Bick S, Mirzaa GM. Carnitine Palmitoyltransferase II Deficiency. 1993. PMID: 20301431