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SLC22A5
solute carrier family 22 member 5
The SLC22A5 gene provides instructions for producing the OCTN2 protein, which is essential for transporting carnitine into cells, especially in the heart, liver, muscles, and kidneys. The SLC22A5 gene plays a critical role in cellular metabolism by directing the synthesis of the OCTN2 protein, a transporter of carnitine.
SLC22A5 is located on the long (q) arm of chromosome 5, at band 5q31.1. Arm ratio per GRCh38 - banding schematic.
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Overview
The SLC22A5 gene, also known as solute carrier family 22 member 5, encodes a protein called OCTN2, which is vital for cellular function. This protein is primarily responsible for the transport of carnitine, a molecule crucial for energy metabolism, into cells throughout the body.
Dysfunction of the SLC22A5 gene, often due to genetic variants, can impair carnitine transport, leading to a build-up of fatty acids and reduced energy production. This can result in conditions such as primary carnitine deficiency.
What the gene does
The SLC22A5 gene directs the production of the OCTN2 protein, a member of the solute carrier family of transporters. The OCTN2 protein is embedded within cell membranes, where it actively transports carnitine from outside the cell into the cytoplasm. Carnitine, largely acquired through diet, is indispensable for cellular energy production.
Specifically, carnitine carries certain types of fats, known as fatty acids, into the mitochondria. Mitochondria are often referred to as the 'powerhouses' of the cell because they convert these fatty acids into energy. This process is particularly important for organs with high energy demands, such as the heart and muscles. During periods of fasting, fatty acids become the primary energy source for these tissues, underscoring the importance of efficient carnitine transport for maintaining metabolic balance.
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Chromosome location
The SLC22A5 gene is situated on the long arm of chromosome 5, specifically at position 5q31.1. This location indicates its precise address within the human genome.
Protein structure
The SLC22A5 gene encodes a protein consisting of 557 amino acids. The OCTN2 protein contains a disordered region spanning amino acids 535-557, suggesting flexibility that may be important for its function or regulation. The overall structure facilitates its role as a transmembrane carnitine transporter.
Key variants
Genetic variants within the SLC22A5 gene can impact the structure and function of the OCTN2 protein. These changes can range from single amino acid substitutions to alterations that introduce premature stop signals, resulting in a truncated, non-functional protein. Such variants can disrupt the protein's ability to transport carnitine effectively into cells.
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.1073A>G | p.Tyr358Cys | Pathogenic/Likely pathogenic | ★★☆☆ | Renal carnitine transport defect |
c.1104_1105insGAGTATCTTTGTG | p.His369fs | Pathogenic | ★★☆☆ | Renal carnitine transport defect |
c.1161T>G | p.Tyr387Ter | Pathogenic | ★★☆☆ | Renal carnitine transport defect |
c.1347del | p.Val448_Tyr449insTer | Pathogenic/Likely pathogenic | ★★☆☆ | Carnitine deficiency |
c.1451-2A>G | - | Pathogenic/Likely pathogenic | ★★☆☆ | Renal carnitine transport defect |
c.16G>T | p.Glu6Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Carnitine deficiency |
c.497+1G>A | - | Pathogenic/Likely pathogenic | ★★☆☆ | Renal carnitine transport defect |
c.517del | p.Leu173fs | Pathogenic | ★★☆☆ | Renal carnitine transport defect |
c.671del | p.Lys224fs | Pathogenic/Likely pathogenic | ★★☆☆ | Renal carnitine transport defect |
c.782_799del | p.Val261_Pro266del | Pathogenic/Likely pathogenic | ★★☆☆ | Carnitine 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
Variants in the SLC22A5 gene are primarily associated with primary carnitine deficiency. This inherited metabolic disorder arises from impaired carnitine transport, leading to insufficient fatty acid metabolism and energy production within cells. While primary carnitine deficiency is the main condition, some research has also explored potential associations with Crohn's disease.
- Primary carnitine deficiency Dedicated page coming soon
Inheritance pattern
Conditions caused by pathogenic SLC22A5 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 SLC22A5 gene is included in several NHS England Genomic Medicine Service approved panels. These include panels for Acute rhabdomyolysis, DDG2P, Hyperammonaemia, Likely inborn error of metabolism, Mitochondrial disorders, Paediatric or syndromic cardiomyopathy, 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 is the main function of the SLC22A5 gene?
The SLC22A5 gene provides instructions for making the OCTN2 protein, which is responsible for transporting carnitine into cells. Carnitine is crucial for moving fatty acids into mitochondria, where they are converted into energy for the body.
What is primary carnitine deficiency?
Primary carnitine deficiency is an inherited metabolic disorder caused by genetic changes in the SLC22A5 gene. These changes impair the OCTN2 protein's ability to transport carnitine, leading to problems with energy production from fats.
Where is the OCTN2 protein found in the body?
The OCTN2 protein, encoded by the SLC22A5 gene, is found in the cell membranes of various tissues throughout the body, including the heart, liver, muscles, and kidneys. These organs have high energy demands and rely on efficient carnitine transport.
References
- Li FY, El-Hattab AW, Bawle EV. Molecular spectrum of SLC22A5 (OCTN2) gene mutations detected in 143 subjects evaluated for systemic carnitine deficiency. Human mutation. 2010. PMID: 20574985
- Koepsell H, Endou H. The SLC22 drug transporter family. Pflugers Archiv : European journal of physiology. 2004. PMID: 12883891
- Amat di San Filippo C, Longo N. Tyrosine residues affecting sodium stimulation of carnitine transport in the OCTN2 carnitine/organic cation transporter. The Journal of biological chemistry. 2004. PMID: 14665638
- Inano A, Sai Y, Kato Y. Functional regions of organic cation/carnitine transporter OCTN2 (SLC22A5): roles in carnitine recognition. Drug metabolism and pharmacokinetics. 2004. PMID: 15499185
- Tein I. Carnitine transport: pathophysiology and metabolism of known molecular defects. Journal of inherited metabolic disease. 2003. PMID: 12889657
- Amat di San Filippo C, Wang Y, Longo N. Functional domains in the carnitine transporter OCTN2, defective in primary carnitine deficiency. The Journal of biological chemistry. 2003. PMID: 14506273
- Lahjouji K, Mitchell GA, Qureshi IA. Carnitine transport by organic cation transporters and systemic carnitine deficiency. Molecular genetics and metabolism. 2001. PMID: 11509010
- Nezu J, Tamai I, Oku A. Primary systemic carnitine deficiency is caused by mutations in a gene encoding sodium ion-dependent carnitine transporter. Nature genetics. 1999. PMID: 9916797