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CPT1A
carnitine palmitoyltransferase 1A
The CPT1A gene provides instructions for producing an enzyme crucial for the body's ability to convert fats into energy, particularly during periods of fasting. CPT1A encodes carnitine palmitoyltransferase 1A, a liver enzyme essential for fatty acid oxidation, the process of breaking down fats for energy.
CPT1A is located on the long (q) arm of chromosome 11, at band 11q13.3. Arm ratio per GRCh38 - banding schematic.
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Overview
The CPT1A gene contains the genetic blueprint for carnitine palmitoyltransferase 1A, an enzyme predominantly found in the liver. This enzyme plays a vital role in metabolising fats, converting them into a usable energy source for the body. This process, known as fatty acid oxidation, is especially important when the body requires energy during fasting periods.
Disruptions to the CPT1A gene's function can lead to metabolic disorders, impacting the body's capacity to properly utilise long-chain fatty acids for energy.
What the gene does
The carnitine palmitoyltransferase 1A enzyme, encoded by the CPT1A gene, is critical for facilitating fatty acid oxidation within liver cells. Specifically, it enables long-chain fatty acids to enter the mitochondria, which are the cell's energy-producing organelles. Before entry, these long-chain fatty acids must be bound to carnitine.
CPT1A acts by connecting carnitine to the long-chain fatty acids, forming a complex that can then cross the inner mitochondrial membrane. Once inside the mitochondria, the carnitine is detached, allowing the fatty acids to undergo further metabolic breakdown to generate energy. This pathway is crucial for providing energy when glucose reserves are low, such as during prolonged fasting.
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Chromosome location
The CPT1A gene is located on chromosome 11, specifically at position 11q13.3. This chromosomal address indicates its precise position on the long arm (q) of chromosome 11. Its presence at this location means it is inherited with other genetic material found in this region.
Protein structure
Domain architecture has not been experimentally characterised in detail for this protein.
Key variants
Variants within the CPT1A gene can alter the production or function of the carnitine palmitoyltransferase 1A enzyme. These genetic changes often lead to a reduction in the enzyme's activity, impairing the body's ability to metabolise long-chain fatty acids effectively.
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.1573dup | p.Glu525fs | Pathogenic | ★★☆☆ | Carnitine palmitoyl transferase 1A deficiency |
c.1593_1594del | p.Glu531fs | Pathogenic/Likely pathogenic | ★★☆☆ | CPT1A-related disorder |
c.1762_1766dup | p.Tyr589Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Carnitine palmitoyl transferase 1A deficiency |
c.1879G>T | p.Glu627Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Carnitine palmitoyl transferase 1A deficiency |
c.2T>G | p.Met1Arg | Pathogenic/Likely pathogenic | ★★☆☆ | Carnitine palmitoyl transferase 1A deficiency |
c.405G>A | p.Trp135Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Carnitine palmitoyl transferase 1A deficiency |
c.562C>T | p.Gln188Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Carnitine palmitoyl transferase 1A deficiency |
c.657G>A | p.Trp219Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Carnitine palmitoyl transferase 1A deficiency |
c.704G>A | p.Trp235Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Carnitine palmitoyl transferase 1A deficiency |
c.740C>T | p.Pro247Leu | Pathogenic/Likely pathogenic | ★★☆☆ | Carnitine palmitoyl transferase 1A 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 CPT1A gene are primarily associated with Carnitine Palmitoyltransferase I Deficiency, a condition where the body struggles to use certain fats for energy. This deficiency can cause significant health problems, particularly during fasting. Additionally, some CPT1A gene variants may increase the risk for other serious liver conditions, such as acute fatty liver of pregnancy (AFLP), which can progress rapidly to liver failure.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic CPT1A 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
The CPT1A gene is considered in UK clinical genomics, with several panels listing it. It is included on NHS Genomic Medicine Service panels for Hyperammonaemia, Likely inborn error of metabolism, and Undiagnosed metabolic disorders, all with a 'green' status indicating their clinical utility.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the role of the CPT1A gene?
The CPT1A gene provides instructions for making an enzyme called carnitine palmitoyltransferase 1A, which is vital for breaking down fats into energy. This process is particularly important for the liver during periods of fasting.
What happens if the CPT1A gene doesn't work correctly?
If the CPT1A gene has variants that affect its function, the body may struggle to convert long-chain fatty acids into energy. This can lead to Carnitine Palmitoyltransferase I Deficiency, a metabolic condition with potential health issues, especially during fasting.
Is CPT1A deficiency an inherited condition?
Yes, Carnitine Palmitoyltransferase I Deficiency is typically inherited in an autosomal recessive pattern. This means an individual must inherit two copies of a variant CPT1A gene, one from each parent, to develop the condition.
References
- Akkaoui M, Cohen I, Esnous C. Modulation of the hepatic malonyl-CoA-carnitine palmitoyltransferase 1A partnership creates a metabolic switch allowing oxidation of de novo fatty acids. The Biochemical journal. 2009. PMID: 19302064
- 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
- Bennett MJ, Boriack RL, Narayan S. Novel mutations in CPT 1A define molecular heterogeneity of hepatic carnitine palmitoyltransferase I deficiency. Molecular genetics and metabolism. 2004. PMID: 15110323
- Ramsay RR, Zammit VA. Carnitine acyltransferases and their influence on CoA pools in health and disease. Molecular aspects of medicine. 2004. PMID: 15363637
- Bonnefont JP, Djouadi F, Prip-Buus C. Carnitine palmitoyltransferases 1 and 2: biochemical, molecular and medical aspects. Molecular aspects of medicine. 2004. PMID: 15363638
- Gobin S, Thuillier L, Jogl G. Functional and structural basis of carnitine palmitoyltransferase 1A deficiency. The Journal of biological chemistry. 2003. PMID: 14517221
- Gobin S, Bonnefont JP, Prip-Buus C. Organization of the human liver carnitine palmitoyltransferase 1 gene ( CPT1A) and identification of novel mutations in hypoketotic hypoglycaemia. Human genetics. 2002. PMID: 12189492
- Brown NF, Mullur RS, Subramanian I. Molecular characterization of L-CPT I deficiency in six patients: insights into function of the native enzyme. Journal of lipid research. 2001. PMID: 11441142
- Adam MP, Bick S, Mirzaa GM. Carnitine Palmitoyltransferase 1A Deficiency. 1993. PMID: 20301700